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Research Papers

J. Med. Devices. 2009;3(2):021001-021001-6. doi:10.1115/1.3131729.

Good arthroscopic view is important to perform arthroscopic operations (minimally invasive surgery in joints) safely and fast. To obtain this, the joint is irrigated. However, optimal irrigation settings are not described. To study the complex clinical practice of irrigation, a physical simulation environment was developed that incorporates the main characteristics for performing arthroscopy. Its irrigation capacities were validated with patient data. The physical simulation environment consists of a specially designed knee phantom, all normally used arthroscopic equipment, and registration devices for two video streams, pressures, and flows. The physical embodiment of the knee phantom matches that of human knee joints during arthroscopic operations by the presence of important anatomic structures in sizes comparable to human knee joints, the presence of access portals, and the ability to stress the joint. The hydrostatic and hydrodynamic behavior of the knee phantom was validated with pressure and flow measurements documented during arthroscopic knee operations. Surgeons confirmed that the knee phantom imitated human knee joints sufficiently. The hydrostatic parameters of the knee phantom could be tuned within the range of the human knee joints (restriction: 0.026629.3Ns2/m8 versus 0.01431.22×1018Ns2/m8 and capacitance: 6.89m5/N versus 7.50×109m5/N). The hydrodynamic properties of the knee phantom were acceptably comparable to those of the human knee joints. The physical simulation environment enables realistic and conditioned experimental studies to optimize joint irrigation. The foundation has been laid for evaluation of other surgical instruments and of training of surgical skills.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):021002-021002-12. doi:10.1115/1.3131727.

A new planar robotic exoskeleton for upper-limb motor assessment has been developed. It provides independent control of a user’s shoulder, elbow, and wrist joints in the horizontal plane. The lightweight backdriveable robot is based on a novel cable-driven curved track and carriage system that enables the entire mechanism to be located underneath the user’s arm. It has been designed to extend the assessment capabilities of an existing planar robotic exoskeleton. This paper presents the design and performance of the new robot.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):021003-021003-7. doi:10.1115/1.3148835.

The maintenance of a clear view on the operation area is essential to perform a minimally invasive procedure. In arthroscopy, this is achieved by irrigating the joint with a saline fluid that is pumped through the joint. At present, the arthroscopic sheaths are not designed for optimal irrigation, which causes suboptimal arthroscopic view. The goal of this study is to present new design concepts and their technical evaluation to optimize irrigation. We focused on decreasing the fluid restriction and stimulating turbulent inflow streams. This is achieved by combining analysis of clinical practice, fluid mechanics theory, and experiments. A distinction is made between a three- and a two-portal technique. For a three-portal technique, the design concept consisted of a conventional sheath (4.5mm) used with a smaller diameter arthroscope (2.7mm). This resulted in a decreased fluid restriction. For the two-portal technique, a partition is designed, which separates the inflow and outflow streams in this sheath. Practical embodiments of the concepts are evaluated experimentally, in comparison with conventional sheaths. The setup consisted of a simulated arthroscopic operative setting of a knee joint. The main discriminating measures are the irrigation time, the fluid restriction, the flow, and the pressure in the joint. The results show that the proposed concept for the three-portal technique decreased the irrigation time significantly by 25%, and the concept with the partition for the two-portal technique decreased the irrigation time by 67% (analysis of variance, p<0.05). Different sheath tips showed no significant differences, leaving the straight shaft as the preferred embodiment. The simulation environment proved to be a suitable platform to test devices in a conditioned setting. The new sheath is expected to be a valuable improvement in achieving optimal irrigation.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):021004-021004-15. doi:10.1115/1.3148836.

The medical device development process has become increasingly complex in recent years. The advent of new technology concepts, stricter regulatory requirements, and the ever increasing importance of reimbursement decisions for successful device commercialization require careful planning and strategy-setting, coordinated decisions, and consistent, rigorous business processes. The design and implementation of such processes, often captured in development models and accompanying standard operating procedures, have become a key determinant of the success of device commercialization. While various models may exist in the device industry, no comprehensive development model has been published. This paper reviews existing model representations and presents a new comprehensive development model that captures all aspects of device development and commercialization from early-concept selection to postmarket surveillance. This model was constructed based on best-practice analysis and in-depth interviews with more than 80 seasoned experts actively involved in the development, commercialization, and regulation of medical devices. The stage-gate process includes the following five phases: (1) initiation - opportunity and risk analysis, (2) formulation - concept and feasibility, (3) design and development - verification and validation, (4) final validation - product launch preparation, and (5) product launch and postlaunch assessment. The study results suggest that stage-gate processes are the predominant development model used in the medical device industry and that regulatory requirements such as the food and drug adminstration (FDA’s) Quality Systems Regulation play a substantive role in shaping activities and decisions in the process. The results also underline the significant differences between medical device innovation and drug discovery and development, and underscore current challenges associated with the successful development of the increasing number of combination products.

Commentary by Dr. Valentin Fuster

Technical Briefs

J. Med. Devices. 2009;3(2):024501-024501-4. doi:10.1115/1.3116251.

Infants with Down syndrome show an altered pattern of motor development at early childhood. Treadmill-walking training can be used to promote the earlier attainment of motor milestones in infants with locomotion deficiencies but quantitative data on their motor development are limited to gait laboratory studies. Our purpose was to develop, validate, and test a low-cost portable system for detecting infant steps on a treadmill while training. The system includes five infrared distance sensors, which were placed on a motorized treadmill to record the location of the feet of the infant during walking and thus measure his/her step length and cadence. The system was validated using synthetic objects, with a healthy 13-month-old infant. Pilot studies were then conducted in additional five infants with Down syndrome (aged 11–28 months) to determine step length (17.5–22.3 cm) and cadence (0.33–2.16 steps/s) at baseline, as well as at follow-ups 1 month and 3 months after the first trial. Measurements were repeatable per session and agreed with values reported in the literature. These pilot studies indicate the potential utility of the present system in quantitative monitoring of the process of acquisition of initial gait in infants with Down syndrome at the care facility where routine therapy is given.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):024502-024502-4. doi:10.1115/1.3148837.

Successful commercialization of medical technologies increasingly requires developers and manufacturers to think early-on about regulatory approval and reimbursement strategies for their new devices. This can be particularly challenging in the case of monitoring devices, where demonstrating the effectiveness and finding the coding and coverage can often be a complicated and lengthy process, particularly with the given current reimbursement policy. In this paper, we use three technology case studies to examine how firms are navigating the status quo and illustrate the importance of incorporating a comprehensive understanding of current market and regulatory constraints into the development and commercialization process. The case studies suggest that viable approaches can include pairing a monitoring technology with a therapy, or relying on hospital-pay or patient-pay models that are based on demonstration of direct benefits or cost-savings to these parties. The results emphasize that successful innovation in monitoring technologies increasingly requires a very closely aligned engineering, business, and health-economic strategy. Developing a comprehensive understanding of the specific value drivers and policy-induced constraints can contribute substantially to achieving the true benefits of monitoring technologies.

Commentary by Dr. Valentin Fuster

Design Innovation

J. Med. Devices. 2009;3(2):025001-025001-8. doi:10.1115/1.3139835.

This paper focuses on the design and implementation of a percutaneous catheter-based device to provide physicians with an externally controlled tool capable of manipulating and cutting specific chordae tendinae within the heart to alleviate problems associated with some forms of mitral valve (MV) regurgitation. In the United States alone, approximately 500,000 people develop ischemic or functional mitral regurgitation per year. Many of these patients do not possess the required level of health necessary to survive open-heart surgery, and the development of a chordal cutting procedure and device is needed to allow these patients to receive treatment. A deterministic design process was used to generate several design concepts and then evaluate and compare each concept based on a set of functional requirements. A final concept to be alpha prototyped was then chosen, further developed, and fabricated. Experiments showed that the design was capable of locating and grabbing a chord and that ultrasound imaging is a viable method for navigating the device inside of the human body. Once contact between the chord and radio-frequency (RF) ablation tip was confirmed, the chord was successfully ablated.

Commentary by Dr. Valentin Fuster

2009 Design of Medical Devices Conference Abstracts

J. Med. Devices. 2009;3(2):027501-027501-1. doi:10.1115/1.3157549.
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Abstract
Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027502-027502-1. doi:10.1115/1.3134763.
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Loss of mobility due to lower limb paralysis is common consequence of thoracic level spinal cord injury (SCI). In the US there are approximately 253,000 persons with SCI. The wheelchair is the most common form of mobility for individuals with paraplegia but there remains a need for assistive technology that can enable paraplegics to walk and reach in the periphery of wheelchair. A new concept is presented that combines functional electrical stimulation (FES) with an energy storing orthosis (ESO) that contains a fluid power system to store and transfer energy during the gait cycle. Elastic energy storage elements on the orthosis hip and knee joints hold the leg in a flexed equilibrium position. Stimulation of the quadriceps extends the knee, placing excess energy in both the equilibrium spring and an energy transfer element. The stored energy is transferred to the hip where it is discharged and used to extend the hip against its equilibrium spring which also aids in forward progression. A new step is initiated by releasing the hip and knee joints from the straight leg position to the flexed position. The concept is realized using gas springs and pneumatic cylinders. Gas springs act as flexed energy storage elements. Lower air cylinder and the tubing acts as an accumulator and the upper cylinder acts as hip joint actuator. The system uses 2 way proportional solenoid actuated pneumatic valves for control during extension. The conceptual design of the ESO was completed and implemented in a dynamic simulation model (MSC ADAMS) and in a benchtop prototype for engineering measurements. Of the 14 joules of energy available from quadriceps, 8.9 joules of energy is utilized for doing work against springs and inertial forces; 5.4 joules is stored in pneumatic system; of which 1.4 joules is required for hip extensions and the remaining will be used for forward progression. No studies were conducted with human subjects. A hydraulic fluid power system was investigated for better control and braking possibilities but was not adopted because of difficulities in accumulator design and high fluid friction losses. A Matlab code was used to calculate the torques required at joints to support standing. Commerical braces are being used for improved user comfort. A wrap spring brake is being designed to maintain standing posture without FES or any active energy input. Technical feasibility of the ESO prototype will be evaluated using two subjects with paraplegia.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027502-027502-1. doi:10.1115/1.3134784.
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Cardio-pulmonary resuscitation (CPR) plays an important role in the outcome of sudden cardiac arrest, where survival rates continue to be very low, about 5%. CPR has evolved significantly from the days when it was standard practice to flap the arms of victimes, or roll their bodies back and forth over a wooden barrel. Today, many people know the standard technique of giving chest compressions. Others may know about enhancement devices (e.g., ResQPOD) that use a basic mechanics concept of creating negative thoracic pressure during the decompression phase of CPR. This is done by adding inflow resistance to the patient's airway, such that a vacuum is created at each chest decompression. The vacuum pulls blood into the thorax, in effect “priming the pump” with more blood, which is then ejected in the next compression phase. We present an enhancement to the above proven concept of airway restriction during CPR by further adding total airway occlusion to the inflow and outflow of air at appropriate times, by use of a CPR enhancement device (CED). With a face mask and electronic airway valve, maximal vacuum and positive pressures are created in the thorax to enhance blood circulation during cardiac arrest. A CPR cycle is proposed with five phases including two for free air exchange, without the need to interrupt compressions, and adhering to AHA guidelines of 100 compressions per minute. To test the CED, a human cardiopulmonary model is described that allows blood pressure changes to be measured with the various forms of CPR, new and conventional. Preliminary data from testing both CED and standard CPR on the thorax model were found in terms of mean, systolic and diastolic pressure. T-tests evaluated statistical significance. During normal CPR, average systolic pressure was found to be 35.3±0.6 mmHg. When the CED was applied, the average systolic pressure was found to be 62.9±4.5 mmHg (p=0.0002). Average diastolic pressure for normal CPR was found to be 30.4±0.4 mmHg while that of the CED was observed to be 28.6±1.2 mmHg (p=0.095,NS). The MAP calculated from standard CPR resulted in an average of 32.0±0.4 mmHg, while that using the CED was 40±2.1 mmHg, (p=0.002). Based on this preliminary testing and data analysis, the CED shows a significant improvement in systolic and mean arterial pressure in comparison to standard CPR. This supports the CED five phase method that provides positive pressure and vacuum in the cardiopulmonary system during resuscitation. Future work will compare the CED to other CPR enhancement devices.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027503-027503-1. doi:10.1115/1.3134785.
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Implantable medical devices and home monitors make use of wireless radio communication for both therapeutic functions and remote monitoring of patients' vital signs. While our past work showed that lack of cryptographic protection results in disclosure of private medical data and manipulation of therapies (Halperin , IEEE S&P, 2008) our present work shows that even using encryption is insufficient to protect the confidentiality of patient telemetry. Our experiment analyzes the security of data traffic patterns of two sets of real medical telemetry: a corpus from PhysioNet (an online biomedical research database) and a network trace of a live disaster drill using Harvard's CodeBlue medical sensor network (Chen , DCOSS, 2008). Our work shows that even if a wireless medical device uses encryption, patient data can leak to unauthorized parties who need not be near the patient. Our measurements show that data packet timing information and headers distinguish the types of medical and monitoring devices even if traditional cryptographic mechanisms are used. Furthermore, the highly repetitive nature of medical data, such as ECG or respiration signals, leads to additional privacy vulnerabilities that cannot be easily mitigated by means of encryption without significant modification. Data compression technology further exposes encrypted telemetry to cryptanalysis. The information leakage of telemetry could facilitate unauthorized tracking of a patient because an ECG is known to uniquely identify a person in a predetermined group (Biel , IEEE I&M, 2002). Moreover, our study shows that data packet padding, encryption, authentication, and other common defenses against security threats require significant energy, storage, and computation that impose on the already scarce battery and space resources. Two of our experiments show how to automatically recover data from encrypted telemetry using Bayesian classifiers. In one experiment, we encrypted an ECG signal. By observing only the length of the digitally encrypted data, we were able to reconstruct sufficient information about the original ECG data that we determined the patient's heart rate. Using similar techniques, we recovered a leaked respiration signal that visually matches the original signal. Our findings show the weakness of using common cryptographic techniques on highly periodic and often compressed medical telemetry. Our work further discusses techniques to mitigate these security and privacy risks in wireless medical telemetry systems. However, all known techniques require extra energy, computation, and bandwidth from the medical device. The lesson learned is that encryption is not enough to protect the privacy of medical telemetry, and that reasonable assurance for security and privacy will require an energy budget. Future design of medical devices will have to make difficult tradeoffs between battery life versus security and privacy. This work was supported by NSF grants CNS-0627529, CNS-0716386, and CNS-0831244.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027503-027503-1. doi:10.1115/1.3134837.
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Objective: To design a ‘smart’ leg press machine that improves upon current rehabilitative practices for degenerative knee disorders such as osteoarthritis as well as injury induced knee pathologies. As its design entails, the machine provides rehabilitative assistance through strength training of upper leg muscles, with focus on the vastus medialis and vastus lateralis of the quadriceps group. The Therapress is designed to further improve the rate and quality of joint rehabilitation. The TP1600i is unique to current physical therapy practices because it incorporates three documented and proven strategies to combat quadriceps weakness: strength training, electrotherapy, and biofeedback [1,2]. The machine is designed to aid the user in regaining lost quadriceps strength, a condition indicative of poor knee health [3]. The machine incorporates a novel package of biofeedback, automated continuous variable resistance, and progress assessment, while maintaining subject specificity. The Therapress system utilizes a LabVIEW interface, which acquires and processes physiological signals recorded from the subject, as well as serves as a controller for output. These signals include surface electromyography (EMG) of the quadriceps, reaction forces at the foot (an indirect measurement of exercise resistance), and knee range of motion (ROM). Additionally, the subject is outfitted with stimulatory electrodes which function to characterize muscle recruitment using the Central Activation Ratio (CAR), as well as to therapeutically excite the muscle and induce accelerated hypertrophy [4]. Automated continuous variable resistance is achieved through a resistive hydraulic cylinder, which utilizes a servo motor to change the orifice size of partially overlapping valves during and between exercise sets. The resistance is adjusted based on user input of exertion and pain levels into the LabVIEW interface. The footplate of the machine houses four force sensing units to measure the resistance offered by the cylinder. A biofeedback arm attached to the system provides the subject with real-time data of their performance, including integrated EMG activity, ROM, and force production. Inclusion of biofeedback in quadriceps exercise regimens has been shown to increase strength gain [2]. The design allows the user to be in control of the exercise intensity at all times, while the machine works to maximize the efficacy of the protocol. The TP1600i is designed as a cost effective and time efficient alternative for the rehabilitation of debilitating knee disorders in a physical therapy protocol, and its ease of operation may qualify it for home use as well.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027504-027504-1. doi:10.1115/1.3134838.
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Magnetic bearings are becoming increasingly popular in ventricular assist devices. In most cases, blood fills a portion of the gap between the magnetic actuators and rotor. Understanding the effects of the operating fluid on magnetic suspension is necessary, particularly when the device geometry features a relatively large gap (typically defined as greater than 150 um and as large as 2 mm in some pumps). A large gap reduces cell damage and allows unrestricted flow, it but increases the distance and amount of material through which magnetic fields must pass. These net effects of the operating fluid on the magnetic suspension can be characterized in terms of a contribution to the overall damping and stiffness of the system. This contribution may be caused by traditional tribological properties (density and viscosity) as well as the magnetic properties of the medium. This research isolates the effects of fluid diamagnetism on a magnetically levitated blood pump. Experimental transient and frequency responses of the system operating at 3000 to 6000 rpm are presented while pumping different liquid media: Blood, water, and fluids with similar densities and viscosities to each, but different magnetic susceptibilities. In order to calculate the stiffness and damping coefficients, a mathematical model of the system is iteratively updated to match experimental transient response. The resulting coefficients are validated in the frequency domain by means of simulations, which agree with experimental frequency response data. The relationship between diamagnetism, damping and stiffness coefficients of the test fluids with known magnetic susceptibility is also used to obtain a quantitative estimate of the magnetic susceptibility of blood.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027504-027504-1. doi:10.1115/1.3134839.
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Benign Prostatic Hyperplasia (BPH) is a non-cancerous growth of the prostate gland affecting about 50% of the men over age 50. As men age, the prostate continues to grow leading to increased prostate volume, which may cause lower urinary tract symptoms (LUTS). These symptoms can include the inability to completely empty the bladder, urine retention, and a profound sensation of urgency. Direct Current (DC) ablation may be applied to treat these symptoms as a minimally-invasive alternative to surgery, medication, or thermal ablation, by causing tissue necrosis within the lateral lobes of the prostate. The objective of this study was to evaluate the effects of DC ablation in canine prostates by investigating how the resulting necrosis would change the macrostructure of the prostate for the potential treatment of symptomatic BPH. DC ablation is achieved by passing direct current through two electrodes in tissue, causing the formation of hydrogen ions at the anode and hydroxyl ions at the cathode. These ions diffuse through the tissue causing a pH of 1 at the anode, and 13 at the cathode. The extreme anti-physiological pH regions cause cellular necrosis and form in a predictable manner that is directly proportional to the charge delivered. The controlled shape and size of the lesions allow for predictable necrotic zones and enable treatment optimization. Treatment was performed on 6 acute and 8 chronic canine subject by performing a laparotomy and inserting electrodes through the prostate capsule. Acute subjects were sacrificed before recovery, while chronic subjects were sacrificed after 1, 3, 20, 40, and 60 days to investigate the healing cascade of the prostate after treatment. The chronic subjects were monitored for changes in urination or defecation patterns. Urine and blood samples were collected to evaluate the subjects' health throughout the study. Both macro-visual and pathological analyses were done to evaluate tissue response all acute and chronic subjects. Cellular necrosis within the prostate was significant and exhibited a dose response within the range of 0.07 to 0.10 cm3/coulomb for each electrode pair. The does response is defined as the ratio of necrotic tissue created, to charge delivered. Necrotic prostate cells resulted in voids with minimal scar tissue and a visible reduction in prostate mass. The treatment followed tissue planes constraining necrotic zones to the region between the prostate capsule and prostatic urethra. Both normal and hyperplastic tissues were treated and exhibited necrosis. No necrosis was observed outside the prostate. DC ablation has been demonstrated to create well-defined, predictable, and repeatable regions of cellular necrosis and structural changes in canine prostates. This technology may offer promise for the treatment of symptomatic BPH with an appropriately designed delivery system. Other potential applications include other benign and malignant tumors within the body.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027505-027505-1. doi:10.1115/1.3134840.
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There is a need to measure contact pressures at the femoral component and tibia plate of a knee arthroplasty implant to determine the wear and tear of the polyethylene (PE) insert of the implant. Today, most pressure monitoring systems for knee arthroplasty implants are either limited to in vitro or intraoperative use, or cannot measure contact pressures at the polyethylene surface. Here, we are developing a wireless passive sensor system for measuring the contact pressure at the knee arthroplasty in vivo. The sensor system is made of a pressure-sensitive magnetic layer embedded under the top surface of a PE insert used for mapping the contact pressures with the femoral components. The pressure-sensing layer consists of a grid of pressure and stress sensitive magnetoelastic thin strips that alter their magnetic properties with applied force. Measurements are taken at pressure points located at the crossings of the grid. The magnetization of each sensing strip is remotely measured by using an AC magnetic field to excite the material to generate higher-frequency fields, which are then detected through external detection coils. The responses of these sensing strips are fed into an algorithm to determine the pressure loadings at all pressure points, which allows for real-time, in vivo determination of pressure profiles on the PE insert. By using an array of magnetoelastic sensing strips, we have demonstrated the remote detection of pressure across a surface. The 2nd order harmonic amplitude of a 30 mm×1.5mm magnetoelastic strip decreased linearly with increasing pressure. For this sensing strip, the rate of decrease was about 0.1 (normalized to unstressed signal level) per 200 kPa. An algorithm was also developed to determine the pressures at all pressure points from the responses of the sensing strips. Experimental results have shown that the algorithm can accurately map the pressure profile of a 3×3 sensing strip array. Further works include developing a fabrication process for safely embedding the sensing strips into a PE insert, and modifying the algorithm for a larger sensing strip array.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027505-027505-1. doi:10.1115/1.3134841.
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There is a high level of patient appeal and physician acceptance of motion preservation as the future treatment of symptomatic and painful degenerative disc disease. However, spinal artificial disc replacement is still in its infancy. We have been designing, developing and evaluating motor articulated implants for use in bone-spinal disc surgery for Asian population. Apart from the generally smaller built of Asian compared to the American and European, the motor articulated implant should make provisions for the difference in eastern and western lifestyles. In the eastern world, we generally sit on a lower platform. Frequent activities like squatting result in a different stress-strain profile on the lower spine of an Asian compared to that of the Westerner. Preserving the motion of flexion bending in human lumbar spine is important. The motion preservation characteristics have to be maintained without compromising device durability, bone-device interfaces and corrective intervention. A systematic approach was adapted in designing the implant. Physical size of the implant should replicate the actual Intravertebral Disc (IVD). Implant should be able to fit into vertebral body. This is aid by shaping the spine vertebral body to accommodate the implant. A motor articulated implant must have suitable spaces for the implementation of sensors to detect forces and motors to control the motion of the prototype. The device must be able to receive real-time sensory inputs which can then modulate the implant orientation in bending accordingly. A prototype of the implant device has been fabricated to study its motion preservation capabilities. The prototype comprises of a parallel manipulator mechanism where the top plate is linked to the base plate by independent kinematic chains. The mechanical structure is made of Aluminium 6061. The mechanical parts were also put through the chemical process of anodizing for a good finishing surface. In the prototype device, we used three DC micromotors (Faulhaber) for actuation. Due to the small dimension, fibre optics pressure sensors were used. Three customized sensors were developed, calibrated and deployed on the upper plate. A PIC32 microprocessor was used to compute the compliance motion of the prototype when subjected to forces during flexion bending motion. The computer simulation of the kinematics of the parallel mechanism demonstrated the implant's flexion bending capabilities. We are conducting biomechanical experiments with this prototype implant deployed between L3–L5 of an artificial spinal column. The prototype device should achieve motion preservation capabilities comparable to the existing implants. More computer simulation will also be conducted to improve the mechanical design and control mechanisms of the proposed disc implant.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027506-027506-1. doi:10.1115/1.3134931.
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Autism is one of the five pervasive development disorders that may cause severe impairment to a child. Depending on the degree of the symptoms, autism may cause severe impairments in one's social life such as social interaction and communication with other individuals. They may also face challenges in learning, concentrating, sensation and interacting with their surroundings. According to the Center for Disease Control (CDC), 1 in 150 8-year old children in many areas in the United States were diagnosed with autism. It is also known from recent studies that with early diagnosis we can intervene earlier which allows better assistance and treatment. Therefore, it is critical to have an objective assessment tool to assist diagnosis and for management. We have developed an affordable, reliable system that provides evidence based tools for assessment of children with autism. This system can detect various repetitive behavioral patterns often seen in children with autism and enables long term monitoring of repetitive behaviors. Therefore, it can be used to assist doctors, therapists, caregivers and parents with diagnosis and treatment of children with autism. This system incorporates 2 different sensor platforms which include environmental and wearable sensors. The system consists of a 3-axis accelerometer, small microcontroller and a Bluetooth module to transmit data to a base station such as a PC for analysis. We have customized this wearable device to integrate these modules which can be worn by a child. The environmental sensor configuration is composed of a microphone which records the acoustic data of the subject within the room. Using this sensor system, we are able to achieve the necessary information for assessment and therapy in autism research. We have analyzed the 3-axis accelerometer and acoustic data with an intelligent machine learning algorithm. The algorithm extracts time-domain and frequency domain features from the accelerometer data and applies statistical learning techniques to detect repetitive behavioral patterns. For acoustic data, we used sparse signal representation techniques to detect repetitive patterns that indicate vocalization behaviors. We have achieved an average of 89% in classification accuracy for detecting behavioral patterns. Based on the real data collected from children with autism, we were able to detect and recognize four self-stimulatory behaviors of children with autism. In one instance in which a subject had a tantrum, using the correlation between the hand flapping ratio and vocalization intensity, we were able to predict this extreme behavior. Our study opens an application in which devices could be used in a classroom environment to predict extreme behaviors in order that the stress of children with autism could be diverted accordingly so that their actions would be more socially agreeable.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027506-027506-1. doi:10.1115/1.3134998.
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An active cannula is a surgical device capable of dynamically changing its curved shape in response to rotation and translation of the several precurved, concentric, superelastic tubes from which it is made. As the tubes move with respect to one another in response to input motion at their bases (outside the patient), they elastically interact, causing one another to bend. This bending can be harnessed to direct the cannula through winding trajectories within the human body. An active cannula has the potential to perform a wide range of surgical tasks, and it is especially well suited for guiding and aiming an optical fiber (e.g. BeamPath from OmniGuide, Inc.) for laser ablation. Controlling the trajectory of the laser requires control of the shape of the active cannula, and in particular the position and orientation of its tip. Prior work has shown that beam mechanics can be used to describe the shape of the cannula, given the translations and axial angles of each tube base. Here, in order to aim the laser, we invert this relationship (obtaining the “inverse kinematic”), solving for the translations and axial angles of each tube, given a desired position and orientation of the cannula tip. Experimental evaluation of inverse kinematics was carried out using a prototype consisting of three tubes. The outermost tube is straight and rigid (stainless steel), with an outer diameter (OD) of 2.4 mm. The 1.8 mm OD middle tube is superelastic Nitinol, with a preshaped circular tip. The 1.4 mm OD innermost tube is Nitinol and is not precurved, representing the straight trajectory of a laser emanating from the tip of the cannula. We assessed the accuracy of the inverse kinematics by computing the necessary tube translations and rotations needed to direct the beam of the “laser” to sequential locations along a desired trajectory consisting of two line segments that meet at a corner. These inputs were then applied at tube bases to direct the laser to thirty points along the trajectory on a flat surface 100 mm away the cannula base. The position of the tip of the simulated laser was measured using an optical tracker (Micron Tracker H3-60, Claron, Inc.). Mean error between desired and actual positions was 3.1 mm (maximum 5.5 mm). This experiment demonstrates proof of concept for laser guidance, and establishes the accuracy of the inverse kinematic model. We note that these results are applicable to guidance of a wide range of medical devices in addition to lasers. Relevant references, as well as images of our prototype and experimental data described here can be found in an online version of this abstract at http://research.vuse.vanderbilt.edu/MEDLab/. This work was supported by NSF grant #0651803, and NIH grant #1R44CA134169-01A1.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027507-027507-1. doi:10.1115/1.3135043.
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The tooth is a biological entity comprising of a hard enamel layer, encasing the softer (but still hard) dentine which conceals the much softer pulp chamber. Dental caries, commonly known as tooth decay, is the localized demineralization of enamel or dentine caused by the acidic by products of bacteria. Current methods of detection and diagnosis routinely used in the dental surgery are limited to the subjective act of visual inspection (with aide of a metal probe known as an explorer) and bitewing X-ray. Neither method provides quantitative information about the state of the disease in the tooth for accurate diagnosis and subsequent treatment planning. Such methods are also poor at detecting disease in the early (and most treatable) stages. There are, however, new technologies, generally optically based, making their way into the dental clinic, including Quantitative Light Fluorescence and the DiagnoDent tool. Both methods are able to improve the detection rates of dental caries, however, the outputs from these tools are still somewhat subjective and not quantitative, in particular providing no information on the depth of a lesion. We are reporting on work carried out using the technique of Fibre Optic Confocal Microscopy (FOCOM) in order to produce a device which can record depth profiles through the tooth and allow detection and quantification of subsurface lesions. The method has been shown to detect caries lesions and this paper concentrates on the miniaturisation of the tool for use in the oral cavity within the dental clinic. Two types of miniature lenses, GRIN and aspheric, are investigated using a computer simulation followed by experimental verification. The subsequent choice of the latter is then reported in a desktop system in the near infrared to produce depth profiles through extracted teeth with these profiles showing different characteristics between sound enamel and lesioned enamel. Results with the system used to monitor the change in surface reflection from a tooth during acid erosion of the enamel surface. The results from this new diagnostic instrument thus have applicability for both detecting and following caries lesions during a planned treatment programme of remineralization as well as to monitor the effects of acid erosion a growing dental problem caused by the consumption of acidic soft drinks.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027507-027507-1. doi:10.1115/1.3135078.
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Indirect laryngoscopy allows practitioners to “see around the corner” of a patient's airway during intubation. Inadequate airway management is a major contributor to patient injury, morbidity and mortality. The purpose of the present study was to evaluate the video quality of commercially available video laryngoscopy systems. A team of four investigators at the University of Nebraska at Omaha and the Peter Kiewit Institute performed intubation simulations using a number of video laryngoscopy systems. Testing was done with a Laerdal Difficult Airway Manikin (Laerdal Medical Corp., Wappingers Falls, NY) in a setting that simulated difficult airways, adverse lighting conditions and various system configurations (e.g., maximizing screen contrast, minimizing screen brightness, maximizing screen color hue, etc.). Systems included the STORZ C-MACTM (KARL STORZ Endoscopy, Tuttlingen, Germany), a prototype developed by STORZ (a McIntosh #3 video blade with USB connectivity to an ultra mobile PC; “UMPC”) and a GlideScope® Portable GUL (Verathon Inc., Bothell, WA). Equipment was evaluated based on investigator's perceptions of the color (“C”), clarity (“L”) and brightness (“B”) of the image onscreen for each of the systems. Perceptions were given one of three possible ratings: High=3, Moderate=2 or Low=1. Statistics were performed using a two-tailed Wilcoxon Rank Sum test for independent samples. A summary of the results of the testing are shown below (shown as “Mean±Standard Deviation”):

