Review Article

Advances in Diagnostic Methods for Zika Virus Infection

[+] Author and Article Information
Carlos A. Herrada, Md. Alamgir Kabir, Rommel Altamirano

Department of Computer Engineering and
Electrical Engineering and Computer Science,
Florida Atlantic University,
Boca Raton, FL 33431;
Asghar-Lab, Micro and
Nanotechnology in Medicine,
College of Engineering and Computer Science,
Boca Raton, FL 33431

Waseem Asghar

Department of Computer Engineering and
Electrical Engineering and Computer Science,
Florida Atlantic University,
Boca Raton, FL 33431;
Asghar-Lab, Micro and
Nanotechnology in Medicine,
College of Engineering and Computer Science,
Boca Raton, FL 33431;
Department of Biological Sciences,
Florida Atlantic University,
Boca Raton, FL 33431
e-mail: wasghar@fau.edu

1Corresponding author.

Manuscript received March 13, 2018; final manuscript received July 31, 2018; published online November 5, 2018. Assoc. Editor: Yaling Liu.

J. Med. Devices 12(4), 040802 (Nov 05, 2018) (11 pages) Paper No: MED-18-1054; doi: 10.1115/1.4041086 History: Received March 13, 2018; Revised July 31, 2018

The Zika virus (ZIKV) is one of the most infamous mosquito-borne flavivirus on recent memory due to its potential association with high mortality rates in fetuses, microcephaly and neurological impairments in neonates, and autoimmune disorders. The severity of the disease, as well as its fast spread over several continents, has urged the World Health Organization (WHO) to declare ZIKV a global health concern. In consequence, over the past couple of years, there has been a significant effort for the development of ZIKV diagnostic methods, vaccine development, and prevention strategies. This review focuses on the most recent aspects of ZIKV research which includes the outbreaks, genome structure, multiplication and propagation of the virus, and more importantly, the development of serological and molecular detection tools such as Zika IgM antibody capture enzyme-linked immunosorbent assay (Zika MAC-ELISA), plaque reduction neutralization test (PRNT), reverse transcription quantitative real-time polymerase chain reaction (qRT-PCR), reverse transcription-loop mediated isothermal amplification (RT-LAMP), localized surface plasmon resonance (LSPR) biosensors, nucleic acid sequence-based amplification (NASBA), and recombinase polymerase amplification (RPA). Additionally, we discuss the limitations of currently available diagnostic methods, the potential of newly developed sensing technologies, and also provide insight into future areas of research.

Copyright © 2018 by ASME
Your Session has timed out. Please sign back in to continue.


