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### Research Papers

J. Med. Devices. 2008;2(2):021001-021001-8. doi:10.1115/1.2918739.

In hypertension and aging, central elastic arteries become stiffer and hence the central pulse pressure is augmented due to the increase in the pulse wave velocity and the early return of reflected waves to the heart from the periphery. Valuable information on arterial properties, such as stiffness, can be obtained from both central (aortic) and peripheral (radial) pressure wave forms. A feasibility study for the noninvasive estimation of arterial stiffness using pressure waves detected by a pneumatic cuff wrapped around the upper arm is presented. The propagation and reflection of arterial pressure waves (generated by the heart) in the central elastic arteries are simulated using a simplified water hammer acoustic model. Furthermore, a lumped parameter model is used to describe the transmission of the pressure waves from the brachial artery to the cuff external wall. By combining the two models, we were able to simulate the pressure contours in the brachial artery and illustrate how these pressures transmit to the cuff’s external wall. The effects of aortic stiffness are investigated by simulating the model at different values of aortic elastic moduli and observing the pressure augmentation and the timing of feature points. This work was done as part of the development of a noninvasive diagnostic device by Pulsecor Ltd. The model results obtained in this work are in agreement with published experimental results and the device output; hence, the model can be used to develop the device’s stiffness estimation algorithm.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):021002-021002-7. doi:10.1115/1.2912817.

Automating image-guided therapy and registering a medical image to a patient require knowledge of the locations of both the medical image source (e.g., ultrasound) and the surgical tool with respect to a global coordinate system that is known relative to the patient. Also, sturdiness of the medical instrumentations is essential. A novel compact stabilizer-tracker integrated assembly is designed to serve as a holder that can be used to support, manipulate in six degrees-of-freedom, and firmly lock-in-place ultrasound imaging probes and other instruments for use in image-guided surgery as well as to provide the position and orientation of the probe in 3D space with respect to a known reference origin. The stabilizer’s configuration allows a clinician to easily manipulate an ultrasound probe in 3D space, and demonstrate improved sturdiness when locked. A reliable validation technique using forward kinematics was used to evaluate the performance of the holder. Performance tests show that the tracker assembly can acquire the position and orientation of the ultrasound probe with an average displacement accuracy of $0.66mm$ and roll, pitch, and yaw angular accuracies of $0.24deg$, $0.38deg$, and $0.19deg$, respectively. The improved sturdiness demonstrated by the compact-sized stabilizer and the high accuracy of the tracking mechanism make the integrated holder mechanism well suited for use in image-guided robot-assisted brachytherapy. It is anticipated that this will lead to improvement in accuracy and clinical outcomes for the procedure. The novel tracker can also be used to acquire the positions and orientations of other passive mechanisms of complex designs.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):021003-021003-8. doi:10.1115/1.2918740.

The size and limited dexterity of current surgical robotic systems are factors that limit their usefulness. To improve the level of assimilation of surgical robots in minimally invasive surgery (MIS), a compact, lightweight surgical robotic positioning mechanism with four degrees of freedom (DOFs) (three rotational DOFs and one translation DOF) is proposed in this paper. This spatial mechanism based on a bevel-gear wrist is remotely driven with three rotation axes intersecting at a remote rotation center (the MIS entry port). Forward and inverse kinematics are derived, and these are used for optimizing the mechanism structure given workspace requirements. By evaluating different spherical geared configurations with various link angles and pitch angles, an optimal design is achieved, which performs surgical tool positioning throughout the desired kinematic workspace while occupying a small space bounded by a hemisphere of radius $13.7cm$. This optimized workspace conservatively accounts for collision avoidance between the patient and robot or internally between the robot links. This resultant mechanism is highly compact and yet has the dexterity to cover the extended workspace typically required in telesurgery. It can also be used for tool tracking and skills assessment. Due to the linear nature of the gearing relationships, it may also be well suited for implementing force feedback for telesurgery.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):021004-021004-4. doi:10.1115/1.2931550.

Pin loosening is a frequent complication associated with the use of halo orthoses. Efforts to reduce pin loosening incidence include increasing the number of halo pins, increasing the torque specification, and proactively retightening the halo pins. Although these approaches lower pin loosening incidence rates, none addresses the cause of pin loosening, which is the inability of current halo ring designs to accommodate changes in geometry of the skull. A novel four-pin adaptive halo ring is introduced that can accommodate changes in geometry of the skull and provide a nearly constant pin force. To quantify pin loosening in a halo ring, tests were performed using a fixture that was capable of simulating the changes in skull geometry that are responsible for pin loosening. Both the four-pin adaptive halo and a conventional halo were tested. After $1.1mm$ of radial recession of the skull at the pin site, the average halo pin force in the conventional halo decreased by 78% while the average halo pin force in the four-pin adaptive halo decreased by 12%. In addition, the four-pin adaptive halo had significantly less variation in initial halo pin force ($p$-value $<0.0001$) than that of the four-pin adaptive halo.

Commentary by Dr. Valentin Fuster

J. Med. Devices. 2008;2(2):025001-025001-7. doi:10.1115/1.2902856.

Enemas containing the anti-inflammatory drug mesalamine are an effective treatment for a distal form of inflammatory bowel disease (IBD). An IBD patient discovered that a generic mesalamine enema was more difficult and painful to use than the proprietary version. A study was initiated to determine whether these differences were measurable in the laboratory using conventional mechanical test equipment. Differences among three bottle types (the proprietary brand and two generic versions) were quantified by mechanical testing. The compressive force required to squeeze the drug from each bottle was measured, tensile testing was performed on the bottle wall, and stiffness of the nozzle tips was studied via bend testing. The thickness of the bottle walls and the inner diameter (ID) of the nozzles were also recorded. The work required to expel the drug from the generic versions during bottle compression was significantly greater than for the proprietary $(p<0.01)$. This was likely due to the wall thickness being greater in the generics; the elastic moduli of the three bottles were similar. The ID of the nozzles was smaller for the generic bottles, suggesting additional resistance to flow. Increased flow resistance was also observed for bottles in which lubricant obstructed the nozzle opening. The work required to bend the nozzle was greater in the generics than in the proprietary $(p<0.01)$. These differences between the generic and proprietary bottles are consistent with the patient’s subjective experience. Poor bottle performance may adversely affect patient compliance with this treatment. Improved bottle design (such as tighter tolerances for wall thickness, nozzle ID, and nozzle stiffness) and manufacturing controls (e.g., preventing the nozzle lubricant from impeding delivery of the drug) could be achieved through the development of a standard specification for enema bottles. An optimal bottle design is suggested.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):025002-025002-9. doi:10.1115/1.2931551.

This paper describes the initial design and optimization of a compliant endoscopic suturing instrument. The emerging field of Natural Orifice Transluminal Endoscopic Surgery (NOTES) requires innovative instruments to meet the size limitations inherent in this type of minimally invasive surgery; using compliant mechanisms is proposed as one method of meeting this requirement. The compliant design was modeled and optimized to maximize the distal opening and provide a puncture force of at least $4.6N$, while being small enough to fit within a $3.3mm$ working channel. The design utilizes contact for stress relief and intertwining parts for added deflection. ANSYS ® was used for finite element analysis including contact and nonlinear deformations. A prototype was fabricated from the optimized geometry and experimentally tested. The best geometry is predicted to have a distal opening of $14.6mm$ at the tips and supply a puncturing force of $4.83N$. The force supplied at the tip was measured and was found to exceed the required $4.6N$. The prototype successfully passed two complete sutures and qualitative results are provided. The results of the study will lead to further refinements and improvements in future designs.

