{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:41:14Z","timestamp":1770597674817,"version":"3.49.0"},"reference-count":62,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T00:00:00Z","timestamp":1614902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R56AI138659"],"award-info":[{"award-number":["R56AI138659"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008982","name":"National Science Foundation","doi-asserted-by":"publisher","award":["NSF CAREER Award 1942487"],"award-info":[{"award-number":["NSF CAREER Award 1942487"]}],"id":[{"id":"10.13039\/501100008982","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Humanity in Science Award","award":["Humanity in Science Award"],"award-info":[{"award-number":["Humanity in Science Award"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sensors"],"abstract":"<jats:p>The detection of viruses using imaging techniques is challenging because of the weak scattering of light generated by the targets of sizes in the nanometer range. The system we have developed overcomes the light scattering problems by utilizing antibody-coated microbeads of higher index of refraction that can specifically bind with viruses and increase the acceptance angle. Using the new technology, we have developed a portable, cost-effective, and field-deployable platform for the rapid quantification of HIV-1 viral load for point-of-care (POC) settings. The system combines microfluidics with a wide field of view lensless imaging technology. Highly specific antibodies are functionalized to a glass slide inside a microchip to capture HIV-1 virions. The captured virions are then bound by antibody-conjugated microbeads, which have a higher refraction index. The microbeads\u2014HIV-1 virions complexes generate diffraction patterns that are detected with a custom-built imaging setup and rapidly and accurately quantified by computational analysis. This platform technology enables fast nanoscale virus imaging and quantification from biological samples and thus can play a significant role in the detection and management of viral diseases.<\/jats:p>","DOI":"10.3390\/s21051819","type":"journal-article","created":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T11:46:09Z","timestamp":1614944769000},"page":"1819","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Development of a Point-of-Care Assay for HIV-1 Viral Load Using Higher Refractive Index Antibody-Coated Microbeads"],"prefix":"10.3390","volume":"21","author":[{"given":"Mazhar","family":"Sher","sequence":"first","affiliation":[{"name":"Asghar-Lab, Micro and Nanotechnology in Medicine, College of Engineering and Computer Science, Boca Raton, FL 33431, USA"},{"name":"Department of Computer &amp; Electrical Engineering and Computer Science, Florida Atlantic University, Boca Raton, FL 33431, USA"}]},{"given":"Benjamin","family":"Coleman","sequence":"additional","affiliation":[{"name":"Department of Electrical and Computer Engineering, Rice University, 6100 Main Street, Houston, TX 77005, USA"}]},{"given":"Massimo","family":"Caputi","sequence":"additional","affiliation":[{"name":"Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL 33431, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0458-8430","authenticated-orcid":false,"given":"Waseem","family":"Asghar","sequence":"additional","affiliation":[{"name":"Asghar-Lab, Micro and Nanotechnology in Medicine, College of Engineering and Computer Science, Boca Raton, FL 33431, USA"},{"name":"Department of Computer &amp; Electrical Engineering and Computer Science, Florida Atlantic University, Boca Raton, FL 33431, USA"},{"name":"Department of Biological Sciences (Courtesy Appointment), Florida Atlantic University, Boca Raton, FL 33431, USA"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,5]]},"reference":[{"key":"ref_1","unstructured":"(2021, January 01). (2020, 01-18-2020). 90-90-90: Treatment for All. Available online: https:\/\/www.unaids.org\/en\/resources\/909090."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1080\/07388551.2020.1751058","article-title":"Advances in HIV diagnosis and monitoring","volume":"40","author":"Kabir","year":"2020","journal-title":"Crit. Rev. Biotechnol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7653","DOI":"10.1038\/s41598-018-25943-2","article-title":"Antiretroviral drugs alter the content of extracellular vesicles from HIV-1-infected cells","volume":"8","author":"DeMarino","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.antiviral.2009.10.002","article-title":"The development of antiretroviral therapy and its impact on the HIV-1\/AIDS pandemic","volume":"85","author":"Broder","year":"2010","journal-title":"Antivir. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/S0140-6736(10)60676-9","article-title":"Antiretroviral therapy and management of HIV infection","volume":"376","author":"Volberding","year":"2010","journal-title":"Lancet"},{"key":"ref_6","first-page":"346","article-title":"Adherence to anti-retroviral therapy and its determinants in HIV\/AIDS patients: A review","volume":"12","author":"SeyedAlinaghi","year":"2012","journal-title":"Infect. Disord. -Drug Targets (Former. Curr. Drug Targets-Infect. Disord.)"},{"key":"ref_7","first-page":"1","article-title":"Antiretroviral drugs alter the content of extracellular vesicles from HIV-1-infected cells","volume":"8","author":"DeMarino","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Pant Pai, N., Peeling, R.W., Smith, B.D., and Dowdy, D. (2014). Point-of-Care Tests for HIV, Related Coinfections, and Blood-Borne Infections, Hindawi.","DOI":"10.1155\/2014\/625082"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1093\/nar\/30.6.1292","article-title":"Real-time PCR in virology","volume":"30","author":"Mackay","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"112041","DOI":"10.1016\/j.bios.2020.112041","article-title":"Recent advances in lab-on-a-chip technologies for viral diagnosis","volume":"153","author":"Zhu","year":"2020","journal-title":"Biosens. Bioelectron."