ECDC, 2015, “ Rapid Risk Assessment: Zika Virus Epidemic in the Americas: Potential Association With Microcephaly and Guillain-Barré Syndrome,” European Centre for Disease Prevention and Control, Stockholm, Sweden, accessed Mar. 6, 2018, http://ecdc.europa.eu/en/publications/Publications/zika-virus-americas-association-with-microcephaly-rapid-risk-assessment.pdf
U.S. CDC, 2018, “ Facts About Microcephaly,” Centers for Disease Control and Prevention, Atlanta, GA, accessed Feb. 24, 2018, https://www.cdc.gov/ncbddd/birthdefects/microcephaly.html
Panchaud, A. , Stojanov, M. , Ammerdorffer, A. , Vouga, M. , and Baud, D. , 2016, “ Emerging Role of Zika Virus in Adverse Fetal and Neonatal Outcomes,” Clin. Microbiol. Rev., 29(3), pp. 659–694. [CrossRef] [PubMed]
Tang, H. , Hammack, C. , Ogden, S. C. , Wen, Z. , Qian, X. , Li, Y. , Yao, B. , Shin, J. , Zhang, F. , Lee, E. M. , Christian, K. M. , Didier, R. A. , Jin, P. , Song, H. , and Ming, G. L. , 2016, “ Zika Virus Infects Human Cortical Neural Progenitors and Attenuates Their Growth,” Cell Stem Cell, 18(5), pp. 587–590. [CrossRef] [PubMed]
Faria, N. R. , Azevedo, R. , Kraemer, M. U. G. , Souza, R. , Cunha, M. S. , Hill, S. C. , Theze, J. , Bonsall, M. B. , Bowden, T. A. , Rissanen, I. , Rocco, I. M. , Nogueira, J. S. , Maeda, A. Y. , Vasami, F. , Macedo, F. L. L. , Suzuki, A. , Rodrigues, S. G. , Cruz, A. C. R. , Nunes, B. T. , Medeiros, D. B. A. , Rodrigues, D. S. G. , Queiroz, A. L. N. , da Silva, E. V. P. , Henriques, D. F. , da Rosa, E. S. T. , de Oliveira, C. S. , Martins, L. C. , Vasconcelos, H. B. , Casseb, L. M. N. , Simith, D. B. , Messina, J. P. , Abade, L. , Lourenco, J. , Alcantara, L. C. J. , de Lima, M. M. , Giovanetti, M. , Hay, S. I. , de Oliveira, R. S. , Lemos, P. D. S. , de Oliveira, L. F. , de Lima, C. P. S. , da Silva, S. P. , de Vasconcelos, J. M. , Franco, L. , Cardoso, J. F. , Vianez-Junior, J. , Mir, D. , Bello, G. , Delatorre, E. , Khan, K. , Creatore, M. , Coelho, G. E. , de Oliveira, W. K. , Tesh, R. , Pybus, O. G. , Nunes, M. R. T. , and Vasconcelos, P. F. C. , 2016, “ Zika Virus in the Americas: Early Epidemiological and Genetic Findings,” Science, 352(6283), pp. 345–349. [CrossRef] [PubMed]
Brasil, P. , Pereira , J. P., Jr., Moreira , M. E. , Ribeiro Nogueira, R. M. , Damasceno, L. , Wakimoto, M. , Rabello, R. S. , Valderramos, S. G. , Halai, U. A. , Salles, T. S. , Zin, A. A. , Horovitz, D. , Daltro, P. , Boechat, M. , Raja Gabaglia, C. , Carvalho de Sequeira, P. , Pilotto, J. H. , Medialdea-Carrera, R. , Cotrim da Cunha, D. , Abreu de Carvalho, L. M. , Pone, M. , Machado Siqueira, A. , Calvet, G. A. , Rodrigues Baiao, A. E. , Neves, E. S. , Nassar de Carvalho, P. R. , Hasue, R. H. , Marschik, P. B. , Einspieler, C. , Janzen, C. , Cherry, J. D. , Bispo de Filippis, A. M. , and Nielsen-Saines, K. , 2016, “ Zika Virus Infection in Pregnant Women in Rio De Janeiro,” N. Engl. J. Med., 375(24), pp. 2321–2334. [CrossRef] [PubMed]
Pacheco, O. , Beltrán, M. , Nelson, C. A. , Valencia, D. , Tolosa, N. , Farr, S. L. , Padilla, A. V. , Tong, V. T. , Cuevas, E. L. , Espinosa-Bode, A. , Pardo, L. , Rico, A. , Reefhuis, J. , González, M. , Mercado, M. , Chaparro, P. , Martínez Duran, M. , Rao, C. Y. , Muñoz, M. M. , Powers, A. M. , Cuéllar, C. , Helfand, R. , Huguett, C. , Jamieson, D. J. , Honein, M. A. , O. , and Martínez, M. L. , “ Zika Virus Disease in Colombia—Preliminary Report,” New Engl. J. Med. (epub).
Musso, D. , and Gubler, D. J. , 2016, “ Zika Virus,” Clin. Microbiol. Rev., 29(3), pp. 487–524. [CrossRef] [PubMed]
Rodriguez, Y. , Rojas, M. , Pacheco, Y. , Acosta-Ampudia, Y. , Ramirez-Santana, C. , Monsalve, D. M. , Gershwin, M. E. , and Anaya, J. M. , 2018, “ Guillain-Barre Syndrome, Transverse Myelitis and Infectious Diseases,” Cell Mol. Immunol., 15, pp. 547–562.
Kuwabara, S. , 2004, “ Guillain-Barre Syndrome: Epidemiology, Pathophysiology and Management,” Drugs, 64(6), pp. 597–610. [CrossRef] [PubMed]
Araujo, A. Q. , Silva, M. T. , and Araujo, A. P. , 2016, “ Zika Virus-Associated Neurological Disorders: A Review,” Brain, 139(8), pp. 2122–2130. [CrossRef] [PubMed]