Commentary by Dr. Valentin Fuster

### 2008 Design of Medical Devices Conference Abstracts

J. Med. Devices. 2008;2(2):027501-027501-1. doi:10.1115/1.2942410.
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Abstract
Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027502-027502-1. doi:10.1115/1.2924269.
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Medical innovation is often delayed by the difficulty in developing cooperation among practicing physicians, academics and medical device developers. In Rochester, Minnesota, the Mayo Clinic Division of Engineering has excelled at integrating these specialties, facilitating medical device innovation for the past $60years$. In 1948, Mayo Clinic combined an instrument shop with an engineering design services team and created the Division of Engineering. This enabled a unique partnership between physicians, researchers, and product developers. Early innovations from this team include the Mayo heart-lung machine, cardiac monitoring, advances in aero-medicine, surgical stereotaxy, and early transfusion equipment. Today, the Mayo Division of Engineering consists of mechanical, chemical, electrical, biomedical, and software engineers, machinists, and a scientific glass-blower. The division works in close collaboration with project proponents (primarily physicians) within the clinical environment to analyze problems, propose designs, and deliver a clinical solution. From custom 3-D models for support pre-surgical planning to endoscopic heart valve repair devices, the team identifies opportunities and delivers systems that can be quickly translated into medical practice.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027503-027503-1. doi:10.1115/1.2927390.
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Introduction: Cardiac auscultation accuracy is poor: 20% to 40%. Audio-only of 500 heart sounds cycles over a short time period significantly improved auscultation scores. Hypothesis: adding visual information to an audio-only format, significantly $(p<.05)$ improves short and long term accuracy. Methods: Pre-test: Twenty-two 1st and 2nd year medical student participants took an audio-only pre-test. Seven students comprising our audio-only training cohort heard audio-only, of 500 heart sound repetitions. 15 students comprising our paired visual with audio cohort heard and simultaneously watched video spectrograms of the heart sounds. Immediately after trainings, both cohorts took audio-only post-tests; the visual with audio cohort also took a visual with audio post-test, a test providing audio with simultaneous video spectrograms. All tests were repeated in six months. Results: All tests given immediately after trainings showed significant improvement with no significant difference between the cohorts. Six months later neither cohorts maintained significant improvement on audio-only post-tests. Six months later the visual with audio cohort maintained significant improvement $(p<.05)$ on the visual with audio post-test. Conclusions: Audio retention of heart sound recognition is not maintained if: trained using audio-only; or, trained using visual with audio. Providing visual with audio in training and testing allows retention of auscultation accuracy. Devices providing visual information during auscultation could prove beneficial.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027504-027504-1. doi:10.1115/1.2927393.
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Moisture levels in medical device packages influence a variety of crucial device properties, e.g. mechanical properties, corrosion and leach rates, drug potency, and ultimately shelf life. This is especially true for drug releasing and biodegradable device materials. It is therefore important to establish a high degree of control and accuracy of the humidity levels at all relevant stages in the production process as well as in the final package. In the current study we demonstrate a newly developed method for accurate headspace moisture trace level analysis in medical device packages using extractive gas phase Fourier transform infrared (FTIR) spectroscopy. Volumetric aliquots were extracted, using a specially designed extraction assembly, from the headspace of medical device relevant packages. The headspace water concentration was analyzed using a validated gas phase FTIR system1. Water bands in the spectral region $1600–2200cm$ 1 were chosen for the quantitative analysis. Sample spectra were compared, with a least square fit procedure, to water reference spectra at known concentration. Accurate quantification was demonstrated for headspace water vapor concentrations less than $100ppm$. This is considerably lower than feasible with conventional package headspace moisture analysis techniques. The results of this study demonstrate the benefits of using extractive gas phase FTIR for low level moisture analysis of small headspace volumes.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027505-027505-1. doi:10.1115/1.2927429.
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There are upwards of 250,000 cases of infections due to the use of percutaneous devices in the US every year, with an estimated cost of \$25,000 per incident. Improving the longevity of these devices is thus of significant clinical and economic importance. Current antimicrobial and junctional healing approaches do not allow for in situ modulation of therapeutic effects. In this work we are developing bioactive vibrational magnetoelastic (ME) materials for use as a remotely activated tunable coating promoting cell differentiation and inhibition of bacterial adhesion at the tissue-implant interface. ME sensors are currently used as an in situ method of measuring biological processes. The objective of this study was to develop an ME antimicrobial coating conducive to cell growth and characterize the antimicrobial and cell inductive response towards frequency-amplitude modulated vibrations. A thin film of Chitosan, a natural polymer with antimicrobial properties, was applied to the material using spin coating and quantified with profilometry and scanning electron microscopy. Custom built activation coils were constructed measuring resonant frequencies and amplitudes of coated and uncoated ME material. Based upon collected data a representative curve was created modeling the changes in resonant frequency and amplitude. Tunable vibrations induced a 30% decrease in bacterial adhesion when compared to non-vibrated controls. Currently we are testing the effectiveness of these coatings at promoting epithelial cell differentiation in addition to inhibition of bacteria adhesion.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027506-027506-1. doi:10.1115/1.2932432.
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A breast stabilization device or breast cradle has been developed for use in interventional procedures. The device is a three-dimensional collapsible linkage that, when actuated, lightly compresses the breast while pulling it away from the chest wall. The compression provides the pressure needed to hold the breast firm during needle biopsy, ablation, or other procedures while being more comfortable than bilateral compression plates. By collapsing radially in an open configuration, the cradle provides nearly full access to the breast, as compared to the restrictive two-dimensional layout of grid-based bilateral compression plates. By pulling the breast away from the chest wall, the breast cradle may reduce the incidence of lung puncture or other medical errors. Several iterations of the device were developed, including rigid-joint models and a compliant-joint model. The rigid models more precisely show the kinematics of the device, but the manufacturability and assembly of the joints may be tedious in a production environment. Conversely, the compliant model may be more easily mass-produced, although the design would be more complex and costly. To provide a proof-of-concept for the compliant-joint design, a rapid prototyping machine was used to quickly produce several models that could be produced by other means (i.e. vacuum forming or injection molding) in full production. These models will be tested with breast phantoms in a magnetic resonance imaging (MRI) environment to ensure compatibility. Other tests will be performed to ensure patient comfort amongst various breast sizes and shapes.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027507-027507-1. doi:10.1115/1.2932435.
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Radiation therapy using state-of-the-art helical tomotherapy treatment is largely automatic after the doctor creates the dosage plan. The system currently has no method to detect if the patient moves out of alignment during treatment, a capability that could improve treatment accuracy. This cross disciplinary project combines the fields of computer vision with medical physics. The creation of a minimally invasive, vision-based, total-body tracker that can interact with the helical tomotherapy system to detect when a patient becomes misaligned has been explored. The tolerances are tight, by measuring when the patient moves just $5mm$ out of alignment, the uncertainty in radiation dose delivery can be greatly reduced. A stereoscopic vision system uses infrared reflective markers to track the patient. Using these data points, boney structures, such as the head, can be tracked independently, providing roll, pitch, and yaw information about their pose. Initial results compared vision-based patient-positioning tolerances with those of traditional megavoltage CT-scans. Simulation-based results have explored the efficacy of tracking large portions of the patient’s body.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027508-027508-1. doi:10.1115/1.2932440.
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Background: A functional analysis of current laparoscopic surgical technology prompted a redesign to provide multiple functionalities within a single tool. Novel mechanisms were needed to actuate and deploy functional tips to the surgical site from their storage locations. Methods: Functional Decomposition was used to determine problems with the current minimally invasive surgery (MIS) paradigm. Axiomatic Design was used to ensure an efficient design. Quality Function Deployment was used to mathematically determine important design criteria. Results: The actuation mechanism transfers squeezing motion from the hand through a gear train to the distal end of the tool where a pin-slot mechanism actuates the tool tip. An ergonomic slider mechanism translates linear thumb motion into rotation of the tool’s shaft through a gear train. A binary ratcheting mechanism is used to lock or unlock the tool with identical motions. Methods for indexing functional tips within the tool and interfacing the tips with a lead screw were designed for a modular tool. Rotary indexing of the tool cartridge is done using a Geneva-type mechanism and cam∕follower to provide positive locking once the tip is in place. Proper alignment of the tool tip with the actuation∕shuttling screw is accomplished using a screw∕wedge assembly. Conclusions: Benefits include multiple functionalities in a single tool, ergonomic benefits of an increased I∕O force scaling, decreased out-of-plane motion required to rotate the tool’s shaft and decreased cognitive effort required to lock and unlock the tool’s jaws.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027509-027509-1. doi:10.1115/1.2932564.
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Evaluation of spinal implants is limited by difficulties in testing biological structures. Soft tissues primarily control spinal biomechanical responses. The objective of this study is to show controllability of the synthetic soft tissue properties of the mechanical analogue lumber spine. The development of an analogue spine would answer a multitude of clinical questions and improve implant design. Polyester fibers in a wave pattern were embedded in a shore-A F55 polyurethane matrix to mimic the nonlinear properties of human ligaments. Ligaments with four different volume fractions (Vf) of fibers were tested to failure in tension using specially designed jigs in a MTS MiniBionix. Polyester fibers oriented at $+∕−30degrees$ were embedded in F55 polyurethane to simulate the annulus fibrosis (AF). Discs with three different Vf’s and F5 polyurethane for the nucleus pulposus were tested in compression to $1.25mm$ using a self-aligning jig. Displacement control was used for all specimens at a rate of $0.04230mm∕sec$. For the ligaments, the initial stiffness and strain at toe was similar and the mean secondary stiffness in MPa was $187±5%$, $307±5%$, $422±2%$, and $511±3%$ as the Vf increased. For the discs, the mean initial and (secondary) stiffness in N∕mm was $158±14%$$(658±6%)$, $150±5%$$(666±8%)$, and $74±3%$$(1230±2%)$ as the AF Vf increased. The results showed that synthetic soft tissue properties are controllable and properties measured fall within the range of human cadaveric literature values. A wide variety of analogue models can be developed utilizing the control of soft tissues.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027510-027510-1. doi:10.1115/1.2934346.
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Eight patients with treatment-resistant depression (TRD) underwent adjunctive chronic VNS for periods up to $14months$. Although the patients denied dieting or change in activity level, there was a slow and highly significant loss of weight accompanied by decreased metabolism in the ventromedial prefrontal cortex, a cortical area involved in interoception with dense connections to the hypothalamus. The loss of weight was proportional to the initial weight. Weight loss was not related to change in depression scores. Neuromodulation through VNS may offer a novel approach to weight regulation.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027511-027511-1. doi:10.1115/1.2934349.
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A micropump, which includes a mixing function, has been fabricated. For the application to LOC (Lab On a chip), the micropump utilized PBS (Phosphate Buffered Saline) solution as the working medium. The solution is commonly used in biochemistry and cell culturing. The portable system and low energy consumption are important to realize the LOC device. In spite of a low voltage of $4V$, the flow rate of the micropump was $0.02466ml∕min$. The new micropump shows more enhanced performance than existing micropumps. The micropump uses Lorentz force actuation. The Lorentz force acting onto the ionic current in the PBS solution generates the fluid flow in the micropump. For the accurate prediction on flow direction, a computer simulation has been made using commercial CFD code. The results of simulation showing circulation direction were verified by experiment. The fluid circulation from each electrode combined and acted as the mixer in the micropump. The micropump was fabricated $20.2mm$ in length, $1mm$ in width and 400 $μm$ in electrode length. To measure accurately, a high speed digital camera was used.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027512-027512-1. doi:10.1115/1.2936115.
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Introduction: A covered stent is one whose length and circumference is enclosed with a membrane or fabric like material. Current covered stents have been used in the treatment of failed saphenous vein grafts in coronary bypass and coronary artery perforations. Covered stents have also been proposed in treating brain aneurysm. However, none of these applications showed satisfactory results. The deficiencies of the covered stents are 1) Large wall thickness 2) Rigidity 3) Non-biodegradable polymer with poor endothelialization. Materials and methods: Aligned poly(L-lactide-co-epsilon-caprolactone) [P(LLA-CL)] nanofiber was lon-gitudinally deposited on to a bare metal stent (BMS) by a patent pending electrospinning technique. The NCS were deployed following the instruction to evaluate the expandability. Biocompatibility of the nanofiber was characterized by cell culture, degradation and drug eluting study. Results: The cell viability of Porcine smooth muscle cells (PSMC) on the nanofiber was initially low but caught up after $2weeks$. SEM images showed 100% of cell confluence on the nanofiber after $2months$. Significant amount of ECM protein was detected on P(LLA-CL) nanofiber ($0.07mg∕cm2$ at day 70). Complete degradation of P(LLA-CL) is expected within $6months$. Paclitaxel released from drug loaded nanofiber was shown to inhibit PSMC growth but kill Hela cells. NCS was successfully fabricated and deployed without tearing the nanofiber. Conclusions: NCS was successfully fabricated. P(LLA-CL) was chosen for the “cover” with proved superiorities on biocompatibility, cell viability, degradability and drug loading capacity. Future work will be animal study to prove that NCS can reduce in-stent restenosis and promote endothelialization.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027513-027513-1. doi:10.1115/1.2936118.
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Nano-porous Ta coatings have been developed to render Nitinol medical devices fully radiopaque. These coatings are deposited atom by atom in a unique PVD process that utilizes a cylindrical cathode and operates at conditions that produce low substrate temperatures. As a result, complex 3D shapes are coated with high uniformity and the critical Nitinol mechanical properties are unchanged. Because these coatings consist of a nano-porous columnar structure they are able to withstand strains of at least 8% without delamination or cracking. X-ray and fluoroscopic imaging shows that Nitinol stents with these coatings are highly visible and reveal the entire 3D shape of the device instead of only point markers. The benefits of these coatings are easier, faster and more reliable implantation procedures, especially for difficult to visualize medical devices such as bifurcated stent-grafts. Ta is extremely biocompatible. Thirty-day and $6‐month$ porcine studies have shown that there is no difference in stenosis, intimal thickness, injury score or inflammation score for stents with this nano-porous Ta coating compared to a bare Nitinol stent. In addition, measurement of corrosion breakdown potential show higher values for Ta on Nitinol than Nitinol alone. Aside from radiopacity, these Ta coatings, hold the potential for other highly desirable functions such as controlled drug delivery without polymers and enhanced re-endothelialization. Studies are currently underway to understand the drug loading and release kinetics as a function of a pore size and aspect ratio.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027514-027514-1. doi:10.1115/1.2936120.
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The number of minimally invasive vascular interventions is increasing, and the device most frequently used is a guidewire, along which devices are delivered to the intervention site. Procedural failure can occur due to improper guidewire and∕or device selection. To facilitate guidewire and device guidance, we investigated the reproducibility of guidewire paths in vessel phantoms. Several trained users repeatedly passed guidewires of different flexibility through the phantoms under pulsatile flow conditions. Afterwards, the 3D paths were reconstructed and compared. In addition, the 3D paths were calculated using graph representation techniques. Points in the vessel lumen in planes perpendicular to the vessel centerline were generated. All points in adjacent planes were joined generating a vector set in a graph representation in which the edge weights were functions of the angle between contiguous vectors. The optimal path through this weighted directed graph was then determined using a Dijkstra’s (shortest path) algorithm. The guidewire paths appear reproducible across users but not across materials. The average RMS difference of repeated placements was $0.17±0.02mm$ (plastic-coated guidewire), $0.73±0.55mm$ (steel guidewire) and $1.15±0.65mm$ (steel vs plastic-coated). For the guidewire modeling, the average RMS distance between the actual and simulated guidewire path was $0.7mm$; computation time was $3s$. For a given guidewire, these results indicate that the guidewire path is relatively reproducible in shape and position. The ability to predict the guidewire path inside vessels may facilitate calculation of vessel-branch access and force estimation.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027515-027515-1. doi:10.1115/1.2936218.