• C-MAC–L=2.13±0.99, C=1.75±0.89, B=2.5±0.93, Total=6.38±2.5

• GlideScope®–L=2.38±0.92, C=1.38±0.52, B=2.38±0.92, Total=6.13±1.96

• UMPC–L=1.88±0.83, C=1.75±1.04, B=1.88±0.83, Total=5.5±2.2

Testing showed that there were no significant differences between image clarity, color, brightness or overall score of any of the tested systems (α=0.05). Since there were no significant differences in video quality between the three systems, the choice of system falls to user preference, which can vary from person to person, and qualitative analysis of features that are outside the scope of this study. Investigators plan to evaluate additional video laryngoscopy solutions in an effort to create a platform-agnostic video laryngoscopy suite. Funding by KARL STORZ Endoscopy. Investigators were blinded to funding source until after testing was completed. The authors wish to thank Dr. W. Bosseau Murray for his insightful comments.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027508-027508-1. doi:10.1115/1.3135121.
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Colon cancer is the second leading cause of cancer-related death in the United States. Colonoscopy is the best technology available to detect and treat abnormalities within the colon. It is a procedure that enables a gastroenterologist to evaluate the appearance of the inside of the colon by inserting a flexible tube with about 3/8 in diameter into the anus, and then advancing it slowly, under visual control, into the rectum and through the colon. This procedure is often onerous due to that the driving of the bending section (tip) of the scope and perforation may occur with the rate of 1 out of 1700 procedures. The tip driving system consists of two angulation knobs, two chain-sprocket mechanisms, a series of ring-pivot mechanism, and two pair of wires. Rotating each knob extends and retracts a pair of wires which changes the orientation of the bending section. The up/down angulation knob generates an elevation motion and the left/right angulation knob generates an azimuth motion. Based on the traditional colonoscopy, this work developed an intelligent technology to extend and enhance the diagnostic and surgical capability of the instrument. This intelligent colonoscope includes an image-based control of the tip to release a doctor from onerous work, advanced imaging systems for diagnostics, and advanced human-machine interfaces to facilitate the doctor's operation in an effective manner. In the realization of the bending section driving automation, the driving mechanism design is one of the key issues. In our design of the bending section motion control mechanism, the handle of the colonoscope and the motors are fixed on a holder. The holder can travel along a track. The track can be fixed on any flat surface such as a desk in order to enlarge the motion range of the colonoscope body. Belt mechanism is used to translate the motion from motors to the knobs. The belt pulley is fixed on the driving knob through four equally distributed screws. In order to keep the belt tied all the time, a rocker mechanism with a spring is used between the motor and the knob. Two motors are used to drive the two angulation knobs. Two limit switches are used to identify the homing position of the two motors. The driving torque is limited through the constraint of the current supplied to the motor by an amplifier to avoid the damage to the mechanical system. Together with the motion control system, the mechanism has been lab-tested using an artificial colon. It is observed that the mechanism performs well to accomplish the automation of the knob driving tasks. The system has also been tested using a pig in the animal lab of a hospital satisfactory results have been obtained.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027508-027508-1. doi:10.1115/1.3135146.
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Harnessing skeletal muscle for circulatory support would improve on current blood pump technologies by eliminating infection-prone drivelines and expensive transcutaneous transmission systems. Here we describe an implantable muscle energy converter (MEC) designed to transmit the contractile energy of the latissimus doris muscle in hydraulic form. The MEC weighs just 290 grams and comprises a metallic bellows actuated by a rotary arm fixed to the humeral insertion of the muscle via a looped artificial tendon. The housing is anchored to the ribcage using a perforated mounting ring (83 mm diameter). Lessons learned through six design iterations have produced a pump with excellent durability, energy transfer efficiency, anatomic fit, and tissue interface characteristics. This report describes recent improvements in MEC design and summarizes results from in silico, in vitro, and in vivo testing. The components most subject to wear in this device are the stainless-steel bellows, spring-loaded lip seals, and load-bearing surfaces (bearings, cams and shafts). Roller bearings supporting the camshaft and cam follower were replaced with needle bearings for better stress distribution and longer cycle life. Camshaft bearings were improved still further by changing to a full-complement configuration to lower stress concentration and reduce lateral (off-axis) shaft movement that could reduce lipseal life. Bellows cycle life was estimated using ANSYS V11 finite element analysis (FEA) software with a mesh size of 0.002”. In this simulation a pressure of 22 psi was applied to the internal surface of the bellows and compression length was set to the longest possible stroke (0.177”). All load-bearing surfaces were analyzed for fatigue stress and cycle life under these same loading conditions following closed form equations. Results show that the overall durability of the MEC device can be expected to exceed 450 million cycles, resulting in a minimum working life of 14.5 years given a 1 Hz cycle rate. Lipseal durability was tested empirically in a 37°C saline bath using a cycling apparatus designed specifically for that purpose. After 55 days (12.3 million cycles) the test was stopped and the unit disassembled and inspected. The shaft and seals showed evidence of contamination buildup in front of the lip seal but not behind it, indicating that the seal had functioned properly throughout the test period. Importantly, implant studies in 30–35 Kg dogs (n=7) confirm excellent anatomic fit, patient comfort, and device functionality to one month. These results suggest that muscle-powered cardiac assist devices are feasible and that efforts to further develop this technology are warranted.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027509-027509-1. doi:10.1115/1.3135148.
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In the world, approximately 800,000 total hip replacements are implanted, while, at least 50,000 hip replacements are performed in the United Kingdom each year. Orthopaedic surgeons have traditionally delayed joint replacement surgery in patients younger than 60 due to its limited survivorship time and biological effect inside the human body. The highest percentage (71%) hip joint failure was caused by aseptic loosening of the femoral and acetabular components and the war rate and debris are the accepted causes of that aseptic loosening. The wear particles, either ion or stable form, can react with proteins and change the pH value of albumin solutions inside the human body, causing damage to the DNA resulting in genotoxicity. There has been a great deal of research into the materials, dimension of the prosthesis, surface roughness, and lubrication effect by surface coating. But it is very rare to apply surface texture technique to a metallic prosthesis bearing surface although it has proven very successful in many engineering applications including automobile industry due to secondary lubrication effect and hydrodynamic effect. A TE 77 high frequency friction simulator has been used for the experiment where specimens were manufactured with 50 mm diameters and 50μm clearance. A dynamic loading was applied synchronized with Hip CD 98 while the temperature was controlled at 37°C. The output data including friction coefficient, friction force and contact pot were recorded in connected computer via COMPEND 2000 software. The surfaces were inspected after and before test under scanning electronic microscopy. The plateau honed surfaces were produced on the moving specimens with controlled load, speed and various grade of emery paper using a specially designed tool. The friction coefficient was recorded 0.035 for the honing surface which was made by 30 kg laod and 60 emery paper, 0.04 for the honing surface profile made by 30 kg load and 150 emery paper and 0.06 for plane surface after one million cycles. The rest of surfaces profiled surface were broken down before one million cycles. That made a conclusion that plateau honing surface made with 30 kg load and 60 emery paper was best surface texture profile (45° honed angle, 40±10μm width and 35±10μm depth honing) for the metal on metal hip prosthesis. The comparison experiment was continue for plane surface and plateau honing surface of 60 emery paper and 30 kg load up to one and half millions cycles. It was found that the friction coefficient (0.03) was further reduced 0.005 after one and half million cycles for plateau honing surface but it was increased nearly double (0.065) for plane surface. The static friction coefficient was also reduced 38% in case of that plateau honing surface. The contact pot profile which is an indicator of fluid film thickness was noticed higher in plateau honing surface. This was evidence that the lubrication distribution was better in plateau honed surface which should provide longer life of joint, reduce wear and improves acceptability of metal on metal hip joints.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027509-027509-1. doi:10.1115/1.3135150.
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Visual, vibrotactile, and auditory cues have proven successful in numerous applications to supplement or in some cases completely replace missing sensory information. Sensory substitution using vibrotactile stimulation has been effective in improving postural stability during stationary tasks and tasks involving perturbed stance. The challenge increases, however, when designing a wearable device that provides meaningful information during a dynamic task such as walking. Techniques that directly apply the feedback strategies effective in stance (trunk tilt) to walking have largely proven ineffective (excluding heel-to-toe walking, which is essentially a series of standing balance tasks). We have demonstrated a device for correcting vestibulopathic gait using a novel feedback methodology that was co-developed with physical therapists specializing in balance rehabilitation. The device supplies vibrotactile cues based on factors during walking that are considered important by physical therapists, including gait velocity, stride length, and gaze. The device consists of three independent units, each consisting of an inertial measurement unit (IMU), vibrotactile display, and microprocessor. Head tilt (which approximates eye gaze), trunk tilt, stride length, and velocity are estimated by the IMUs and displayed to the patient in the form of vibrotactile cues on the head, trunk, and tibia, respectively. Algorithms were developed to estimate stride length and gait velocity in real time from measured heel-strike and toe-off events. Feedback of the head pitch angle is provided continuously to the subject, while gait velocity and stride length feedback are provided during heel strike events only. Preliminary results demonstrate that healthy subjects can interpret this feedback to correct their head pitch and adjust their stride length and gait velocity.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027510-027510-1. doi:10.1115/1.3135151.
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Postural imbalance can result from various vestibular (central and peripheral), neurological, orthopedic, and vascular disorders, as well as sensory conflicts, head injuries, infections, medications, and aging. Balance rehabilitation has been shown to improve the quality of life of individuals with balance disorders by facilitating the development of compensatory strategies which mitigate dizziness, improve balance, and increase the ability to perform activities of daily living. The goal of this work is to design a cell phone based balance training device that can be used in the home to assist a patient with therapist-assigned balance exercises or in an environment where access to balance therapy is limited (i.e., rural regions in the developing world). The prototype comprises an iPhone (iPhone SDK, Apple), an auxiliary pager motor (Samsung GH31-00154C), and an audio amplifier (Analog Devices SSM2301). Body motion is detected by on-board tri-axial accelerometers, and a tilt estimate is computed using a low-pass filter. The phone's native pager motor and an auxiliary pager motor are used to provide real-time vibrotactile cues of body tilt along a single axis. The phone is worn on the small of the back to provide anterior-posterior vibrotactile trunk tilt feedback during stance, and worn near the right hip to provide medial-lateral vibrotactile trunk tilt feedback during gait. Auditory files direct the user through a series of standard balance rehabilitation exercises. A summary of the user's performance is displayed on the phone's screen following completion of the exercise.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027510-027510-1. doi:10.1115/1.3135152.
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3D imaging has become a standard tool in medical diagnostics and, while software is available to visualize volumetric data sets, we do not yet have software that can efficiently transform 3D scan data to solid models that are useful for engineering design and analysis. Why not? Currently, deriving solid models from 3D scans involves 3 steps: (1) segmentation: identification of voxels associated with the structure; (2) polygonization: computing a set of polygons that approximate the surface of the structure; and (3) repair: removing stray voxels and polygons, specifying connectivity, and establishing consistent orientation. Significant progress has been made on accurate, automated segmentation (recent work by Hu et al. (Image Segmentation and Registration for the Analysis of Joint Motion From 3D MRI,” Proc SPIE 6141 , pp. 133–142, Medical Imaging: Visualization, Image-Guided Procedures, & Display, 2006), combining graph cuts with level sets is of particular interest) but effective polygonization cannot be guaranteed. In the worst case, manual repairs are needed to patch holes and remove stray elements. Even if a valid boundary representation (b-rep) model is obtained, accurate models contain so many polygons that modeling operations become unfeasible. Moreover, regardless of accuracy, the surface of a polyhedral model will never be truly smooth. In previous work (Storti, D., et al., Artifact vs. Anatomy: Dealing With Conflict of Geometric Modeling Descriptions,” SAE 2007 Transactions Journal of Passenger Cars: Electronic and Electrical Systems, Paper No. 2007-01-2450, Vol. 116, pp. 813–823, 2007), we proposed overcoming the barriers to creating solid models from 3D scans by employing a new solid modeling description, wavelet SDF-reps, that lies much closer to the native 3D scan format and eliminates polygonization. Here, we focus on the ability to produce models with smooth surfaces that are important for various biomedical simulations. For example, careful studies of joint function involve detailed modeling of ligament wrapping; i.e., connective tissue moving across bone surface as the joint configuration changes. Realistic behavior cannot be obtained if the ligament is snagging on or snapping across convex vertices of a polyhedral model. Similarly, haptic simulation of a catheter navigating through the circulatory system cannot be realistic if the catheter gets stuck in concave vertices of the anatomical model. How can the new modeling format address such issues? Wavelet SDF-reps take advantage of a by-product of the segmentation algorithm (Hue et al.) which converts the raw voxel intensity values to a grid of signed distance values. Applying an appropriate interpolant such as Daubechies wavelets (Daubechies, I., Wavelets, CBMS-NS Series in Applied Mathematics, SIAM Publications, Philadelphia, 1992) then produces an implicit or function-based (f-rep) solid model of the segmented structure. Wavelet SDF-reps are inherently multi-resolution and support significant data compression and medial axis computation. We illustrate the capability of wavelet SDF-reps to support smooth models and enable analysis of curvature features.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027511-027511-1. doi:10.1115/1.3135154.
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The ability to target cancer cells using an appropriate drug delivery system can significantly reduce the associated side effects from cancer therapies and can help in improving overall quality of life post cancer survival. Integrin α5β1 is expressed on several types of cancer cells, including colon cancer, and plays an important role in tumor growth and metastasis. Thus, the ability to target the integrin α5β1 using an appropriate drug delivery nano-vector can signficantly help in inhibiting tumor growth and reducing tumor metastasis. In this study we have designed functionalized stealth liposomes (liposomes covered with polyethylene glycol (PEG)) that specifically target the integrin α5β1. The PEG provides a steric barrier allowing the liposomes to circulate in the blood for longer duration and the functionalizing moiety, the PR_b peptide specifically recognizes and binds to integrin α5β1 expressing cells. PR_b is a novel peptide sequence, designed in our lab, that mimics the cell adhesion domain of fibronectin, and includes four building blocks, RGDSP (the primary recognition site for α5β1), PHSRN (the synergy site for α5β1), a (SG)5 linker, and a KSS spacer. In this study, we demonstrate that by optimizing the amount of PEG and PR_b on the liposomal interface we can engineer nano-vectors that bind to CT26.WT, HCT116, and RKO colon cancer cells in a specific manner and are internalized through α5β1-mediated endocytosis. Stealth liposomes functionalized with an RGD containing peptide bind to colon cancer cells and internalize, but they have much lesser efficiency than PR_b-targeted stealth liposomes, and more importantly they are not as specific since many integrins bind to RGD. PR_b-targeted stealth liposomes are as cytotoxic as free 5-Fluorouracil (5-FU) and exert the highest cytotoxicity on CT26.WT cells compared to RGD-targeted stealth liposomes and non-targeted stealth liposomes. In order to further increase the efficacy of the system we have designed peptide-functionalized stealth liposomes that are pH-sensitive and exhibit triggered release under mild acidic conditions present in endocytotic vesicles. The proposed targeted delivery system has the great potential to deliver a therapeutic load directly to colon cancer cells, in an efficient and specific manner.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027511-027511-1. doi:10.1115/1.3135155.
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Atrial fibrillation (AF) is a common heart rhythm disorder, effecting about 20% of cardiac surgical patients. While often benign, it leads to a prolonged hospital stay, and potentially to malignant arrhythimas. Many anti-arrhythmic drugs have been used to both prevent and treat post-operative AF and other post-operative arrhythmias; however, they have potentially harmful side-effects (e.g., hypotension, pulmonary fibrosis). Cardioversion is often the therapy of last resort to restore a perfusable rhythm. We propose a novel, innovative concept that allows for local pharmacological and electrical therapy of the heart. We have shown in animal models that such delivery increases the efficacy of the therapy and reduces side effects. Several variations of the device have been conceived and prototypes are currently being developed. The simplest version is a multi-port infusion catheter incorporated into a temporary pacing lead. Placement of the device would be trivial for surgeons, who routinely place temporary pacing leads prior to closing the chest. Removal of the device post-operatively would be equally simple. More complex iterations include an expandable wick to maintain the infused drug in a desired location. Designs may also include epicardial defibrillation capabilities, which would lower the energy required for defibrillation. To demonstrate proof of principle, cadaver and animal investigations were performed. In a fresh cadaver, a sternotomy and pericardiotomy was performed. A catheter was placed in the pericardium, and an infusion of radio-opaque contrast was administered under fluoroscopy. The majority of the contrast collected near the pulmonary veins, which are often the origin of atrial arrhythmias. To evaluate the efficacy of drugs administered into the pericardium as compared with drugs administered through the conventional route (intravenously), animal studies in swine were performed. Results demonstrated that pericardially administered metoprolol had a greater and more lasting effect on heart rate than when given intravenously. Additionally, during pericardial delivery myocardial contractility was better preserved. Only trace amounts of metoprolol were found in the circulation. Thus pericardial delivery may enhance certain therapeutic effects of drugs while limiting side effects. Currently, studies are underway to evaluate the efficacy other pharmacologic agents delivered into the pericardium. Should our animal studies continue to show promising results, we anticipate moving into clinical trials. Development and refinement of prototype delivery devices will also continue as we pursue this promising new therapy for post-operative arrhythmias.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027512-027512-1. doi:10.1115/1.3135156.
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Vascular support structures are an important tool for treating valve stenosis. A large population of patients are treated for valvular disease and the principal mode of treatment is the use of percutaneous valvuloplasty. Stent devices are proving to be an improved treatment method; these devices now account for 20% of treatments in Europe. This new technology provides highly effective results at minimal cost and short duration of hospitalization. Accurate and reliable structural analysis provides essential information to the design team in an environment where in vivio experimentation is extremely expensive, or impossible. This paper describe the design of vascular support structure (stents), to provide designers with estimates of the critical parameters which are essential to restore the functions of the endothelium of the Aorta during and after implantation without injuring it. Stent geometries were uniquely defined using the following parameters. (a) Diameter of the aorta; (b) Distance between the aortic root and the coronary artery roots; (c) Position of the coronary arteries; (d) Diameter of the coronaries; (e) Stent–Endothelium Mechanics. Keeping these parameters into consideration a novel stent model was designed to suit its requirement for percutaneous replacement. The 3D geometry of the repeatable units of the stent was generated using SOLIDWORKS modeling software. Using the repeating unit geometry of each stent design, solid models were generated. The unit consisted of 8 lips with two non crossing struts making a circular diameter of 16 mm at the center and 18 mm at either ends. The upper and the lower portions of the prosthesis has a high radial force, the upper portion flared to fix the stent firmly in the ascending aorta and the lower portion to expand against the calcified leaflets and to avoid recoil. The middle portion which bears the valve is constrained and narrower to avoid obstruction of the coronary arteries. This varying diameter of different parts of the stent creates the blunt hooks at either end of the stent. The methodology described in this paper is proposed as a method to compare and analyze the existing stents and the ones proposed here. However, further analysis and studies are needed before these stents are fabricated and deployed. Animal experiments are being planned currently for this purpose.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027512-027512-1. doi:10.1115/1.3135157.
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Over 2 million adults in the United States are affected by atrial fibrillation (AF), a common cardiac arrhythmia that is associated with decreased survival, increased cardiovascular morbidities, and a decrease in quality of life. AF can be initiated by ectopic beats originating in the myocardial sleeves surrounding the pulmonary viens. Pulmonary vein (PV) isolation via radio frequency ablation is the current gold standard for treating patients with drug-refractory AF. However, cryoablation is emerging as a new minimally-invasive technique to achieve PV isolation. Cryoablation is fast gaining acceptance due to its minimal tissue disruption, decreased thrombogenicity, and reduced complications (RF can lead to low rate of stenosis). One important question in regard to this technology is whether the PV lesion is transmural and circumferential and to what extent adjacent tissues are involved in the freezing process. As ice formation lends itself to image contrast in the body, we hypothesized that intraprocedural CT visualization of the iceball formation would allow us to predict the extent of the cryolesion and provide us with a measure of the adjacent tissue damage. Cryoablation was performed using a prototype balloon catheter cryoablation system (Boston Scientific Corporation). CT visualization of iceball formation was assessed both in vitro and in vivo. Initial in vitro studies were performed in agarose gel phantoms immersed in a 37°C water bath. Subsequently, in vivo cryoablations were performed in 5 PV ostia in 3 crossbred farm swine. The catheters were positioned in the ostia under fluoroscopic guidance. CT scans of the thoracic region were obtained every 2.5 minutes. Animals were sacrified 6 days after the procedures. Gross pathology and histology of tissues in the region of interest were evaluated. Significant metal artifacts from the catheter and edge artifacts from the tissues surrounding the cryoballoon were observed under CT imaging both in vitro and in vivo. In vitro, it was found that the size of the iceball was comparable to that observed visually during freezing of agarose gel phantoms. In vivo, contrast change consistent with iceball formation was observed during the ablation in two out of five veins. The most clearly delineated iceball also yielded the clearest morbidity. In this case, esophageal injury on the anterior side proximal to the cryoablation site was noticed during necropsy of the animal in which the iceball was visualized. Transmural and circumferential lesions were obtained in all PVs ablated. We have shown that CT can be used to visualize iceball formation in vitro and in vivo (with limitations) using our cryoablation system. While the iceball in vitro is easily visualized, iceball growth in vivo is most evident once the iceball has grown beyond the PV into the adjacent tissues. This suggests that while CT cannot easily visualize iceball growth in the PV wall itself, it may still be an important tool to guide clinicians and reduce potential morbidities in adjacent tissues. The authors acknowledge Dan Busian (Fairview University Medical Center, Minneapolis, MN) and Dr. Erik Cressman for assistance with CT imaging.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027513-027513-1. doi:10.1115/1.3135192.
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Thermal ablation therapies are currently used for the treatment of select renal masses. Such treatments are limited to tumors that are small (<3 cm diameter), exophytic, and away from vital structures such as ureter or intestine. Novel treatment approaches are geared towards increasing the size of the thermal lesion created, limiting damage to collateral normal tissues, reducing local recurrence and distant metastases as well as improving the imaging potential of the therapy. Previous studies have demonstrated the enhancement of thermal therapies in pre-clinical murine models of solid tumors by intravenously infusing 33 nm TNF-α and PEG coated gold nanoparticles (CYT-6091, Cytimmune Sciences Inc.) prior to ablation. This study investigates the enhancement of thermal ablation therapy by CYT-6091 in a translational animal model of renal tumors. New Zealand White rabbits (37 for radiofrequency ablation (RFA), 20 for cryoablation) had VX-2 tumors implanted into their bilateral kidneys. The tumors were allowed to grow for 14 days to a size of 1 cm. For RFA, the rabbits were split into 3 treatment groups of 10 rabbits each and a sham group of 7 rabbits. The groups were treated with CYT-6091 (200 μg/kg) only, RFA only, or CYT-6091 (200 μg/kg) followed 4 hours later by RFA. For cryoablation, 2 treatment groups of 10 rabbits each were used. The groups were treated with cryoablation only or CYT-6091 (200 μg/kg) followed 4 hours later by cryoablation. The kidneys were harvested 3 days later for RFA and 7 days later for cryoablation. Gross and microscopic measurements of the ablation size as well as histological analysis using H&E staining were performed. The RFA plus CYT-6091 group had a larger zone of complete cell death than the RFA only group when measured both on gross sectioning (0.32±0.03 vs. 0.22±0.07cm3, p=0.015) and on microscopic examination (0.30±0.07 vs. 0.23±0.03cm3, p=0.03). Overall this was a 23% increase in ablation volume. This difference in ablation size was due to a replacement of partially ablated tissue at the periphery in the RFA only group by completely ablated tissue in the RFA plus CYT-6091 group. Thus this zone of partially ablated tissue was smaller in the RFA plus CYT-6091 group than the RFA only group (0.08±0.02cm3 vs. 0.13±0.05cm3, p=0.01). Excessive tumor growth into the ablation lesion at day 7 following cryoablation prevented accurate measurements in these groups; however, a significant decrease in the rate of peritoneal carcinomatosis (metastases) was obtained in the cryo plus CYT-6091 group compared to the cryoablation alone group (1/10 vs. 8/10, p=0.04). We have shown that use of CYT-6091 prior to thermal ablation therapy in a rabbit kidney tumor model can minimize the zone of partial treatment at the periphery of the thermal lesion and thus maximize the complete kill zone in RFA while significantly decreasing the rate of metastases in cryoablation. These data provide preliminary evidence for the efficacy of adjuvant use of CYT-6091 for thermal ablation therapies in a large animal translational tumor model.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027513-027513-1. doi:10.1115/1.3135194.
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Microfluidic channels have been proposed as a method for removal of cryoprotective agents from cell suspensions [Fleming, Longmire, and Hubel, J. Biomech. Eng. 129, 703 (2007)]. The device tested consists of a rectangular cross section channel of 500 μm depth, 25 mm width, and 160 mm length, through which a cell suspension and wash stream flow in parallel. Cryoprotective agents diffuse from the cell stream to the wash stream and the wash stream is discarded. The washed cell stream is then ready for use. This device must be capable of removing 95% of the dimethyl sulfoxide (DMSO) from the cell stream with minimal cell losses. Our previous studies have demonstrated our ability to remove DMSO [Mata, Longmire, McKenna, Glass, and Hubel, Microfluid. Nanofluid. 5, 529 (2008)]. The next phase of the investigation involves characterizing the influence of flow conditions on cell motion through the device. To that end, Jurkat cells (lymphoblasts) in a 10% DMSO solution were flowed through the microfluidic channel in parallel with a wash stream composed of phosphate buffered saline solution (PBS). Average cell stream velocities were varied from 0.94 to 8.5 mm/s (Re 1.7 to 6.0). Cell viability at the outlet was high, indicating that cells are not damaged during their passage through the device. Gravitational settling caused an accumulation of cells near the bottom of the channel, where flow velocities are low. Cell settling leads results in an initial transient period for cell motion through the device. For the initial portion of cells flowing through the device, cells tend to accumulate in the device until a critical device population time is reached. Cell recovery (number of cells out of the device divided by the number of cells input to the device) is high (90–100%) after the device has been fully populated. For a single stage device with average cell stream velocities of 6 mm/s, cell recovery was 90–100%. As more stages are added to the device, the population time for the device increases. Gravitational settling of cells also leads to a time-varying cell concentration from the input syringe to the inlet of the channel, as well as cell losses due to cells remaining in the horizontally-oriented syringe. Reorienting the syringes to a vertical position eliminates these losses. Cell motion within the channel can be modulated by the flow conditions used. For sufficiently high Reynolds numbers, the Segre-Silberberg effect [Segre and Silberberg, J. Fluid Mech. 14, 115 (1962)] can be used to move cells from the low velocity region of the cell stream to a higher velocity region thereby reducing the transient portion of processing the cells and improving overall recovery of cells through the device.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027514-027514-1. doi:10.1115/1.3135195.
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The primary function of the ventricular chambers of the heart is to provide the proper volume of blood to the entire body that fulfills its energy requirements under a wide variety of normal and pathologic settings. If the ventricles are unable to perform this task properly, and the functions of the body deteriorates despite optimal medical management, mechanical methods are utilized to either complement or replace the pumping function of the cardiac ventricles. This presentation will describe the evolution of a non-invasive method of assisting the circulation called “counterpulsation,” and the current state of the development of an “External Left Ventricular Assist Device” (XLVAV). In this method, in the first part of the cardiac cycle, when the heart is relaxed, cardiac diastole, the device exerts a positive pressure external to the lower extremities. This increases coronary artery blood flow and cardiac output. Then when the ventricle contracts, cardiac systole, the device exerts a negative pressure, thus drawing blood away from the heart into the lower extremities, resulting in a reduction of the work and energy requirement of the left ventricle. Experimental and clinical data will be presented that describe the following successive stages of development: 1. The initial experience of Osborn in 1962 using a pressure suit and air actuation was tested in a canine model and in normal volunteers, but was not successful since sufficient pressure was not exerted on the vascular bed of the lower extremities. 2. The initial experimental experience of Birtwell and Soroff in a canine model in 1962 using water as the actuating medium. 3. The construction of a device by Birtwell with cuff-type actuators around the legs, thighs and buttocks that were inflated with water. The cuffs had rigid shells to allow pressure to be exerted to the limbs. The device was successful in increasing diastolic pressure and coronary blood flow and was used successfully in a multicenter study as an initial treatment of patients with acute myocardial infarctions. However, since the device could only apply positive pressure, it could not be used to reduce systolic pressure. 4. The device was then modified to also apply negative pressure during cardiac systole, a major step forward, and tested in a multicenter study in patients with cardiogenic shock following myocardial infacrtions with an impressive increase in the survival rate from 15% to 45%. However, the device presented logistical and patient movement problems. 5. The next evolution in the device design was the use of air to inflate the actuator cuffs. This represented a significant breakthrough, and has been successfully used in the treatment of angina pectoris by increasing coronary blood flow and the promotion or creation of collateral circulation in the myocardium. The serious shortcoming of this device is that is cannot produce negative pressure during cardiac systole, i.e., the only means of assisting the left ventricle in patients with Congestive Heart Failure. 6. The device to be described can apply negative as well as positive pressure to the lower extremities using air as the actuating medium. The device is mobile and compact, and should be effective in the treatment of patients with Congestive Heart Failure both in the hospital setting and in the home, Acute Myocardial Infarction as well as Angina Pectoris.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027514-027514-1. doi:10.1115/1.3135196.
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Swallowable capsule-based cameras (e.g., the Given Imaging PillCam and competitors) are rapidly becoming the gold standard for diagnosis in the gastrointestinal (GI) tract. However, definitive diagnosis is still often precluded by the inability to control capsule position and orientation. This has inspired a number of active positioning strategies including augmenting the capsule with legs or other appendages, or incorporating magnets which can apply forces and torques in response to an external magnetic field. Furthermore, the loose, mucous coated, elastic intestine is generally deflated during capsule passage, making it challenging to view the entire internal surface adequately without the insufflation that is relied upon in traditional endoscopy. To address these challenges, we propose a new fluid-powered system that permits insufflation from a wireless capsule platform. This is accomplished by carrying a small reservoir of biocompatible liquid onboard the capsule which vaporizes and expands when released through a small onboard solenoid valve. The internal components of the capsule consist of two 3V Lithium coin cell batteries (VL621, Panasonic, Inc.) which charge 3 Tantalum capacitors (TAJB157M006R, AVX Corporation, Inc.) that fire the solenoid valve (S120, Lee Company, Inc.). In our initial proof-of-concept study, we have packaged all components in a 26 mm long by 11 mm diameter capsule. The fluid used in initial experiments is biocompatible Perfluoropentane, although any of a variety of biocompatible fluids that can be liquefied with light pressurization may be used. Perfluoropentane, developed for lung lavage, is a liquid at room temperature and becomes gaseous at body temperature. We note that pneumatic pressure produced in this way may be used for a variety of objectives, including powering biopsy collection devices or other mechanisms within the capsule, or being vented to inflate the intestine. In initial experiments, we have harnessed the pressure to inflate a balloon at the front of the capsule which can distend tissue and thereby improve image quality. In experimental tests, only 0.2 ml of fluid was consumed in inflating the balloon to sufficient pressure to distend porcine intestine (see http://research.vuse.vanderbilt.edu/MEDLab for images of these experiments). Optimization of the capsule body and electrical components is currently underway. Including a wireless camera, all components are expected to fit within the dimensions of a commercial PillCam.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027515-027515-1. doi:10.1115/1.3135242.
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Colonoscopy provides a minimally invasive tool for examining and treating the colon without surgery, but current colonoscope designs still cause a degree of pain and mechanical trauma to the colon wall. The most common colonoscopes are long tubes inserted through the rectum with fiber optic lights, cameras, and biopsy tools on the distal end. The stiffness required to support these tools makes it difficult for the scopes to navigate the twisted path of the colon without causing mechanical trauma inside the colon wall or distorting its shape. The shaft of the colonoscope often causes looping (alpha, reverse alpha, or n), and it is very difficult to advance the distal tip of the colonoscope with looping. In order to avoid looping and minimize mechanical trauma, the author expanded on a design by Zehel et al., who proposed surrounding a flexible colonoscope with an external exoskeleton structure with controllable stiffness. The stiffenable exoskeleton device is comprised of rigid, articulating tubular units, which are stiffened or relaxed by four control cables. The stiffened or relaxed exoskeleton device guides navigation and provides stability for the colonoscope when it protrudes beyond the exoskeleton device for examination and procedures. This research determined the design requirements of such an exoskeleton device and tested requirements of such an exoskeleton device and tested its behavior in a colonoscopy training model. Moreover, the stiffenable exoskeleton device can be operated in purely a mechanical way, which is safe as a class II medical device, and no additional modification of the colonoscope is needed to use the stiffenable exoskeleton device. Colonoscopy training model is used to test the stiffenable exoskeleton device. First, the endoscopist inserted the colonoscope into the colonoscopy training model up to the end of the stiffenable exoskeleton device along the shaft of the colonoscope to the distal tip of the colonoscope, and then locked the stiffenable exoskeleton device and advanced the shaft of the colonoscope to examine the colon. When the distal tip reached the cecum, he or she unlocked the stiffenable exoskeleton device, retracted the shaft of the colonoscope and the stiffenable exoskeleton device, and checked for polyps or other colon disease. Also, the endoscopist can insert the stiffenable exoskeleton device and a colonoscope alternatively by stiffening and releasing the exoskeleton device. In that way, endoscopist can advance the colonoscope and the exoskeleton structure inch-by-inch without causing mechanical trauma in the rectum and the sigmoid colon. The endoscopist tested the stiffenable exoskeleton device using the colonoscopy training model and fulfilled its objectives. Several other diagnostic procedures involving the stomach, esophagus and the nose could also benefit due to the improvements provided by the stiffenable exoskeleton technology.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027515-027515-1. doi:10.1115/1.3135243.
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Stents are commonly associated with the mechanical support of the coronary arteries to improve blood flow and retain residual plaque following various angioplasty procedures. However, they are becoming more frequently used in other vessels in the human body, such as the carotid and femoral arteries. The femoral arteries transverse through the hip region, and are the sites of potential plaque build-up. Thus the design of a stent for the specific biomechanical stresses and conditions of this location is of growing interest. The effectiveness of stent designs are quantified by their ability to survive in the human body without failing mechanically, dislocating, or invoking a major inflammatory response. Common methods of failure are mechanical, including fractures and dislocations. Several different instruments are commercially available for the testing of stents under various stresses and application frequency. However, these machines generally test with small bending angles or they apply nonphysiological axial, radial and torsional loads; thus they are not idealized for motions to mimic accurate biomechanical motion. Specifically, for the design of a stent localized in the hip region, a test for significant bending cases is necessary. The placement of stress on a mock artery should be applied solely to the ends of a mock artery to remove any radial or axial stresses not caused directly from the bending motion. Furthermore, visualization of the stent inside the mock artery is desired for tracking displacement of the stent and cycle count until failure. The ability to quantify the mechanical failure and dislocation of stent designs under extreme bending conditions is a prerequisite to the optimization of physical stent designs and of stent spacing, orientation and placement. We compare a proprietary stent-like design (Innovasc Inc., Honolulu, HI) placed at fixed intervals versus a commercially available SMART stent (Cordis Corporation, Warren, NJ). Both designs are intended to retain the arterial plaque while minimizing the stress applied to the artery wall to prevent restenosis. The new stent prototype designs are uniquely configured to enable points of stress reduction along the length of interest. Early preliminary experiments with the Innovasc design show promising results in the reduction of restenosis in porcine models. Stent designs are tested in mock arteries of latex and silicone. The mock arteries are selected for internal diameters and thicknesses to match artery properties. Two symmetric cylinders holsters are allowed to rotate freely and are affixed to the ends of the mock arteries. A simple linkage system drives the two cylinders together and apart, allowing for the mock arteries to bend at a fixed angle of 120 degrees at frequencies (∼10–20 Hz) without external stresses for one million cycles. Images are captured using a X-Stream Vision High-Speed CMOS camera (Integrated Design Tools, Tallahassee, FL) via a trigger system. Failure points and dislocations are noted and measured using the NIH ImageJ imaging software.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027516-027516-1. doi:10.1115/1.3135244.
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It is often difficult for persons who are extremely overweight to find exercise systems that are accessible and safe to use. Seating is required to handle heavier loads of up to 500 lbs. and provide safe access to the exercise unit. Additionally, the exercise should not cause additional pain or possible damage if the person needs to suddenly stop. A multidisciplinary team of undergraduate engineers participated in a training course to interview a non-technical customer to determine design requirements and then underwent a rigorous design process to implement the best solution. Mechanical analysis was performed to determine the best solution for the concept, materials, and resistance. An exercise machine with a rotating chair was selected as the best solution. The chair rotates 90 degrees so that the user can sit down without having to step onto the machine. Once the user sits, the chair can then rotate 90 degrees until the chair is in the exercise position; in either position the chair locks into position for stability. This particular concept uses a bicyle exercise. This exercise minimizes impact on the knees, which is a safety issue for patients with knee problems. A sitting position for this exercise eliminates the stability issue raised with a standing exercise, where there is worry of falling. This exercise is beneficial for cardiovascular exercise. Resistance is implemented using a magnet. Fluid resistance and fly-wheel resistance would create too much momentum which was not desired by the customer. Electrical analysis was performed to determine the best method to sense heart rate, speed, and computer interface. Wired handles were selected to monitor the heart rate. These are hand held and are much easier to use than a chest strap. An optical sensor was used to sense speed. It was placed near the center of the wheel and rotations were indicated by a tab to break the connection in the sensor. This method was selected over a Hall effect sensor because it is a much simpler sensing method that does not require an addition magnetic component that is not too accurate a low speeds. The computer interface was a Motorola HC12s since it had the necessary I/O interfaces and was low cost. A custom interface was created with seven segment displays to show the heart rate and time of exercise. The system was then developed, tested, and delivered to the customer for use. This project was supported by Grant No. 0607883 from the National Science Foundation.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027516-027516-1. doi:10.1115/1.3136711.
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Interdisciplinary settings have been highlighted for creative user-close development of products and services. Similarly, user involvement in the actual design process has been presented as a way to make attractive products that will earn market shares. But will an interdisciplinary setting in itself generate the beneficial spin-offs we expect? Will including the end-user on the development team ensure better products that are more successful on the market? A study has been set up to create a work model for Clinical Innovation Teams (CIT) at the Sister Kenny Research Center in Minneapolis, MN, to facilitate the research and development process, and provide guidance to work in a creative and innovative way around rehabilitation technology development. The CITs consist of clinicians, such as nurses, occupational therapists, physical therapists, physicians, engineers and engineering students, and in some cases patients. The CITs combine the interdisciplinary setting and end-user involvement with a custom work-model. The work-model emphasizes the strengths of the teams and provides tools to overcome the obstacles and challenges that these kind of teams face. The technological depth and clinical experience is combined with a structured project work-model. The teams work interdisciplinary by pairing research with actual patient needs to develop rehabilitation technology and medical devices to address those needs. The first tool in the work model is an Innovation Handbook for development projects at the Sister Kenny Research Center, especially written for this specific setting. The second tool is a report with recommendations to the management on how to create a work environment where innovation can occur and where creative ideas are welcome, as well as how to engage clinicians into research. The report also addresses aspects of workplace design, recommendations on how to deal with uncertainties that come when moving between clinical care and research and ideas of how to ensure quality of care and maintain productivity when clinicians engage in research activities. The third tool in the work model is a schematic illustration of how the important elements of innovation management is paired with the design process, and how a project will benefit from good management and where it will suffer from insufficient support. This project has been supported by the City of Minneapolis, the Sister Kenny Research Center and the Product Innovation Engineering Program of Sweden (PIEp). Corresponding author: L. Oddsson; e-mail: lars.oddsson@allina.com