WHO, 2016, “ WHO Statement on the First Meeting of the International Health Regulations (2005) (IHR 2005) Emergency Committee on Zika Virus and Observed Increase in Neurological Disorders and Neonatal Malformations,” World Health Organization, Geneva, Switzerland, accessed Aug. 21, 2018, http://www.who.int/mediacentre/news/statements/2016/1st-emergency-committee-zika/en/
Martinez-Pulgarin, D. F. , Acevedo-Mendoza, W. F. , Cardona-Ospina, J. A. , Rodriguez-Morales, A. J. , and Paniz-Mondolfi, A. E. , 2016, “ A Bibliometric Analysis of Global Zika Research,” Travel Med. Infect. Dis., 14(1), pp. 55–57. [CrossRef] [PubMed]
Posen, H. J. , Keystone, J. S. , Gubbay, J. B. , and Morris, S. K. , 2016, “ Epidemiology of Zika Virus, 1947-2007,” BMJ Glob. Health, 1(2), p. e000087. [CrossRef] [PubMed]
Wikan, N. , and Smith, D. R. , 2016, “ Zika Virus: History of a Newly Emerging Arbovirus,” Lancet Infect. Dis., 16(7), pp. e119–e126. [CrossRef] [PubMed]
Duffy, M. R. , Chen, T. H. , Hancock, W. T. , Powers, A. M. , Kool, J. L. , Lanciotti, R. S. , Pretrick, M. , Marfel, M. , Holzbauer, S. , Dubray, C. , Guillaumot, L. , Griggs, A. , Bel, M. , Lambert, A. J. , Laven, J. , Kosoy, O. , Panella, A. , Biggerstaff, B. J. , Fischer, M. , and Hayes, E. B. , 2009, “ Zika Virus Outbreak on Yap Island, Federated States of Micronesia,” N. Engl. J. Med., 360(24), pp. 2536–2543. [CrossRef] [PubMed]
Musso, D. , Nilles, E. J. , and Cao-Lormeau, V. M. , 2014, “ Rapid Spread of Emerging Zika Virus in the Pacific Area,” Clin. Microbiol. Infect., 20(10), pp. O595–596. [CrossRef] [PubMed]
Baud, D. , Gubler, D. J. , Schaub, B. , Lanteri, M. C. , and Musso, D. , 2017, “ An Update on Zika Virus Infection,” Lancet, 390(10107), pp. 2099–2109. [CrossRef] [PubMed]
Brito, C. A. , and Cordeiro, M. T. , 2016, “ One Year After the Zika Virus Outbreak in Brazil: From Hypotheses to Evidence,” Rev. Soc. Bras. Med. Trop., 49(5), pp. 537–543. [CrossRef] [PubMed]
Chang, C. , Ortiz, K. , Ansari, A. , and Gershwin, M. E. , 2016, “ The Zika Outbreak of the 21st Century,” J. Autoimmun., 68, pp. 1–13. [CrossRef] [PubMed]
Dasti, J. I. , 2016, “ Zika Virus Infections: An Overview of Current Scenario,” Asian Pac. J. Trop. Med., 9(7), pp. 621–625. [CrossRef] [PubMed]
Kindhauser, M. K. , Allen, T. , Frank, V. , Santhana, R. S. , and Dye, C. , 2016, “ Zika: The Origin and Spread of a Mosquito-Borne Virus,” Bull. World Health Organ., 94(9), pp. 675–686C. [CrossRef] [PubMed]
Besnard, M. , Lastère, S. , Teissier, A. , Cao-Lormeau, V. M. , and Musso, D. , 2014, “ Evidence of Perinatal Transmission of Zika Virus, French Polynesia, December 2013 and February 2014,” Eurosurveillance, 19(13), p. 20751. [CrossRef] [PubMed]
Patino-Barbosa, A. M. , Medina, I. , Gil-Restrepo, A. F. , and Rodriguez-Morales, A. J. , 2015, “ Zika: Another Sexually Transmitted Infection?,” Sex Transm. Infect., 91(5), p. 359. [CrossRef] [PubMed]
Sharma, A. , and Lal, S. K. , 2017, “ Zika Virus: Transmission, Detection, Control, and Prevention,” Front. Microbiol., 8, p. 110. [PubMed]
Besnard, M. , Lastere, S. , Teissier, A. , Cao-Lormeau, V. , and Musso, D. , 2014, “ Evidence of Perinatal Transmission of Zika Virus, French,” Euro Surveill., 19(13), p. 20751. https://www.eurosurveillance.org/content/10.2807/1560-7917.ES2014.19.13.20751
Perera-Lecoin, M. , Meertens, L. , Carnec, X. , and Amara, A. , 2013, “ Flavivirus Entry Receptors: An Update,” Viruses, 6(1), pp. 69–88. [CrossRef] [PubMed]
Saiz, J. C. , Vazquez-Calvo, A. , Blazquez, A. B. , Merino-Ramos, T. , Escribano-Romero, E. , and Martin-Acebes, M. A. , 2016, “ Zika Virus: The Latest Newcomer,” Front. Microbiol., 7, p. 496. [PubMed]
Heinz, F. X. , and Stiasny, K. , 2017, “ The Antigenic Structure of Zika Virus and Its Relation to Other Flaviviruses: Implications for Infection and Immunoprophylaxis,” Microbiol. Mol. Biol. Rev., 81(1), p. e00055-16.
Okafor II , Ezugwu, F. , and Ekwochi, U. , 2016 “ Zika Virus: The Emerging Global Health Challenge,” Diversity and Equality in Health and Care, 13(6), pp. 394–401. http://diversityhealthcare.imedpub.com/zika-virus-the-emerging-global-health-challenge.php?aid=17625