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For more than $40years$, the replacement of diseased natural heart valves with prosthetic devices has dramatically improved the quality and length of the lives of millions of patients. Bioprosthetic heart valves (BHV), which are composed of biologically derived tissues, have good hemodynamic performance and do not require the anticoagulation therapy necessary when mechanical heart valves are implanted. However, these bioprostheses continue to fail due to structural failure resulting from poor tissue durability and faulty design. AHA∕ACC guideline recommends use of BHV for patients $65years$ or older, primarily due to its current $10–15years$ of limited durability. Clearly, an in-depth understanding of the biomechanical behavior of BHV is essential to improving BHV design to reduce rates of failure and increase its durability. Objective: develop a robust computational model to simulate BHV deformations and optimize its design. Methods: Experimentally driven, nonlinear, anisotropic material models are used for modeling the mechanical properties of valve leaflets; A novel method of constructing parametric finite element models is used to rapidly generate 3D free-from geometries of BHV for valve design optimization; Valve design parameters, such as peak stresses and effective orifice area (EOA) are evaluated. Results: multiple applications of the approach demonstrate the feasibility of utilizing computational biomechanics in BHV design. The computational approach provides us with an efficient new platform to develop and optimize the next generation heart valve design such as transcatheter valve and valve repair device design.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027516-027516-1. doi:10.1115/1.2936216.
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We have developed a technique to measure gas non-intrusive in scattering media, such as human tissue. The technique was first demonstrated for test samples in 2001 by our group and utilizes diode laser absorption spectroscopy to monitor molecular oxygen and water vapor. The focus of medical application has been on sinuses, both maxillary and frontal sinuses and the potential of the technique has been shown on volunteers. A spin-off company named GasPorOx AB has been formed with the aim to develop a product used to improve the diagnosis of the sinus infections. A portable fiber-guided system has been developed and is used in an ongoing initial clinical trial in collaboration with the Ear, Nose and Throat Clinic, the Oncology and Diagnostic radiology clinics at the Lund University Hospital.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027517-027517-1. doi:10.1115/1.2936213.
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Subcutaneous tissue is frequently the target site for placement of continuous, real-time metabolic sensors. Since the 1960s, numerous research groups have developed needle-like sensor designs, patterned after the Clarke Electrode, to monitor glucose in subcutaneous tissue. These designs perform well in vitro but often fail in vivo due to sensor instability and tissue response. None of these studies focused on the mechanical properties of implanted sensors and how these properties may affect in vivo performance. To investigate the role of sensor stiffness on short term functionality we developed a low stiffness subcutaneous sensor patterned after the Clarke Electrode and tested it in rodents. The purpose of this study was two-fold. The first goal was to demonstrate the in vivo functionality of the flexible sensor. The second goal was to evaluate the effect of stiffness on functionality by co-implanting stiff and flexible sensors. In the first series of studies the low stiffness sensors provided glucose level measurements that fell within the A and B regions of the Clarke Error Grid 93.0% of the time. The results of the second study yielded similar accuracy; however, no performance difference was seen between the stiff and flexible sensors. We concluded that the flexible sensor works for at least $3days$ after implantation in the subcutaneous tissue of freely moving rats and that the key property of low stiffness has no differential effect on the accuracy of the sensor in the freely moving rodent model of these studies.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027518-027518-1. doi:10.1115/1.2936212.
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Blood sugar management is particularly critical in the neonatal intensive care unit where the incidence of hypoglycemia is high and patients run the risk of brain damage. The staff at most hospitals obtain glucose levels in infants by drawing blood from the heel, which is a cause for recurrent pain. Some infants undergo this procedure every $1–3hours$ for up to a few months. Our goal is to design a minimally invasive device that allows for real-time glucose monitoring in very low birth weight infants in the neonatal intensive care unit (NICU). This glucose monitor will reduce the amount of pain and physiological stress on the infants, decrease the risk of hypoglycemia in neonates and reduce the workload on hospital staff. There is currently much room for emerging technologies in this market as it trends towards less pain and faster responses. The device should only slightly hinder the infant’s motion, be as painless as possible, and all materials used in contact with the body need to be biologically inert and cause no irritation or allergic reaction. The device will utilize a microneedle array to extract interstitial fluid and draw it through a hydrophilic polyurethane membrane and into a polarimetry chamber. Circularly polarized light will be passed through the chamber and the differential absorbance of left and right polarized light will be used to calculate the glucose concentration. A literature and patent review showed that each separate portion could be used in an effective device for minimally invasive, continuous glucose monitoring.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027519-027519-1. doi:10.1115/1.2936209.
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Objective: To optimize the assessment of muscle weakness in critically ill patients in the intensive care unit (ICU) by development non-invasive, reproducible assessment devices and application protocols. Methods: For over $5years$ we evaluated weakness in ICU patients by employing a prototype non-invasive muscle force assessment system. We determined peak torques, peak rates of torque development and decay of the ankle dorsiflexors after supramaximal peroneal nerve stimulation. We continue to test modifications of our devices (i.e. different stabilizing boots, extendable leg support systems, electrodes) so to optimize this important clinical assessment. Results: Measurements were performed in over 30 severely ill adult patients. During their illnesses, one observed dramatic reductions in stimulated torques, and during the recovery period, values increased to 70–80% of initial values. In those patients who died, the values continuously decreased until death. Throughout these investigations, several technical problems arose: i) the current device could not be used on patients in a prone position; ii) the mechanism used to adjust and lock ankle slipped; iii) edema made nerve stimulation difficult (altered skin conductance and difficult to maintain electrode position); iv) device was bulky for positioning (e.g., weight), and∕or v) stimulus parameters could not be readily adjusted. Discussion: Stimulated muscle force assessment can be used to study ICU patients’ forces. Nevertheless, next generation force assessment systems should be smaller, lighter, more portable, with a simple angle adjustment means, easier to use with a computer-controlled stimulator and include EMG recordings.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027520-027520-1. doi:10.1115/1.2936201.
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Driver drowsiness is one of the major causes of deadly traffic accidents. Continuous monitoring of drivers’ drowsiness thus is of great importance for preventing drowsiness-caused accidents. Previous psychophysiological studies have shown that heart rate variability (HRV) has established differences between waking and sleep stages. This offers a way to detect driver’s drowsiness by analyzing HRV, which is typically measured and analyzed from electrocardiogram (ECG) signal. Although ECG measurement techniques are well developed, most of them involve electrode contacts on chest or head. Wiring and discomfort problems inherent in those techniques prevent implementing them on cars. This research develops two non-intrusive real-time ECG measurement methods for drivers. In the first method, each half of the steering wheel is wrapped with conductive fabric as electrode and is isolated to each other. In the second one, two pieces of conductive fabric with the same dimension are placed on the driver seat’s backrest. Signals from conductive fabric electrodes are filtered by differential low pass, band pass and notch filters to amplify ECG signals and suppress noise. Noise whose frequency overlaps with the frequency range of ECG signal cannot be eliminated by these filters. To address this challenge, an adaptive filter is employed for baseline noise cancellation. Experimental tests show that both ECG measurement methods can provide clear ECG signals for further HRV analysis, although signals from the steering wheel are of better quality. Test results also demonstrate that the adaptive filter can effectively cancel baseline noise.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027521-027521-1. doi:10.1115/1.2936180.
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Middle ear implantable hearing devices as an emerging and effective technology can offer advantages to the individuals with mild to moderately severe sensorineural hearing loss. Several devices with piezoelectric or electromagnetic transducers have been developed. A totally implantable hearing system (TIHS) consisting of a subcutaneous microphone, sound processor, and electromagnetic transducer has been investigated. The design of the TIHS has incorporated the bioengineering approaches based on a 3D finite element (FE) computational model of the human ear and the FE analysis of electromagnetic coupling of the transducer. In this paper, we report the technologies developed for the TIHS and experimental measurements in bench setup and human temporal bones with the TIHS prototype. The tests conducted on the device to characterize its performance across the auditory frequency range include: 1) mass loading effect on residual hearing with the passive implant, 2) effectiveness of the electromagnetic coupling between implanted coil and magnet, and 3) function characterization of whole unit in response to acoustic input across the skin. The results indicate that the TIHS prototype tested in human cadaver ears or temporal bones shows satisfactory performance of the system. The data obtained from those preliminary studies will be used for future clinical trails of the TIHS.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027522-027522-1. doi:10.1115/1.2932441.
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The initial step in the repair of a thermal or chemical burn is wound debridement, the removal of the dead skin covering the burn. Afterwards, the exposed wound is covered with a viable biological dressing, the scabs re-form and the process must be repeated until the wound is fully healed. Of the various methods of wound debridement, surgical excision is the most popular. The process uses stainless steel cutting blades mounted on different types of handles which have built-in adjustments for controlling the depth of the excision. The main problems with this treatment method are excessive bleeding and lack of high-precision control of the cutting depth. Recent advances have been made in healing treatments for thermal and chemical burns using a variety of techniques to debride damaged tissue, including the use of medical lasers, such as CO2 and Er:YAG lasers. Excision using laser beams has been shown to be associated with significantly reduced morbidity, since the amount of blood lost during debridement is significantly reduced because the depth of treatment is more precise and the process has a cauterization cycle built-in. One drawback to the available laser systems is that they all require the surgeon to move a hand piece over the damaged area. This process requires great operator skill and is time consuming for an injury with a large surface area. Small hand held scanners attached to the end of articulated arms have mitigated this drawback to some extent, but the scanned areas are relatively small and the surgeon still needs to move the scanner head over larger injuries. This project describes the development of an automated, 3D vision guided laser debridement system with a large maximum working area for efficiently treating injuries with large areas or a multitude of smaller injuries distributed over a large area. This system is designed to be fail-safe, and performs precise debridement automatically and quickly with minimal surgeon involvement.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027523-027523-1. doi:10.1115/1.2932447.
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Colonoscopy, the gold-standard for screening colorectal cancer and inflammatory bowel disease, is performed using a flexible endoscope. Flexible endoscopes lack functionality in that only the frontal view from the distal tip is available to aid navigation, creating a tunnel vision effect that often results in disorientation. Our objective is to design a new fiber-based technology that can track the 3D shape of the scope in real-time. This will allow us to create a navigational aid display to guide the clinician in colonoscopy. In the design of our endoscope shape tracker, laser light is sent through a single optical fiber that has been marked with differentiable fluorescent dyes. The shape tracker is designed to be inserted into the biopsy channel of current endoscopes, providing an easy but drastic upgrade. As the fiber bends, laser light leaks out and irradiates the dyes, whose fluorescence is measured by a spectrometer to establish a relationship between the intensity of fluorescence and curvature. Initial findings indicate that there is as much as a ∼40% increase in fluorescence intensity when the fiber’s bend radius decreased from 58 mm to 11 mm. While our initial results are restricted to one degree of bending at one point along the fiber, we have the basis for building a fully capable multi-axis shape tracker using a single optical fiber. Future work involves optimization of the manufacturing process and sensor resolution.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027524-027524-1. doi:10.1115/1.2934348.
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Structures that direct neurite extension are important for regeneration following spinal cord injury and peripheral nerve injury. Within the spinal cord, neurons encounter a glial scar environment that impedes regeneration. In the peripheral nervous system, endogenous regeneration cannot occur across nerve gaps greater than $2mm$. Current repair strategies use guidance conduits to channel axonal growth towards distal targets. While showing promise, conduit walls do not provide a suitable environment for neuronal attachment or extension, and axonal growth within conduits remains tortuous. Hence, there is a need for development of three-dimensional (3D) structures that use contact guidance—rather than confinement—as a means of guided regeneration. Our laboratory has developed aligned, electrospun fiber matrices that have been shown to direct neurite extension in vitro. In addition, a gradient of the glycoprotein laminin-1 has been adsorbed onto aligned microfiber matrices to stimulate directional growth. These matrices were then manipulated into 3D conduit structures. Novel polymeric conduits that utilize contact guidance and contain gradients of molecules that stimulate directional growth have the potential to foster fast, directed regeneration into and through conduit structures.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027525-027525-1. doi:10.1115/1.2934387.
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Integrated multi-layer fluidic chips, with hundreds of elastomeric valves, are useful in immunoassays, protein crystallization, cell culture and several other applications. Although the devices are micro-scale, because valves are actuated pneumatically, each chip requires a relatively large pneumatic control system for operation. Fulfilling the great promise of microfluidics, for instance building throwaway, portable, massively parallel, point-of-care diagnostic systems is unlikely until there is a solution for actuating micro-valves electrically. We introduce a combination of materials—shape memory alloys (SMAs) and elastomersto solve this problem. SMAs offer among the highest work per unit volume of any actuator, and elastomers have the ability to absorb the energy and return the SMA to its original configuration, while providing electric and thermal insulation. Using this marriage of materials, with PDMS (elastomer) and Ni/Ti wires (SMA), we built electrically activated micro-fluidic valves, peristaltic pumps and multiplexers. The first generation valve design needs 50 to 250 mA current in the on state, with power requirements of about 0.5 W. It can hold back >1 atmosphere of pressure and run for thousands of cycles, actuating at sub-second speeds. The dead volume is <1 nano-liter. Crucially, these devices are assembled on printed circuit boards, like conventional electronic components. Thus, the technology used in assembling electronics is applicable to assembling fluidic chips, and both electronics and fluidics can be integrated on one platform for biomedical applications.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027526-027526-1. doi:10.1115/1.2934540.
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Within $6months$ from the initial procedure, restenosis is observed in 40% of the cases treated with coronary stenting. Exact reasons for restenosis are yet to be explored. Stenting is a mechanical process which causes large stress in the arterial wall. This may lead to the activation of stent related stenosis. The primary objective of this study is to investigate the relation between the stresses developed in the arterial wall and the restenosis rate. A three-dimensional model based on finite element method has been built which includes the stent, the plaque and the artery. The simulated result shows high stress concentrations at the contact areas of the stent and the plaque. The over flaring of the end struts causing arterial trauma may lead to restenosis.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027527-027527-1. doi:10.1115/1.2936206.
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An affordable, user-friendly and reliable infrastructure that supports evidence based tools for health assessment of children with Autistic Spectrum Disorder (ASD) has been developed. This system can detect the behaviors of children at various stages of autism and enables the therapist and parents to monitor, assist diagnosis and therapies of autistic children. The system incorporates 2 different sensor platforms which are wearable and static. The wearable system consists of a 3-axis accelerometer, small micro processor and a Bluetooth module to transmit data to the base station. This wearable device integrates these 3 modules to a customized Printed Circuit Board (PCB) which can be worn as a cuff or could be sewed into the sleeves of a child's shirt. The static sensor is composed of an audio sensor and a webcam which detects the sound/speech and captures video 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. Based on the data collected and our preliminary analysis, we were able to detect and recognize several self-stimulatory behaviors of a child with autism. The device allows for a continuous monitoring of the activities and self-stimulatory behaviors. It benefits both therapists and parents by helping them to better understand the behaviors of an autistic child and it will also enable early diagnosis of ASD.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027528-027528-1. doi:10.1115/1.2936203.