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027517-027517-1. doi:10.1115/1.3136169.
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In order to expand the applications for implanted rechargeable batteries, and to reduce the frequency of battery replacement procedures, we are investigating a recharging technique complimentary to and improving on the current RF recharging technique. Although the first applications deal with batteries that could be implanted in human bodies to power neurostimulators, sensors, and drug pumps, non-medical applications may exist. Using a transmitter-receiver arrangement, we have recharged batteries wirelessly using ultrasound at several frequencies between 0.75 and 3.0 MHz. Rechargeable implantable batteries of 35, 200 and 600 mA-hr were charged at rates of up to 0.75 C, where C is the charging rate (charging current/maximum battery charging current). Typically the intervening medium was one centimeter of a tissue mimicking liquid (TML), however some in vitro experiments have also been performed. Charging was accomplished at distances of up to 20 centimeters in water, and even through millimeters of plastic and centimeters of aluminum. Temperature measurements were made on both transmitting and receiving transducers, and in the TML. As expected there were significant increases in temperature at the higher charging currents. Experimentally we determined that the “overall efficiency” of the charging process, viz. E=(Ibatt*Vbatt)/(net electrical power)input, was closely correlated with the observed heating. That is, the lower the efficiency, the higher the input electrical power required, the more transducer heat was produced and conducted into and through the medium. The critical issues were the coupling of the transmitter and receiver to the medium, and the efficiency of conversion of the receiver output to charging power by the charging circuitry. These depend on the mechanical and electrical impedances, and we improved the efficiency considerable by appropriate impedance matching. Active and passive methods of cooling the transducers and intervening medium have been constructed and successfully tested. With our system, recharging times will be limited not by heating considerations, but only by the optimum rate at which a given battery can accept charge.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027517-027517-1. doi:10.1115/1.3136421.
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Temperature and pH-sensitive ABC triblock polymers were prepared to form hydrogel membranes capable of changing their structure in response to environmental stimuli, allowing drug release, from a micro implantable device, in short and repetitive pulses. We have previously investigated the capacity of hydrogels to sustain open loop oscillatory behavior, with application in rhythmic hormone release. This novel oscillator is mediated by feedback instability between swelling/shrinking of the hydrogel and an enzyme reaction, whose product modifies pH in the hydrogel. The objective of this work was to prepare and characterize triblock polymer-based hydrogels, to overcome limitations of conventional hydrogels. Our strategy involves reversible arrangement of A and C thermosensitive domains within a strong network, whereas B block is also pH-sensitive. The triblock was mainly based on the use of NIPAAm (N, isopropylacrylamide) and AA (acrylic acid) monomers. Polymers were synthesized by reversible addition fragmentation chain transfer (RAFT) polymerization. Polymers molecular weight (Mn) and polydispersity index (PDI) were determined by matrix-assisted laser desorption ionization/mass spectrometry (MALDI). Monomers conversion was assessed by NMR and copolymers composition by NMR and pH-titration. Temperature and pH responsiveness was studied by turbidity and light scattering experiments. ABC triblock presented Mn close to 40,000 Da and was nearly monodisperse (PDI<1.1). The monomers conversion was 92%, 97% and 39% for A, B and C blocks, respectively. The opposing effects of hydrophobicity and ionization on the aggregation behavior of the diblock have been highlighted through the turbidity and light scattering data. AB diblock cloud points were 32, 34, 35.5 and 37°C for 3, 5, 10 and 20% of AA, respectively. Micelles or aggegrates were observed depending on pH and temperature. ABC triblock polymers with controlled architecture and Mn distribution were synthesized and fully characterized. The results suggest that these block polymers are promising materials for stimul-responsive hydrogel membranes applied to medical devices. Work supported by the Swiss National Fund for Scientific Research and an NSF-funded MRSEC (DMR#0819885) at the University of Minnesota.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027518-027518-1. doi:10.1115/1.3136424.
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Nitric Oxide (NO) is small, free radical gas that has been shown to have a wide variety of physiological functions, including the ability to hinder tumor angiogenesis at high, but non lethal, concentrations [1]. Previous work suggests that if NO could be effectively delivered in vivo to tumors of patients currently undergoing chemotherapy treatments at the appropriate levels, less damaging chemotherapy treatments could be used against cancer [2]. This could increase the overall survivability of cancer patients, especially in those prone to the harmful effects of chemotherapy: children, elderly, and those of weak immune systems. If NO is especially successful at preventing and eliminating tumor growth, angiogenesis, and carcinogenesis the need for stressful chemotherapy treatments could be eliminated altogether. This project is focused on developing novel photosensitive NO donors that can be incorporated into polymeric systems and used in a fiber optic drug delivery system. Development of these NO-releasing polymers will allow continued investigation of NO's role in tumor death by precisely controlling the surface flux of NO that cells are exposed to. Generating specific surface fluxes of NO from polymer films has been demonstrated by using polymer films that contain photoinitiated NO donors [3], prepared by synthesizing S-nitrosothiol (RSNO) derivitized polymer fillers that are blended into hydrophobic polymers and cast into a film. These films generate and sustain a surface flux of NO based on the wavelength and intensity of light used [3]. Polymers releasing NO are more promising as an NO donor than simply injecting NO into samples because they allow for spatial and temporal control of NO delivery. The specific concentration of NO needed to produce desirable effects on tumor cells (i.e., apoptosis) is not known. Data will be presented that show the synthesis and NO-release properties of novel RSNOs based on the nitrosation of benzyl mercaptan thiols. Specifically, UV-Vis spectrum of benzyl mercaptan in toluene and S-nitrosobenzyl mercaptan after the addition of t-butyl nitrite will be presented. We are currently investigating the effects of varying NO-surface fluxes generated from photolytic NO donating polymer films on aortic smooth muscle cell cultures obtained from mice. Once we have established that we can quantitatively determine the effects of different levels of NO on the proliferation of smooth muscle cell cultures, work will begin to apply this methodology and these novel NO-releasing polymeric systems to begin investigating what durations and surface fluxes of NO are necessary to have tumorcidal effects on specific cancer cells.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027518-027518-1. doi:10.1115/1.3136423.
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Transcranial Direct Current Stimulation (tDCS) is a non-invasive procedure where a weak electrical current (260 μA to 2 mA) is applied across the scalp to modulate brain function. tDCS has been applied for therapeutic purposes (e.g., addiction, depression, mood and sleep disorders) as well as cognitive performance enhancement (e.g., memory consolidation, motor learning, language recall). Despite safety and cost advantages, the developments of tDCS therapies have been restricted by spatial targeting concerns using existing two-channel systems. We have developed novel technology for High-Density tDCS (HD-tDCS) that improves spatial focality. To determine optimal stimulation electrode configurations, based on application specific constraints, we developed a HD-tDCS targeting software. High resolution (gyri/sulci precise) MRI derived finite element (FE) human head models are generated by segmenting grey matter, white matter, CSF, skull, muscle, fatty tissue, eyes, blood vessels, scalp, etc. The models comprised >10 million elements with >15 million degrees of freedom. The induced cortical electric field/current density values are calculated; activation of either radially and tangentially oriented neuronal structures are considered. Our HD-tDCS hardware (4×1-C1, 4×4-S1) currently supports the ‘4×1-Ring’ and the ‘4×4-Strip’ electrode configurations. The peak cortical electric field was matched to ‘conventional’ large rectangular-pad tDCS stimulation; however, the spatial focality was significantly enhanced by 4×1 configuration. Using patient specific head models, our software interface allows simple and rapid screening of stimulation electrode configurations. After selecting a target region, clinicians can customize the electrode configuration to balance: 1) cortical surface and brain depth stimulation focality; 2) total applied current/voltage; and 3) electrode/scalp current density. Our HD-tDCS system allows non-invasive, safe, and targeted modulation of selected cortical structures for electrotherapies that are individualized as well as optimized for a range of therapeutic applications.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027519-027519-1. doi:10.1115/1.3136426.
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Biomedical devices that contact blood and tissue universally inspire a host response that often compromises the function of the device (i.e., intravascular sensors become coated with thrombi, artificial vascular grafts become coated with thrombi, artificial vascular grafts become occluded with thrombus formation and neointimal hyperplasia). Nitric oxide (NO) has been shown to be a potent inhibitor of platelet adhesion and activation and has been implicated in mediating the inflammatory response and promoting would healing. We are currently developing NO-releasing compounds based on S-nitrosothiols derived from substituted aromatic compounds that utilize light as an external on/off trigger capable of releasing precisely controlled surface fluxes of NO. The level of NO generated is dependent on the wavelength and intensity of light shown on the compounds. Data will be presented that show the synthesis and NO-release properties of three novel compounds, S-nitroso-2-methoxybenzene, S-nitroso-3-methoxybenzene and S-nitroso-2-chlorobenzene. Ultimately, these compounds will be tethered to the surface of polymer fillers that will then be blended into hydrophobic polymers and used as coatings on biomedical devices. A model system that will be used to demonstrate the utility of this approach will be a multi-element fiber optic sensors that will contain sensing elements capable of measuring blood gases and NO-releasing fibers that locally generate enough NO to inhibit clot formation on the sensor surface, thus allowing the sensor to function reliably in vivo.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027519-027519-1. doi:10.1115/1.3136753.
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Diabetes has been the focus of intense research for more than half a century both in academia and in industry. The number of diabetes cases (especially type II) continues to increase due to the obesity pandemic in western societies and the cost of treatment of diabetes and its severe side effects will undoubtedly continue to drive development of wide ranging technological means to better understand and treat diabetes. Tight blood sugar regulation has been shown to delay or limit side effects and prolong lifespan in patients. Continuous glucose monitoring (CGM) is expected to provide information that can be used in better regulating patient behavior, or as part of a closed loop feedback control system for administering insulin at appropriate times. Our approach to CGM involves a hydrogel whose swelling depends on glucose concentration, coupled to an LC microresonator circuit, whose resonant frequency depends on hydrogel swelling due to impingment of the hydrogel on one plate of the microcapacitor. The whole sensor is microfabricated and implantable. Wireless determination of the resonant frequency permits continuous glucose sensing without chronic skin breach. We are in the process of designing hydrogels that swell/shrink with decreasing/increasing glucose concentration to test for hypoglycemia or hyperglycemia. In collaboration with Professor Babak Ziaie's group at Purdue, a first generation microdevice was fabricated. Since the full sensor requires a significant investment in time and money for its fabrication, the incorporation and testing of diverse hydrogel systems in the full device is unrealistic at the present stage of development. We are currently fabricating a testbed device to allow for the selection of lead hydrogels, which will evaluate quantitatively the relationship stimuli/pressure. Few examples exist in the literature to measure the swelling pressure of hydrogels under isochoric conditions (V=constant) experimentally. We will describe our progress toward the fabrication of a test device to evaluate the pressure developed by a hydrogel sample inside a cavity. We used a commercial pressure die with a very small piezoresistive element (500μm by 500μm), and packaged it such that the pressure sensitive membrane was in contact with a hydrogel sample a few tens of μm thin separated from the external environment by a commercial Anodisc? membrane (0.02 and 0.2 μm pore diameter). Details of design and preliminary results will be presented.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027520-027520-1. doi:10.1115/1.3136756.
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A first student project to put pedals on a wheelchair for exercise and propulsion was unsuccessful. The need remained and in June of 2005 the “Eureka” event occurred. Seeing a five-year-old on her training-wheel-equipped bicycle suggested that a fifth wheel could be added in the center between the wheelchair's two large rear wheels, and a mast supported by the fifth wheel's axle could extend forward to support a front axle and pedal set. A chain drive completed the propulsion system. There are no pedal-powered wheelchairs currently on the market. Around 2001 a product (EZChair) without retractable pedals was on the market but withdrawn. A team at the University of Buffalo invented and patented a pedal-powered wheelchair in 1993 (US Patent 5,242,179), but it was not commercialized. Also, a Japanese company designed and built a series of fifth-wheel wheelchair designs. Between 2006 and late 2008 we built many prototypes incorporating geometries that permitted retracting the pedal. For compactness a “Pedalong” with three telescoping tubes was built but it proved impossible to secure tightly. In the next design twin telescoping tubes passing above and to the rear of the rear axle provided the desired extension. A clamp at the front of the outer tube provided tightness of the assembly. In the Northwestern research program (see below), there was some success, but awkwardness in operation prevented commercialization. In October 2008 a major design change from a fifth wheel in the center to a powering of the two standard rear wheels was begun. This required a new chain path geometry and addition of a differential to the drive train. With the new design user control, arm-powering and braking through the rear wheels is retained, and chair stability is improved. Twelve individuals with chronic post-stroke hemiplegia (>6 months post-stroke event) participated in a study to examine the metabolic energy expended when participants performed a 6-minute walk test, a 6 minute leg-propelled wheelchair trial (using the Pedalong), and a 6 minute arm-propelled wheelchair trial. VO2, VCO2, and distance traveled were measured using a portable metablic cart system and wheel-based distance measurement system. The Pedalong and walking trials showed equivalent oxygen consumption levels, but manual pushing was, on average, significantly less. All three modes (walking, leg-propelled and arm-propelled) resulting in similar distances traveled within the 6 minute period. The leg-propelled trials generated the greatest amount of VCO2 during expiration compared with the other modes. This means that more of the available oxygen is being utilized (metabolized) during the leg-propelled mode and so, a greater number of calories were being burned during this 6-minute test.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027520-027520-1. doi:10.1115/1.3136841.
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With the increased interest of MRI guided interventional procedures in modern medical treatments, image distortion and artifact formation based on material selection and orientation within the MRI scanner are central concerns for precise object localization. The goal of this study was to illustrate the artifact behavior of materials with various magnetic susceptibilities and radio frequency conductivity values corresponding to object orientation relative to the primary magnetic field. To test the effects of orientation on image distortion and image artifacts, 0.125 inch cylindrical test samples of various materials were imaged using a clinical Siemens 3 Tesla MR scanner. Modern medical instrumentation and surgical utensils are typically made from highly paramagnetic materials (e.g., titanium, nitinol, or stainless steel) which also have high RF conductivities. The combination of these two material properties cause both primary magnetic field (B0) and RF field (B1) inhomogeneities which lead to local image distortions. A change in the local magnetic field induces errors within the slice selection gradient, as the precessional frequency of the proton nuclei in the desired region of interest will not correspond to the exact spatial location on the object and will excite a broader region due to the RF conductivity of the material. Conversely to more traditional surgical materials, diamagnetic materials (e.g., bismuth, pyrolytic carbon, water, most plastics) are free from the susceptibility artifacts due to B0 inhomogeneities and thus offer a level of MR compatibility that traditional materials cannot. A specific testing phantom was built to fit a clinical wrist coil. The phantom consisted of an aqueous solution of gadolinium and copper sulfate to increase image contrast and a rotatable turret post for sample positioning. The particular materials studied were chosen to demonstrate the wide variation in both magnetic susceptibility values and RF conductivities (e.g., 6A1-4V titanium, 316L stainless steel, carbon fiber, 6061 T6 aluminum, brass, copper, beryllium copper). ImageJ software measured the overall pixel area and major dimension of each MR image artifact at 0, 45, and 90 degree orientations of each test sample relative to B0. The results of the measurements indicated measurable increases in signal are of the paramagnetic and highly conductive test specimens orientated orthogonal to the primary magnetic field. For instance, two common medical grade materials such as 316L stainless steel and 6Al-4V titanium resulted in artifact area increases of 770±10% and 234±10%, respectively, relative to the actual cross sectional area of the sample. Conversely, the more diamagnetic materials, carbon fiber and beryllium copper demonstrated increased artifact areas of 8±10% and 12±10%, respectively. Errors in artifact area percentage growth measurement are primarily attributed to manual image segmentation and variation in coil positioning within the MRI bore. The results indicate that MR image artifact size and object distortion characteristics can be influenced by both material selection and object orientation relative to the primary magnetic field. In the interest of accurate navigation of image guided equipment and devices, interventional devices should be tested for image distortion in multiple orientations. This work is supported by MIMTeC, a National Science Foundation Industry University Collaborative Research Center and by NIH Grant P30 NS057091.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027521-027521-1. doi:10.1115/1.3136843.
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Piezo-resistive actuation of a microcantilever induced by biomolecular binding such as DNA hybridization and antibody-antigen binding is an important principle useful in biosensing applications. As the magnitude of the forces exerted is small, increasing the sensitivity of the microcantilever becomes critical. In this paper, we are considering to achieve this by geometric variation of the cantilever. The sensitivity of the cantilever was improved so that the device can sense the presence of antigen even if the magnitude of surface-stresses over the microcantilever was very small. We consider a `T-shaped' cantilver that eliminates the disadvantages while improving the sensitivity simultaneously. Simulations for validation have been performed using Intellisuite software (a MEMS design and simulation package). The simulations reveal that the T-shaped microcantilver is almost as sensitive as a thin cantilever and has relatively very low buckling effect. Simulations also reveal that with an increase in thickness of the cantilever, there is a proportional decrease in the sensitivity. This paper presents an analytical modeling and simulation studies of a piezoresistive cantilever used as MEMS based biosensor for the detection of cardiac markers. Diagnosis of Myocardial Infarction was achieved by the nanomechanical deflection of the microcantilever due to adsorption of the Troponin I complex. The deflection of the microcantilever was measured in terms of the piezoresistive changes by implanting boron at the anchor point where there is maximum strain due to the adsorption of the analyte molecules. The biochemical interactions between the Cardiac Troponin I (cTnl) complex and the immobilized antibodies would cause change in resistance of the piezoresistor integrated at the anchor point. A ‘T’ shaped microcantilever design was proposed for the study. The distal end of the device was coated with gold. The sensitivity of the cantilever was improved so that the device can sense the presence of antigen even if the magnitude of surface-stresses over the microcantilever was very small. To obtain an application specific optimum design parameter and predict the cantilever performance. The miniaturization of the cantilever-based biosensor leads to significant advantages in the absolute device sensitivity.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027521-027521-1. doi:10.1115/1.3136844.
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The development of bio-artificial organs (sequestered cell cultures, implanted within an isolating membrane) is complicated by dynamic and interrelated variables. The primary objective of an implanted membrane for sequestration of insulin producing cells is to provide a barrier to the host's immune system. Implicit in this structural relationship in systems designed for the treatment of diabetes is the ability to create an environment that is favorable to the sequestered cells' viability and at the same time facilitate the availability of the released insulin in a kinetic relationship consistent with the normal physiology. This investigation conducted under a Phase I SBIR grant explored methods to promote a favorable interaction between islets harvested from neonate rats with a polyurethane membrane during in-vitro culture experiments. Laminin (LAM) extracellular matrix was used to stabilize islets within polyurethane membranes or within cell culture well inserts. Results indicated that insulin produced by islets enclosed within the polyurethane membranes with and without LAM was present for up to six weeks. However, when evaluating the Glucose Stimulated Insulin Secretion (GSIS) there was no evidence of Insulin Response in any of the treatment groups. Further study using LAM and islets in the presence of a cell culture insert (8.0 micron polycarbonate membrane) demonstarted that LAM impeded flow of media through the membrane. When media sampled from the well was compared to inside the insert at the 11.2 mM glucose phase of the GSIS, the average insulin concentration from the well was <45.8% of that found inside the cup. In addition, there was evidence of a positive effect on β-cell rate of cell division in the presence of LAM. The average number of brdU labeled cells per islet was significantly greater following prolactin (PRL; positive control @ 500 ng/ml), laminin–1 (50 μg/ml) or the combination of PRL and LAM. The increases relative to the control islets averaged across the replications were: Laminin +1.5 times, Prolactin +5.9 times, PRL and LAM +6.8 times. In summary, there was no evidence of GSIS in experiments where laminin–1 was used to stabilize neonate rat islets within a polyurethane membrane. These results suggest that the presence of ECM on the inside of the polyurethane membrane impeded the insulin of the polyurethane membrane impeded the insulin diffusion kinetics through the membrane. The only potentially positive results from this study are that there is evidence of insulin diffusion over time indicating that the islets are functional, but a an unknown level of physiologic utility. Support for this study was provided by NIH SBIR Grant #1 R43 DK75220-01. Dr. Robert Sorenson, University of MN, and his lab graciously provided the neonate rat islets and advice.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027522-027522-1. doi:10.1115/1.3136846.
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Technological advancements in endoscopy design are in current development due to the increased demand for minimally invasive medical procedures. One such advancement is reducing the overall size of the endoscope system while maintaining the resolution and field-of-view (FOV). Reduction of size results in less tissue damage and trauma during operation as well as faster recovery times for patients. Additionally, areas that are inaccessible by today's endoscope designs will be possible to examine. Current endoscopes use either a bundle of optical fibers (optical waveguides) and/or one or more cameras having an array of detectors to capture an image. Thus, the diameter of these devices employed for remote imaging cannot be reduced to smaller than the image size. Even if one ignores additional optical fibers used for illumination of a region of interest, the scope diameter is therefore limited by the individual pixel size of a camera or by the diameter of optical fibers used to acquire the image. Therefore, it is apparent to achieve scopes with less than 3 mm overall diameter using current technologies, resolution and/or FOV must be sacrificed by having fewer pixel elements. All commercially available scopes suffer from this fundamental tradeoff between high image quality and small size. More recently, our research has been working on developing a 2-D electro-optic scanner potentially be implemented for clinical endoscopic imaging application. The proposed optical device has several unique advantages. Electro-optical scanning offers a sensitive, facile, accurate, and superb quality method to capture images of physical and biological tissues. In addition, the minute physical size of the imaging system has a much needed advantage over conventional imaging systems. The proposed design is based on the fact that the propagation direction of a light beam can be changed when the index of refraction of an electro-optic medium is altered by the application of an external electric field. The basic design of the system consists of a thin film electro-optic polymer waveguide with built-in cascaded prisms structure for horizontal beam deflection and an electro-optic grating structure for vertical beam deflection. The cascaded prisms are combined with the electro-optic polymer to create a voltage-controlled horizontal beam deflection. A grating coupler, a structure that is commonly used as light coupling device for dielectric waveguide, is combined with the EO polymer to create the vertical controlled beam deflection. A collimated light beam coupled into the waveguide by a mechanical coupler via an optical fiber cascaded down these two deflection stages. When the beam exits, the emitted light beam is displaced along two orthogonal directions in a raster pattern. A photodetector array integrated in the same substrate captured the reflected intensity. The scanned imaged is then analyzed and reconstruct based on the received signal.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027522-027522-1. doi:10.1115/1.3136848.
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For many clinicians, their effectiveness is dependent on the force they manually apply to their patients. However, current care strategies lack quantitative feedback making it difficult to provide consistent care over time and among several clinicians. We have developed a disposable force-sensing glove that provides real-time quantitative feedback in the clinical setting. To minimally affect a clinician's function, obtain maximal signal to noise in a medical environment, and maintain patient safety, a fiber optic sensor has been developed for this application. A disposable nitrile glove with embedded fiber optic force sensor has been developed and initially tested for clinical efficacy. The sensor's design is based on the bendloss properties of optical fiber whereby the attenuation of light through a fiber is related to the bending of that fiber through a series of corrugated teeth. The sensor is fabricated in two parts, sandwiching the fiber between alternating teeth. When force is applied across the sensor, the teeth engage the fiber and bend it along an elastic, repeating profile. the specific light attenuation is dependent on the amount of bending that the fiber experiences between the teeth and can be used to measure the load applied to the sensor. Fabricated at 10×8×1 mm, the sensor achieves an appropriate clinical thickness and minimally affects normal clinical thickness and minimally affects normal clinical function. It provides real-time force feedback up to 90 lbs with 0.1 lb resolution. The sensitivity of the sensor follows an exponential relationship with strong agreement to theoretical calculations. Because the calibration curve is non-linear, the sensor is most sensitive at low forces allowing detection of extremely delicate forces such as the pulse from the carotid artery. Each glove is fabricated with a single sensor embedded in the fingertip or palm and a magnetic connector couples the glove with a non-disposable wrist cuff. The wrist cuff houses the power supply, light source, and photodetectors. The fibers are nonpermanently coupled to their respective sources and detectors completing the optical path from source, through the fiber and sensor, to the detector. The light intensity is then transmitted to the display module which calibrates and displays the force graphically in real-time. The display module records, summarizes, and stores the data from each clinical session allowing clinicians to collaborate on treatment protocols and provide consistent care over time. Initial results from current clinical trials with physical therapists at the University of Minnesota have indicated improved recovery time after surgery. Twenty-four ACL reconstruction patients have been monitored post-operation for five weeks and the experimental group treated with the glove has demonstrated significantly faster recovery to normal range of motion than the control group. It has been suggested that the quantification of patient evaluation allowed the clinicians to recommend adjustments to at-home stretching regimens, contributing to faster healing times. Similar clinical studies are planned for chiropractic care and other physical therapy procedures. This fiberoptic force sensing glove represents a new biomedical tool which can impact patient evaluation and care by providing clinicians with a quantified sense of touch.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027523-027523-1. doi:10.1115/1.3155366.
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Temperature and pH-sensitive ABC triblock polymers were prepared to form hydrogel membranes capable of changing their structure in response to environmental stimuli, allowing drug release, from a micro implantable device, in short and repetitive pulses. We have previously investigated the capacity of hydrogels to sustain open loop oscillatory behavior, with application in rhythmic hormone release. This novel oscillator is mediated by feedback instability between swelling/shrinking of the hydrogel and an enzyme reaction, whose product modifies pH in the hydrogel. The objective of this work was to prepare and characterize triblock polymer-based hydrogels, to overcome limitations of conventional hydrogels. Our strategy involves reversible arrangement of A and C thermosensitive domains within a strong network, whereas B block is also pH-sensitive. The triblock was mainly based on the use of NIPAAm (N, isopropylacrylamide) and AA (acrylic acid) monomers. Polymers were synthesized by reversible addition fragmentation chain transfer (RAFT) polymerization. Polymers molecular weight (Mn) and polydispersity index (PDI) were determined by matrix-assisted laser desorption ionization/mass spectrometry (MALDI). Monomers conversion was assessed by NMR and copolymers composition by NMR and pH-titration. Temperature and pH responsiveness was studied by turbidity and light scattering experiments. ABC triblock presented Mn close to 40,000 Da and was nearly monodisperse (PDI<1.1). The monomers conversion was 92%, 97% and 39% for A, B and C blocks, respectively. The opposing effects of hydrophobicity and ionization on the aggregation behavior of the diblock have been highlighted through the turbidity and light scattering data. AB diblock cloud points were 32, 34, 35.5 and 37.5°C for 3, 5, 10 and 20% of AA, respectively. Micelles or aggegrates were observed depending on pH and temperature. ABC triblock polymers with controlled architecture and Mn distribution were synthesized and fully characterized. The results suggest that these block polymers are promising materials for stimuli-responsive hydrogel membranes applied to medical devices. Work supported by the Swiss National Fund for Scientific Research and an NSF-funded MRSEC (DMR#0819885) at the University of Minnesota.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027523-027523-1. doi:10.1115/1.3147086.
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Microelectrodes are routinely used for recording from ensembles of neurons for clinical and neuroscience research applications. The quality of the neural recording is highly dependant on the electrical properties of the microelectrode. Lowering the impedance of the electrode-electrolyte interface can improve the signal-to-noise ratio and the ability of the microelectrode to record from more distant neurons. Therefore, tetrodes, which are made by twisting four 12.7 μm nichrome wires together, are usually gold plated to lower impedances to 200–500 kΩ (measured at 1 kHz) before implantation. A further reduction in impedance could drastically improve recording quality but is not possible with standard gold electroplating methods without causing crossed connections (shorts) between the wires. Keefer et al. (2008, Nature Nanotechnology) reported that they could reduce electrode impedance and improve neural recordings by adding multi-walled carbon nanotubes to the gold plating solution, producing a “rice-like” texture on electrode coatings. We replicated this coating and were able to lower tetrode impedances to 120–150 kΩ without crossed connections. Furthermore, we found that by decreasing the electroplating current density and the concentration of multi-walled carbon nanotubes in the gold plating solution, we could create a 40–90 kΩ coating on each tetrode wire without any crossed connections. A scanning electron microscope (SEM) image revealed this 40–90 kΩ coating to be thick and globular with nano-scale texture, distinct from the “rice-like” coating of Keefer et al. The nano-scale texture coating had a large effective surface area likely responsible for the great reduction in impedance. In comparison, an SEM image of a standard gold-plated tetrode showed a thin coating with primarily lateral growth. The carbon nanotubes act as electroplating inhibitors by adsorbing onto the electrode surface and changing the dynamics of the gold electrocrystallization. We confirmed this by replacing the carbon nanotubes with polyethylene glycol (PEG), a known electroplating inhibitor, recreating the nano-scale texture and 40–90 kΩ tetrode impedances. By varying the concentration of electroplating inhibitors and the electroplating current, the dynamics of gold electrocrystallization can be controlled. This gives the ability to design an electrode coating with a specific shape, thickness, and texture that can be tailored to a specific application. Creating a low-impedance coating with a nano-scale texture using electroplating inhibitors can improve the recording quality of microelectrodes and can allow for the use of smaller microelectrodes that were previously limited by their high impedance. Supported by a grant from the Institute for Engineering in Medicine (U Minnesota) and training grant support from T32-EB008389. Corresponding author; email: redish@umn.edu