Lanciotti, R. S. , Kosoy, O. L. , Laven, J. J. , Velez, J. O. , Lambert, A. J. , Johnson, A. J. , Stanfield, S. M. , and Duffy, M. R. , 2008, “ Genetic and Serologic Properties of Zika Virus Associated With an Epidemic, Yap State, Micronesia, 2007,” Emerg. Infect. Dis., 14(8), pp. 1232–1239. [CrossRef] [PubMed]
Musso, D. , Rouault, E. , Teissier, A. , Lanteri, M. C. , Zisou, K. , Broult, J. , Grange, E. , Nhan, T. X. , and Aubry, M. , 2017, “ Molecular Detection of Zika Virus in Blood and RNA Load Determination During the French Polynesian Outbreak,” J. Med. Virol., 89(9), pp. 1505–1510. [CrossRef] [PubMed]
Bonaldo, M. C. , Ribeiro, I. P. , Lima, N. S. , dos Santos, A. A. C. , Menezes, L. S. R. , da Cruz, S. O. D. , de Mello, I. S. , Furtado, N. D. , de Moura, E. E. , Damasceno, L. , da Silva, K. A. B. , de Castro, M. G. , Gerber, A. L. , de Almeida, L. G. P. , Lourenço-de-Oliveira, R. , Vasconcelos, A. T. R. , and Brasil, P. , 2016, “ Isolation of Infective Zika Virus From Urine and Saliva of Patients in Brazil,” PLOS Neglected Trop. Dis., 10(6), p. e0004816. [CrossRef]
Yang, L. , Wang, K. , Li, H. , Denstedt, J. D. , and Cadieux, P. A. , 2014, “ The Influence of Urinary pH on Antibiotic Efficacy Against Bacterial Uropathogens,” Urology, 84(3), p. e731737. [CrossRef]
Baliga, S. , Muglikar, S. , and Kale, R. , 2013, “ Salivary pH: A Diagnostic Biomarker,” J. Indian Soc. Periodontol., 17(4), pp. 461–465. [CrossRef] [PubMed]
Stiasny, K. , and Heinz, F. X. , 2006, “ Flavivirus Membrane Fusion,” J. Gen. Virol., 87(Pt. 10), pp. 2755–2766. [CrossRef] [PubMed]
Calvet, G. A. , Santos, F. B. , and Sequeira, P. C. , 2016, “ Zika Virus Infection: Epidemiology, Clinical Manifestations and Diagnosis,” Curr. Opin. Infect. Dis., 29(5), pp. 459–466. [CrossRef] [PubMed]
Shan, C. , Xie, X. , Ren, P. , Loeffelholz, M. J. , Yang, Y. , Furuya, A. , Dupuis , A. P., II, Kramer , L. D. , Wong, S. J. , and Shi, P. Y. , 2017, “ A Rapid Zika Diagnostic Assay to Measure Neutralizing Antibodies in Patients,” EBioMedicine, 17, pp. 157–162. [CrossRef] [PubMed]
Hologic, 2018, “ Aptima Zika Virus Assay,” Hologic, Marlborough, MA, accessed Mar. 16, 2018, https://www.hologic.com/sites/default/files/package-insert/AW-15406_003_01.pdf
Nanobiosym Diagnostics, 2017, “ Gene-RADAR Zika Virus Test Instructions for Use,” Nanobiosym Diagnostics, Cambridge, MA, accessed Mar. 17, 2018, https://www.fda.gov/downloads/MedicalDevices/Safety/EmergencySituations/UCM547674.pdf
Altona Diagnostics, 2017, “ RealStar® Zika Virus RT-PCR Kit U.S. Instructions for Use,” Altona Diagnostics, Hamburg, Germany, Mar. 17, 2018, https://www.fda.gov/downloads/MedicalDevices/Safety/EmergencySituations/UCM501027.pdf
Abbott, 2016, “ Real Time Zika Instructions for Use,” Abbott, Chicago, IL, accessed Mar. 17, 2018, https://www.fda.gov/downloads/MedicalDevices/Safety/EmergencySituations/UCM530358.pdf
Vela Diagnostics, 2016, “ Sentosa® SA ZIKV RT-PCR Test Instructions for Use,” Vela Diagnostics, Kendall, Singapore, accessed Mar. 17, 2018, https://www.fda.gov/downloads/MedicalDevices/Safety/EmergencySituations/UCM522374.pdf
Thermo Fisher Scientific, 2017, “ TaqPath Zika Virus Kit Instructions for Use,” Thermo Fisher Scientific, Foster City, CA, accessed Mar. 17, 2018, https://www.fda.gov/downloads/MedicalDevices/Safety/EmergencySituations/UCM569943.pdf
CDC, 2017, “ Trioplex Real-Time RT-PCR Assay,” Center for Disease Control & Prevention (CDC), Atlanta, GA, accessed Mar. 17, 2018, https://www.fda.gov/downloads/MedicalDevices/Safety/EmergencySituations/UCM491592.pdf
Siemens, 2016, “ VERSANT Zika RNA 1.0 Assay Kit,” Siemens, Tarrytown, NY, accessed Mar. 17, 2018, https://www.fda.gov/downloads/MedicalDevices/Safety/EmergencySituations/UCM514170.pdf
Luminex, 2017, “ xMAP® MultiFLEX™ Zika RNA Assay Instructions for Use,” Luminex, Austin, TX, acessed Mar. 17, 2018, https://www.fda.gov/downloads/MedicalDevices/Safety/EmergencySituations/UCM515137.pdf
ARUP Laboratories, 2016, “ Zika Virus Detection by RT-PCR Test Instructions for Use,” ARUP Laboratories, Salt Lake City, UT, accessed Mar. 17, 2018, https://www.fda.gov/downloads/MedicalDevices/Safety/EmergencySituations/UCM523094.pdf
Viracor Eurofins, 2017, “ Zika Virus Real-Time RT-PCR Test Instructions for Use,” Viracor Eurofins, Lees Summit, MO, accessed Mar. 19, 2018, https://www.fda.gov/downloads/MedicalDevices/Safety/EmergencySituations/UCM512035.pdf