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A weight bearing indicator (WBI) has been developed and is undergoing clinical trials and commercialization. The most recent version of the device includes load range indication ability. The WBI is installed in a patient’s medical appliance (e.g. cam walker boot, surgical shoe) and allows patients recovering from lower extremity injuries to self monitor their rehabilitation. It is a simple and inexpensive mechanical device that utilizes the reversible buckling phenomena of a snap dome to provide a tactile ‘click’ and an audible ‘snap’ when a specified ground load on the bottom of a patient’s foot, which has been prescribed by an orthopedist or podiatrist as the partial weight bearing (PWB) upper limit, has been met or exceeded. A clinical study involving 20 subjects showed that PWB compliance improved when comparing the WBI device to standard of care approaches such as verbal instruction and the weight scale method. Specifically, PWB compliance improved from 58% and 45% body weight (BW) for verbal instruction and weight scale method, respectively, to 33% BW for the WBI device. In addition, PWB compliance using the WBI device was not dependent on subject weight like the standard of care approaches. Sometimes patients are instructed not only to avoid exceeding an upper load limit, but also to maintain their limb load above a lower limit as well. A newer version of the WBI has been developed that provides two distinct clicks to a patient corresponding to an upper and lower load limits.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027529-027529-1. doi:10.1115/1.2936202.
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Current methods for pathogen detection require days before a result is available, while biosensors offer the advantage of quick, on the spot results. In this project we present the proof of concept of a biosensor that uses giant magnetoresistance (GMR) sensors and a microfluidic system. The bioprobe consists of a 30 bp oligonucleotide, $5′$ functionalized with a thiol group (T-DNA30) immobilized on a gold surface. Hybridization was tested with a $5′$-biotinylated oligonucleotide complementary to T-DNA30 to which Streptavidin-R-Phycoerythrin was attached later. The difference in fluorescence between the target sample and control samples was observed using a scanning laser confocal fluorescence microscope. The GMR device consists of an $Ir0.8Mn0.2∕Co0.9Fe0.1∕Cu∕Co0.9Fe0.1∕Ni0.82Fe0.12$ multilayer structure. Magnetic nanoparticles were deposited directly on the surface of the GMR sensors. An external magnetic field was employed to polarize the nanoparticles, which can then be detected by comparing the resistance change loops of the GMR sensors before and after their deposition. A transparent elastomer, polydimethylsiloxane (PDMS), was used for the microfluidic system. The system comprises two microfluidic channels separated by a $200μm$ PDMS wall. The channel width is $200μm$ and its height $100μm$. The PDMS channel was permanently bonded to the SiO2 surface of the GMR sensor. The integrated biosensor will immobilize thiolated DNA on the gold surface below which the GMR device is located. For hybridization, biotinylated DNA will be used. Finally, magnetic nanoparticles, coated with streptavidin will be attached to the hybridized DNA and detected by the GMR device.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027530-027530-1. doi:10.1115/1.2936200.
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Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027531-027531-1. doi:10.1115/1.2924274.
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According to the most recent report of American Heart Association (AHA), heart disease, stroke and other cardiovascular diseases continue to remain not only the no.1 killer of Americans but also a major cause of permanent disability among American workers. Recently, many research efforts have been carried out to apply artificial intelligence (AI) to auscultation based method for rigorous detection/classification of heart murmurs but accuracy rates are not always high. All of the proposed AI techniques rely on converting the heart sound to an electrical signal and processing that signal to optimize the AI for murmur detection and classification. However, all these techniques fail to recognize that the electrical signal coming out of the cochlea is very different than the electrical signal coming out of the microphone or any other electrical sensor which is commonly used for converting heart sound to electrical signal. In this research paper, we want to take a novel approach to pre-process the electrical heart sound signal before it goes to AI for murmur detection/classification by altering the electrical signal in a similar way as is done by the human cochlea before sending the signals to the brain. Our hypothesis is that cochlea like pre-processing will change the spectral contents of the heart sound signal to enhance the murmur information which can then be efficiently detected and classified by AI circuitry. Using this approach, we plan to develop an AI based system for heart murmur classification/ detection with success rate comparable to that of an expert cardiologist.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027532-027532-1. doi:10.1115/1.2932757.
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It was hypothesized that the nonlinear load-displacement relationship displayed by bone could be conferred on an implant by tailoring its structure, yielding an enhanced mechanical stimulation of the tissues. Composite structures would feature piezoelectric properties that could also stimulate osteogenesis. Preliminary mechanical and electromechanical investigations of such porous structures are presented. Initial trial bowtie specimens with various aspect ratii were made from Nickel powder via a solid free form process and from stainless steel shim stocks. Poled Barium Titanate plates were sandwiched between stainless steel bowtie cells to create composite structures. Results: Under quasi-static compression, the Nickel structures displayed a nonlinear mechanical behavior at small strains and an overall strain-stress relationship similar to bone. Under cyclic compressive tests to 0.6 percent strain, all structures presented a repeatable nonlinear strain-stress behavior. The curves were fitted by a second-order polynomial whose coefficients are function of the relative density of the structure to a power n. Composite stainless steel/BaTiO3 bowtie structures confirmed that their electromechanical properties can be tailored. Discussion: Certain patients present metabolic degeneration that hamper bone healing. A ductile and tough structural material with piezoelectric properties such as the new composite structures in development presents the potential to overcome those limitations. They could have the advantages of existing devices without some of the drawbacks. Those porous implants may reduce the needs, costs, and risks linked to the additional use and implementation of an electrical stimulator and BMPs. Furthermore, the solid free form technique gives control over the mechanical properties of the structure. Thus, the mechanotransduction activity of biologic cells can be fully exploited to trigger a faster implant-tissue bonding, which could lead to reduction of surgical cost and time.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027533-027533-1. doi:10.1115/1.2932346.
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A novel method to generate uniform biodegradable microspheres for drug delivery applications has been developed. A liquid phase containing the dissolved microsphere matrix material reaches a continuous phase through a silicon membrane with micron-sized perforations, where it forms microdroplets. The solvent diffuses out of the droplets into the continuous phase leading to the formation of solid microspheres. Experiments with poly (lactic-co-glycolic acid) (PLGA) as the matrix material produced microspheres of which 95% had a diameter between 1 and $2μm$, a smaller size and a narrower size distribution than those reported elsewhere using glass or ceramic membranes. Such microspheres will be useful for the intravascular application and pharmaceutical drug delivery with a slow release of the drug at narrowly defined rates. Drug desorption and biodegradation rates induce controllable drug release from functionalized biodegradable microspheres. Those rates are directly proportional to microsphere size. One problem in conventional methods is how to achieve a desired average size and a narrow size distribution of the microspheres. Using a perforated silicon membrane, the size of the microdroplets mainly depends on the pore size and the speed of the continuous phase. By controlling these two parameters, it will be possible to fabricate monodisperse microspheres. The MEMS based approach to microsphere fabrication provided in this paper allows a better control over microsphere dimensions and therefore better control over drug delivery than those reported elsewhere.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027534-027534-1. doi:10.1115/1.2924272.
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Drug delivery via inhalation of drug aerosols has long been a standard procedure for the treatment of respiratory ailments. A number of researchers have explored the use of inhaled drugs as a novel way to administer new, often aggressive, drugs. However, conventional inhalers release medication uniformly in the mouth inlet. This approach leads to low inhaler efficiency characterized by high deposition in the upper oral airway. Kleinstreuer and Zhang (2003) have shown that a controlled release of drug particles at a specific location in the mouth inlet greatly increases drug efficiency and allows targeting of specific affected sites within the lung. The methodology was further validated experimentally using a fixed exit position nozzle∕inhaler system and model airway∕lung structure. Motivated by these results, this work presents the design and fabrication of a shape memory alloy-enabled (SMA) “smart inhaler system”. Incorporating a flexible nozzle capable of moving the exit position to any desired location, the smart inhaler system will be a robust system capable of treating many patients. The system employs several novel techniques in the area of smart actuator design and implementation. Ref: Kleinstreuer, C., and Zhang, Z. (2003). Targeted drug aerosol deposition analysis for a four-generation lung airway model with hemispherical tumors, ASME Journal of Biomechanical Engineering, 125(2), 197–206.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027535-027535-1. doi:10.1115/1.2927395.
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Objective: Amend a real-time, high-throughput method of bacterial growth detection for use as a model of biofilm response to co-administered pharmaceuticals during the treatment of devise associated infections. Background: Biofilms are the root etiology for chronic infections, particularly in regard to infections in patients with implanted medical devices. Calcium channel blockers (CCBs) are used for control of hypertension and angina and are commonly prescribed to elderly patients. We address potential interference of commonly prescribed CCBs with levofloxacin for treatment of Pseudomonas aeruginosa biofilms. Methods: Inoculum of $1–3×106CFU∕mL$ in the log phase were seeded into each well of a polystyrene plate. Biofilms developed over $6h$ at $37°C$, was washed and medium containing various CCBs plus levofloxacin was added to the biofilm. OD measurements were obtained at $1h$ intervals over $90h$ at $37°C$. Changes in turbidity were kinetically measured with a vertical photometer with a wide-band filter. Results: Mibefradil and diltiazem appear to be strongly antagonistic toward levofloxacin where both of them decrease antibiofilm effect of levofloxacin and they encourage the selection of resistant mutants from biofilm. Discussion: Implanted medical devices are quite common and are subjected to biofilm infections. Increasing multi-drug resistance underscores the need to conserve current antibiotics by judicious use. This necessitates consideration of evidence regarding antagonistic or synergistic activity of commonly prescribed drugs of different classes toward commonly used antibiotics. The combinations described here show vital and previously unreported effects of some CCBs when co-prescribed with levofloxacin on Pseudomonas aeruginosa biofilm.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027536-027536-1. doi:10.1115/1.2927430.
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The ElectroNanospray process (Nanocopoeia, Inc) transforms drugs and polymers into many nanoscale material states including powders, liquids, encapsulated particles, and coatings. This allows application of polymers and drugs to the surface of medical devices such as coronary stents in a single-stage process. A model drug delivery system consisting of a polymer matrix (arborescent polyisobutylene-polystyrene, or arbIBS) and either dexamethasone or sirolimus was studied by various characterization techniques. Modification of ElectroNanospray process parameters resulted in surface coatings with rich morphologies that are revealed by SEM, Atomic Force Microscopy (AFM) and Confocal Raman Microscopy were employed to monitor the drug release process in situ, through which the mechanism of the drug-eluting process may be proposed. A Confocal Raman microscope fitted with underwater objective was used to image arbIBS∕drug films incubated in phosphate-buffered saline over $12h$ and at various film depths. Drug migrated from more concentrated areas into the surrounding polymer and toward the surface, beginning as early as $5min$ after placing the sample in buffer and continuing throughout the $12h$ period. High drug levels remained in the more concentrated areas at the end of incubation, suggesting the potential for prolonged release. SEM and AFM images taken from samples post incubation showed the appearance of nanoscale pores $∼100nm$ in diameter in areas corresponding in size and distribution to the Confocal Raman planar image areas of increased drug concentration. Confocal Raman microscopy offers a powerful new technique for demonstrating real-time drug release from therapeutic medical device coatings.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027537-027537-1. doi:10.1115/1.2927436.
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Our laboratory has previously developed an injectable hydrogel blend consisting of agarose and methylcellulose that solidifies at physiological temperatures. This study examined the feasibility of loading a chemical species into the hydrogel blend for controlled release. Free radical formation and excessive inflammation following initial central nervous system (CNS) trauma contribute to secondary injury. Therefore, the anti-oxidant glutathione and the anti-inflammatory cytokine interleukin-10 (IL-10) were loaded into the hydrogel blend for the purposes of neutralizing free radicals generated and inhibiting excessive inflammation following CNS injury, respectively. Using Ellman’s reagent, glutathione release from the hydrogel was monitored, and data from these experiments reveal that the agarose-methylcellulose hydrogel blend delivers glutathione for up to five days in vitro. Similar experiments were performed on IL-10 release, which was released for up to four days. Recent experiments have focused on implementing the glutathione-containing hydrogel in a neuronal culture model that contains elevated levels of free radical. In addition, other experiments have focused on implementing the IL-10-containing hydrogel in a monocyte culture model and observing the effects of tissue necrosis factor alpha $(TNF‐α)$ production. Based on these preliminary findings, hydrogel blends consisting of agarose and methylcellulose loaded with glutathione and∕or IL-10 could potentially spare uninjured neurons from secondary injury. Future experiments will utilize a rat spinal cord injury model to further evaluate the efficacy of the hydrogel system. In addition to its use as an injury intervention, the hydrogel system also has the potential for use as a coating in implantable devices, especially in the CNS.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027538-027538-1. doi:10.1115/1.2932336.
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Hepatities C Virus (HCV) is a significant health problem worldwide due to the lack of effective vaccines. HCV plasmid DNA (pDNA) vaccine represents a promising means to induce a Th1-biased cell-mediated response which tends to be associated with HCV clearance. However, the immune responses induced by naked pDNA vaccine in large animals as well as in humans are usually too weak to show sufficient protection against new infections. Therefore, it is interesting to look for new ways to deliver HCV pDNA vaccine. In this research, carbon nanotube (CNT) is used as a carrier to deliver the pDNA vaccine of HCV to induce high immune responses, because CNT has some excellent properties such as high strength and good biocompatibility. One of the key approaches to make this idea work is to treat CNT so that it can bind with HCV pDNA with good stability. An approach called 1, 3-dipolar cycloaddition of azomethine ylides was modified. We analyzed the complex of f-CNTs combined with pDNA vaccines expressing HCV E2 protein by using Enzyme-linked immunospot (ELISPOT) or Enzyme-linked immunosorbent assay (ELISA) assay in vitro. The result showed that the CNT approach can induce stronger protective immune responses than the needle delivery of naked pDNA vaccine. We have also found an optimal way to treat CNT in light of the highest immune response in the same testing environment. The success of this research will warrant testing HCV vaccine in large animal models and human clinical trials.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027539-027539-1. doi:10.1115/1.2932344.
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Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027540-027540-1. doi:10.1115/1.2932349.
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Drug targeting systems are important research areas for many diseases treatments (e.g., cancer, nerve damage, heart and artery, diabetic, eye and other medical treatments). Currently, magnetic field, electric field, ultrasound, temperature, UV light and∕or mechanical force systems are considered more for research and development. Magnetic targeted drug delivery system is usually preferred because targeted systems improve the therapeutic index of drug molecules by minimizing the toxic side effects on healthy cells and tissues. In this study, magnetic nanoparticles $(∼10nm)$ were prepared by a chemical coprecipitation of ferric and ferrous chloride salts in the presence of a strong base (ammonium hydroxide) and used for a drug delivery purposes. An oil-in-oil emulsion∕solvent evaporation technique was chosen for the synthesis of nanocomposite spheres. Percentages of magnetic nanoparticles (%5, %10, %20 and%30) and poly(D,L-lactide-co-glycolide) were combined together to produce nanocomposite particles with diameters of $500nmto1.2micronmeter$. The effect of particle concentrations on nanocomposite particle size and distribution and morphology were investigated by using scanning electron microscopy (SEM) and laser light scattering (LLS). Additionally, external magnetic fields with various magnet distance, magnetic field, pump speed and solid contents were applied to the nanocomposite particles in a liquid media to find out the effect of variables for the targeting of drug carrying nanocomposite spheres.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027541-027541-1. doi:10.1115/1.2932424.
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Ferrofluids are composed of nanoscale magnetic nanoparticles (iron, cobalt, nickel, or their oxides) and strongly polarized in the presence of magnetic field. After coating the surface of these nanoscale particles $(∼10nm)$ by surfactant molecules (e.g., oleic acid, tetramethylammonium hydroxide, citric acid, etc.), they become fully stable and do not aggregate or segregate under the strong magnetic field. Ferrofluids are used for various applications, including medical (cancer detection ∕ curing, pharmaceutical, MRI), ferrofludic seal around the spinning drive shafts, liquid coolant (megaphones and loudspeakers), friction reducer ∕ shock absorber, earthquake, as well as defense, aerospace, grain size measurement and heat transfer. Ferrofluids are produced at extreme high or low pH values in order to prevent agglomeration of the nanoparticles caused by van der Waals and magnetic forces. This limits the application of ferrofluid for various fields because of the oxidation, corrosion as well as harmful effect to body. In this study, magnetite (Fe3O4) nanoparticles $(∼10nm)$ were produced by coprecipitation of iron (II) and iron (III) chloride salts in the presence of ammonium hydroxide, and stabilized using first citric acid at $100°C$ and a fatty acid at room temperature. Measured pH value of the ferrofluid was 7.0. As is known, magnetite nanoparticles that have excellent magnetic saturation $(∼78emu∕g)$ are desirable for those applications due to the strong ferromagnetic behavior, less sensitivity to oxidation and relatively low toxicity compared to many other magnetic materials (e.g., iron, nickel and cobalt).