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/s40588-018-0105-y","article-title":"Microfluidics: An untapped resource in viral diagnostics and viral cell biology","volume":"5","author":"Simpson","year":"2018","journal-title":"Curr. Clin. Microbiol. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"8719","DOI":"10.1038\/srep08719","article-title":"Paper and flexible substrates as materials for biosensing platforms to detect multiple biotargets","volume":"5","author":"Shafiee","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.bios.2009.06.023","article-title":"Quantum dot-based HIV capture and imaging in a microfluidic channel","volume":"25","author":"Kim","year":"2009","journal-title":"Biosens. Bioelectron."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1936","DOI":"10.1021\/acs.chemrev.9b00692","article-title":"Single-virus tracking: From imaging methodologies to virological applications","volume":"120","author":"Liu","year":"2020","journal-title":"Chem. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Daaboul, G.G., Freedman, D.S., Scherr, S.M., Carter, E., Rosca, A., Bernstein, D., Mire, C.E., Agans, K.N., Hoenen, T., and Geisbert, T.W. (2017). Enhanced light microscopy visualization of virus particles from Zika virus to filamentous ebolaviruses. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0179728"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4727","DOI":"10.1021\/nl103210p","article-title":"High-throughput detection and sizing of individual low-index nanoparticles and viruses for pathogen identification","volume":"10","author":"Daaboul","year":"2010","journal-title":"Nano Lett."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Bohren, C.F., and Huffman, D.R. (1998). Absorption and Scattering of Light by Small Particles, WileyVCH.","DOI":"10.1002\/9783527618156"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3255","DOI":"10.3389\/fmicb.2018.03255","article-title":"Electron microscopy methods for virus diagnosis and high resolution analysis of viruses","volume":"9","author":"Franzke","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1016\/0042-6822(73)90068-8","article-title":"Quantitative assay for plant viruses using serologically specific electron microscopy","volume":"56","author":"Debrick","year":"1973","journal-title":"Virology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e2019","DOI":"10.1002\/rmv.2019","article-title":"Virus detection by transmission electron microscopy: Still useful for diagnosis and a plus for biosafety","volume":"29","author":"Roingeard","year":"2019","journal-title":"Rev. Med Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S1386-6532(99)00027-X","article-title":"Diagnostic electron microscopy is still a timely and rewarding method","volume":"13","author":"Biel","year":"1999","journal-title":"J. Clin. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1128\/CMR.00027-09","article-title":"Modern uses of electron microscopy for detection of viruses","volume":"22","author":"Goldsmith","year":"2009","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1042\/BC20070173","article-title":"Viral detection by electron microscopy: Past, present and future","volume":"100","author":"Roingeard","year":"2008","journal-title":"Biol. Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S1386-6532(01)00151-2","article-title":"Diagnostic virology: The need for electron microscopy: A discussion paper","volume":"22","author":"Biel","year":"2001","journal-title":"J. Clin. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1097\/QAI.0000000000002555","article-title":"Near Point-of-Care HIV Viral Load: Targeted Testing at Large Facilities","volume":"86","author":"Ganesh","year":"2021","journal-title":"J. Acquir. Immune Defic. Syndr. (1999)"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Ilyas, S., Simonson, A.E., and Asghar, W. (2019). Emerging Point-of-Care Technologies for Sickle Cell Disease Diagnostics. Clin. Chim. Acta.","DOI":"10.1016\/j.cca.2019.10.025"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1007\/s10404-018-2117-6","article-title":"Quantitative analysis of sperm rheotaxis using a microfluidic device","volume":"22","author":"Rappa","year":"2018","journal-title":"Microfluid. Nanofluidics"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"7474","DOI":"10.1021\/acsomega.9b00499","article-title":"Microfluidic chip for detection of fungal infections","volume":"4","author":"Asghar","year":"2019","journal-title":"ACS Omega"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1080\/14737159.2017.1285228","article-title":"based analytical devices for clinical diagnosis: Recent advances in the fabrication techniques and sensing mechanisms","volume":"17","author":"Sher","year":"2017","journal-title":"Expert Rev. Mol. Diagn."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Kabir, M.A., Zilouchian, H., Sher, M., and Asghar, W. (2020). Development of a Flow-Free Automated Colorimetric Detection Assay Integrated with Smartphone for Zika NS1. Diagnostics, 10.","DOI":"10.3390\/diagnostics10010042"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"8159","DOI":"10.1039\/C8RA07607C","article-title":"Development of a flow-free magnetic actuation platform for an automated microfluidic ELISA","volume":"9","author":"Coarsey","year":"2019","journal-title":"RSC Adv."