Quest Diagnostics, 2017, “ Zika Virus RNA Qualitative Real-Time RT-PCR Instructions for Use,” Quest Diagnostics, Cypress, CA, accessed Mar. 19, 2018, https://www.fda.gov/downloads/MedicalDevices/Safety/EmergencySituations/UCM498278.pdf
ELITechGroup, 2016, “ Zika ELITe MGB Kit Instructions for Use,” ELITechGroup, Bothell, WA, accessed Mar. 19, 2018, https://www.fda.gov/downloads/MedicalDevices/Safety/EmergencySituations/UCM532553.pdf
Siemens Diagnostics, 2017, “ ADVIA Centaur Zika Test Instructions for Use,” Siemens Diagnostics, Tarrytown, NY, accessed Mar. 19, 2018, https://www.fda.gov/downloads/MedicalDevices/Safety/EmergencySituations/UCM576528.pdf
Chembio Diagnostic, 2018, “ DPP Zika IgM Assay System Instructions for Use,” Chembio Diagnostic, Medford, NY, accessed Mar. 19, 2018, https://www.fda.gov/downloads/MedicalDevices/Safety/EmergencySituations/UCM577856.pdf
DiaSorin, 2017, “ LIAISON XL Zika Capture IgM Assay Instructions for Use,” DiaSorin, Stillwater, MN, accessed Mar. 20, 2018, https://www.fda.gov/downloads/MedicalDevices/Safety/EmergencySituations/UCM551082.pdf
CDC, 2017, “ Zika MAC-ELISA Instructions for Use,” Center for Disease Control & Prevention (CDC), Atlanta, GA, accessed Mar. 20, 2018, https://www.fda.gov/downloads/MedicalDevices/Safety/EmergencySituations/UCM488044.pdf
InBios International, 2017, “ ZIKV Detect IgM Capture ELISA Instructions for Use,” InBios International, Seattle, WA, accessed Mar. 20, 2018, https://www.fda.gov/downloads/MedicalDevices/Safety/EmergencySituations/UCM517147.pdf
U.S. CDC, 2017, “ Types of Zika Virus Test,” U.S Centers for Disease Control & Prevention (CDC), Atlanta, GA, accessed Mar. 21, 2018, https://www.cdc.gov/zika/laboratories/types-of-tests.html
U.S. CDC, 2017, “ Trioplex Real-Time RT-PCR Assay,” U.S. Centers for Disease Control & Prevention (CDC), Atlanta, GA, Apr. 2, 2018, http://www.cdc.gov/zika/pdfs/trioplex-real-time-rt-pcr-assay-instructions-for-use.pdf
Coarsey, C. T. , Esiobu, N. , Narayanan, R. , Pavlovic, M. , Shafiee, H. , and Asghar, W. , 2017, “ Strategies in Ebola Virus Disease (EVD) Diagnostics at the Point of Care,” Crit. Rev. Microbiol., 43(6), pp. 779–798. [CrossRef] [PubMed]
Safavieh, M. , Coarsey, C. , Esiobu, N. , Memic, A. , Vyas, J. M. , Shafiee, H. , and Asghar, W. , 2017, “ Advances in Candida Detection Platforms for Clinical and Point-of-Care Applications,” Crit. Rev. Biotechnol., 37(4), pp. 441–458. [CrossRef] [PubMed]
Charrel, R. N. , Leparc-Goffart, I. , Pas, S. , de Lamballerie, X. , Koopmans, M. , and Reusken, C. , 2016, “ Background Review for Diagnostic Test Development for Zika Virus Infection,” Bull World Health Organ., 94(8), pp. 574–584. [CrossRef] [PubMed]
U.S FDA, 2018, “ Zika Mac-ELISA Instructions for Use,” U.S Food and Drug Administration (FDA), Atlanta, GA, accessed Apr. 2, 2018, https://www.fda.gov/downloads/MedicalDevices/Safety/EmergencySituations/UCM488044.pdf
Priyamvada, L. , Quicke, K. M. , Hudson, W. H. , Onlamoon, N. , Sewatanon, J. , Edupuganti, S. , Pattanapanyasat, K. , Chokephaibulkit, K. , Mulligan, M. J. , Wilson, P. C. , Ahmed, R. , Suthar, M. S. , and Wrammert, J. , 2016, “ Human Antibody Responses After Dengue Virus Infection Are Highly Cross-Reactive to Zika Virus,” Proc. Natl. Acad. Sci. U. S. A., 113(28), pp. 7852–7857. [CrossRef] [PubMed]
Nicolini, A. M. , McCracken, K. E. , and Yoon, J. Y. , 2017, “ Future Developments in Biosensors for Field-Ready Zika Virus Diagnostics,” J. Biol. Eng,, 11, p. 7.
Lee, W. T. , Wong, S. J. , Kulas, K. E. , Dupuis , A. P., II , Payne, A. F. , Kramer, L. D. , Dean, A. B. , St George, K. , White, J. L. , Sommer, J. N. , Ledizet, M. , and Limberger, R. J. , 2018, “ Development of Zika Virus Serological Testing Strategies in New York State,” J. Clin. Microbiol., 56(3), p. JCM-01591.
Shan, C. , Ortiz, D. A. , Yang, Y. , Wong, S. J. , Kramer, L. D. , Shi, P.-Y. , Loeffelholz, M. J. , and Ren, P. , 2017, “ Evaluation of a Novel Reporter Virus Neutralization Test for Serological Diagnosis of Zika and Dengue Virus Infection,” J. Clin. Microbiol., 55(10), pp. 3028–3036. [CrossRef] [PubMed]