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027524-027524-1. doi:10.1115/1.3147087.
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The ability to record neural ensembles from awake, behaving animals is one of the most important and successful components of the neuroscience experimental toolbox. However, even the most advanced modern systems have limitations due to the physical coupling of the recording site with the headstage. These systems can only record from a limited number of structures at any one time and have particular difficulty recording large ensembles from animals with thin skulls (e.g., mice, songbirds). Current systems cannot record from fragile structures (spinal cord, peripheral nerves and ganglia) during behavior because the wire electrodes would shred the fragile nerves as the animal moves. We propose the concept of a neural nanoprobe that is physically decoupled from a separately implanted waystation. Because the nanoprobes are not connected to the waystation by physical wires, multiple nanoprobes could be placed in multiple neural structures, all transmitting to a single, separate waystation. Because the nanoprobes effectively float in the cellular matrix, they are safe to put in fragile structures. The waystation does not need to be implanted in the fragile structures; it only needs to be electrically coupled to them. The first step to the realization of this device is a low-power, high-fidelity method for communicating between the nanoprobe and the waystation. In this abstract, we report a successful test proving the viability of using the brain itself as the conducting medium through which the nanoprobe and waystation can communicate. Initial tests show that neural signals from multiple transmission sites can be sent to a single, separated receiver. We first identified the current-loss of sine-waves transmitted through live (anesthetized) brain tissue. We found negligible current-loss across frequencies ranging from 100 kHz–50 MHz across distances as much as 15 mm. As these frequencies are larger than any known frequencies used by neural signals, they are unlikely to interfere with neural function. We next measured the ability to transmit and receive pre-recorded neural signals (sampled at 20 kHz), using pre–recorded signals to determine the fidelity of transmission. The two different signals were transmitted, received, and successfully demodulated with high-fidelity, even with transmission currents as low as 2 μA. Both the transmitters and the receiver each had their own battery power supply to ensure that they used separate, floating grounds. Finally, to ensure that the intra-brain communication signals did not interfere with neural activity, we recorded extra-cellular potentials before, during, and after the test. No changes were observed in spike shape, spike frequency, bursting, or other cellular properties, demonstrating the safety of this technique. Supported by a grant from the Institute for Engineering in Medicine (U Minnesota) and training grant support from T90-DK070106. Corresponding author; email: redish@umn.edu