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027542-027542-1. doi:10.1115/1.2932429.
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A calibration phantom that can be used to measure the temporal resolution of a CT scanner was designed utilizing a deterministic design process. The system was first defined in terms of a set of functional requirements based on parameters of the imaging modality. It was necessary to generate multiple time-varying signals visible to the scanner, each with a pre-determined temporal frequency. Roll-off in the scanner’s ability to resolve the modulation of certain signals would be used to determine the scanner’s temporal resolution. Based on size limitations imposed by the scanning environment, the phantom utilizes multiple planetary gear assemblies, driven by a common shaft, to achieve a wide range of rotational velocities. Results obtained with an alpha prototype agreed with the theory. It was determined that further development of the phantom was necessary to increase the sensitivity of the measurement. The latest prototype phantom has been used to measure the temporal resolution of two different scanners and it was shown that temporal resolution of each is different from the gantry rotation time.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027543-027543-1. doi:10.1115/1.2932434.
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Breast biopsy guided by imaging techniques is widely used to evaluate suspicious masses within the breast. Current procedure allows the physician to determine location and extent of a tumor in the patient breast before inserting the needle. There are several problems with this procedure: Complex interaction dynamics between needle and breast tissue will likely displace the tumor from its original position necessitating multiple insertions, causing surgeons’ fatigue, patient’s discomfort, and compromising integrity of the tissue specimen. We present a new concept for real-time manipulation of a tumor using a robotic system that monitors the image of the tumor to generate appropriate external force to position the tumor at a desired location. The objective is to demonstrate that it is possible to manipulate a tumor in real-time by applying controlled external force in an automated way such that the tumor does not deviate from the path of the needle. We have demonstrated efficacy of this approach on breast phantoms. The robotic system consists of an ultrasound probe for image acquisition, a guiding mechanism for automatic probe orientation, image processing algorithm for extracting tumor position and PID (proportional-integral-derivative) controlled actuators for tumor manipulation. We have successfully tested this system for accessing mobile lesions during multiple needle insertion trials. This approach has the potential to reduce the number of attempts a surgeon makes to capture the desired tissue specimen, minimize tissue damage, improve speed of biopsy, and reduce patient discomfort.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027544-027544-1. doi:10.1115/1.2932436.
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Objective: A measurement of rotational stiffness of the human eye is necessary, without exerting forces to the eye. Background: Strabismus is a disorder in which the visual axes of the eyes are misaligned. In strabismus surgery, the muscles that drive the eye are altered to compensate for the deviating angle of the eye. Unfortunately, between 20% and 50% of these operations need resurgery. A sensitivity analysis has suggested that one cause for an erroneous outcome of surgery is due to interindividual differences in rotational stiffness induced by tissue surrounding the eye. Methods and Results: A measurement device comprising a moment transferring linkage mechanism was developed. A moment is transferred to the eye without imposing a stationary point of rotation. The mechanism is attached to the eye and has three degrees of freedom. The eye is free to rotate under the applied moment. The applied moment and the resulting angle are measured to calculate the rotational stiffness of the eye. Parasitic forces are minimized by keeping friction, inertia and stiffness in the mechanism to a minimum. In addition, the three degrees of freedom of the mechanism are statically balanced. Conclusion: Preliminary tests have shown the feasibility of the measurement in a sterile environment in people that are in horizontal position.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027545-027545-1. doi:10.1115/1.2932444.
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A typical operation in otolaryngology takes place under the microscope. The surgeon works with a large set of very delicate tools, which are managed by a scrub nurse∕tech. In practice, the surgeon is intimately familiar with all instruments, which can number into hundreds but the nurse might not be. This situation can lead to miscommunication and longer operations. Any delay is a costly proposition. Typical costs during procedures can be \$250 per $15minute$ interval and every minute counts. Scrub nurse responsibilities include organization of instruments and their sterilization. During operation the surgeon requests an instrument, the technician must be able to identify it from a list of hundreds and place it correctly in the surgeon’s hand. The instruments might be microscopically different and look very similar. Each instrument is several hundred dollars and difficult to replace or repair. This study looks at the steps needed to automate the activities of a scrub nurse. First step towards this goal is the study of haptic and spoken language interfaces. The robot must know when to pick up a new instrument and when to release it. Next the robot must be able to plan out a stable and collision free motion and grasping movement. To enable all of this vision based localization of surgeon’s hands, instrument palette and any obstacle movement is necessary.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027546-027546-1. doi:10.1115/1.2932446.
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Objective: To develop a clinically feasible apparatus for measuring and marking patient’s gravity line position on spinal x-ray images. Background: Spinal balance of patients with deformity or instability is an important clinical parameter for patient diagnosis, surgery planning and treatment outcome evaluation. Traditional assessment of spinal balance is performed on full spine x-ray images using C7 plumb line relative to central sacral line in the coronal plane or posterior superior corner of S1 in the sagittal plane. Researchers have developed measurement techniques using a force plate synchronized with x-ray equipment and offline x-ray image processing. The complexity of these techniques limits their clinical applications. In this study, we present a new system to mark gravity line directly on an x-ray image. Methods: The system consists of a force plate, a signal conditioner and processor, a motion controller and a motor assembly that moves a radio-opaque marker. The processor calculates the location of gravity line and marker position, and transmits motion commands to the motion controller, which drives a motor assembly and moves the marker to appropriate positions. The acquired x-ray image has a mark indicating the instantaneous gravity line position. Evaluation: A prototype was installed in the radiology department. More than 200 patients were instructed to stand on the force plate. Exposure was performed as in routine x-ray imaging. The system does not affect routine x-ray workflow and provides valuable information for spine surgeons.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027547-027547-1. doi:10.1115/1.2932448.
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Objectives: The purpose of this study is to establish pressure, distension and other parameters involved that produce tissue injury during vigorous physical activities in women, so that superior methods and devices for diagnosing and treating urinary incontinence (UI) can be created. Background: A higher prevalence of daily UI in a female athlete population was found compared to that of a randomly selected and age matched sample population, but the mechanism of UI is not clearly understood. Methods: Mechanical tissue properties of affected organ structures were determined by using specimens from cadavers. A realistic geometric model of the female pelvis was developed from patients’ specific CT images. The finite element model was built by combining the mechanical tissue properties and the geometry of organs involved, and the finite element analysis (FEA) was then performed using ABAQUS 6.7 to simulate the biomechanical response of the female pelvis during physical activities. Results: Tissue specimens from 11 cadavers were tested which included specimens of the bladder, uterus, pelvic muscle, vagina and urethra. A finite element model was built with approximately 500,000 tetrahedral elements. The force level and resulting organ displacements in the female pelvis during physical activities were investigated successfully by using the FEA method. Discussion: The knowledge of force level and organ displacements during physical activities helps to understand the mechanisms of UI occurring during physical activities.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027548-027548-1. doi:10.1115/1.2932467.
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Tongue motion control results from a complicated series of interactions between multiple tongue muscles. Surgical intervention could possibly affect speech while at the same time producing positive benefits as reduction of retro-palatal collapse. The goal of the study was to represent the tongue as a quantifiable structured geometry specifying the various muscle regions as locally varying directional fields and use this model to determine the affect of altered muscle structure on tongue motion. A quantitative computer simulation of the human tongue was constructed around a finite element model. Muscle morphology was generated from segmentation of images from the Visible Human project and MRI images. The extrinsic and intrinsic muscles were represented as directional fields at a large number of elements. Muscle contraction was produced as a stress controlled region of a locally varying directional field. A Lagrangian formulation of an Ogden hyperelastic material was used for the passive isotropic components and muscle fibers were represented by strain energy and pressure functions. Validation of the model was obtained by comparing tongue displacement or strain patterns generated with various muscle activation patterns with those obtained from tracked MRI images. Quantifiable differences in the motion of the tongue caused by alteration of specific muscle morphology or activation patterns were used to identify regions of the tongue that may be affected by surgical implants and may help in the understanding of patterns of muscle activation in the study of speech and sleep apnea.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027549-027549-1. doi:10.1115/1.2932506.
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Advanced design of human artificial joints requires an in-depth understanding of the dynamic interaction between the very stiff bone replacement material and the softer viscoelastic cartilage replacement material. It must take into account both the large displacement gross motions as well as the small displacement elastic responses. A co-simulation methodology has been developed in BRG LifeMOD, connecting Adams∕Solver, a large displacement multi-body dynamics code, to Marc, a nonlinear finite element code. This efficient co-simulation approach allows for each code to handle that portion of the system for which it is most capable, while adding the potential to work across multiple CPUs and operating systems as desired. The method was applied using LifeMOD∕KneeSIM to simulate an artificial knee joint, containing cobalt chromium steel and ultra-high molecular weight polyethylene contact elements, undergoing a normal walking gait to predict kinematics, forces and the resulting wear patterns.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027550-027550-1. doi:10.1115/1.2932596.
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Temporomandibular joint disorder afflicts 10 million Americans, many of whom have osteoarthritis of the temporomandibular joint (TMJ). This condition can inflict severe pain and disrupt the lives of sufferers in many ways. Partial or total replacement of the temporomandibular joint is a last resort treatment option. Surgeons at Mayo Clinic believe a new hemijoint implant design coupled with unique surgical technique can improve joint kinematics and reduce pain. They are currently investigating a patent-pending implant design in a series of patient trials. The Division of Engineering at Mayo Clinic has developed a novel process for fabricating TMJ implants for this study. Computed Tomagraphy (CT) images of the surgical site are first converted into a 3D computer model of the mandibular fossa and condyle area. A fused deposition modeling process is used to create a plastic model of the anatomy, and the surgeons use that model to create a wax mold of the implant. The wax mold is laser scanned to create a 3D CAD model that can be machined with a standard four axis milling machine out of implant grade CoCrMo material. Because of the unique shape of the implant, the machining takes place in two phases, with the implant being refixtured between machining phases using a high strength industrial adhesive. Finally, the implant is polished, inspected, passivated and sterilized for surgery. This fabrication process has allowed Mayo Clinic surgeons to quickly and accurately test their unique implant design.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027551-027551-1. doi:10.1115/1.2934344.
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This study describes the design of a new wireless and passive sensor for in vivo strain monitoring at knee replacements. In a total knee arthroplasty, the proximal end of the tibia and the two femoral condyles are replaced with artificial components, and a high-density polyethylene insert is placed between the two components. The wear and tear of the polyethylene insert is considered a threat to the long-term survival of many knee implants. We have designed a wireless, implantable strain sensor to study the stresses experienced by the polyethylene insert. The sensor, which is embedded within the insert, is comprised of a magnetically soft material (sensing element) and a magnetically hard material (biasing element) separated by a deformable∕flexible layer. Under AC magnetic field, the sensing element generates a secondary, higher-order mode magnetic flux that can be measured with a magnetic inductive coil. Additional stresses to the sensor deform the flexible layer, altering the higher-order magnetic flux and thus allowing remote measurement of compressive forces. The advantages of this sensor are, its wireless and passive nature, small size, and cost effectiveness. The remote query nature of this sensor allows long-term implantation and real-time monitoring of human body. Experimental results have shown that the sensor responded linearly with applied stress and demonstrated good repeatability and stability. We believe that the outcome of this project will greatly improve public health by leading to a better implant design and providing a convenient way to detect wear and tear of knee implants.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027552-027552-1. doi:10.1115/1.2934345.
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The number of osteoporotic hip fractures is projected to increase two to three fold in the next $30years$. This will lead to increased mortality and nursing home placement with significant costs to our society. Although in clinical trials drug and hormone therapies have shown an important decrease in fracture risk there is a significant role of surgical implantation treatments to further reduce the risk in specific subpopulations. Strength testing was completed on four pairs of osteoporotic, two pairs of osteopenic, and two pairs of normal cadaver femurs. The fracturing was recorded with a video camera at 4000 frames per second. The specially designed test fixture was instrumented with three load cells to measure the femoral forces. Force and moment data were recorded simultaneously and correlated with the frames. The fracture force at the greater trochanter was used to characterize the strength of implanted∕nonimplanted osteoporotic femurs. All femurs began fracturing within about $60ms$ at a test speed of $100mm∕s$. During the first $20ms$, the relationship between force and displacement was nonlinear, but linear thereafter until the fracture occurs. The fracture events resolved completely within $10–20ms$. The average strength increase of the implanted femurs was 79% compared to the nonimplanted controls. The simultaneous acquisition of fracture images and load data is a powerful tool to understand and characterize numerically the femoral fracture. This methodology allows the researcher to define the best metrics to compare competing reinforcement materials, implant designs and surgical procedures.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027553-027553-1. doi:10.1115/1.2934347.
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Natural and synthetic hydrogels have attracted much attention for nerve regeneration. Previous studies have shown that electrical charge has significant effect on stimulation of neurite outgrowth. In this work, incorporation of a positively charged monomer into the photocrosslinkable oligo(polyethylene glycol) fumarate (OPF) hydrogel has been investigated. We have evaluated the effect of localized positive charge on neurite outgrowth in culture with an objective that positively charged hydrogels ultimately can be used for stimulating in vivo nerve regeneration. The effect of charged modification has been also studied on mechanical properties and swelling ratio of these hydrogels. Our data indicated that with increasing charge density hydrogels swelling ratio increased in water, however it remained constant in PBS. We also demonstrated that compressive modulus and tensile strength of the hydrogels improved with incorporation of electrical charge into the hydrogels. Biodegradation of modified hydrogels was investigated in a series of biomimetic solutions. OPF hydrogels appeared to be more susceptible to oxidative degradation as opposed to the hydrolytic degradation in enzymes and acidic solution, and the degradation rate was correlated to the PEG molecular weight and charge density of the hydrogels. To investigate the effect of charge modification on nerve cell attachment and differentiation, dissociated dorsal root ganglion (DRG) cells were plated onto the modified and unmodified hydrogels surfaces. DRG cells attached and extended their neurites more readily on the surface of positively charged hydrogels as opposed to the unmodified hydrogels.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027554-027554-1. doi:10.1115/1.2934352.
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Microfluidics can be used in a variety of medical applications. In this study, a microfluidic device is being developed to remove cryoprotective agents from cells post thaw $(1–150ml)$. Hematopoietic stem cells are typically cryopreserved with Dimethyl sulphoxide (DMSO), which is toxic upon infusion. Conventional methods of removing DMSO results in cells losses of 25–30%. The overall objective of this study is to characterize the influence of flow geometry on extraction of DMSO from a cell stream. For all the flow geometries analyzed, flow rate fraction, Peclet Number, and channel geometry had the greatest influence on extraction of DMSO from the cell stream. The range of flow rate fractions that can achieve the desired removal ranges between 0.10 and 0.30. Similarly, the range of Peclet numbers is 250–2500. Distinct differences in channel length could be observed between the different flow configurations studied. The flow rates and channel geometries studied suggest that clinical volumes of cell suspensions $(1–100ml)$ can be processed using a multi-stage microfluidic device in short periods of time $(<1hr)$.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027555-027555-1. doi:10.1115/1.2934478.
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Polymerase chain reaction (PCR) is the most commonly used molecular biology technique to amplify nucleic acid (DNA and RNA) in vitro. This technique is highly temperature sensitive and thermal management has an important role in PCR operation in reaching the required temperature set points at each step of the process (denaturing, annealing and elongation). In this work, an innovative microfluidic PCR thermal cycling device is designed to increase the heating∕cooling thermal cycling speed while maintaining a uniform temperature distribution throughout the substrate containing the aqueous nucleic acid sample. The device design is incorporating the jet impingement and micro-channel thermal management technologies utilizing a properly arranged configuration filled with a porous medium. Porous Inserts are attractive choices in heat transfer augmentation. They provide a very large surface area for a given volume which is a key parameter in heat transfer processes. Various effective parameters that are relevant in optimizing this flexible thermal cycler are investigated such as thermal cycler configuration, thickness of inlet and exit fluid channels, fluid flow rate and velocity, the porous matrix material and properties, and utilization of thermal grease. An optimized case is established based on the effects of the cited parameters on the temperature ramp, temperature distribution and the required power for circulating the fluid in the thermal cycler. The results indicate that the heating∕cooling temperature ramp (temperature change per heating∕cooling cycling time) of the proposed device is considerably higher $(150.82◻C∕s)$ than those in literature. In addition, the proposed PCR offers a very uniform temperature in the substrate while utilizing a low power.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027556-027556-1. doi:10.1115/1.2936116.
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Introduction: While catheters have proven effective in numerous cardiovascular procedures, their functionality and versatility can be greatly improved by incorporating active steering capabilities to the catheter tip. Shape memory alloy (SMA) actuation is ideally suited to this application, as these materials offer superior power density, energy density and biocompatibility. In this research, we investigate the transient behavior of an SMA-actuated active catheter to optimize its design and enable precise computer-controlled navigation. Methods: The active catheter prototype consists of a central beam actuated by a single SMA tendon, both enclosed by an outer Teflon sleeve. Joule heating is used to generate tip deflections, which are measured in real time using a dual-camera imaging system. SMA actuation is described using the Seelecke-Muller-Achenbach single-crystal model whose parameters are experimentally derived from stress-strain characteristics of the SMA tendon measured at different temperatures. These characteristics are used to optimize the design parameters of the catheter to maximize the bending response. The effects of outer sleeve thickness on the transient behavior of the catheter are also studied. Results: The catheter’s bending mechanics are described using a circular arc model, which is experimentally validated. Catheter actuation is found to be slower with increased sleeve thickness, as explained by heat transfer analysis. Dynamic simulation of the system model shows excellent correlation to experimental data for low frequency actuation.