Garg, H. , Sedano, M. , Plata, G. , Punke, E. B. , and Joshi, A. , 2017, “ Development of Virus-Like-Particle Vaccine and Reporter Assay for Zika Virus,” J. Virol., 91(20), p. JVI-00834.
Wong, S. J. , Furuya, A. , Zou, J. , Xie, X. , Dupuis, A. P. , Kramer, L. D. , and Shi, P.-Y. , 2017, “ A Multiplex Microsphere Immunoassay for Zika Virus Diagnosis,” EBioMedicine, 16, pp. 136–140. [CrossRef] [PubMed]
Shafiee, H. , Asghar, W. , Inci, F. , Yuksekkaya, M. , Jahangir, M. , Zhang, M. H. , Durmus, N. G. , Gurkan, U. A. , Kuritzkes, D. R. , and Demirci, U. , 2015, “ Paper and Flexible Substrates as Materials for Biosensing Platforms to Detect Multiple Biotargets,” Sci. Rep., 5(1), p. 8719. [CrossRef] [PubMed]
Sher, M. , Zhuang, R. , Demirci, U. , and Asghar, W. , 2017, “ Based Analytical Devices for Clinical Diagnosis: Recent Advances in the Fabrication Techniques and Sensing Mechanisms,” Expert Rev. Mol. Diagn., 17(4), pp. 351–366. [CrossRef] [PubMed]
Posthuma-Trumpie, G. A. , Korf, J. , and van Amerongen, A. , 2009, “ Lateral Flow (Immuno) Assay: Its Strengths, Weaknesses, Opportunities and Threats. A Literature Survey,” Anal. Bioanal. Chem., 393(2), pp. 569–582. [CrossRef] [PubMed]
Martinez, A. W. , Phillips, S. T. , Whitesides, G. M. , and Carrilho, E. , 2009, Diagnostics for the Developing World: Microfluidic Paper-Based Analytical Devices, ACS Publications, Washington, DC.
Bedin, F. , Boulet, L. , Voilin, E. , Theillet, G. , Rubens, A. , and Rozand, C. , 2017, “ Paper-Based Point-of-Care Testing for Cost-Effective Diagnosis of Acute Flavivirus Infections,” J. Med. Virol., 89(9), pp. 1520–1527. [CrossRef] [PubMed]
Draz, M. S. , Moazeni, M. , Venkataramani, M. , Lakshminarayanan, H. , Saygili, E. , Lakshminaraasimulu, N. K. , Kochehbyoki, K. M. , Kanakasabapathy, M. K. , Shabahang, S. , and Vasan, A. , 2018, “ Hybrid Paper–Plastic Microchip for Flexible and High‐Performance Point‐of‐Care Diagnostics,” Adv. Funct. Mater., 28(26), p. 1707161. [CrossRef]
Martinez, A. W. , Phillips, S. T. , Butte, M. J. , and Whitesides, G. M. , 2007, “ Patterned Paper as a Platform for Inexpensive, Low-Volume, Portable Bioassays,” Angew. Chem. Int. Ed. Engl., 46(8), pp. 1318–1320. [CrossRef] [PubMed]
Tokel, O. , Inci, F. , and Demirci, U. , 2014, “ Advances in Plasmonic Technologies for Point of Care Applications,” Chem. Rev., 114(11), pp. 5728–5752. [CrossRef] [PubMed]
Adegoke, O. , Morita, M. , Kato, T. , Ito, M. , Suzuki, T. , and Park, E. Y. , 2017, “ Localized Surface Plasmon Resonance-Mediated Fluorescence Signals in Plasmonic Nanoparticle-Quantum Dot Hybrids for Ultrasensitive Zika Virus RNA Detection Via Hairpin Hybridization Assays,” Biosens. Bioelectron., 94, pp. 513–522. [CrossRef] [PubMed]
Pardee, K. , Green, A. A. , Takahashi, M. K. , Braff, D. , Lambert, G. , Lee, J. W. , Ferrante, T. , Ma, D. , Donghia, N. , Fan, M. , Daringer, N. M. , Bosch, I. , Dudley, D. M. , O'Connor, D. H. , Gehrke, L. , and Collins, J. J. , 2016, “ Rapid, Low-Cost Detection of Zika Virus Using Programmable Biomolecular Components,” Cell, 165(5), pp. 1255–1266. [CrossRef] [PubMed]
Safavieh, M. , Kanakasabapathy, M. K. , Tarlan, F. , Ahmed, M. U. , Zourob, M. , Asghar, W. , and Shafiee, H. , 2016, “ Emerging Loop-Mediated Isothermal Amplification-Based Microchip and Microdevice Technologies for Nucleic Acid Detection,” ACS Biomater. Sci. Eng., 2(3), pp. 278–294. [CrossRef] [PubMed]
Song, J. , Liu, C. , Mauk, M. G. , Rankin, S. C. , Lok, J. B. , Greenberg, R. M. , and Bau, H. H. , 2017, “ Two-Stage Isothermal Enzymatic Amplification for Concurrent Multiplex Molecular Detection,” Clin. Chem., 63(3), pp. 714–722. [CrossRef] [PubMed]
Song, J. , Mauk, M. G. , Hackett, B. A. , Cherry, S. , Bau, H. H. , and Liu, C. , 2016, “ Instrument-Free Point-of-Care Molecular Detection of Zika Virus,” Anal. Chem., 88(14), pp. 7289–7294. [CrossRef] [PubMed]
Chotiwan, N. , Brewster, C. D. , Magalhaes, T. , Weger-Lucarelli, J. , Duggal, N. K. , Ruckert, C. , Nguyen, C. , Garcia Luna, S. M. , Fauver, J. R. , Andre, B. , Gray, M. , Black, W. C. T. , Kading, R. C. , Ebel, G. D. , Kuan, G. , Balmaseda, A. , Jaenisch, T. , Marques, E. T. A. , Brault, A. C. , Harris, E. , Foy, B. D. , Quackenbush, S. L. , Perera, R. , and Rovnak, J. , 2017, “ Rapid and Specific Detection of Asian- and African-Lineage Zika Viruses,” Sci. Transl. Med., 9(388), p. eaag0538.