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027524-027524-1. doi:10.1115/1.3147223.
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Molecular imprinting is a well established technology that mimics biological recognition systems using artificial materials. This involves synthesizing a nanostructured polymeric host in the presence of a target molecule to generate complementary binding sites that are selective for a molecule of interest. The technique offers a platform for developing simple and inexpensive systems with a vast array of applications such as; chromatography, separation, catalysts purification, solid phase extraction, biosensors, medical diagnostics and drug delivery. Elevated levels of some proteins in the blood can lead to a number of medical conditions. Incorporating these polymers into a device for blood purification to remove such molecules can be used as a means to combat these problems. Protein imprinting was studied from a novel perspective using protein coated micro crystals (PCMCs). PCMCs are nanostructured particles made via a rapid 1-step process developed by Moore et al. (2001). The use of a novel PCMCs strategy in molecular imprinting has allowed the retention of selected protein native conformation in organic media and the creation of access pores lined with nanocavities which facilitate protein extraction and re-introduction into the imprinted polymer. This technique has enabled us to overcome many of the challenges faced when using conventional imprinting methodology, such as protein insolubility in aprotic solvents, protein insolubility in aprotic solvents, protein denaturation and aggregation as a result of polymerization conditions and the permanent entrapment of the protein template in the cross linked polymer network.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027525-027525-1. doi:10.1115/1.3147253.
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Urinary incontinence (UI) has been known as a prevalent concern among parous and elderly women. However, recent studies have shown an unexpectedly high occurrence of UI in young physically fit female athletes who are actively participating in vigorous physical activities. Those study results motivated us to explore the relationship between daily intensive exercise and the occurrence of UI. As the first step to advance our understanding of this problem, an ambulatory device was developed for recording urological response to the intense force levels to which female athletes are subjected. The device consists of three types of wearable sensors, including 1) a +/– 25g tri-axial accelerometer, 2) a 360° biaxial inclinometer and 3) a urinary leakage detector or ULD. It also contains a compact data logger for real-time data recording with high frequency and precision (125 Hz, 16-bit A/D converter). The accelerometer and inclinometer help to determine the force levels developed in the body during physical activities at which urinary leakage occurs. Two types of ULD sensors have been designed: (1) copper lattice ULD, and (2) thermistor array ULD. Copper lattice ULD senses the UI based on the fact that urine drops reduce the resistance of the copper lattice resulting in a voltage change. The thermistor array ULD makes use of the finding that leaked urine is warmer than the surface of the skin, such that the integrated thermal components respond to urine leakage differently. In addition, a thermoelectric cooler is applied to produce a constant reference temperature. The entire device is small, lightweight, nonintrusive, and can be worn comfortably by subjects on their wrists or low back for at least 3 hours of continuous data recording. The test results from the recruited female athletes show that the three sensors can simultaneously record the intensity of activity and the corresponding urine leakage. However, for the copper lattice ULD, substantial sweat developed during the vigorous activity which produced an artifact and prevented the device from detecting the occurrence of urine leakage. The recently designed thermistor array ULD is less sensitive to sweat, resulting a more reliable sensor than is provided by the copper lattice ULD. The wearable sensor based device enables us to determine if urinary incontinence in female athletes occurs during vigorous physical activities or as a result of the fatigue caused by these activities. This conclusion facilitates the understanding of the mechanism of UI and assists trainers and coaches with the design of an appropriate training program that reduces the occurrence of UI in these female athletes.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027525-027525-1. doi:10.1115/1.3147259.
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Thrombosis remains an important problem in both bare-metal and drug eluting stents. Platelet accumulation appears to be highly shear dependent in uniform parallel plate and stenosis models. This study was performed to evaluate thrombus formation location and size with respect to time for a stent. A three-dimensional laminar flow field was modeled via computational fluid dynamics through a stent-containing coronary sized vessel. Platelet deposition and accumulation was then simulated using a shear dependent accumulation function. The platelet deposition rate is given by the function: 3.2γ̇+67 platelets/mm2 /s, where γ̇ is the shear rate, which comes from a linear regression to data presented in Ku and Flannery 2007. A three-dimensional stent with a helical strut matrix design and a pitch of 21 mm was designed around a 3 mm diameter vessel. Square strut designs of 0.15mm×0.15mm and 0.30mm×0.30mm were considered, with each strut embedded halfway into the vessel. A 30° section of the stent was modeled because of stent symmetry. The inlet was set at a mean Reynolds number of 200 by specifying a pressure differential across the length of the vessel. Thrombus growth based on shear rate was set through the equation: dΦ/dt=(3.2γ̇+67)(Vplatelet/V)n=0MAn. V is volume, Φ is the volume fraction of thrombus, M is the number of surrounding faces that are either a wall face or are neighboring a computational cell denoted as occluded by thrombus, associated with area, A. Each term without a subscript pertains to the local computational cell prescribed as undergoing thrombus growth. Thrombus cell occlusion was assumed to occur when thrombus filled 80% of the cell's volume. Maximum shear rates occur near the edges along the inner blood surface side of the stent struts. Thrombus growth increases more in the axial direction of the stent relative to the radial direction for the larger strut size. Conversely, the thrombus growth is more uniform in all directions along the smaller struts. The difference emanates from the two distinctly localized high shear contours near the edges of the larger stent struts, while the high shear regions were less distinct for the smaller strut size. Quadrupling the cross sectional area of a strut increases the initial maximum shear rate along the strut by 50%, in addition to doubling the available surface area for platelet deposition. Therefore, increasing strut size has a threefold effect on platelet deposition rate, leading to faster vessel occlusion. This computational technique may be extended to approximate where thrombus may grow to completely occlude a blood vessel and the length of time occlusion would take. The CFD modeling technique may also be used to evaluate thrombus deposition on medical devices such as heart valves and ventricular assist devices.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027526-027526-1. doi:10.1115/1.3147265.
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During balance rehabilitation, physical therapists typically provide verbal instruction and/or physically reposition a patient to demonstrate proper postural position and movements. We have developed a wireless device that enables an expert (such as a physical therapist) to map his/her movements to a trainee in a hands-free fashion. The trainee is subsequently able to mimic the motion of the expert by interpreting positional cues presented via vibrotactile feedback to the relevant body segments. This device will potentially enable a therapist to aid multiple patients simultaneously and/or remotely, or enable a trainee (such as an athlete or student) to replicate expert movements. The device comprises an Expert Module (EM) and Trainee Module (TM). Both the EM and TM are composed of six degree-of-freedom inertial measurement units, microcontrollers, and batteries. The TM also has an array of vibrating actuators that provides the user with vibrotactile biofeedback. The expert dons the EM, and his/her relevant body position is computed by an algorithm based on an extended Kalman filter that provides asymptotic state estimation. The captured body position information is transmitted wirelessly to the trainee, and directional instructions regarding the desired motion/position are displayed via vibrotactile feedback. The trainee is instructed to move in the direction of the vibration sensation until the vibration is eliminated. While prior work has demonstrated the use of vibrotactile stimulation for improved motor learning, this portable and wireless device is suitable for use outside of a laboratory environment. Five healthy young blindfolded subjects were instructed to mimic recorded expert anterior-posterior trunk tilt motion using the aforementioned device in a series of proof-of-concept studies designed to investigate the effects of changing the feedback activation threshold and varying the nature of the feedback. To characterize the efficacy of the system, we performed a cross correlation of expert and trainee trunk tilt angle while varying the threshold angle difference at which vibrotactile feedback was applied. Preliminary results showed that subjects performed best at 0.5 and 0.75 degree thresholds among those tested (0.5, 0.75, 1.0, 1.25, 1.5). The normalized mean cross correlations for the 0.5 and 0.75 threshold conditions were 0.96 and 0.97 respectively, while the mean differences between expert and trainee trunk tilt angles were 1.1 and 1.2 degrees respectively. Further studies at 0.5 and 0.75 threshold conditions confirmed that proportional plus derivative feedback of the angle difference resulted in superior performance compared to proportional or derivative feedback alone. Repetition of the task was not significant suggesting that trainees could immediately use the device to accurately replicate expert anterior-posterior trunk tilt movements.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027526-027526-1. doi:10.1115/1.3147267.
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Dehydration is a common problem in healthy individuals as well as the elderly and chronically ill. People are often poorly attuned to hydration, and despite widespread awareness of the problem, fatal and near-fatal episodes occur frequently. Typical indicators of hydration status include changes in body weight, urine specific gravity, blood plasma levels, and bioelectrical impedance. Challenges to estimating hydration status from these indicators include the invasive nature of some methods as well as the cost and time required. We have developed a noninvasive device for monitoring hydration status. Our design is inspired by the traditional clinical protocol that approximates fluid loss on the order of 1-2% dehydration by assessing radial pulse before and after a supine to standing transition. The prototype comprises an inertial measurement unit (Xsens MTi) and a wearable heart rate monitor (Polar S810i). In order to compare heart rate behavior under normal and low hydration levels, fluid loss equivalent to 1-4% of the baseline body weight was induced by exercise in three healthy subjects during two data collection sessions. In the first (control) session, subjects replaced fluids every 15 minutes during exercise to maintain their body weight within 0.2% of their baseline value. Fluids were not replaced during the second (test) session, and subjects lost an average of 1.2% of their body weight. Heart rate and body position measurements were recorded before and after exercise while subjects performed repeated supine-to-standing movements and knee-to-chest stretching exercises (supine position only). All post-processing was performed using MATLAB (The MathWorks). Average heart rate was calculated over a 10 second period. Pilot data demonstrates the device's ability to detect hydration changes on the order of 1% in one-third the time required by the traditional clinical protocol (30 seconds compared to 90 seconds). The average rise time from baseline to maximum heart rate and the maximum heart rate following supine-to-standing transitions were significantly longer and greater, respectively, in the dehydrated subjects. Although not statistically significant, the average heart rate during knee-to-chest stretching exercises was elevated in the dehydrated state.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027527-027527-1. doi:10.1115/1.3147268.
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To overcome the limitations of existing ablation techniques, we propose a novel combinatorial approach that would utilize the thermal and chemical destructive effects of exothermic chemical reactions, such as an acid/base neutralization reaction, to treat solid tumors. Thermochemical ablation is a potential technique for percutaneous probe-based tumor therapy. It involves simultaneous intratumoral delivery of multiple reagents resulting in thermal energy released by an exothermic reaction to ablate tumor tissue with concurrent generation of a hyperosmolar byproduct that could accentuate tumor destruction. Besides the benefit of synergistic thermal and chemical effects for tumor tissue destruction, this technique is potentially highly cost-effective, easy to implement, and able to treat larger sized tumors. Our hypothesis is that thermochemical ablation can create an evenly distributed zone of coagulation in tumor tissue without systemic toxicity. A prototype device assembled using off-the-shelf components is being investigated in our lab for concurrent intraparenchymal delivery of an acid and a base. The distal portion of the multi-lumen device allows for passive mixing of the reagents before entering the tissue. The prototype device also satisfies other desirable design criteria such as rigidity to penetrate body tissue, reduced diameter, chemical stability to reagents, etc. However, the device can be improved upon by incorporating additional characteristics such as optimized imaging characteristic for real-time visualization and localization within tumor tissue, MRI compatibility, thermal insulation, improved mixing at the tip, etc. Our lab is currently working on improving the design of the infusion device as well as assessing the feasibility of the thermochemical ablation technique in vitro and in vivo. While currently being targeted conservatively for palliative therapy of unresectable or late-stage aggressive malignancies such as hepatocellular carcinoma, thermochemical ablation has potential use in the therapy of a majority of solid tumors such as breast cancer, lung cancer, prostate cancer, renal cancer, sarcomas, etc.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027527-027527-1. doi:10.1115/1.3147270.
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To avoid revision surgeries in artificial joint replacements and to allow young people to have a joint replacement, using biological joint replacement created by tissue engineering is a promising alternative. Several research groups have tissue engineered bone [Warnke 2004] and cartilage [Chung 2007] separately. The tissue engineering of a joint, consisting of bone and cartilage is the next frontier. The present study focuses on the design of a novel device, named Endoreactor, that is employing the mechanosensitivity of cells to create a joint-like-structure (JLS) consisting of a bone and cartilage sandwich, similar to an amphiarthrosis, by applying a mechanical loading regime to a stem cell seeded scaffold construct during endocultivation. This way, the patients who will eventually need the new joint will serve as their own bioreactor, having the joint grow in their own body. In the JLS, the outside layers are designed to become bone, using a 6 mm thick scaffold with high stiffness. The center layer is a 4 mm thick scaffold which is compliant so as to experience more strain than the outside scaffolds to stimulate cartilage formation. Compression is realized by placing the JLSs between the long links of a kite-shaped four-bar linkage. This Endoreactor is powered by natural body motion through connection to the musculoskeletal system of the host, which in the experimental phase is a Gottingen minipig. The loading frequency and rest versus active time is dictated by the activity level of the minipig. This results in a natural loading pattern that is employed for the stimulation of cartilage formation in the JLS. A tensile force created during ambulation is converted into compressive action between the two long links of the mechanism. A mechanical stop limits the motion. This way controlled intermittent dynamic compression between 2.5% and 12.5% is realized in the cartilage layer of the JLS. All functions are integrated into a single piece compliant mechanism which is produced out of titanium using 3D rapid prototyping by selective laser melting technology. The mechanism can be fitted with cages that hold the scaffolds for bone and cartilage in place and protect them from external loads while being implanted. A safety spring was added to accommodate for large actuation excursions. A number of prototypes were produced and tested for fatigue, plastic deformation, failure load, and displacements of the long links at the JLS locations under different axial loads. These tests confirmed the proper mechanical functioning of the Endoreactor. Work with animal models making use of the device to culture an amphiarthosis-like joint is foreseen in the near future. This work was carried out at part of MYJOINT: Living Bioreactor—Growing a New Joint in a Human Back, EU FP6-2004-NEST-C-1, Proposal No. 028861.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027528-027528-1. doi:10.1115/1.3147272.
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Enhanced fibroblast activity at the soft tissue-implant interface can dramatically decrease the stability, function, and lifespan of biomedical implants such as bone anchored prostheses. Although bone anchoring systems dramatically improve prosthetic limb mechanical stability, uncontrolled fibrosis at the soft tissue-mounting post interface is a significant problem. The aberrant cell growth leads to irregular skin folds that prevent proper sealing to the bone anchoring post and also serves as a site for opportunistic infection and failure of the prosthetic system. We are developing a bioactive vibrational coating to control fibrous tissue overgrowth. The coating is based on a magnetoelastic (ME) material that can be set to vibrate at a predetermined amplitude and frequency using a controlled magnetic field. We hypothesize that small local vibrations can be used to selectively control cell adhesion and gene expression to promote and maintain functional stability at the implant-tissue interface. For bone anchored prostheses, the ME coating would be applied around the mounting post at the soft tissue interface. The specific aims of this work were to (1) modify the coating for use in contact with a biologic environment and (2) determine if local vibrational strain can efficiently control cell attachment to the coating without significantly influencing viability. First, two common biocompatible polymers, polyurethane and chitosan, were deposited as thin films on the ME coating to allow for its use in tissue culture. An indirect cytotoxicity test was used to determine fibroblast (L929) viability in media conditioned for 24 and 48 hours with uncoated, chitosan coated, and polyurethane coated ME materials. Results demonstrated that both polymer coatings returned cell survival to levels statistically indistinguishable from controls (cells cultured on tissue cultured polystyrene, TCP) with cell viability over 96% under all coating conditions. Second, the affect of local vibrations on cell adhesion was tested in vitro. A cell viability assay (Calcein-AM) followed by fluorescent imaging was used to quantify attachment and viability of fibroblasts cultured directly on the bioactive ME material. Results clearly indicated that controlled local vibrations can induce complete cell detachment from the ME material compared with non-vibrated controls at up to 72 hours post-seeding. Further, cells detached via applied vibrations showed no significant decrease in viability compared to adherent controls. These results suggest the potential for this novel coating to effectively control fibrous tissue overgrowth using the mild application of tunable local vibrations, a significant and cost-effective approach that could improve the stability, function, and lifespan of biomedical implants and reduce the need for surgical revision.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027528-027528-1. doi:10.1115/1.3147375.
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Despite the success of multiple-port minimally invasive intervention (MII) systems, current research is fast moving away from standard, kinematically rigid MII instruments toward more flexible, highly articulated devices, such as robotic catheters, probes, and forceps. These new devices afford surgeons the same dexterity and range of motion as multiple-port systems while using only a single incision. Single-port MII devices hold the promise of facilitating procedures in small, geometrically complex spaces, such as those seen cardiothoracic surgery, with even lower risks of infection and patient discomfort than possible with multiple-port systems. However, the mechanical sophistication of these robotic devices requires careful consideration of morphological design to ensure that the complexity and cost of design is not economically prohibitive enough to outweigh the clinical benefits of improved robot flexibility. This study focuses on the intelligent design of a kinematically redundant, single-port MII robot architecture by way of morphological optimization. This MII device morphology is optimized to access the cardiothoracic cavity through a single 12 mm subxiphoid port and reach several regions of interest, consistent with procedures such as epicardial ablation and therapeutic substance injection, with minimal physiologic disturbance. The optimization process employs a recently developed morphological fitness metric to measure a candidate morphology's ability to navigate the cardiothoracic environment and perform surgical maneuvers with high end-effector flexibility while maintaining safe distances from anatomical structures. This fitness metric uses a Jacobian-based formulation to quantify a robot's capacity to avoid collisions with motion impediments and to minimize the mechanical torque required for the intended task. In addition to performance-based criterion, this optimization process also considers design factors such as part manufacturability and expense which heavily influence economic feasibility. Morphological optimization is performed by searching the mechanical design parameter space, which consists of part dimensions and linkage types, using genetic algorithms. The execution of specific surgical maneuvers is simulated for each candidate morphology until the fitness metric is maximized. Final simulations of the optimized device morphology working in the cardiothoracic cavity are performed to demonstate the functional advantages of the optimized single-port robot over current multiple-port systems.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027529-027529-1. doi:10.1115/1.3147380.
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Uterine leiomyoma (fibroid or myoma) is the most common indication for hysterectomy in premenopausal women. Cryomyolysis is a uterus sparing procedure in which a myoma is frozen by a cryoprobe, thereby causing tissue necrosis upon thawing and eventual reduction in myoma size. Unfortunately, although the iceball is readily visualized (by ultrasound-US or magnetic resonance-MR), the tissue at the periphery of the iceball is not completely destroyed. One potential solution to this problem is the use of cryosurgical adjuvants that increase cryosurgical image guidance and efficacy. Previous work in our lab has shown that TNF-α (native or as the nanodrug, CYT-6091, Cytimmune Sciences, Inc.) can act synergistically with cryosurgery to destroy all prostate cancer within an iceball. Building on this work, the current study was designed to test TNF-α as an adjuvant in an in vivo model of uterine fibroid (ELT-3) in a nude mouse. The aims of this study are to characterize in vivo: 1) the destruction of the uterine fibroid over time after cryosurgery; 2) the effect of TNF-α pre-treatment on enhancement of cryosurgery; 3) the effect of TNF-α dose, pre-treatment time and mode of delivery on the above and to note any toxicities. ELT–3 rat uterine fibroid cells were grown in the hind limb of female nude mice. TNF-α at various dose (2μg and 5μg) was administered at 1, 2 and 4 hours before cryotreatment in native or CYT-6091. Native TNF-α was injected either intra-tumorally or peri-tumorally. Injecting TNF-α solution into the center of the tumor comprised the intra-tumoral approach. For peri-tumoral injection, TNF-α solution was injected at each one of eight evenly distributed points spanning the circumference of the tumor base. CYT-6091 was administered by i.v. injection only. Cryosurgery was performed with a modified 1 mm diameter cryoprobe tip (120°C). Freezing was allowed to continue to the visible edge of the tumor. Injury was assessed by measuring tumor-growth delay. Baseline tumor size was measured on day 0; fold-changes in tumor size are reported relative to size at day 0. Toxicity was evaluated by survival rate. Groups were 4–6 animals in each group. The data suggests that pre-treatment with TNF-α before cryosurgery significantly enhances visually guided destruction of uterine leiomyoma, and that the dose, timing and mode of delivery are important variables in optimization of this combination treatment. First, it was observed that at least four hours pretreatment with TNF-α is required to obtain the synergistic effect of TNF-α and cryoinjury. Second, peri-tumoral injection of native TNF-α, was the most effective delivery method to enhance cryoinjury at low dose (2μg), however it was also the most toxic method at high dose (5μg). On the other hand, CYT-6091, although less effective than peri-tumoral injection at 2μg, was the safest delivery mode (0% lethality at 2μg; 33% at 5μg). Finally, CYT-6091 delivery at 5μg with cryosurgery resulted in a dramatic tumor growth delay compared with cryosurgery alone. Therefore, i.v. injection of CYT-6091 followed by cryosurgery allowed the highest dose of TNF-α, the least toxicity and the best overall myoma reduction. Funding: R01 CA075284, American Medical Systems, Inc. TNF-α and CYT-6091: Cytimmune Sciences, Inc.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027529-027529-1. doi:10.1115/1.3147382.
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A novel transaortic ventricular cannula, known as the ‘double barrel’ cannula (DBC), is designed to minimize the invasiveness of Ventricular Assist Device (VAD) implantation by combining the inlet and outlet cannulae into a single dual lumen cannula. Both flows will pass through a single opening in the apex of the Left Ventricle with the outflow then continuing past the aortic valve, into the aortic arch. This design offers several potential advantages over the current state-of-the-art. These include less invasive surgery and providing mechanical support to the septum. By routing the outflow through the aortic valve, the need to access the external structure of the ascending aorta is eliminated thereby eliminating the need for open heart surgery. In determining the DBC's design, close attention has been paid to the outflow portion of the cannula, which passes through the aortic valve. It was anticipated that this portion of the DBC could have the largest impact on the device's usability in practice. The object of this study was to test the performance of the valve with the cannula passing through it. Three different geometries are circular, equilateral triangular, and one-third semicircular. Experiments measuring aortic insufficiency during the diastolic phase were conducted. The experiment was designed to analyze several geometries passing through an aortic valve under diastolic flow conditions. All experiments used a simple flow loop which allows a natural porcine aortic valve to be viewed from downstream. The loop was driven with a pneumatic ventricular simulator in order to produce a cyclic flow. Three cannulae cross-sections were molded from RTV11 Silicone. During this test, High Speed Cinematography and flow rate measurement were used to quantify valve sealing and leakage. All data was collected and analyzed for the three cross-sectional geometries during diastole. The performances of the three geometries were compared using American Heart Association guidelines of aortic insufficiency (Al) diagnosis. The flow rate data was integrated in order to determine the volume of ventricle ejection and valve regurgitation. All three geometries exhibit low and acceptable levels of Al (15%Al), with the circular geometry causing the least amount of Al at 7.1%. The experimental control (Porcine aortic valve with no cannulae) exhibited an Al or 2.4%, validating both the harvested aortic valve and experimental flow loop for further testing. Using the high speed cinematography, several phenomena were observed during the sealing of the porcine valve; including leaflet folding leaflet bunching, and cannula displacement due to valve closure.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027530-027530-1. doi:10.1115/1.3147384.
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Medical, therapeutic and technological advancements, including the use of neonatal incubators and the development of neonatal intensive care units (NICUs), have significantly increased the survival of premature and ill infants. However, high levels of noise in the NICU result in numerous adverse health effects, including hearing loss, sleep disturbances and other forms of stress. Even normal levels of ambient noise may be of considerable risk for the most premature infants. It is well documented that the mammalian auditory system is most vulnerable to environmental influences immediately after the time that it first begins to function. In humans, the critical period spans approximately weeks 24–30 of gestation, which corresponds to the age when the most extremely premature infants are now able to survive ex utero. Premature infants are, therefore, at high risk for environmentally-induced hearing loss. Development of techniques that increase the amount of protection against noise-induced hearing loss (NIHL) could significantly improve quality of life, both while neonates are in the NICU, and long term. The long-term goal of our research is to develop a version of an existing active noise cancellation (ANC) system that can be used to reduce sound levels in NICU incubators, in a manner that does not require considerable space. The core component of the ANC system is a carbon nanotube-based transparent actuator, which is controlled by an adaptive controller so that an exact out-of-phase anti-noise can be produced from the actuator (Yu et al, 2005, 2007). The basic principle of the ANC system is to cancel the unwanted primary noise through the introduction of a destructive anti-noise sound. Experimental results showed that a reduction of greater than 15 dB in the primary noise can be achieved by the ANC system (Yu et al. 2007). Ultimately, this transparent actuator could be built into the side of an infant incubator, providing noise protection without adding equipment to the already crowded NICU environment. Before human trials can begin, animal studies must be completed to demonstrate that the ANC system can prevent the hearing loss that results from exposure to incubator noise during the critical period. One complication in animal testing is that individual species respond to different frequency ranges. For example, the human cochlea is most sensitive to sound frequencies between 2 and 5 kHz, while mice respond best between 8 and 16 kHz. It was hypothesized that a frequency translation based on the cochlear frequency/place relationship could be used to convert incubator noise into an appropriate stimulus for testing of the ANC in mice. Neonatal mice were exposed to untranslated incubator noise (IN) or frequency-shifted incubator noise (FSIN) during the critical period, and hearing sensitivity was measured following the noise exposure. IN had no effect on acoustic thresholds, but FSIN caused a moderately severe (60–70 dB) high frequency hearing loss in all mice tested. Based on these data, the FSIN stimulus represents the first accurate model of neonatal noise-induced hearing loss. Future experiments will use this model to test the ability of the ANC system to protect against NIHL.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027530-027530-1. doi:10.1115/1.3147386.
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During the delivery of a transcatheter aortic valve, the native leaflets are pressed toward the vessel wall when the stented valve is deployed, but the proximity of the native leaflets to the coronary ostia following deployment is not fully understood. Fluoroscopic (F) and endoscopic (E) video footage was gathered from isolated human hearts (n=3). Balloon valvuloplasty (BAV) was performed with a non-compliant balloon, followed by contrast injection into the coronary ostia. Images (F) captured the perpendicular distance from the balloon to the ostia (ostium depth). A nitinol stent was delivered to the aortic position trans-apically. Images (E) measured the distance between the native aortic leaflet and the lowest point of the coronary ostium (ostium height). Additionally, cadaveric hearts (n=23) underwent extensive anatomical analyses using a 3D digitizing arm in addition to the described procedures. BAV in perfusion fixed hearts gave left and right ostium depths of 5.28±1.49 and 5.34±1.85. Images (E) from the perfusion fixed human hearts showed left and right ostium heights of 3.2±2.9 mm and 4.3±2.4, respectively. 2 of the 23 perfusion fixed human hearts studied had negative ostia heights, but the effect on coronary flow is not known.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027531-027531-1. doi:10.1115/1.3147387.
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A wide variety of materials and chemicals are used in the development, production, cleaning, packaging, sterilization and shipment of medical devices. Some of these materials are used in large quantities and are often a source of waste. Some materials, such as poly vinyl chloride (PVC) plastics, have toxicity concerns. Additionally, many chemicals including chlorinated solvents and ethylene oxide are carcinogenic or highly toxic and can be detrimental to the environment and public health. While the medical device industry is highly regulated in the United States by the Food and Drug Administration, new green initiatives in the European Union are modifying the regulatory oversight of chemicals, materials, and their manufacture. In addition, hospitals are working to reduce waste and pollution as part of their operations and are increasingly asking vendors to assist them. Minimizing waste and pollution associated with medical devices can improve a company's environmental performance and save money. The primary focus in medical device manufacturing is patient safety and compatibility. Environmental considerations, which can include potential cost savings, are often overlooked in the design and process development phases. Numerous pollution prevention and energy efficiency options exist for medical device manufacturers. These options can be integrated into the development, design and process protocols, and engineering change orders when designing a new product or improving an existing part. By having a process design evaluation plan that includes environmental considerations, companies can effectively manage the creation of waste streams, toxicity of material inputs, and process efficiencies as a mechanism at both the front-end and the duration of the product line. These options often cut costs and can help reduce current and prospective regulatory burdens. The Minnesota Technical Assistance Program (MnTAP) at the University of Minnesota has been assisting businesses with pollution prevention and cost savings for 25 years. MnTAP's engineers and scientists have worked with the medical device industry to reduce the quantity of packaging and waste associated with cardiac catheters, reduce the use of toxic cleaning solvents, minimize the use of PVC, and research safer disinfection and sterilization methods. This poster includes case studies of the above mentioned projects, an overview of less toxic sterilization methods, and tools for medical device manufacturing that meet FDA requirements, but reduce waste and toxicity during production and use.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027531-027531-1. doi:10.1115/1.3147389.