Topics: Catheters
Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027557-027557-1. doi:10.1115/1.2936117.
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Abdominal aortic aneurysms (AAA), which claim the lives of 15,000 Americans annually, occur when the aortic walls are weakened to the point of bulging or rupture. Besides aorta replacements, AAA is commonly treated with an endovascular aortic repair procedure that reinforces the aorta by inserting a stent via a leg artery. While this procedure is effective, failure of the stent may increase the pressure of the AAA sac and cause the aorta wall to rupture. Therefore, monitoring of the pressure in the AAA sac is critical for post surgery assessment. We present the design and fabrication of a wireless passive pressure sensor for measuring the pressure of an AAA sac after stent placement. The sensor is made of a hermetically sealed chamber with two opposite membranes. A magnetically soft film is attached on one of the membranes, and a permanent magnetic film is placed on the other. As the membranes deflect due to changes in sac pressure, the separation distance between the magnetic elements changes. This in turn varies the magnetic harmonic fields of the magnetically soft film, allowing remote pressure monitoring with the use of a magnetic coil. Compared to Endosure, a wireless passive sensor developed by CardioMems that operates by remotely measuring the resonant frequency change of a capacitive-inductive circuit, the proposed device is thinner and can be miniaturized to a long and thin strip. Its signal is also not reduced by the electrically dense body since it is interrogated through magnetic fields.