Wang, X. , Yin, F. , Bi, Y. , Cheng, G. , Li, J. , Hou, L. , Li, Y. , Yang, B. , Liu, W. , and Yang, L. , 2016, “ Rapid and Sensitive Detection of Zika Virus by Reverse Transcription Loop-Mediated Isothermal Amplification,” J. Virol. Methods, 238, pp. 86–93. [CrossRef] [PubMed]
Karthik, K. , Rathore, R. , Thomas, P. , Arun, T. R. , Viswas, K. N. , Dhama, K. , and Agarwal, R. K. , 2014, “ New Closed Tube Loop Mediated Isothermal Amplification Assay for Prevention of Product Cross-Contamination,” MethodsX, 1, pp. 137–143. [CrossRef] [PubMed]
Chan, K. , Wong, P.-Y. , Parikh, C. , and Wong, S. , 2018, “ Moving Toward Rapid and Low-Cost Point-of-Care Molecular Diagnostics With a Repurposed 3D Printer and RPA,” Anal. Biochem., 545, pp. 4–12. [CrossRef] [PubMed]
Chan, K. , Weaver, S. C. , Wong, P.-Y. , Lie, S. , Wang, E. , Guerbois, M. , Vayugundla, S. P. , and Wong, S. , 2016, “ Rapid, Affordable and Portable Medium-Throughput Molecular Device for Zika Virus,” Sci. Rep., 6(1), p. 38223. [CrossRef] [PubMed]
Sharma, S. , Zhuang, R. , Long, M. , Pavlovic, M. , Kang, Y. , Ilyas, A. , and Asghar, W. , 2018, “ Circulating Tumor Cell Isolation, Culture, and Downstream Molecular Analysis,” Biotechnol. Adv., 36(4), pp. 1063–1078.
Yu, S. , Rubin, M. , Geevarughese, S. , Pino, J. , Rodriguez, H. , and Asghar, W. , 2018, “ Emerging Technologies for Home‐Based Semen Analysis,” Andrology, 6(1), pp. 10–19. [CrossRef] [PubMed]
Fennel, R. , and Asghar, W. , 2017, “ Image Sensor Road Map and Solid-State Imaging Devices,” NanoWorld, 1(4), pp. 10–14. https://www.researchgate.net/publication/317648790_Image_Sensor_Road_Map_and_Solid-State_Imaging_Devices
Kanakasabapathy, M. K. , Pandya, H. J. , Draz, M. S. , Chug, M. K. , Sadasivam, M. , Kumar, S. , Etemad, B. , Yogesh, V. , Safavieh, M. , and Asghar, W. , 2017, “ Rapid, Label-Free CD4 Testing Using a Smartphone Compatible Device,” Lab Chip, 17(17), pp. 2910–2919. [CrossRef] [PubMed]
Islam, M. , Asghar, W. , Kim, Y.-T. , and Iqbal, S. M. , 2014, “ Cell Elasticity-Based Microfluidic Label-Free Isolation of Metastatic Tumor Cells,” British Journal of Medicine and Medical Research, 4(11), pp. 2129–2140.
Ilyas, A. , Asghar, W. , Ahmed, S. , Lotan, Y. , Hsieh, J.-T. , Kim, Y.-T. , and Iqbal, S. M. , 2014, “ Electrophysiological Analysis of Biopsy Samples Using Elasticity as an Inherent Cell Marker for Cancer Detection,” Anal. Methods, 6(18), pp. 7166–7174. [CrossRef]
Asghar, W. , Yuksekkaya, M. , Shafiee, H. , Zhang, M. , Ozen, M. O. , Inci, F. , Kocakulak, M. , and Demirci, U. , 2016, “ Engineering Long Shelf Life Multi-Layer Biologically Active Surfaces on Microfluidic Devices for Point of Care Applications,” Sci. Rep., 6(1), p. 21163. [CrossRef] [PubMed]
Asghar, W. , Ramachandran, P. P. , Adewumi, A. , Noor, M. R. , and Iqbal, S. M. , 2010, “ Rapid Nanomanufacturing of Metallic Break Junctions Using Focused Ion Beam Scratching and Electromigration,” ASME J. Manuf. Sci. Eng., 132(3), p. 030911. [CrossRef]
Ilyas, A. , Asghar, W. , Kim, Y.-T. , and Iqbal, S. M. , 2014, “ Parallel Recognition of Cancer Cells Using an Addressable Array of Solid-State Micropores,” Biosens. Bioelectron., 62, pp. 343–349. [CrossRef] [PubMed]
Mok, J. , Mindrinos, M. N. , Davis, R. W. , and Javanmard, M. , 2014, “ Digital Microfluidic Assay for Protein Detection,” Proc. Natl. Acad. Sci. U.S.A., 111(6), pp. 2110–2115. [CrossRef] [PubMed]
Lin, Z. , Cao, X. , Xie, P. , Liu, M. , and Javanmard, M. , 2015, “ PicoMolar Level Detection of Protein Biomarkers Based on Electronic Sizing of Bead Aggregates: Theoretical and Experimental Considerations,” Biomed Microdev., 17(6), p. 119. [CrossRef]
Valera, E. , Berger, J. , Hassan, U. , Ghonge, T. , Liu, J. , Rappleye, M. , Winter, J. , Abboud, D. , Haidry, Z. , Healey, R. , Hung, N. T. , Leung, N. , Mansury, N. , Hasnain, A. , Lannon, C. , Price, Z. , White, K. , and Bashir, R. , 2018, “ A Microfluidic Biochip Platform for Electrical Quantification of Proteins,” Lab Chip, 18(10), pp. 1461–1470. [CrossRef] [PubMed]