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Automated diagnosis of heart pathology is extremely desirable in today's medical environment. The sounds of auscultation collected through a stethoscope are the simplest, fastest, and least invasive way to detect heart pathology. Upgrades in microphones, digital signal processing techniques, and computing power are making the translation of the sound into a digital medium complete. It is this completeness that allows separation between various heart states. Using a digital stethoscope available on the market, the researchers were able to separate aortic stenosis (AS) and normal (N) heart sounds using a modified Eigen classifier based upon the assumption that the data is drawn from multivariate Gaussian distributions with different means and covariance matrices. Human heart sound data was collected by a cardiologist using a commercially available Littmann Model 4000 electronic stethoscope (3M, Maplewood, MN). All data was collected via an approved Human Subjects Institutional Review board protocol. Auscultation data from 69 supine patients (36 female, 33 male, age range 18–93, average 54 years, Body Mass Index (BMI) range 16–47, average 29) from the second right intercostals space on both N and patients with AS. Diagnosis was confirmed using a standard trans-throacic echocardiogram. Eighteen normal and fourteen AS patients were used to develop normal and AS decision spaces. For each patient, approximately seven cardiac cycles were collected. The data was segmented into systole and diastole through a computerized playback program. The cardiologist determined location of S1 and S2. After segmentation, a mean heart cycle S1, systole, S2, diastole for the patient was calculated. The means for all fourteen AS patients was used to normalize the data. The normalized seven heart cycles were placed into a [3400×98] matrix that defined AS. The same was done for the normal population. These matrices were used as input for the singular value decomposition. Each measured auscultation signature was projected on the dominant scaled principal components. Eigen vectors were scaled to get the unit variances for the principal components. The entries of the feature vectors are the distances between the projected measured signatures and the centroids of the N and AS clusters. Distances between the resulting hyperspheres were calculated and projected on a two-dimensional graph of distance versus number of cycles. The first application of the Quadratic Model yielded some overlap between N and AS data. However, the data clearly separated. The input auscultation signatures were then segmented according to S1, systole, S2 and diastole and clearly aligned in the input matrices. The signatures were re-sampled to a 70 BPM cardiac cycle. Events within each segment were not aligned. The result of the standardization and alignment was clear separation between the N and AS decision spaces. There is great interest in the research community in algorithms that can be used to determine heart pathology from auscultation based heart sounds. The Quadratic Model shows 100% separation between N and AS data when S1 and S2 are properly segmented and re-sampled. When systole is isolated as the decision making attribute, separation increases by a hundred–fold.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027532-027532-1. doi:10.1115/1.3147482.
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Arthritis, degenerative disc disease, spinal stenosis, and other ailments lead to the deterioration of the facet joints of the spine, causing pain and immobility in patients. Dynamic stabilization and arthroplasty of the facet joints have advantages over traditional fusion methods by eliminating pain while maintaining normal mobility and function. In the present work, a novel dynamic stabilization spine implant design was developed using computational analysis, and the final design was fabricated and mechanically tested. A model of a fused L4–L5 Functional Spinal Unit (FSU) was developed using Pro/Engineer (PTC Corporation, Needham, MA). The model was imported into commercial finite element analysis software Ansys (Ansys Inc., Canonsburg, PA), and meshed with the material properties of bone, intervertebral disc, and titanium alloy. Physiological loads (600N axial load, 10 N-m moment) were applied to the model construct following the protocol developed by others. The model was subjected to flexion/extension, axial rotation, and lateral bending, and was validated with the results reported by Kim et al. The validated FSU was used as a base to design and evaluate novel spine implant designs, using finite element anlysis. A comparison of the flexion-extension curve of six designs and an intact spine was carried out. Range of motion of the new designs showed up to 4 degrees in flexion and extension, compared to less than one degree flexion/extension in a fused spine. The design that reproduced normal range of motion best was optimized, fabricated and prepared for mechanical testing. The finalized dynamic stabilization design with spring insert was implanted into a L4-L5 FSU sawbone (Pacific Research Laboratories, Vashon, WA) using Stryker Xia pedicle screws. The construct was potted using PMMA, and was subjected to flexion/extension, axial rotation, and lateral bending loads using MTS mechanical testing machine. The stiffness of the design was assessed and compared with computational analysis results.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027532-027532-1. doi:10.1115/1.3147483.
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According to the American Heart Association, approximately 166,200 out-of-hospital cardiac arrests occur each year. It is estimated that a victim's chances of survival are reduced by 7-10 percent for every minute that passes without treatment. Obviously, time is very critical in such situations. In most cardiac arrest cases, there is little to no warning to the victim that their heart has stopped and thus no time to notify others that emergency care is immediately required. To help alert the victim and others that a cardiac arrest episode has occurred, an ambulatory alarm and notification system has been built for individuals at high risk of cardiac arrest. The cardiac arrest alert system uses a ring-style photoplethysmograph that is connected to an armband unit which performs signal processing and wireless transmission and possesses an audible alarm. A wristband interface provides visual and tactile warnings, a reset button and a threshold adjuster. If the user's heart rate goes outside the preset range or is not detected by the system, a visual and tactile warning notifies the user of the situation. If the device is not reset or the problem not rectified within several seconds, the device then goes into full activation mode and sounds a loud alarm to notify nearby individuals who may be able to provide emergency assistance to the user. In full activation mode, the device also wirelessly transmits a signal to a central unit that, when signaled, automatically calls 911 and plays a pre-recorded message that states the incident and specifies the location. An additional phone number can also be stored so that another notification call is automatically performed. The central unit has a speaker so that the notification message is locally audible as well. In emergency situations, the cardiac arrest alert system will provide a life-saving service by rapidly alerting the user as well as nearby individuals and emergency respondents who can provide immediate assistance.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027533-027533-1. doi:10.1115/1.3147486.
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Transcranial Direct Current Stimulation (tDCS) is a non-invasive procedure where a weak electrical current (260 μA to 2 mA) is applied across the scalp to modulate brain function. tDCS has been applied for therapeutic purposes (e.g., addiction, depression, mood and sleep disorders) as well as cognitive performance enhancement (e.g., memory consolidation, motor learning and language recall). Despite safety and cost advantages, the developments of tDCS therapies have been restricted by spatial targeting concerns using existing two-channel systems. We have developed novel technology for High-Density tDCS (HD-tDCS) that improves spatial focality. Integral to the system are specialized HD-tDCS electrodes (<12 mm diameter) which allow safe and comfortable passage of current across the scalp. Here we evaluate a range of HD-tDCS electrode designs for comfort as well as test electrode over-potential, pH, and temperature. Passing 2 mA current for 22 minutes, both anodal and cathodal stimulations were evaluated independently. Subjective sensation during forearm stimulation was evaluated in 8 subjects. The benefits of skin electrical or chemical pre-conditioning were tested. Conductive Rubber, Ag, AgCl, pellet electrodes and AgCl ring electrodes were evaluated in combination with salty gels (Signa and CCNY4) and nominally electrolyte free gel (Lectron). The use of AgCl ring electrodes in combination with CCNY4 gel resulted in no significant pH, temperature, or over-potential changes under either polarity stimulation and was well tolerated by subjects. HD-tDCS may thus be applied with 2 mA per electrode for up to 22 minutes without skin irritation. Moreover, skin pre-conditioning can eliminate sensation such that HD-tDCS can be applied in a blinded fashion and under a broad range of therapeutic and performance enhancement applications. Our HD-tDCS system allows non-invasive, safe, and targeted modulation of selected cortical structures for electrotherapies that are individualized as well as optimized for a range of therapeutic applications.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027533-027533-1. doi:10.1115/1.3147487.
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Bowel resection surgery is a commonly performed operation used to treat a variety of gastro-intestinal tract disorders, including cancer. The surgery entails excising the diseased portion of intestine, and then creating a surgical anastomosis, or reattachment of the remaining ends. One of the major complications following bowel resection surgery is breakdown or leakage from the anastomosis, which affects 20% of patients, with an associated 10-15% mortality rate. The surgical creation of anastomosis frequently involves dividing blood vessels and can introduce unrecognized twists and tension on the intestine. As a result, the blood supply to the site of anastomosis is often hampered, limiting the oxygen supply that is essential for adequate anastomotic healing. We are proposing a device that enables surgeons to obtain real-time feedback on local tissue oxygen saturation (SpO2) during operative procedures. Such data will not only help surgeons realize any bowel oxygenation compromising maneuvers, but also help perform an anastomosis at the site of maximal tissue oxygenation, thus minimizing the occurrence of postoperative anastomotic leakage and improve patient outcomes. This report details the specifications, fabrication, operation and performance of a handheld wireless pulse oximeter suitable for the intraoperative measurement of tissue SpO2 during bowel surgery. The device adapts principles and technology developed for non-invasive pulse oximetry, and introduces tissue interface, physician tools, and signal processing algorithms for intra-operative application. The handheld device includes local display of SpO2 level (<1 s refresh) at the contacted tissue, and signals the operator on degraded signal quality/faults. An onboard micro-controller digitizes and processes signals transduced through a controlled LED array. Signal processing and display parameters were optimized for operating room conditions. A disposable functionally-transparent cover provides both device and tissue protection. Through serial or Bluetooth wireless transmission (250 Kbps), SpO2 and pulse signals can be processed on a PC or operating room VI. The incorporation of a pressure sensor to increase accuracy and robustness is explored. The device was validated intra-operatively on rodent and bovine surgical models.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027534-027534-1. doi:10.1115/1.3147488.
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There is a growing interest in the use of Deep Brain Stimulation (DBS) for the treatment of medically refractory movement disorders and other neurological and psychiatric conditions. The extent of temperature increases around DBS electrodes during normal operation (joule heating and increased metabolic activity) or magnetic coupling (e.g., MRI) remain poorly understood, and methods to mitigate temperature increases are actively investigated. Indeed, brain function is especially sensitive to the changes in temperature including neuronal activity, metabolic functions, blood-brain barrier integrity, molecular stability, and viability. We developed technology to control tissue heating near DBS leads by modifying the thermal properties of lead materials. A micro-thermocouple was used to measure the temperature near DBS electrodes immersed in a saline bath. 3387 and 3389 Leads were energized using Medtronic DBS stimulators. The RMS of the driving voltage was monitored. Peak steady-state temperature was determined under different RMS values. A micro-positioning system was used, which allowed the generation of temperature field map. We developed and solved a finite element method (FEM) bio-heat transfer model of DBS incorporating realistic DBS lead architecture. The model was first validated using the experimental results (by matching saline thermal conductivity and electrical conductivity) and was then applied to develop methods to control temperature rises in the brain using heat-sink technology. Experimental measurements are consistent with theoretical predictions including: 1) Peak temperature increases directly with the RMS square of the applied voltage, such that different waveforms with the same RMS induce the same peak temperature rise; 2) Peak temperatures increases with contact proximity such the maximal temperature rise was observed using adjacent contacts of lead 3389; 3) Temperature decayed over 2 mm distance away from energized contacts. FEM results demonstrated the central role of lead materials (material properties and geometry) in controlling temperature rise by conducting heat: namely by acting as passive heat sinks. We report that the relatively high thermal conductivity of exiting DBS lead wiring affects the temperature field, indicating the importance of detailed lead architecture. We then demonstrate how modifying lead design to optimize heat conduction can effectively control temperature increases; the manifest advantages of this approach over complimentary heat-mitigation technologies is that heat-sink controls include: 1) insensitive to the mechanisms of heating (e.g., nature of magnetic coupling); 2) does not interfere with device efficacy (e.g., the electric fields induced in the tissue during stimulation are unaffected); and 3) can be practically implemented in a broad range of implanted devices (cardiac/neuro-prothethics, pumps...) without modifying device operation or implant procedure.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027534-027534-1. doi:10.1115/1.3147490.
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Studies have shown residual limb volume can vary 11% to 7% in a single day due to changing activity level or weight. However, volume changes of only 3% to 5% can cause users to have difficulty putting on their prosthetic socket. Many existing volume compensation methods are cumbersome, rely on the amputee to maintain the appropriate pressure level, or allow only for a decrease in limb volume. Automatic compensation for volume gain and loss is therefore needed; however, the complexity of designing such sockets renders a traditional fabrication methods cost prohibitive or technically infeasible. Selective Laser Sintering (SLS), a rapid manufacturing (RM) technology, addresses both of these concerns. SLS is a layer-based RM technology that relies on a high power laser to fuse powder particles into a solid object. Minute detail, directly from a 3D CAD model, is possible and a technique has been established for manufacturing prosthetic sockets with passive compliant regions using SLS. Based on this SLS RM technique, steps toward developing a transtibial Nylon prosthetic socket that automatically adapts to volumetric changes in a residual limb will be described. A design methodology was developed to use RM including concept generation, refinement, and final verification. In concept generation, analogies, such as “Chinese Fingertraps” and balloons, were coupled with a review of socket designs in literature and industry and interviews with prosthetists. Inflation of a bladder integrated into the wall of a SLS socket is one of the promising design concepts generated, but the concept needs further refinement. In order to confidently design an inflatable SLS prosthetic, it is critical to understand the relationship between applied pressure and deflection. A testing specimen—5.08 cm diameter thinwalled membrane—was designed to simulate a bladder integrated into the wall of a SLS socket. Several thicknesses were also used to investigate the effects of this parameter on inflation. Preliminary tests were conducted using compressed air for quantifying pressure vs. displacement. During the tests, leakage through open porosity (due to low density) was detected. Density is strongly related to energy transmitted to the part during sintering. The energy concentration is quantified as the Andrew's Number (AN), the inverse relationship of laser power (LP) to laser scanning speed (SSP) and scan spacing (SS). Therefore, to determine the optimal AN—and therefore increase density—an experiment varying LP and SS (SSP is a manufacturer setting) to determine their effects on apparent density and tensile strength was completed. The optimal AN, 1.63 J/cm2 for Nylon 12 powder, was based on highest apparent density and tensile strength. Using this AN, additional deflection samples were tested. Initial results showed a maximum deflection of 2.1 mm at .145 MPa for a 1.3 mm thick membrane. In comparison, changing the volume of a 3D scan of a patient's residual limb by 6% in a 10.9 cm diameter region on the posterior distal tibia socket end, as recommended by a prosthetist, requires a 5.8 mm displacement. Therefore, early results suggest that a single bladder will not meet deflection requirements, influencing the design of multiple larger regions and use of a more flexible material. Results from these experiments will help eliminate concepts which cannot deflect the necessary amount for the volume change, further refining the concepts towards a solution.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027535-027535-1. doi:10.1115/1.3147492.
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Using Visible Heart® methodologies we imaged coronary artery bypass grafts (CABGs) and coronary stents in isolated beating human hearts and perfusion fixed human hearts. Due to the varying cardiac health of the donor hearts it has been possible to see progressive levels of stent endothelialization and vascular calcification. The isolated heart model uses a clear Krebs–Henseleit buffer in place of blood, allowing for the unique opportunity to image the coronary vessels. In the isolated human heart a fiberscope was inserted into either the native coronary artery or the CABG with the heart in sinus rhythm. In order to verify cardiac function during the imaging process the following measurements were read at a sampling rate of 5 kHz: ECG, aortic flow, and ventricular pressures. Perfusion fixed hearts were fixed in an end diastolic state achieved by applying pressures comparable to physiological conditions. This process causes the coronary arteries to fix in a dilated state. CABGs of human hearts were then imaged using fluoroscopy (angiograms) and fiberscopic techniques. The stented native coronary arteries of human hearts were imaged via fluoroscopy and by dissection. Through a variety of imaging techniques and using Visible Heart® methodologies we have obtained a unique visualization of a CABG and a coronary artery stent in a beating human heart during sinus rhythm. Investigative studies in perfusion fixed human hearts have provided a more complete anatomical imaging study of stent endothelialization in the native coronary arteries and vascular calcification in bypass grafts.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027535-027535-1. doi:10.1115/1.3147495.
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A prototype device (patent pending) has been created, and successfully used, to fuse tissue membranes as an alternative to sutures or staples. The joining, or coaptation, is accomplished through the controlled application of laser heating and pressure to induce protein denaturation and subsequent tissue fusion, through renaturation and intertwining, across the interface. Lasers have been used by a number of researchers to close wounds in controlled laboratory tests over the last 15 years. Many encouraging results have been obtained; however, no commercial delivery systems are currently available. This is due primarily to two factors: requiring an inordinate amount of experience on the part of the operator to detect changes in tissue appearance, and attempting to achieve general applicability for multiple tissue systems, i.e., a one-size-fits-all approach. Different combinations of system performance parameters may be required for different types of tissues. The present device overcomes these barriers as it is tailored for the particular application of septal laser fusion, namely for the coaptation of mucoperichondrial membranes. The optimal laser performance characteristics are pre-set for nasal tissue and packaged in an easy to use device. The important parameters involved in fusing biological tissues using radiation from laser sources are identified. The development of the device followed from computational modeling of the fusion process based on engineering first-principles from heat transfer, fluid dynamics and optics, and from experimental results on a particular tissue system. The experiments were designed and analyzed using orthogonal arrays, employing a subset of the relevant parameters, i.e., laser irradiance, dwell time and spot size, for a range of wavelengths. The in vitro fusion experiments employed 1 cm by 1 cm sections of equine nasal mucosa having a nominal thickness of 1 mm.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027536-027536-1. doi:10.1115/1.3147496.
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Isolated mammalian hearts have been used to study cardiac physiology, pharmacology, and biomedical devices in order to separate myocardial characteristics from the milieu of the intact animal and to allow for increased control over experimental conditions. Considering these benefits and that MRI is the “gold” standard for measuring myocardial function, it was considered desirable to have a system which would allow simultaneous MR imaging of an isolated beating heart. Here we describe a unique portable system, which enables physiologic perfusion of an isolated heart during simultaneous MR imaging. A two unit system was designed to physiologically support a large mammalian isolated heart during MR imaging were a modified Krebs-Henseleit perfusate was used as a blood substitute. The first unit, which resides in an adjacent support room next to the scanner, contains all electronically powered equipment and components (with ferromagnetic materials) which cannot operate safely near the magnet, including (1) a thermal module and custom tube in tube heat exchanger warming the perfusate to 38°C; (2) a carbogen tank (95% O2 5% CO2) and hollow fiber oxygenator; and (3) two centrifugal blood pumps which circulates and pressurizes the left and right atrial filling chambers. The second unit, which resides next to the magnet and is free of ferromagnetic materials, receives warmed, oxygenated perfusate from the first unit via PVC tubing. The isolated hearts were connected to the second unit via four cannulae sutured to the great vessels. A support system placed inside the scanner on the patient bed secured the hearts and cannulae in the correct anatomical position. To date, this system was tested in a 1.5 T Siemens scanner using swine hearts (n=2). The hearts were arrested with St. Thomas cardioplegia and removed via a medial sternotomy. After cannulation of the great vessels, reperfusion, and defibrillation, four-chamber and tagged short-axis cine loops were acquired using standard ECG gating. Tagged short-axis images obtained at the base, mid-ventricle, and apex were used to measure the following functional parameters for one heart: LV end-diastolic volume=38.84 ml, LV end-systolic volume=23.23 ml, LV stroke volume=15.6 ml, LV ejection fraction=40.18%, and peak LV circumferential strain=16%. The feasibility of MR imaging an isolated, four-chamber working large mammalian heart was demonstrated using a custom designed and built portable MRI compatible perfusion system. This system will be useful in studying in vitro cardiac function (including human hearts) and developing MRI safe biomedical devices and MRI guided therapies in a controlled setting.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027536-027536-1. doi:10.1115/1.3147498.
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For this work, a peristaltic micropump was fabricated. Actuation of the micropump was accomplished with piezoelectric cantilevers. To date, a minimal number of soft polymer-based micropump designs, have explored the use of piezoelectric materials as actuators. The fluidic channel for the micropump was fabricated using PDMS and soft lithography. A novel and very simple template fabrication process was employed, where the use of a mask and clean room facilities was not required. Replica molding to the template produces both, a channel measuring 95μm in height, and a rounded cross-sectional geometry, the latter of which is known to be favorable for complete valve shutoff. Clamps were adhered to the tips of the cantilevers, and used to secure in place aluminum valves. The valves had finely machined tips [3mm×200μm(L×W)] on one surface. These tips served as contact points for the valve making contact with the PDMS membrane surface, and were used for the purpose of opening and closing the channels. The cantilevers were secured in place with in-house manufactured micropositioners, which were used to position the valves directly over the PDMS channel. The micropump was thoroughly tested where the variables characterized were maximum attainable backpressure, flow rate, valve open/close characteristics, and valve leakage. The effect of the phase difference (60°, 90°, and 120°) between the square wave signals delivered to each of the three cantilevers was investigated for flow rate and maximum attainable backpressure. Of the three signal phases, the 120° signal demonstrated the largest flow rate range of 52–575 nL/min (0.1–25 Hz), as well as the highest attainable backpressure value of 36,800 Pa (5.34 psi). The valve shutoff characteristics for this micropump was also examined. Fluorescein was trapped inside the microchannel, where the fluorescent signal was monitored throughout the valves open/close cycle with the aid of an epifluorescent microscope. It was found that the fluorescent signal went to zero with the valve fully closed, supporting the conclusion that the valve completely closes off the channel. Further evidence of this claim was demonstrated by observing the valve leakage characteristics. An electronic pressure sensor was used to collect data for this experiment, where it was found the valve was able to hold off 36,800 Pa (5.34 psi), only loosing 2% of this pressure over 10 minutes. In conclusion, it has been shown this micropump outperforms many existing micropump designs, and is suitable for integration into a variety of both macro, and microdevice platforms. Experiments are currently underway to examine how the flow and valving characteristics change for valves with different tip dimensions. A discussion will also be given for improved fabrication techniques, where injection molding is currently being used as the fabrication method to examine the performance changes associated with different cross-sectional PDMS channel geometries. The end goal for use of this micropump is twofold; 1) integration into a micro-free flow separation device, and 2) integration into a capillary electrophoresis instrument for use in direct-sampling neuroscience experiments.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027537-027537-1. doi:10.1115/1.3147500.
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While the function of central and peripheral nervous system decreases (caused by aging, vestibular deficiency or stroke), maintaining of body stability become hard. Studies indicate that movement coordination of axial segments (head, thorax, and pelvis) in a dynamic state such as walking disrupted in these pathologic conditions. In recent years goniometry and cinematography have been widely used to measure active or passive range of motion (ROM) in asymptomatic adults. The aim of this investigation is to design and implement a new method by evidence based approach for estimating the level of impairment in segment stability and improvement after treatment by measuring quality or quantity of movement among axial segments. Ultrasound based coordinate measuring system (CMS) can continuously measure motion in three dimensions during the course of time in a dynamic condition. The measuring procedure is based on the travel time measurement of ultrasonic pulses that are emitted by miniature transmitters (markers) to three microphones built into the compact device. Our system consist electronic, mechanic and software sections. Electronic board include: 40 KHz pulse oscillator, PRF pulse generator, sensor drivers, high voltage analog switches, 60 dB Amplifier, signal detector and CPU. Transmitter sensors which have been mounted on body send ultrasonic burst signals periodically and other 3 sensors which arranged on a T-shape Mechanical base receive the 3 dimensional coordinate of these transmitters. After sending 3D coordination data to PC via serial port, a complex and elaborative Visual Basic software calculate the angular dispersion, angular rate acceleration for each also calculate the stabilization parameters among segments such as Al (anchoring index) and cross-correlating between head and trunk coordinates.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027537-027537-1. doi:10.1115/1.3147503.
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The challenge of having a medical device robustly and reversibly adhere to a tissue in a minimally-invasive way during a clinical procedure is significant and has yet to be solved. Materials that could perform this adhesion would be valuable for use in a wide array of devices, including wired and wireless endoscopes for gastrointestinal interventions; cardiovascular devices such as mobile robots that transverse the heart surface or fixation devices for open heart surgery; and for adhering craniectomy devices to the skull during decompressive treatment. Fibrillar patterned adhesives inspired by the micro- and nano-scale structures on the feet of geckos have been widely studied and synthesized and have shown great potential for reversible adhesion in dry environments. Preliminary work has also been conducted to enhance the adhesion of these materials in wet conditions by coating them with polymers that include dopamine methacrylamide (DMA), a synthetic sticky polymer inspired by the material found naturally in the holdfasts of mussels. These coated materials demonstrated wet adhesion enhancement at the nano-scale, but not at the macro-scale and not when compared to unpatterned materials. In this work, we take previously-developed gecko-inspired patterned arrays of fibers with mushroom-shaped tips which have demonstrated enhanced adhesion with respect to unpatterned materials in dry conditions and coat them with these same synthetic mussel-inspired polymers to enhance adhesion in fully-submerged wet environments. DMA-containing polymers were synthesized through a multistep process and applied to an array of micro-scale polyurethane fibers by stamping. Material samples were tested in a custom-built adhesion measurement system in contact with a 6 mm glass hemisphere in both dry and wet conditions. Flat DMA-stamped samples demonstrated as much as 7 times enhancement over uncoated samples, while patterned, coated samples demonstrated as much as 23 times adhesion enhancement. The sample also maintained 65% of its adhesive ability over 100 test cycles. These materials are the first to demonstrate reversible fibrillar adhesion in wet conditions at the macro-scale with respect to both unpatterned and uncoated materials on non-flat surfaces using intermolecular forces instead of suction forces. Versatile reversible materials capable of adhering to non-flat surfaces in wet conditions should continue to be studied for their value for a wide array of medical device applications.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027538-027538-1. doi:10.1115/1.3147506.
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Cochlear implants continue to be used in the treatment of profound deafness. Because of the tonotopic nature of the cochlea, more controlled insertion is perhaps the most important factor affecting device performance. The implant stiffness, and therefore the scala tympani (ST) wall contact force, contributes to insertion difficulties. Attempts to correlate the implant carrier structural properties and the intracochlear contact forces during insertion are limited. Researchers in the Michigan Center for Wireless Integrated Microsystems are developing perimodiolar-shaped silicon and parylene-based thin film cochlear electrode arrays and backing devices for a more controllable implantation. We report a method developed for measuring the thin film actuated electrode array rigidity to quantify the ST and modiolus wall contact forces during and after insertion. The method used a pneumatically actuated polyethylene terephthalate (PET) monolithic electrode actuator using pressurized air (0–200 kPa) for actuation. The prototype actuators consisted of PET tubes with an ID of 365 μm and a wall thickness of 58 μm. Force calculations using cantilever beam bending theory were performed to estimate the tube bending forces as a function of internal pressure and therefore variable structural stiffness. Based on estimations, a method was developed to measure such small forces avoiding the use of commercially available, relatively insensitive load cells. A fixture was fabricated incorporating two brass microcantilevers (reference and deflection arms) sensitive to sub-mN forces applied by the actuator on the deflection arm of the cantilevers. Microcantilver deflection data, captured by an interferometric microscope, was used to calculate the actuator force and eventually the reaction force acting on the actuator. The implant actuation forces ranged from 0–0.76 mN over an actuation pressure range of 0–140 kPa, from nearly straight to the relaxed perimodiolar post-implantation shape. For estimating the implant rigidity (EI), the actuator stiffness and the actuation pressure was correlated. The actuator stiffness at different actuation pressures was obtained both theoretically (using beam bending theory and PET tube structural properties) and experimentally (using the derived unconstrained actuator deflections at measured actuator forces). The theoretical and experimental stiffness values ranged from 3.6E-08 to 5.34E-07 N/μm and 2.5E-08 to 7.8E-06 N/μm respectively over the working pressure range. The calculated rigidity constant (EI) of the best prototype insertion tool from the experimental stiffness measurement was 6.71E06 Nμm2. The insertion tool-ST wall contact forces were calculated, using the estimated rigidity, in a hypothetical insertion situation. Force calculations assumed that the implant is equipped with actuator deflection feedback sensors and the actuator's stiffness remains constant over its entire length for a given operating pressure. A contact force of 1.19 mN was found acting on the cochlear ST wall when the insertion tool hits the wall and deflects by 200 μm at an actuation pressure of 140 kPa.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027538-027538-1. doi:10.1115/1.3147512.
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Adaptive seating has been defined as the customized prescription and application of sitting support devices based on therapeutic principles. It is recognized that for children with neuromuscular disorders that result in poor postural control, a comfortable adaptive seating system that provides them with the support needed to maintain a sitting position can be essential for raising their overall level of well being. These systems are also used to try and prevent or to slow the progression of skeletal deformities. However, problems with current adaptive seating systems do exist. After extensive research into these problems we developed a novel adaptive seating system which aims to improve on current designs. It includes a number of innovative features including