Topics: Pressure , Sensors , Aneurysms
Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027558-027558-1. doi:10.1115/1.2936119.
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Poor positioning of needles and catheters may result in repeated attempts at correct placement, injury to adjacent structures or infusions into inappropriate spaces. Existing catheter insertion methods do not uniformly provide feedback of the tip location, nor prevent the needle from going beyond the target space. The purpose of this research was to develop a design tool to be used to create a new catheter insertion device. This device would advance a needle in firm tissue but automatically release it upon entrance into the desired space. The system studied consisted of a flexible filament (OD $∼0.9mm$) in compression passing through a tube (ID $1.22mm$) with both straight and curved sections. A mathematical model based on oil drilling methods was developed to predict the compressive force dissipated in the filament for any given tube geometry. A correction factor on one of the two terms in the model was necessary to achieve best results, but proved to be accurate for all $100+$ tests completed. With it, this model accounted for the following parameters: Angular displacement of tube bends, radial clearance, coefficient of friction, lengths, tube and filament radii, number of bends, moment of inertia, and modulus of elasticity. Implementation of this model should allow for a more safe and effective catheter insertion device.

Topics: Design , Catheters
Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027559-027559-1. doi:10.1115/1.2936214.
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We report a novel frequency multiplexed optical coherence tomography (FM-OCT) system that is capable of measuring depth-resolved tissue birefringence from a single record of a single detector. The FM-OCT system utilizes polarization-maintaining-fiber based components. The orthogonal channels of the polarization-maintaining-fiber and the cross-terms are frequency multiplexed. After recording the interference signal, a set of digital band-pass filters extract the polarization information. A rapid scanning optical delay line in the reference arm compensates for dispersion and allows a real-time display of tissue birefringence. The axial resolution provided by a superluminescent diode working at $855nm$ with $28nm$ bandwidth is $12μm$. The accuracy and sensitivity measurements suggest that the FM-OCT system is suitable for depth-resolved birefringence characterization of biological tissue.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027560-027560-1. doi:10.1115/1.2936204.
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Falls are the most common cause of injuries and the primary etiology for accidental deaths in the elderly population. The ability to quickly take a step is of paramount importance in maintaining balance. Previous research has shown a significant correlation between the time it takes to execute a step and the risk of experiencing a future fall. Consequently, a method that can quickly and accurately measure step behavior may be used to identify individuals with an increased risk of falling. The current project has built a prototype device that can be used in a clinical setting to easily and efficiently measure parameters of step execution. The step is performed under either single task (motor task only) or dual task conditions (motor task while performing an attention demanding cognitive task). Data can be stored in a relational data base and a clinical report that reflects fall risk can be printed. The current project is part of the Swedish PIEp initiative (Product Innovation Engineering Program), a federally and industry supported program that promotes innovation and technology commercialization in engineering education through development of innovation knowledge, experience and education including exchange of students and personnel between industry and academia on a national and international level.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027561-027561-1. doi:10.1115/1.2927432.
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For drug release or physiological sensing with advanced functionality, an implanted device must have an interface that permits passage of drugs or analytes while blocking immunoproteins and other physiological fouling agents. To this end, we have developed a composite membrane which integrates the nanoscale size selectivity of block-copolymers with the mechanical strength and order of micromachined silicon. A silicon wafer was coated with low-stress silicon nitride (LSN) and patterned with $20μm$ squares on the bottom side by photolithography. These squares were etched through the underlying silicon, using the LSN on the top side as an etch-stop. Poly(styrene)-poly(isoprene)-poly(lactide) (PS-PI-PLA) triblock terpolymer was spin-coated onto the top-side LSN surface and annealed under vacuum. The PLA domains self-assembled into cylinders perpendicular to the coating, nearly spanning it. The PLA was etched away, leaving $40nm$ pores in the polymer film. The device was subjected to hydrofluoric acid to remove the LSN capping the microscale pores and a final, brief oxygen plasma etch removed any PS capping the nanoscale pores. The resulting composite membrane consists of a $80nm$ thick PS layer with $40nm$ wide pores overlaying a $100μm$ thick silicon support with $20μm$ wide pores. Preliminary mechanical tests have demonstrated the membrane’s robustness. Such membranes should provide immuno-isolation without retarding small molecule transport and should integrate well with the burgeoning number of BioMEMS devices under development.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027562-027562-1. doi:10.1115/1.2932431.
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Due to the tendency of ovarian cancer to spread in small sections throughout the abdominal cavity, it is presently difficult to detect early stage cancer recurrence following the primary de-bulking of initial tumors. Because metastases may initially be isolated and too small to detect with conventional scanning techniques such as CT scan and MRI, direct laparoscopic examination of the peritoneal cavity is often conducted. At present, this must be performed in a full operating room, and with the patient under full anesthesia; as a result, such examinations are performed infrequently and at high costs. An implantable port has been designed which enables repeated access of a rigid tool such as a laparoscope to the abdominal cavity with only local anesthesia. The port consists of a tube and a suturing flange, inside of which is a tricuspid valve that prevents fluid backflow out of the peritoneal cavity, even at zero backpressure. The port is implanted through the abdominal wall and sutured to the fascia just below the skin at the time of the primary debulking. Then, when examination is necessary, a commercially available trocar can be inserted through the skin and fat under local anesthesia to interface with the port, thereby enabling all functionality of normal laparoscopic procedures with minimal impact to the patient. Thus, this device has the potential to enable rapid monitoring of metastases in an outpatient setting, and may also be used for drug delivery or biopsies.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027563-027563-1. doi:10.1115/1.2932427.
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Both external and implantable devices are becoming more sophisticated and are requiring more on-chip memory to store data from biological sensors. To deal with this complexity, chip designs are moving toward smaller process geometries, which provide added functionality, reduced size, or both, often along with a reduction in dynamic power. However, leakage power begins to increase significantly at the 130nm node if steps are not taken to mitigate the increased transistor leakage. Lower operating voltages and careful transistor design can offset some of this increase. These very changes, however, make it difficult to design a dense, stable low-power SRAM. Nonvolatile memories like FRAM (F-RAM) avoid these difficulties and save power by simply turning off the memory when not in use. This is particularly valuable since many medical devices have very low duty cycle. FRAM provides the added benefit of providing SRAM-like active power, unlike competing nonvolatile technologies. To meet the challenging power requirements of medical devices, a new ultra-low-power 130nm process has been developed. The new process includes a very-high-density, SER-resistant, nonvolatile FRAM and an ultra-low-leakage transistor, coupled with a library that is optimized for low-power operation. This paper compares the power, area and performance of competing process technologies for a typical implantable medical design and highlights the advantages that FRAM provides in low static power through a transparent power-down capability and in low SRAM-like active power.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027564-027564-1. doi:10.1115/1.2932718.
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Objective: To design an external fixator for femoral fracture reduction with improved angulation and adjustability, reduced bulk, and comparative stiffness. Background: The use of external fixator for femoral shaft fixators in children has been a device of choice. The use though satisfactory, the occurrences of wire∕pin tract infections has been widely reported. Moreover, The use of Ilizarov external fixator in adults has been limited due to its bulk. Hence there is a need for improvement on the current external fixators for femoral fractures. Methods: The finite element models of four-ring Ilizarov and hybrid two-ring fixators were developed. These designs were improved upon by incorporating a “modular sliding joint design,” and by reducing the bulk by reducing the number of rings and adding guide plates. Wire length optimization feature was also added in the design. Axial stiffness of the new design was compared with the hybrid design using finite element analysis (FEA). Results and Discussion: The new design has reduced bulk at the proximal region allowing its application in adults. The axial stiffness of the proposed design was found to be comparable with the two-ring hybrid design, as determined from FEA. Sliding joint design allows reduced inventory, quick assembly, and improved angulation over current designs. Wire length optimization may reduce the occurrences of wire tract infections.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027565-027565-1. doi:10.1115/1.2936207.
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Objective: Functional Electrical Stimulation (FES) triggered by manual switch provides brace-free ambulation to wheelchair dependent individuals with spinal cord injuries. An electromyogram (EMG)-based trigger can enhance the coordination between FES-assisted and volitional actions. This study evaluated the gait speed modulation and coordination of the actions of the EMG-triggered FES with the volitional movements during stand-to-walk transition after incomplete spinal cord injury. Methods: two incomplete spinal cord injured (iSCI) subjects (iSCI1: $24years$, C7 motor & C6 sensory; iSCI2: $34years$, T1 motor & C5 sensory) volunteered for this study. Four able-bodied volunteers provided the normative gait data. The Vicon WorkstationTM (Vicon Peak, USA) software acquired lower-body kinematics data using a seven camera motion capture system during stand-to-walk transition. The FES-assisted swing-phase in iSCI subjects was triggered with three command interfaces—manually triggered with a switch, triggered with EMG-based GED, triggered automatically at a user-selected rate. Results and Discussion: The Euclidean distance from origin of the perturbations of 18 joint angles and 18 joint velocities during stand-to-walk transition converged towards zero. It was found from the Mahalanobis distances between each pair of group means that the EMG-triggered FES-assisted iSCI gait was closest to the able-bodied normative gait clusters.