Grahic Jump Location
Fig. 1

Geographical distribution of ZIKV outbreak from 2007 to 2017. This image illustrates the spread of ZIKV from its inception in the small island of Yap to its conclusion in the Americas [18] (Reprinted from The Lancet with permission from Elsevier © 2017).

Grahic Jump Location
Fig. 2

Zika virus external morphology and viral proteins. This illustration depicts the encoded structural components contain the capsid and membrane proteins [29] (Reprinted with permission from The American Society for Microbiology © 2017). The nonstructural portion of the ORF includes an envelope protein and 7 other proteins; NS1, NS2a, NS2b, NS3, NS4a, NS4b, and NS5 [30] (Reprinted with permission of Creative Commons Attribution BY 4.0).

Grahic Jump Location
Fig. 3

CDC recommended tests for ZIKV detection. (a) In RT-qPCR, viral RNA extracted from an infected patient's sample is placed into a reaction mix containing all of the necessary factors for amplification such as ZIKV specific primers (to bind to the RNA template), reverse transcriptase (to make cDNA from RNA), DNA polymerase and dNTPs (to amplify the DNA), a buffer solution (to maintain an optimal environment for the polymerase), and an intercalating fluorescent dye for quantification. Amplification takes place through thermal cycling, and its product is later identified and quantified based on fluorescence. (b) In MAC ELISA, the activity of IgM antibodies is measured in response to ZIKV infection. The process starts when a patient's blood sample is incubated in a well plate containing antibodies against IgM. If IgM is present, then it will strongly bind to the antibodies in the plate. If not, then the patient's sample will be washed away and there would be no reaction when the secondary HRP antibody is added to the plate. (c) PRNT tests are carried out to confirm serological results. In PRNT, a patient's serum undergoes a series of dilutions that are then added to a ZIKV viral suspension, mixed, and incubated alongside cell cultures. If antibodies against ZIKV are present, then there will be a reduction in the number of observable ZIKV plaques [64] (Reprinted with permission of Creative Commons Attribution BY 4.0).

Grahic Jump Location
Fig. 4

Localized surface plasmon resonance biosensor schematics and ZIKV sensitivity. (a) Qdot bimetallic nanohybrids are made by coupling plasmonic nanoparticles such as gold to quantum dots. These hybrids are then infused alongside ZIKV specific DNA loops to the molecular beacon of the biosensor. (b) LSPR relies on the resonance that occurs through the hybridization of viral ZIKV RNA with the complementary DNA loop sequence found in the molecular beacon. This in turn induces a signal that can be picked up, amplified and quantified by nearby quantum dot nanocrystals [77]. (Reprinted with permission of Elsevier © 2017).

Grahic Jump Location
Fig. 5

CRISPR/CAS9 biomolecular sensors. (a) Primers and toehold sensors are selectively designed to match specific ZIKV strains. These sensors, alongside their primers are then infused and freeze-dried into paper effectively completing the biosensor. (b) Adding a patient's sample (fluid) to the paper will cause it to become moisturized and active. If a specific ZIKV strain is present, then a color change from yellow to purple will take place on the surface of the paper, which would be indicative of a positive reaction. This sensor is specific enough to differentiate between closely related flaviviruses and even different ZIKV lineages within a single base resolution, when coupled to a CRISPR/Cas9-based module [78] (Reprinted with permission of Elsevier © 2016).

Grahic Jump Location
Fig. 6

Isothermal amplification technologies; RT-LAMP and RPA amplification. (a) Patients' samples are collected and lysed to extract viral nucleotides. (b) The lysed samples are then filtered through a porous silica membrane inside the microfluidic cassette to isolate ZIKV nucleic acids. Once the nucleotides have been isolated, a colorless leuco crystal violet indicator is pumped into the reaction chamber (where the filter membrane is located) to serve as a marker for amplification. (c) The inside of the device consists of a thermos that has been modified to hold a microfluidic cassette, a heat sink, an isothermal heat source (Mg-Fe alloy), and a heat sink to dissipate heat, while the outside (d) consists of a 3D printed lid for sample collection, and a water port to trigger the isothermal reaction. (e) Photographs depicting the isothermal amplification reactor prior and after use. If ZIKV is found, then the colorless crystal violet indicator reacts and becomes violet in color [81] (Reprinted with permission of ACS Publications: https://pubs.acs.org/doi/10.1021/acs.analchem.6b01632). (f) This modified 3D printer is able to perform high throughput nucleotide extraction, and isothermal amplification all within the same enclosure. Due to its configuration, you can run up to twelve patient samples per run, as this printer holds 96 well plates. The heated bed underneath the plate maintains the temperature at a constant rate, as to not affect the amplification process. (g) RPA amplification can also be performed within a thermos like structure as seen in RT-LAMP. However, this process is not as efficient, as you cannot run as many samples in it [85] (Reprinted with permission of Elsevier © 2018).



Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging and repositioning the boxes below.

Related Journal Articles
Related eBook Content
Topic Collections

Sorry! You do not have access to this content. For assistance or to subscribe, please contact us:

  • TELEPHONE: 1-800-843-2763 (Toll-free in the USA)
  • EMAIL: asmedigitalcollection@asme.org
Sign In