• Active dynamic supports: The backrest and headrest are mounted on gas springs, allowing them to move in order to accommodate the user's task induced movement or abnormal muscle tone. The forces applied to and the position of the supports are monitored and used to control motors attached to the gas springs. This means that the user can, when required, be returned to their original position in a controlled but still dynamic manner. The “floating” nature of these supports, especially the backrest, is also intended to allow for some growth of the user.

• Novel backrest shape: In an attempt to positively influence abnormal hip extensor tone, the user's trunk is given a predominantly lateral rather than posterior type of support. Preliminary results suggest that this approach could have some beneficial effects in terms of reducing abnormal hip extensor tone.

• Multi-planar tilting seat base: Tilting of the base in the saggital and coronal planes can be actuated manually or pre-programmed to do so automatically at set intervals. This aims to improve user comfort and prevent the development of pressure sores and could also be used to accommodate deformities such as pelvic obliquities.

Through these features the novel system has the potential to provide improved comfort, support and functionality for the users and to reduce the burden place on those who care for them.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027539-027539-1. doi:10.1115/1.3147513.
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We report a new sensing technique of proteins using competitive proteins' displacement reaction on a surface, namely Vroman effect. A target protein displaces a pre-adsorbed weak-affinity protein; however a pre-adsorbed strong affinity protein is not displaced by the target protein. In a microfluidic device, we engineer two gold surfaces covered by two known proteins. The sensor allows selective protein detection by being displaced by a target protein on only one of the surfaces. The SPR (Surface Plasmon Resonance) sensorgrams show that three different human serum proteins, immunoglobulin G (IgG), tyroglobulin (Tg) and fibrinogen (Fib) have different adsorption strengths to the surface and the competitive adsorption of individuals controls the exchange sequence. Based on the exchange reaction, we demonstrate that the sensor has a high selectivity for Tg. Immunosensor techniques have become the dominant test methods in diagnostics, therapeutics and protein research, partially due to the highly selective molecular recognition of antibody and antigen. However, they often suffer from cross-reactivity, non-specific adsorption and lack of antibody diversity. Besides these limitations, integrating antibodies on to a transducer is a time-consuming and labor intensive process and often become the bottle neck of high yield sensors. To date, few alternative platforms for the protein detection have been active in biosensor communities. Here, we report a fundamentally different protein detection method that relies on the competitive nature of protein adsorption onto a surface, namely the Vroman effect. The Vroman effect is governed by thermodynamics as it is more thermodynamically stable in nature. By using the technique, we obviate the need to rely on antibodies and their attachment to transducers. Our approach is that one can engineer two surface pre-absorbed by two known proteins; one is a little smaller and the other is a little bigger molecular weight proteins than the target protein. Then, the pair of the surfaces becomes a highly-selective protein sensor since one is displaced an the other is not displaced by the target protein. In its first implementation, we demonstrate that three human serum proteins, IgG, Tg, and Fib, have different adsorption strengths onto a hydrophobic gold surface. The different strengths induce an exchange reaction among them. The displacement strength is ranked in the following order; Fib (340 kDa) > Tg (660 kDa) > IgG (150 kDa). In other words, fibrinogen can displace all other proteins while Tg only can displace IgG. Based on the results, we can identify specific target proteins without using the conventional immunosensor technique. Our results show how to detect Tg using a pair of surfaces pre-adsorbed by two known-size proteins; IgG in channel 1 and Fib in channel 2. Tg displaces IgG in channel 1 but just flows through the fibrinogen-covered surface in channel 2 without any exchange reaction. The differential measurement of the SPR angle change from channel 1 and 2 allows the detection of Tg and the angle change also indicates how many thyroglobulins replace IgG.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027539-027539-1. doi:10.1115/1.3147515.
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The objective of this study is to show a methodical product development process that is infused with innovative elements in strategic locations, which facilitates product quality, technical breakthroughs, speed to market, and how this method can create a system of development involving all stakeholder groups. This process fosters an understanding of advantageous times for ideation activities and reiteration activities to occur. Due to a lack of industry knowledge and practice regarding design, the sub-categorization of steps in this process will lead to understanding of the tasks, costs and timeframes involved in the design phases. The intention of this process definition is also to build an understanding of which functional groups should be involved in research, ideation and design, and develop an understanding of how these groups should collaborate, and which should be responsible for certain product decisions. Although many similarities exist among current development methods, common misconceptions and process deficiencies are prevalent. Innovative aspects of the process are commonly misunderstood, and are often completely lacking or applied at an inefficient juncture of the process. Other times evaluation and research phases are left incomplete, leaping directly to the mechanical development process phase. This causes earlier steps to be done after engineering work is underway, which creates inefficiencies in the process. There is also evidence of a large gap of misunderstanding about what the nature of the design phase really is, which causes it to be left out of the process altogether or ill-applied during the process. We conducted an examination of current studies and process information from medical device companies and evaluated them for the exclusion or placement of key innovative elements. Common similarities were discovered, and a modified development process description was created with the inclusion of elements useful for optimizing innovation and reducing redundancy. Some of the detrimental commonalities include a lack of detail in the research and ideation phases of the process, the tendency for companies to skip around in the process and impeding the ability to hit critical dates, and involving groups and disciplines in the process at incorrect times which stifles innovation and causes bottlenecks. The revised process involves designers in evaluation, research, marketing, engineering, validation and production, finding that it pulls all groups together, linking them to a single process. We found that this model of product development can provide results that will improve performance and acceptance of new medical devices, while increasing innovation and help to uncover breakthrough concepts. Key factors in this process include the practice of planning innovation into the process in the proper places; having a design team involved in all phases to increase product quality; and expending sufficient effort in the highly misunderstood areas of the process. It is also shown that success is achieved if product decisions are made around design criteria derived from the process, with a design team involved in making these decisions. Continued iterations must occur during the appropriate phases, and when the process is followed, bottlenecks are removed, streamlining takes place, innovation can occur, and customer needs are more fully met in the product, increasing overall product quality and launch success.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027540-027540-1. doi:10.1115/1.3147517.
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Nerve conduction studies help to diagnose muscle and nerve diseases and point to the underlying cause and potential treatments. Conduction studies involve stimulating nerve at different points along its course and recording the response with an electrode, conduction velocity is determined by dividing the distance traveled by the time it takes the impulse to travel that distance. While the measurement of time is done electronically and is very accurate, measurement of distance in every commercial laboratory is done by marking the skin and measuring the distance with a flexible tape measure. Such distance measurement is highly error prone and leads to erroneous results and misdiagnosis. We present a device to measure distances along the body surface. It eliminates examiner error in the measurement of distance. It delivers an operator-independent and reproducible measurement and thereby increases accuracy of test results and avoids misdiagnosis. Furthermore, the device saves a significant amount of time. Stopping to pull out a tape measure, reading it and entering the data into the computer, all adds time to the length of the procedure. The measurement device eliminates these steps thereby increasing efficiency. It also transmits the measured distances directly to the computer, thus eliminating error in data entry. The device uses the established optical mouse technology at its core. It can measure displacements with a 0.0635 mm resolution. It is based on a commercial chip set, ADNS-5030 from ‘Avago Technologies.’ The system consists of an optoelectronic sensor which measures changes in position by optically acquiring sequential skin surface images (frames) and mathematically determining the direction and magnitude of movement. The sensor only needs to be pointing at but not touching the skin. The main advantage of this approach is that it is contactless, eliminating the need for disinfection. Although, current limitation of the device is in measuring accurately over non-planar surface due to its considerably large size making it difficult to maneuver over bumpy surfaces. Initial results for measurement studies performed over a diverse subject pool (in terms of skin color, hair density) results are promising with an error less than 9% for distances over 75 mm. A reduction in size of the device would lead to more accurate results as smaller size would help in easy maneuverability. Future implementations will exploit the contactless feature and integrate the measurement in the stimulus probe, reducing testing time and the need to operate multiple devices.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027540-027540-1. doi:10.1115/1.3147523.
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Weakening of muscle and bone tissue after merely a week of exposure to a microgravity environment has been demonstrated to adversely affect the physiological health of astronauts . Innovative solutions meant to replace traditionally bulky resistance-based devices are highly sought by burgeoning private space travel companies as well as other ambitious spaceflight programs that require a robust and effective solution for long durations in microgravity . The purpose of this study is to explore the unique contributions of exoskeleton technology in providing an effective, compact and elegant preventative device through assessing the current ability of exoskeleton technologies in stressing the body, formulating design requirements of an exoskeleton device and highlighting the areas of exoskeleton development that require further work in the realization of a robust microgravity-atrophy solution. An understanding of the abilities and shortcomings of current exoskeleton technologies is necessary to develop and streamline advanced forms of today's space physiological devices . The physiologically familiar structure of an exoskeleton, being built around the human form, would also provide for a greater degree of compactness, affecting everything from launch expenses to living arrangements in any space module. A more effective and persistent method of stressing the body will ultimately allow for a drastic decrease in bone and muscle atrophy, requiring less therapy should any space traveler return to a gravity environment as well as preventing various related ailments during their time in space. In conducting the study, a literature search was performed to identify fundamental design parameters. Designs were then formulated to best fit the required design specifications with difficult or absent features being noted. Initial design concepts based on traditional resistance-based solutions were also developed to further characterize the particular requirements that an exoskeleton would be required to fulfill. These design concepts were then steadily revised into a potential force generation mechanism and device architecture based on factors including human comfort, force generation, effective ranges of motion, materials and geometry. An appraisal of current exoskeleton technology in actualizing the proposed designs and design specifications provides a basis for analysis. The study has uncovered the strong points in exoskeletal designs as well as the major hurdles that, once crossed, will allow exoskeletal technologies to be a viable application in bone and muscle therapies, both in microgravity environments as well as gravity environments. A large hurdle lies in current exoskeleton technologies still utilizing bulky components but past trends have demonstrated a reliable miniaturization in the technology. Particularly important exercises and ranges of motion have been identified and initial designs formulated based on the physiological requirements. The study has demonstrated the need for more efforts in formulating innovative solutions to space-based physiology problems as well as explicitly listing design parameters required for any potential exoskeleton solution.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027541-027541-1. doi:10.1115/1.3147531.
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Accurate detection and classification of heart murmurs by auscultation is suboptimal and not always definitive. The murmur information perceived by the physician brain is the combined effect of both patient's (human) heart and the physician's ear. The information containing the murmur characterization which is retrieved by the human brain resides in the electrical signal coming out of the cochlea. For the very reasons described here, cochlea-like processing has been successfully applied to multiple speech recognition related technologies. This had not, before our prior work, been applied to human heart murmur analysis. Our prior research consisted of three steps: (1) capturing heart sounds, (2) processing the sounds using a cochlea-like filter, and then, (3) classifying each sound as being normal or a murmur using an artificial neural network (ANN). Previously in our research, we used a static cochlea-like filter model in step 2 as described above, which resulted a significant improvement in terms of accuracy of heart murmur classification. Our cochlear filter analysis helped identify information-rich frequency segments in human heart sound. We want to advance the cochlear filter model from a static to a variable frequency selective model with feedback from ANN for better optimization of the heart murmur classification. The heart sounds will be processed in ways more closely replicating the human cochlea than the static cochlear filter. A variable self optimizing cochlear filter will better reproduce the mechanism of the human cochlea in that it will contain a feedback system from ANN to cochlear processing to automatically select the most useful frequencies based upon a threshold mechanism filtering out those frequencies which do not contain significantly useful information about classification of heart murmur. The output of the sounds in the frequency range remaining (variable self-optimizing cochlear filtered sounds) may then be used by the neural network to make a final decision about murmur classification. Our hypothesis is that a variable self-optimizing cochlear filter will significantly improve the accuracy in classification of heart sounds as normal or murmur when compared to a static cochlear filter. Using this approach, we plan to develop an AI based system which will classify heart sounds with a success rate significantly better than the static cochlear filter previously developed.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027541-027541-1. doi:10.1115/1.3147548.
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An estimate of $6 billion is being spent annually to deal with diabetes-related health problems. In the United States, 6% of the population (about 18 million people) has diabetes, either diagnosed or undiagnosed. During their lifetimes, about 15% of diabetic patients will develop a foot ulcer. More than 60,000 of them will end up with amputations of lower extremities due to complications arising from diabetes mellitus, accounting for nearly two-thirds of the total number of nontraumatic amputations performed annually. Previous studies report that has indicated that both the vertical and shear components of ground reaction force play a role in the formation of plantar ulcers. However, the exact relationship between stresses and ulcer formation is still unclear. The reason for that is due to lack of a sensor that is currently available to be able to measure pressure and shear force on the plantar surface simultaneously. It is because of these inadequacies that have motivated the search for a new design to transduce pressure and shear stress based on a multi-layered optical bend loss sensor. We have recently developed a sensor that can be used to measure shear and pressure of an extended area using fiber optic technology. The fiber optic technique that we have developed has also been extended by utilizing an array of microfabricated waveguides made of polydimethylsiloxane (PDMS). For the fiberoptic technique, the pressure/shear sensor consisted of an array of optical fibers lying in perpendicular rows and columns separated by elastomeric pads. A map of pressure and shear stress was constructed based on observed macro bending through the intensity attenuation from the physical deformation of two adjacent perpendicular fibers. Each sensing layer consists of multiple fibers molded into a thin PDMS substrate. In this design, the top layer is composed of a 3 by 3 fiber mesh with 9 intersection points and the bottom layer is made of a 4 by 4 fiber mesh with 16 intersection points. The space between the adjacent fibers is 0.5 cm. The pressured points between the top and the bottom layer are offset by 0.25 cm which is used to increase the shear sensitivity. In the experiment, the sensor was tested with various loading condition. A force image algorithm using neural networks was developed to identify the loading pattern, magnitude and direction of loads that were applied at more than one pressure point. Here 3 loading patterns with 5 different loading directions and 3 different loading magnitudes were tested. The results show a >90% accuracy was obtained using an algorithm with 2 layered neural networks system.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027542-027542-1. doi:10.1115/1.3134782.
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Previous biomechanical models of the penis that have attempted to simulate penile erections have either been limited to two-dimensional geometry, simplified three-dimensional geometry or made inaccurate assumptions altogether. Most models designed the shaft of the penis as a one-compartment pressurized vessel fixed at one end, when in reality it is a two-compartments pressurized vessel, in which the compartments diverge as they enter the body and are fixed at two separate points. This study began by designing simplified two-dimensional and three-dimensional models of the erect penis using Finite Element Analysis (FEA) methods with varying anatomical considerations for analyzing structural stresses, axial buckling and lateral deformation. The study then validated the results by building physical models replicating the computer models. Finally a more complex and anatomically accurate model of the penis was designed and analyzed. There was a significant difference in the peak von-Mises stress distribution between the one-compartment pressurized vessel and the more anatomically correct two-compartments pressurized vessel. Furthermore, the two-compartments diverging pressurized vessel was found to have more structural integrity when subject to external lateral forces than the one-compartment pressurized vessel. This study suggests that Mother Nature has favored an anatomy of two corporal cavernosal bodies separated by a perforated septum as opposed to one corporal body, due to better structural integrity of the tunica albuginea when subject to external forces.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027542-027542-1. doi:10.1115/1.3134783.
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In this paper we detail the rapid design, fabrication and testing of a percutaneous catheterbased device that is envisioned to enable externally controlled manipulation and cutting of specific chordae tendinae within the heart. The importance of this work is that it (a) provides a means that surgeons may use to alleviate problems associated with some forms of mitral valve regurgitation and (b) demonstrates how a deterministic design process may be used to drive design innovation in medical devices while lowering development cost/time/resources. In the United States alone, approximately 500,000 people develop ischemic or functional MR per year. A chordal cutting procedure and device could allow many patients, who would otherwise be unable to survive open-heart surgery, to undergo a potentially life-saving operation at reduced risk. The design process has enabled us to generate a solution to this problem in a relatively short time. A deterministic design process was used to generate several design concepts and then evaluate and compare each concept based on a set of functional requirements. A final concept to be alpha prototyped was then chosen, optimized, and fabricated. The design process made it possible to make rapid progress during the project and to achieve a device design that worked the first time. This approach is important to medical device design as it reduces engineering effort, cost, and the amount of time spent in iterative design cycles. An overview of the design process will be presented and discussed within the context of a specific case study–the rapid design/fabrication of a chordal cutting device. Experimental results will be used to assess: (i) The performance of the catheter in maneuvering into the heart and grasping various structures. (ii) The effectiveness of the catheter's RF ablation tip at cutting chordae inside of a heart. In the first experiment, the catheter was guided to the basal chordae under direct visualization, which showed that the catheter is capable of successfully grasping a chord. During the second experiment, ultrasound was shown to be a viable method of visualizing the catheter within the heart. During this experiment, once contact between the chord and RF ablator tip was confirmed, the chord was successfully ablated. We will also discuss experiments that are currently underway to visualize the catheter utilizing a Trans-Esophageal Echo probe, as well as imaging the mitral valve from the apex of the heart with a laparoscope so that video of the basal chord being grasped and cut can be acquired on a heart whose anatomical structures are intact. A brief synopsis will then be given of how the design process has been used in research and educational collaborations between MIT and local hospitals.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027543-027543-1. doi:10.1115/1.3135153.
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According to the National Center for Health Statistics, cardiovascular diseases remain the number one killer in the United States. Among the various types of cardiovascular diseases, the aortic aneurysm is ranked number nine. The abdominal aortic aneurysm (AAA), in particular, is an abnormal, localized dilation of the abdominal aorta wall caused by weakened or diseased aorta walls. One of the treatments for this disease is using an endovascular surgery at which an endovascular graft is delivered to the aneurysm site through the femoral arteries. The deployment of the endovascular graft will exclude blood flow to the aneurysm, thus preventing further expansion of the aneurysm sac. Although this technique is preferred over open surgeries due to its minimal invasiveness, an event known as the endoleak, where the endovascular graft fails to retain the blood and leads to leakage to the aneurysm sac, may occur. Here, we are developing a novel pressure monitoring system to remotely and continuously measure the pressure in the aneurysm sac. The main component of the system is a pressure-sensitive material, made of a magnetoelastic, magnetically soft film attached or coated on the endovascular graft. When under an AC magnetic field (excitation field), the magnetoelastic film generates a secondary magnetic field. Due to its magnetoelastic property, the amplitude of the secondary field varies with applied stresses, allowing remote pressure monitoring. To eliminate noises from the excitation field, the generated secondary field is measured at twice the excitation frequency to obtain the 2nd-order harmonic field, which is used for tracking the pressure variations. A scaled-up prototype of the pressure monitoring system was constructed and examined to demonstrate the feasibility of this technology. A commercial magnetoelastic thick film, Metglas 2826MB from Metglas, Inc., was attached on a polycarbonate substrate and covered by a thin polycarbonate protective layer. The substrate was then embedded in a plastic tube with flowing liquid to represent the condition of an aorta. Liquid pressure in the tube was altered during the experiment by restricting or relaxing the flow channel. In this study, a 10mm×40mm file (Film A) and a 5mm×40mm film (Film B) were fabricated and tested. The amplitude of the 2nd-order harmonic field produced by the films was inversely proportional to the fluid pressure. It was also shown that films with different sizes exhibited different signal sensitivity with the smaller film (Film B) exhibited greater sensitivity. This experiment indicates that feasibility of the pressure monitoring technology.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027543-027543-1. doi:10.1115/1.3135149.
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Central venous catheter (CVC)-associated infections have substantial impacts on morbidity, mortality, and overall cost of health care. Acinetobacter baumannii causes severe infections, survives on abiotic surfaces, colonizes and develops resistant biofilm on different medical devices including CVC. The cranberry contains proanthocyanidines which possess antiadherent activity against colonic bacteria. This study aimed to assess the use of moxifloxacin/cranberry extract combination against A. baumannii biofilm established on CVC. A. baumannii bioflim was developed on silicone CVC and visualized by electron microscopy. The biofilm was treated according to the method described by Aslam et al. Briefly, segments (1 cm) of silicone CVC (Cook, Inc., Bloomington, IN) were incubated in bacterial suspensions (106 CFU/ml) in Mueller Hinton broth to allow biofilm formation. After incubation at 37°C for 24 h, segments were aseptically removed. Four sets of catheter segments (3 segments/each) were suspended for 6 h at 37°C in one of the following solutions: moxifloxacin (0.16 ug/mL), cranberry aqueous extract (10 mg/mL), Mox-Cran combination, or normal saline (NS) as a control. Catheter segments were rinsed 3 times with NS to remove planktonic bacteria. These segments were individually sonicated for 5 min and vortexed for 30s in 1 ml NS. Aliquots (100 uL) of the sonicated fluids and their dilutions were inoculated onto Mueller Hinton agar plates. Each set of experiments was repeated three times. Bacterial colonies (CFU/cm) were counted after incubation for 24 h. The average colony count of each set of experiment was calculated. The average values of the treated sets were divided by the average value of the control percent for calculation of the percentage biofilm reduction in each treatment as compared to the untreated control (NS). Using ANOVA, the significance level for all analyses was <0.05. The effect of moxifloxacin alone was similar to the untreated control. Cranberry extract could reduce the biofilm by almost 90%. Moreover, MoxDran combination could synergistically and completely (100%) eradicate. A. Baumannii biofilm from CVC. There is a dire need for developing novel strategies against microbial biofilms on medical devices, such as the use of combination between safe anti-adherent extracts with antimicrobial agent as a catheter lock solution, to retrieve the infected vascular catheters. The results of this study revealed a promising antibiofilm activity of moxifloxacin/cranberry extract combination for eradication of mature A. baumannii biofilm from CVC (therapeutic approach). Since biofilm prevention is much easier than its eradication, we hypothesize that impregnation or coating of medical devices, including CVC, with such novel and safe combination might be an outstanding tool against biofilm development (prophylactic approach).

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027544-027544-1. doi:10.1115/1.3136422.
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Transcranial Direct Current Stimulation (tDCS) is a non-invasive procedure where a weak electrical current (260 μA to 2 mA) is applied across the scalp to modulate brain function. tDCS has been applied for therapeutic purposes (e.g., addiction, depression, mood and sleep disorders) as well as cognitive performance enhancement (e.g., memory consolidation, motor learning, language recall). Despite safety and cost advantages, the developments of tDCS therapies have been restricted by spatial targeting concerns using existing two-channel systems. We have developed novel technology for High-Density tDCS (HD-tDCS) that improves spatial focality. Our hardware interface integrates a multichannel stimulating guide with existing two channel tDCS stimulators, and can be configured to target specific brain regions using computational models of current flow and multichannel array accessories. The hardware interface provides real time stimulation quality and safety feedback, and is designed to be MRI and TMS compatible. An electrical “tickle” feature enables skin pre-conditioning to minimize sensation. The full system includes the hardware interface, cable assemblies, head gear, tDCS electrodes, tDCS gel, and electrode adaptors. The head gear allows fixing the electrode adaptors over cortical targets using conventional EEG electrode coordinates. The electrode adaptors “fin” design, tDCS gel composition, and electrode shape are optimized to reduce sensation during direct current stimulation with 2 mA for up to 22 minutes. A five electrode system (4×1-C1), for implementing optimally focal “4×1 ring configuration” protocols, and an 8 electrode system (4×4-S1), that can be configured for “4×4 cortical strip stimulation”, are available. The entire system is robust, intuitive, and ultimately adaptable for home use. Our HD-tDCS system allows non-invasive, safe, and targeted modulation of selected cortical structures for electrotherapies that are individualized as well as optimized for a range of therapeutic applications.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027544-027544-1. doi:10.1115/1.3135198.
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Wireless power holds great promise for solving many power distribution problems. Medical device designers will need to understand the impact of the electromagnetic coupling used for wireless power systems to design safe electromagnetic environments and safe medical devices. One question for designers will be whether or not current standards and requirements used for testing the electromagnetic compatibility (EMC) of medical devices and human exposure go far enough to insure safe environments and safe and reliable medical devices in the presence of wireless power. Electromagnetic energy can be transferred in three ways: through induction, radio frequency waves, or resonant evanescent coupling. Nonradiative inductive coupling uses the magnetic fields created when current is passed through one coil to create a current in a second coil that is located very near the first coil. These systems usually operate in the 50 KHz to 10 MHz range. Radio frequency energy can be transferred through radiating electromagnetic waves over great distances at frequencies from the upper KHz to many GHz. Most recently, work has been done on resonant evanescent coupling which transfers power between resonant objects over a distance of a couple of meters at frequencies from 1–10 MHz. Safety and reliability of medical devices is confirmed by testing EMC emissions and susceptibility to IEC60601-1-2 and supporting standards. For example, one of the supporting standards, CISPR 11 calls for measuring the electric field of radiated emissions over 30 MHz and the magnetic field below 30 MHz at distances of 3–10 meters. Many of the effects of wireless power systems are in the near field and are not covered in the current test standards. The AAMI PC69 series of standards have some near field requirements but these standards tend to be industry specific – such as drug pumps or pacemakers. EMC immunity standards used to test EMC susceptibility barely mention magnetic immunity. The only test for magnetic fields recommends testing fields at the power frequencies of 50 and 60 Hz. There are few standards detailing safe limits for human exposure to the near field effects of wireless power as well. Historically human exposure standards have been based on time average thermal effects on tissue and not medical devices. IEEE's C95.1b has requirements for specific absorption rate limits averaged over a 6 minute period. A pulsed wireless power system could meet these requirements and be safe for exposed tissue, but if a patient has an implanted device, or is wearing an external medical device, the pulsed EM energy could affect it during the pulse. The German BGV B11 standard lists human exposure limits for electric and magnetic fields based on a time average and limits exposure based on which portion of the body is exposed. However, it is meant as a workplace standard not a medical device standard. Currently the FDA does not require meeting either of these standards. It is necessary to determine the appropriate limits and tests to ensure that medical devices safely use wireless power and continue to operate safely in the presence of wireless power.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027545-027545-1. doi:10.1115/1.3136432.
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Magnetic susceptibility mismatch, between human tissue and a foreign metallic object, is one of several factors responsible for image distortions in magnetic resonance imaging (MRI). Combining diamagnetic materials such as bismuth or carbon with paramagnetic materials such as nitinol or titanium can reduce the mismatch in bulk susceptibility of a foreign object and the surrounding tissue. Muller-Bierl et al. have succeeded in reducing MRI field distortion by coating titanium wire with bismuth. Wilson et al. used a pyrolytic graphite mouth shim to improve brain functional MRI performance. Conolly et al. have successfully used pyrolytic graphite in foam to reduce image artifacts at air-tissue interfaces. In this study, it was hypothesized that coating a metallic object with carbon particles suspended in a polymer can reduce the size of image artifacts. Four 6Al-4V titanium discs (2.3mm×9.5mm) were encapsulated in an epoxy-graphite mixture. Mixtures of graphite and epoxy were poured around the titanium discs in molds and allowed to cure. A specimen of titanium was encapsulated in plain epoxy to serve as the control sample. Polycrystalline graphite was mixed at mass ratios of 1:2 and 1:1 to epoxy for two of the samples. Pyrolytic graphite flakes were mixed at a 1:2 mass ratio to epoxy. The sample discs were placed in an aqueous solution of copper sulfate and gadolinium contrast agent inside a wrist imaging coil at the isocenter of a 3 Tesla MRI machine; disc axes were perpendicular to the B0 direction. A T2-weighted gradient echo MRI image was taken in the coronal plane. Echo time, relaxation time, flip angle, and phase encode direction set to 71 ms, 3430 ms, 80 degrees, and right to left respectively. The control sample produced an arrowhead artifact sweeping in the same direction as the static magnetic field vector, B0. The two samples containing powdered polycrystalline graphite produced arrowhead shaped artifacts. The direction of image distortion, however, was opposite from that of the control sample. The change in direction of the image artifact is attributed to the change in bulk magnetic susceptibility of the sample from paramagnetic behavior of titanium encapsulated in plain epoxy to a diamagnetic behavior from the added carbon powder. The titanium sample encapsulated in the pyrolytic graphite-epoxy mixture produced an artifact with irregular outline and no discernable directional bias relative to B0. The hypothesized cause for this difference in artifact shape between the polycrystalline and pyrolytic graphite samples is an increase in air bubble entrapment due to the planar structure of the pyrolytic graphite flakes during the epoxy mixing process. Further study is underway to find a specific carbon-polymer mass ratio and coating thickness that will reduce MR image artifacts that would otherwise appear due to the presence of a metallic object in the MRI region of interest. This work is supported by MIMTeC, a National Science Foundation Industry University Collaborative Research Center and by NIH Grant P30NS057091.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027545-027545-1. doi:10.1115/1.3136430.
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This project aims to investigate the performance of edge-to-edge mitral valve repair (MVR) within reanimated swine hearts. Direct imaging and hemodynamic data of the mitral valve during normal cardiac function (Normal), after an induced prolapse (Prolapse), and post surgical repair (E2E) was obtained. Isolated swine hearts (n=6) were reanimated using a clear Krebs–Henseleit buffer. Mitral prolapse, and regurgitation, in the P2 region was induced by cutting chordae tendinae of the posterior leaflet. An edge-to-edge MVR procedure was performed, suturing the prolapsed P2 region to the A2 region of the anterior leaflet. The mitral valve was imaged using endoscopic cameras in the left atrium and ventricle allowing verification of stitch placement and leaflet coaptation. Analysis of the endoscopic images provided measures of annulus area, orifice area, and regurgitant area. Echocardiography, the standard clinical imaging modality, was used to determine the hemodynamic performance of the valve. Additionally, ECG and left chamber pressures were recorded at a sample rate of 5 kHz. Prolapse of the P2 region was consistently created, and edge-to-edge repair of the mitral leaflet showed full leaflet coaptation. The annulus area of the valve was tracked throughout the procedure and did not show significant variation. The orifice area, defined as the area of the annulus that does not contain leaflets, normalized to the corresponding annulus area for Normal, Prolapse and E2E were: 41±13%, 44±14% and 21±13%, p=0.02. The regurgitant area, normalized to the corresponding annulus area, increased from 2±2% for Normal to 8±3% for the Prolapse and then decreased to 1±1% for the E2E group. The regurgitant fraction, normalized against the maximum observed, for Normal, Prolapse and E2E was 10±6%, 57±26% and 13±13%, p<0.01. Over the course of the experiment the left ventricular (LV) systolic pressure and negative dP/dt reduced from 95 to 54 mm Hg and 743 to 402 mm Hg/s, respectively. Our results show that orifice area was significantly smaller after MVR when compared to Normal and Prolapse periods. There was no significant change in regurgitant area and regurgitant fraction from the Normal to repaired valve as compared to a significant increase in regurgitant area and regurgitant fraction during Prolapse. Low gradients were observed for all three groups, with no indications for symptomatic stenosis. The reduction of LV function was caused by global ischemia and the progressive onset of edema. In this acute assessment of edge-to-edge repair of P2 prolapse, repair does not affect annulus area, decreases orifice area, and successfully eliminates regurgitant area with no evidence of mitral stenosis.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027546-027546-1. doi:10.1115/1.3155367.
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Nitric Oxide (NO) is small, free radical gas that has been shown to have a wide variety of physiological functions, including the ability to hinder tumor angiogenesis at high, but non lethal, concentrations. Previous work suggests that if NO could be effectively delivered in vivo to tumors of patients currently undergoing chemotherapy treatments at the appropriate levels, less damaging chemotherapy treatments could be used against cancer. This could increase the overall survivability of cancer patients, especially in those prone to the harmful effects of chemotherapy: children, elderly, and those of weak immune systems. If NO is especially successful at preventing and eliminating tumor growth, angiogenesis, and carcinogenesis the need for stressful chemotherapy treatments could be eliminated altogether. This project is focused on developing novel photosensitive NO donors that can be incorporated into polymeric systems and used in a fiber optic drug delivery system. Development of these NO-releasing polymers will allow continued investigation of NO's role in tumor death by precisely controlling the surface flux of NO that cells are exposed to. Generating specific surface fluxes of NO from polymer films has been demonstrated by using polymer films that contain photoinitiated NO donors, prepared by synthesizing S-nitrosothiol (RSNO) derivitized polymer fillers that are blended into hydrophobic polymers and cast into a film. These films generate and sustain a surface flux of NO based on the wavelength and intensity of light used. Polymers releasing NO are more promising as an NO donor than simply injecting NO into samples because they allow for spatial and temporal control of NO delivery. The specific concentration of NO needed to produce desirable effects on tumor cells (i.e. apoptosis) is not known. Data will be presented that show the synthesis and NO-release properties of novel RSNOs based on the nitrosation of benzyl mercaptan thiols. Specifically, UV-Vis spectrum of benzyl mercaptan in toluene and S-nitrosobenzyl mercaptan after the addition of t-butyl nitrite will be presented. We are currently investigating the effects of varying NO-surface fluxes generated from photolytic NO donating polymer films on aortic smooth muscle cell cultures obtained from mice. Once we have established that we can quantitatively determine the effects of different levels of NO on the proliferation of smooth muscle cell cultures, work will begin to apply this methodology and these novel NO-releasing polymeric systems to begin investigating what durations and surface fluxes of NO are necessary to have tumorcidal effects on specific cancer cells.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027546-027546-1. doi:10.1115/1.3136754.
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Spatially registered 3D preoperative medical images can improve surgical accuracy and reduce reliance on memory and hand-eye coordination by the surgeon. They enable visualization of internal structures within the anatomy of a patient on the operating table. In the case of biopsy, for example, this would allow the surgeon to guide the needle tip to a tumor though opaque tissue. It has been well established that for soft tissues, image registration can be performed by aligning the preoperative image with a cloud of points that describe the surface of an organ [1]. Collecting this point cloud can be challenging, generally requiring open surgery to permit line-of-sight access for laser triangulation (e.g., the system of Pathfinder Therapeutics, Inc.). We present a conoscopic holography-based system for collecting a point cloud less invasively-through a laparoscopic port. The system consists of a commercial conoscope (Optimet, Inc., Probe Head Mk3), designed for precision machine-shop linear measurements, that is tracked (the surgical tool is also tracked) with an optical tracking system (Claron Micron Tracker H3-60). The conoscope laser beam can, in principle, be aimed through a laparoscopic port. The 1 degree of freedom linear distance measurements it returns are converted into a point cloud using optical tracker information. Proof-of-concept for obtaining point clouds via conoscopic holography and registering them to known shapes is provided in [2]. However, the procedure for collecting these point clouds requires the surgeon to manually `paint' the surface of the organ with the laser beam, aiming it at many points on the surface by manipulating the conoscope base unit, thus pivoting the tube in the laparoscopic port. It would be desirable to relieve the surgeon of this task by creating a system for automatically aiming the laser beam from a stationary conoscope. We hypothesize that this can be done with a suitably designed actuated mirror assembly at the tip of the laparoscopic tube. To assess whether a conoscope can make an accurate distance measurement when reflected by a mirror, we conducted a set of experiments. We placed a front-silvered mirror at a fixed 45 degree angle relative to the conoscope, 12 cm in front of it. Total beam length was 185-315 mm measured in 10 mm increments. The results were similar to direct measurements of the same distance without a mirror. We recorded a standard deviation of error of less than 0.01 mm in each 10 mm increment. A second experiment was then carried out to assess the effect of mirror angle. The laser was swept across a flat surface 105 mm from the mirror by rotating the mirror. The standard deviation of the data points from a true line was less than 0.1 mm along a 175 mm line segment. These experiments indicate the feasibility of using a mirror to aim a conoscopic holographic laser, paving the way for an automatic laparoscopic laser, paving the way for an automatic laparoscopic point cloud collection device to be developed in future work.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027547-027547-1. doi:10.1115/1.3147249.
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Over the past year we have studied the challenges that must be overcome before we can introduce assistive robots in an operating room. We consider top among the issues a human-robot interface and an instrument-robot interface. In order for an autonomous mechanism to serve up instruments it must have domain specific knowledge about the instrument nature. The robot must be able to track the state of each instrument under its management. To this end we examine technical requirements of an instrument server. The second area of interest, and the one more unpredictable, is the problem of interaction between a human and a machine. In the past we have looked at the human speech as a medium of communication with the robot. Going beyond that we also examine the interaction that occurs at the haptic level. Here we would like to know what precisely could be conveyed to the robot and frmo the robot just by a touch? In microscope is undesirable and touch becomes a valuable means of communication.