Commentary by Dr. Valentin Fuster
J. Med. Devices. 2008;2(2):027566-027566-1. doi:10.1115/1.2936183.
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Human thermoregulatory research is fraught with multifaceted physiological issues. A notable quandary is the fact that the human body has several different types of tissues, each with unique heat transfer/conductive properties. The primary goal of our research is to determine how to effectively and appropriately regulate human thermal physiology in the context of medical, occupational, and sporting fields. Of paramount importance is quantifying heat extraction/insertion from various body regions under different heat surplus/deficit situations imposed by environmental conditions and/or metabolic fluctuations, and understanding the associated mechanisms and their relationships. Our laboratory has conducted research involving the simulation of contradictory thermal regimes on the body surface to observe the dynamic process of simultaneous heat insertion and extraction. To achieve this, we have designed a tubing cooling/warming garment through which water circulates and controller (patent #7,089,995) that can provide the desired thermal stimuli in uniform/non-uniform and symmetrical/non- symmetrical patterns. We believe this methodology of divided surfaces for the application of concurrent cooling/warming regimes affords the greatest opportunity to quantify the maximum zonal capabilities for heat transfer. This paradigm allows for the regulation of heat flow in dynamic non-uniform conditions and is particularly suited for the comfort/support of a range of clinical populations (e.g., surgical, multiple sclerosis, burns/trauma, hyper/hypothermia). It is also applicable for the design of protective clothing for personnel in occupational settings (e.g., military, firefighting, space flyers), and for sporting apparel (i.e., a cooling garment/hood/blanket). Our laboratory has used the physiologically designed cooling/warming garment to evaluate individual thermoregulatory profiles elicited by conditions representative of extreme terrestrial and space thermal environments.

Commentary by Dr. Valentin Fuster