Topics: Robots
Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027547-027547-1. doi:10.1115/1.3155368.
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Biomedical devices that contact blood and tissue universally inspire a host response that often compromises the function of the device (i.e., intravascular sensors become coated with thrombi, artificial vascular grafts become occluded with thrombus formation and neointimal hyperplasia). Nitric oxide (NO) has been shown to be a potent inhibitor of platelet adhesion and activation and has been implicated in mediating the inflammatory response and promoting wound healing. We are currently developing NO-releasing compounds based on S-nitrosothiols derived from substituted aromatic compounds that utilize light as an external on/off trigger capable of releasing precisely controlled surface fluxes of NO. The level of NO generated is dependent on the wavelength and intensity of light shown on the compounds. Data will be presented that show the synthesis and NO-release properties of three novel compounds, S-nitroso-2-methoxybenzene, S-nitroso-3-methoxybenzene and S-nitroso-2-chlorobenzene. Ultimately, these compounds will be tethered to the surface of polymer fillers that will then be blended into hydrophobic polymers and used as coatings on biomedical devices. A model system that will be used to demonstrate the utility of this approach will be a multi-element fiber optic sensors that will contain sensing elements capable of measuring blood gases and NO-releasing fibers that locally generate enough NO to inhibit clot formation on the sensor surface, thus allowing the sensor to function reliably in vivo.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027548-027548-1. doi:10.1115/1.3147252.
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A wireless, passive sensor was fabricated for remote monitoring of chemical analytes in the human body. The sensor was made of a magnetically soft film (sensing element) and a permanent magnetic film (biasing element) sandwiching a reversibly swelling hydrogel. When subjected to a low frequency magnetic AC field, the sensing element generated higher-order harmonic magnetic fields that were detected with a remotely located detection coil. In the presence of a DC magnetic field (biasing field), such as that generated from the biasing element, the pattern of the higher-order harmonic magnetic fields varied, and the magnitude of change (referred to as the harmonic field shift) was proportional to the strength of the biasing field. The hydrogel, which acted as a transducer that converted variations in the chemical concentration into changes in dimensions, physically varied the separation distance between the sensing and the biasing elements. This causes a change in the magnitude of biasing field experienced by the sensing element, thus changing its higher-order harmonic field shift allowing remote measurement of chemical concentrations. The novelty of this sensor was its wireless and passive nature, which allows it to be used inside a human body for long term chemical monitoring. A scaled-up prototype was fabricated and tested to demonstrate the pH monitoring capability of the sensor. The main structure of the prototype sensor was a polycarbonate substrate containing a larger rectangular well of 36mm×8mm×4mm on top of a smaller well of 30mm×5mm×2mm (see Fig. 1). The smaller well was filled with hydrogel made of (poly)vinyl alcohol and (poly)acrylic acid. A commercial magnetoelastic thick film, Metglas 2826MB from Metglas Inc., was attached to the step at the bottom of the larger well and allowed to rest on the hydrogel. The DC magnetic field was provided by an Arnokrome III film (Arnold Magnetic Technologies) of 30mm×6mm attached at the bottom of the sensor structure. The sensor was placed on the detection coil, and its response was measured with a spectrum analyzer while exposed to test solutions of varying pH. The sensor's harmonic field shift, when cycled between pH 7 and pH 3, was measured and plotted in Fig. 2. As shown in the figure, the hydrogel swelled when the sensor was exposed to pH 3, decreasing the harmonic field shift. The response and recovery times of the hydrogel were below 2 minutes. This experiment proves the feasibility of the technology for real-time, remote monitoring of pH. Further work includes improving the response time and sensitivity of the hydrogel, as well as miniaturization of the sensor.

Topics: Sensors
Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027548-027548-1. doi:10.1115/1.3147250.
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Urinary continence is maintained through coordination of electrical (nervous) and mechanical (muscles, ligaments and other structures) systems in the body. During micturition, the central nervous system sends a signal to the detrusor and sphincter muscles to coordinate voiding. Pathological problems can undermine either of the two systems and result in urinary incontinence (UI). Thirteen million people in the United States live with UI. Clinical treatments to date are largely mechanical in nature, restoring function through surgical interventions. However, electrically-based treatments, such as electric stimulation, offer a promising alternative. Here we investigate the utility of electrical stimulation of the periurethral neuromusculature to reduce voiding contractions in well-controlled animal experiments. Female Sprague Dawley rats were anesthetized with a ketamine/xylazine/acepromazine cocktail and the bladder was catheterized through a small incision in the bladder dome and was infused with saline. Continuous filling of the bladder triggered related cycles of voiding which was identified through bladder pressure increases and visual urination. The pubic symphysis bone was cut to expose the urethra and a stimulating electrode was placed in the periurethral region. The electrical stimulation parameters were 2.8 mA of current, 200 us pluses, and 20 Hz. The electrical stimulation was done in fifteen minute intervals. Statistically, the rats without electrical stimulation have an average contraction period of 63.1 sec (+/– 31.3 sec) and the rats with electrical stimulation have an average contraction period of 97.2 sec (+/– 43.0 sec). The results showed that the electrical stimulation of the periurethral neuromusculature in the group revealed 54.0% increase in average contraction period and decrease in voiding frequency. Electrical stimulation of the periurethral neuromusculature increases the voiding interval and void volume for the rats. This suggests the existence of an external urinary sphincter to the bladder inhibitory pathway and supports periurethral neuromusculature stimulation as an alternative to spinal nerve stimulation for the treatment of bladder overactivity.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027549-027549-1. doi:10.1115/1.3147377.
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Valvular heart disease is a significant problem. The primary case physician initially does assessment through auscultation. Accuracy in classification of sounds is suboptimal (20 to 40%). Lower frequencies of heart sounds are important in classification of murmurs associated with valvular heart disease. We find stethoscope sound intensity capture falls significantly at the 1500 Hz range and lower. Strategies to improve auscultation accuracy include improving stethoscope features or developing a device that, when used with the stethoscope, augments sound capturing abilities at lower frequencies. Testing necessitated development of a reliable (without significant intra-sound variation) cardiac sound reproduction device. A sound permeable contracting polymer when used with a stethoscope signficantly increases sound intensity captured in the 625 Hz to 1500 Hz range, when tested with a reliable cardiac sound reproduction device. We prepared an air-sealed device with an amplifier, four internal speakers capable of emitting high quality, low frequency sounds, and a listening pad. An existing electronic stethoscope with, and then without, a sound permeable contracting polymer captured three sounds (normal, innocent systolic murmur, pathological systolic murmur) five times per sound. The sounds were placed in computer files. FFTs were constructed. Sound intensity within the 625 Hz to 1400 Hz range, when the sound permeable contracting polymer is used with the electronic stethoscope, relatively improves, on average, approximately 11 dB, compared to sound captured with the same electronic stethoscope without the sound permeable contracting polymer. This difference is numerically statistically significant (p<0.001). Intra-sound variability testing (standard deviation) of FFTs was not significant. A sound permeable contracting polymer used with an electronic recording stethoscope significantly improves sound intensity in an important auscultation frequency range. Intra-sound testing variation was insignificant. A study is underway to demonstrate impact using an absolute reference point. However, as amplification within existing electronic stethoscopes is commercially available, potential variation in relative reference points may be overcome with existing amplification features on electronic stethoscopes, allowing improved capture of heart sounds within the 625 Hz to 1400 Hz range. Limitations include the need for human subject study. Further testing, including human subjects testing is needed prior to application for FDA approval. FDA approval is needed before any use on humans. The methodology should not be utilized clinically without FDA approval.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027549-027549-1. doi:10.1115/1.3147260.
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Computational fluid dynamics (CFD) has been used for developing and evaluating the performance of a novel design of the cardiac axial blood pump (CABP). This device could be used as an implantable pump for boosting blood circulation in patients whose hearts are not providing sufficient output. Based on the Berlin Heart configuration the blood pump has been designed for a flow rate of 5 L/mine and 100 mmHg of head pressure. Finite element analysis method has been performed to predict the shear stress, pressure, velocity, pressure drop on the fluid through the pump and the shear stress on the pump impeller. Also, flow streamlines has been discussed in detail in this study to predict the flow streamlines behavior and the stagnation points. The goal of this work is to design an efficient blood pump to support the blood circulatory system and reduce the shear stress and blood hemolysis during transport through the pump. Our design simulated at several rotational speeds (5000 to 7000) rpm to investigate the relationship between the rotational speeds and shear stress. Results indicate that the rotational speed has a direct correlation with shear stress and pressure drop and at 6500 rpm the pump gives its optimal pressure drop.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027550-027550-1. doi:10.1115/1.3147379.
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Benign prostatic hyperplasia (BPH) is one of the most common disorders and the most common cause of lower urinary tract symptoms (LUTS) in elderly men. Transurethral resection of the prostate (TURP) is considered the gold standard treatment for BPH; however, laser prostatectomy has several advantages over TURP with regard to reduced catheterization and morbidity particularly in high-risk patients. Of the many lasers that can be used in the laser prostatectomy, the GreenLight potassium-titanyl-phosphate (KTP) laser is one of the most commonly used. The optimum outcome of this laser procedure is ablation with minimal coagulation. Our objective was to experimentally and theoretically characterize the KTP laser-tissue interactions in order to understand the laser and tissue parameters that lead to an optimal outcome. The rat hind limb muscle was used as a model for the in vitro study. Q-switched 532 nm laser (GreenLight PV, American Medical Systems, MN) was used and the laser was allowed to scan over the tissue with controlled speed and working distance, distance from the tip of the optical fiber to the tissue's surface. Injury was assessed by digital images of the tissue's cross section in terms of ablation, zone of removed tissue, and coagulation, zone of thermally denatured protein, zones. Ablation simulation was done in Matlab R2008a and the ablation was assumed to be a vaporization process. Thermal properties of water were assumed for the basic first run, where the ablation energy of tissue was assumed to be the vaporization energy of water. Parametric study involving changing the ablation energy, thermal conductivity, and absorption (attenuation) coefficient of tissue was performed. Ablated tissue volume increased with decreased scanning speed and trended to saturate at higher values of working distance and lower scanning speed. The optimal therapeutic outcome (minimal coagulation volume and maximal ablation volume) was achieved at 0 mm working distance and 1 mm/s scanning speed. The simulation was able to capture and predict the effect of the tested parameters (ablation energy, thermal conductivity, and absorption coefficient) on the therapeutic outcome. Notably, decreased ablation energy and thermal conductivity, and increased absorption coefficient were predicted to enhance the KTP laser ablation therapeutic outcome (i.e., reduce coagulation volume and increase ablation volume). This will open avenues to improve KTP laser prostatectomy by modulating optical, thermal, and mechanical properties of prostatic tissue.

Topics: Lasers , Simulation
Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027550-027550-1. doi:10.1115/1.3147378.
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The impetus of this work originated from the advent of high magnetic field magnetic resonance imaging scanners with B0 fields of 4T, 7T, and 9.4T. These ultrahigh magnetic field systems generally improve the signal to noise ratios. However, B1 field non-uniformity also occurs due to the increased RF field frequencies when wavelengths in the head become shorter than its size. As interest in multiple channel transmission line coils increases, the control of the amplitude and phase of individual coil elements is required in order to develop desired B1 field. The choice of the excitation of the coil elements may be determined by convex optimization. Convex optimization is used provides results very fast, when the problem is formulated globally. In addition, convex optimization provides better signal to noise (SNR) ratio when anatomic specific regions are investigated. In this paper, simulation and experimental results are discussed at 9.4T systems based on the number of elements. The primary objective of this study is to increase the signal in a specific target region and decrease the signal and noise in the outside region termed the suppression region. The convex formulations are minimizing the maximum field point in the suppression region while keeping the center of target maximum. Based on this min-max optimization criterion, an iteration method which modifies the selection of suppression fields is also performed to produce better results. The results of the localization on FDTD human data at 9.4T are shown in Fig. 1. In these figures, the axial slices of the center of human head model provided by XFDTD are used after manipulating with MATLAB and the 16 channel head coil is excited. Figure 1 shows an improvement of the homogeneity in the suppression region when the target region is at center. In Fig. 2, received signal localizations are obtained for three different regions of interest (ROI) after using the convex optimization. Note that the selection of ROI is limited by the geometric setting of phantom in the 8-channel TEM head coil. Convex optimization with an iterative method was performed on both the human head and phantom models with operating frequency 400 MHz to design coil channel excitation parameters. By applying the iterative method to the convex optimization, more homogeneous B1 fields are obtained in the suppression region for 9.4T system.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027551-027551-1. doi:10.1115/1.3147509.
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Continuous monitoring of live cell cultures and in-vitro tissues is a major challenge in the study of model systems for cancer research. Specifically, monitoring chemical changes often requires the cells to be stained with specific fluorophores (limited chemical content) or harvested from culture (precluding longitudinal study). Recently, mid-infrared spectroscopy is being increasingly applied to measure chemical content of cells and tissues. There are no reports, however, of in-vitro monitoring of cell cultures. The major reason is the high absorption of water in this spectral region and lack of instrumentation to address this need. This project seeks to apply mid-IR in a non-destructive manner to live cell cultures and tissues while maintaining rich information content. We accomplish this by the design of a contact-method probe. We have designed a fiber optic-base beam guidance geometry and coupled it to a total internal reflection sensing element. The entire sensor is coupled to a commercial spectrometer, thus allowing for rapid translation to other laboratories. It is believed it can be a cost effective solution using current technologies with adequate SNR for down-stream chemometric analysis. One of the major design challenges was to optimally guide and utilize light from the spectrometer within the constraints of leveraging as many commercially available components, processes, and methods to most quickly translate this idea into a working device. Our major task was optical modeling and subsequent fabrication of the device. The optical models show 6 percent throughput is possible using currently available parts; 1 percent is required. The design was implemented with the optical system placed wholly within a single chassis. While a single chassis design allows for miniaturization, it presents substantial alignment challenges due to the lack of degrees of freedom for movement. These challenges are the current work focus. Proof of principle studies are on-going. We anticipate that the goal of continuous cell monitoring and in-vitro cell spectroscopy will be attained upon final integration of the device with our experimental setup.

Topics: Probes
Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027551-027551-1. doi:10.1115/1.3147388.
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Transitioning new research ideas into commercial products is difficult. For medical device design, the task is especially complicated because the commercialization of research ideas requires interdisciplinary teams that understand the nature of the clinical application as well as the abilities of the technology. Device development is complicated by the need to work within a regulated environment which requires well defined processes and significant testing to demonstrate the safety and efficacy of the device. An experienced development team, well versed in the design and manufacturing of medical devices, can greatly enhance the success of a commercialization program. A study of actual programs shows how experience can reduce development times. There are several factors that affect the success of new medical device development including the use of effective development tools and the innovativeness of the product concept. Successful product development may use a number of tools to assist with planning and control of the project. However it is difficult to measure the effect of experience on the success of new product development. In this work, several medical device development programs were studied to determine the role experience plays in improving the time to market for medical devices. Time to market is measured along several dimensions including complexity, technological invention, and uniqueness of clinical application. All designs were completed by the same company. As time progressed, the time to market improved even for complex designs with new technology. Over a ten year period of time, ten significant medical device development projects were executed. All required development of complex electromechanical systems with moderate to high complexity, and more than half developed products for new clinical applications or utilized new technology. After the development group had acquired at least five years of development experience, it was clear that the development times were improving by almost 50% over the predicted development times. Among the factors that contribute to this effect are the development of experts, the creation of design frameworks, and the optimization of processes which improve product development times while reducing project and regulatory risk. Experts with specific experience in systems engineering, program management, electromagnetic compatibility, manufacturability, and usability along with expertise in electronics, mechanical and software design can significantly reduce design times. Technology platforms central to medical devices such as blood and fluid pumps, sensor interfaces, real-time control systems, batteries and power systems are necessary for rapid development. Processes including project planning and tracking, requirements management, configuration management, risk analysis, and manufacturing design transfer are essential for streamlining development as well as ensuring support for regulatory submissions and audits. It has been challenging to demonstrate this effect, which has been anecdotally known for some time, in a quantitative manner. Doing so required studying an organization with not only significant experience over time, but breadth of experience in terms of program risk and complexity. The results of this study quantify the significant benefit of organizational experience in reducing time to market.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027552-027552-1. doi:10.1115/1.3147514.
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Ethicon Endo-Surgery's Harmonic FOCUS is a curved-shear (blade with clamp arm) surgical instrument that combines the intuitive elements of a classic precision instrument with a Harmonic ultrasonic hand piece for a revolutionary multifunction precision device. We propose to describe the unique approach to user research used in the development of the product and how the team used these innovative methods and tools to identify and meet the following design and engineering challenges: 1. Combine the surgical tasks of dissecting, grasping and simultaneously cutting and coagulating into one precision device for the first time. The Harmonic FOCUS was developed as a result of three years of extensive market assessment and a unique research methodology, including a novel process of ethnographically observing and graphically mapping thyroidectomy procedures. 2. Miniaturize the hand piece (transducer) from the existing ultrasonic product line while retaining its clinical performance (speed and hemostasis). The following dramatic and extensive design changes offer improved clinical performance: Reducing the volumetric size of the transducer 55% relative to the predecessor device. Achieving reliable control of clamp force. Curving the blade to resemble typical surgical instruments. Improving speed of operation. Reduction of residual heat. 3. Provide the surgeon with superior and intuitive ergonomics by leveraging elements of a classic precision tool. The team combined the essential elements of a classic precision tool with Harmonic (ultrasonic) technology to develop a revolutionary, multifunctional device with superior and intuitive ergonomics. Surgeons concur with the versatile, comfortable design. 4. Use materials that are all sterilization-compatible. Extensive research was done to identify and use materials that were all compatible with ethylene oxide sterilization. The device is packaged in flexible packaging and ethylene-oxide sterilized prior to sale. Harmonic FOCUS is designed for single-patient use. The Harmonic Blue Hand Piece is sold non-sterile and is qualified for multiple sterilization methods readily available in hospitals. The hand piece can be reused up to 100 times.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027552-027552-1. doi:10.1115/1.3147511.
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Silicon eye can be otherwise called as a complete eye implant. The project overview is given in brief by the description of main components. Here in the silicon eye, a biconcave gel lens is used in connection with a micro controller. A porous silicon nano photodiode is placed before the gel lens. This specially designed transparent diode will help in identifying the intensity of light receiving in the beginning of the processing chain. An effective drainage system (with the help of two valves) will control the working of gel lens. All these components together form the primary circuit to enable the process of auto focusing. The micro controller is connected with all components of the system. The primary circuit is connected to a secondary circuit which consists of an artificial silicon retina and a chemical synapse. By the combined and co-ordinate working of both these will enable vision. The power supply, which all the electrical components here need is given by a series of nano paper batteries placed beneath the retinal layer (carbon nano tubes can also be implemented instead or along with it). The converted electrical impulses (from intensity of light received) will be carried to the visual area of brain through optic nerve by the effective interaction with a number of artificial chemical synapses. Finally this silicon eye will be an effective implant for the damaged eye. And we are sure that this will be a great breakthrough in the modern medicine.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027553-027553-1. doi:10.1115/1.3147558.
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Micropump, an actuation source to transfer the fluid from reservoir to the target place with accuracy and reliability, plays an important role in microfluidic devices. A broad range of micropump applications in biomedical fields are found in the fluid fine regulation and precise control systems for implantable drug delivery, chemical and biological detection, as well as blood transport in cardiology system. A polydimethylsiloxane (PDMS) magnetic composite membrane based on microfabrication with dimensions of 6 mm and 65 μm in diameter and thickness respectively, is employed to actuate a proposed micropump. In micro pumping operation, the fluid flow effects on the actuation and dynamic response of an oscillating membrane are curial to the design of the micropump. Therefore, the resonant frequency of this micro device is estimated considering the added mass and fluid damping to understand the behaviors of the valveless micropump. In this study, the membrane actuation is implemented by a miniaturized electromagnet, which provides an external time-varying magnetic field. The magnetic force on the membrane is proportional to the gradient of the magnetic field and the magnetization of the micro particles embedded in the membrane. The alternating attractive and repulsive magnetic forces on this composite membrane are computed by Finite Element Analysis (FEA). The basic design issues of the electromagnetic actuator involving air gaps, input current signals, and distribution of magnetic flux in the magnetic circuit are presented. Moreover, the magnetic-structure coupling analysis is conducted to determine the maximum deformation and stresses on the membrane, which result from the action of these magnetic forces. Finally, frequency-dependent flow rate of a dual-chamber configuration micropump has been studied. The pumping rate increases almost linearly with the excitation frequency at low ranges and there exists resonant frequencies at which the flow rate will reach a maximum value. After the flow rate peaks, the pumping rate decreases sharply along with the actuating frequencies. The maximum flow rate for the dual-chamber remains at 27.73μl/min under 0.4 A input current with an excitation frequency of 3 Hz. For comparison, a single-chamber micropump reaches a maximum flow rate of 19.61μl/min with a resonant frequency of 4.36 Hz under the same condition.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027553-027553-1. doi:10.1115/1.3147516.
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We are developing computational tools to perform virtual surgeries under physiological conditions with patient-specific anatomies. Virtual surgery can revolutionize the biomedical device (BMD) design and implantation by: enabling the optimization of BMD on the specific patient's anatomy and flow conditions, which has already been shown to significantly affect the hemodynamics; and facilitating surgical planning to select the best location/orientation for BMD implantation. As shown by past research the difference in the implantation, for example, of a bileaflet mechanical heart valve (BMHV) can affect the performance and hemodynamics of the valve. We have developed a powerful CFD tool that can simulate the blood flow through biomedical devices with moving boundaries and the fluid-structure interaction (FSI) under physiologic conditions. This tool has been tested in different applications with complex anatomic configurations, such as aneurysm hemodynamics, Fontan surgeries, and BMHV flows. The FSI simulations of a BMHV flow was validated against in vitro experiments and could capture all the flow features with great accuracy. We have recently carried out FSI simulations of a BMHV implanted in a anatomically realistic aorta in which the left ventricle (LV) was replaced by a pulsatile inflow waveform. In this work, we propose to extend our method to simulate the flow through a BMHV driven by the actual LV motion. The anatomy of the heart is obtained from MRI scan of unhealthy volunteer (St. Jude Hospital) and the left ventricle and the aorta geometry are extracted. The first step is to simulate the flow through a stationary LV with an implanted BMHV to test the capabilities of FSI-CFD tool in real anatomical setting. The second step is to impose theoretical kinematics for LV motion and test the interaction of the BMHV with the flow. The last step is to extract the real patient-specific LV wall motions from MRI data and specify it into the simulation. The shear stress and other parameters will be calculated in the flow field and the cardiovascular walls to identify the locations with high chance of blood cell damage. This work is supported by NIH Grant RO1-HL-07262 and the Minnesota Supercomputing Institute.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027554-027554-1. doi:10.1115/1.3155371.
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Bowel resection surgery is a commonly performed operation used to treat a variety of gastro-intestinal tract disorders, including cancer. The surgery entails excising the diseased portion of intestine, and then creating a surgical anastomosis, or reattachment of the remaining ends. One of the major complications following bowel resection surgery is breakdown or leakage from the anastomosis, which affects 20% of patients, with an associated 10-15% mortality rate. The surgical creation of anastomosis frequently involves dividing blood vessels and can introduce unrecognized twists and tension on the intestine. As a result, the blood supply to the site of anastomosis is often hampered, limiting the oxygen supply that is essential for adequate anastomotic healing. We are proposing a device that enables surgeons to obtain real-time feedback on local tissue oxygen saturation (SpO2) during operative procedures. Such data will not only help surgeons realize any bowel oxygenation compromising maneuvers, but also help perform an anastomosis at the site of maximal tissue oxygenation, thus minimizing the occurrence of postoperative anastomotic leakage and improve patient outcomes. This report details the specifications, fabrication, operation and performance of a handheld wireless pulse oximeter suitable for the intraoperative measurement of tissue SpO2 during bowel surgery. The device adapts principles and technology developed for non-invasive pulse oximetry, and introduces tissue interface, physician tools, and signal processing algorithms for intra-operative application. The handheld device includes local display of SpO2 level (<1s refresh) at the contacted tissue, and signals the operator on degraded signal quality/faults. An onboard micro-controller digitizes and processes signals transduced through a controlled LED array. Signal processing and display parameters were optimized for operating room conditions. A disposable functionally-transparent cover provides both device and tissue protection. Through serial or Bluetooth wireless transmission (250 Kbps), SpO2 and pulse signals can be processed on a PC or operating room VI. The incorporation of a pressure sensor to increase accuracy and robustness is explored. The device was validated intra-operatively on rodent and bovine surgical models.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027554-027554-1. doi:10.1115/1.3155369.
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Transcranial Direct Current Stimulation (tDCS) is a non-invasive procedure where a weak electrical current (260 μA to 2 mA) is applied across the scalp to modulate brain function. tDCS has been applied for therapeutic purposes (e.g. addiction, depression, mood and sleep disorders) as well as cognitive performance enhancement (e.g. memory consolidation, motor learning and language recall). Despite safety and cost advantages, the developments of tDCS therapies have been restricted by spatial targeting concerns using existing two-channel systems. We have developed novel technology for High-Density tDCS (HD-tDCS) that improves spatial focality. Integral to the system are specialized HD-tDCS electrodes (<12 mm diameter) which allow safe and comfortable passage of current across the scalp. Here we evaluate a range of HD-tDCS electrode designs for comfort as well as test electrode over-potential, pH, and temperature. Passing 2 mA current for 22 minutes, both anodal and cathodal stimulations were evaluated independently. Subjective sensation during forearm stimulation was evaluated in 8 subjects. The benefits of skin electrical or chemical pre-conditioning were tested. Conductive Rubber, Ag, AgCl, pellet electrodes and AgCl ring electrodes were evaluated in combination with salty gels (Signa and CCNY4) and nominally electrolyte free gel (Lectron). The use of AgCl ring electrodes in combination with CCNY4 gel resulted in no significant pH, temperature, or over-potential changes under either polarity stimulation and was well tolerated by subjects. HD-tDCS may thus be applied with 2 mA per electrode for up to 22 minutes without skin irritation. Moreover, skin pre-conditioning can eliminate sensation such that HD-tDCS can be applied in a blinded fashion and under a broad range of therapeutic and performance enhancement applications. Our HD-tDCS system allows non-invasive, safe, and targeted modulation of selected cortical structures for electrotherapies that are individualized as well as optimized for a range of therapeutic applications.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2009;3(2):027555-027555-1. doi:10.1115/1.3190476.
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Commercially pure titanium (cp Ti) dental implants have been widely and successfully used with high rates of clinical success in normal situations. However, there is still a lack of reliable synthetic materials to be used either a) when immediate loading of the implant is desired or b) when bone presents compromised conditions due to trauma, infection, systemic disease and/or lack of significant bone volume. Our group has aimed the development of biomimetic strategies of surface modification to obtain metallic implants with osteostimulative capabilities. These surface modifications will provide implants with a rapid rate of newly-formed bone growth and with ossecoalescence, i.e., direct chemical contact with the surrounding tissues. Consequently, the biomimetically-modified implants will be reliably used on those more demanding clinical situations. cp Ti surfaces treated to obtain a combination of an optimal random surface topography (in the micro and nanolevels) with a chemical modification of the naturally-formed titania layer have been proved bioactive. These rough and bioactive surfaces nucleate and grow a homogeneous hydroxyapatite layer both in vitro and in vivo. They stimulate the osteoblasts differentiation and trigger a rapid bone formation that mechanically fixes implants under immediate-loading conditions. A simple process using silane chemistry has been proved specific, rapid, and reliable to covalently immobilize biomolecules on c.p. Ti surfaces. This methodology can be used to develop biofunctionalized implant surfaces with different or combined bioactivities. The biofunctional molecules can be biopolymers, proteins, growth factors, and synthetic peptides specifically designed to be attached to the surface. The bioactive properties of the molecules designed and used can be mineral growing and nucleation, osteoblast differentiation (bone regeneration), fibroblasts differentiation (biological sealing), antibiotic,… Specifically, we have obtained mechanically and thermochemically stable coatings made of recombinant elastin-like biopolymers. The biopolymers bear either a) the RGDS peptide, which is a highly-specific cell-adhesion motif present in proteins of the extracellular matrix for different tissues including bone, or b) an acidic peptide sequence derived from statherin, a protein present in saliva with high affinity for calcium-phosphates and with a leading role in the remineralization processes of the hard tissues forming our teeth. Two different biomimetic strategies have been successfully developed combining topographical modification, inorganic treatments and/or biofunctionalization for improving bioactive integrative properties of c.p. Ti implants.

Topics: Biomimetics
Commentary by Dr. Valentin Fuster

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