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"111490","DOI":"10.1016\/j.bios.2019.111490","article-title":"Development of a multiplex fully automated assay for rapid quantification of CD4+ T cells from whole blood","volume":"142","author":"Sher","year":"2019","journal-title":"Biosens. Bioelectron."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"106326","DOI":"10.1016\/j.optlaseng.2020.106326","article-title":"Design, development, and performance comparison of wide field lensless and lens-based optical systems for point-of-care biological applications","volume":"137","author":"Fennell","year":"2021","journal-title":"Opt. Lasers Eng."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.5858\/arpa.2019-0667-OA","article-title":"Lab-on-a-Chip Zika Detection with Reverse Transcription Loop-Mediated Isothermal Amplification\u2013Based Assay for Point-of-Care Settings","volume":"144","author":"Sharma","year":"2020","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"112417","DOI":"10.1016\/j.bios.2020.112417","article-title":"Smartphone-based sickle cell disease detection and monitoring for point-of-care settings","volume":"165","author":"Ilyas","year":"2020","journal-title":"Biosens. Bioelectron."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.talanta.2013.04.032","article-title":"Determination of the refractive index of microparticles by utilizing light dispersion properties of the particle and an immersion liquid","volume":"115","author":"Niskanen","year":"2013","journal-title":"Talanta"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1016\/j.cpc.2011.12.027","article-title":"Computational wave optics library for C++: CWO++ library","volume":"183","author":"Shimobaba","year":"2012","journal-title":"Comput. Phys. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1016\/j.patcog.2012.11.011","article-title":"Analysis of focus measure operators for shape-from-focus","volume":"46","author":"Pertuz","year":"2013","journal-title":"Pattern Recognit."},{"key":"ref_39","unstructured":"Goodman, J.W. (2005). Introduction to Fourier Optics, Roberts and Company Publishers."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2028","DOI":"10.1039\/c3lc50222h","article-title":"Toward giga-pixel nanoscopy on a chip: A computational wide-field look at the nano-scale without the use of lenses","volume":"13","author":"McLeod","year":"2013","journal-title":"Lab Chip"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1039\/c000453g","article-title":"Compact, light-weight and cost-effective microscope based on lensless incoherent holography for telemedicine applications","volume":"10","author":"Mudanyali","year":"2010","journal-title":"Lab Chip"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"7296","DOI":"10.1073\/pnas.1015638108","article-title":"Lens-free optical tomographic microscope with a large imaging volume on a chip","volume":"108","author":"Isikman","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","first-page":"29","article-title":"On-chip biomedical imaging","volume":"6","author":"Ozcan","year":"2012","journal-title":"IEEE Rev. Biomed. Eng."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1093\/emboj\/cdg143","article-title":"Structural organization of authentic, mature HIV-1 virions and cores","volume":"22","author":"Briggs","year":"2003","journal-title":"EMBO J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1038\/nsmb785","article-title":"The stoichiometry of Gag protein in HIV-1","volume":"11","author":"Briggs","year":"2004","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1007\/s00249-008-0322-z","article-title":"HIV-1\u2013cellular interactions analyzed by single virus tracing","volume":"37","author":"Lampe","year":"2008","journal-title":"Eur. Biophys. J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1146\/annurev-med-092112-143017","article-title":"Emerging technologies for point-of-care management of HIV infection","volume":"66","author":"Shafiee","year":"2015","journal-title":"Annu. Rev. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/S0969-2126(00)00119-2","article-title":"NMR structure of an anti-gp120 antibody complex with a V3 peptide reveals a surface important for co-receptor binding","volume":"8","author":"Tugarinov","year":"2000","journal-title":"Structure"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1126\/science.3629244","article-title":"Functional regions of the envelope glycoprotein of human immunodeficiency virus type 1","volume":"237","author":"Kowalski","year":"1987","journal-title":"Science"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-017-00515-6","article-title":"Envelope glycoprotein mobility on HIV-1 particles depends on the virus maturation state","volume":"8","author":"Chojnacki","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s12977-018-0424-3","article-title":"Super-resolution fluorescence microscopy studies of human immunodeficiency virus","volume":"15","author":"Chojnacki","year":"2018","journal-title":"Retrovirology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2910","DOI":"10.1039\/C7LC00273D","article-title":"Rapid, label-free CD4 testing using a smartphone compatible device","volume":"17","author":"Kanakasabapathy","year":"2017","journal-title":"Lab Chip"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-019-13802-1","article-title":"Holographic detection of nanoparticles using acoustically actuated nanolenses","volume":"11","author":"Ray","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_54","unstructured":"McArthur, C.C. (2016). Microfluidic Technologies for Capturing and Concentrating Human Immunodeficiency Virus-1 (HIV-1) Particles. [Master\u2019s Thesis, University of Kwazulu-Natal]."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2709","DOI":"10.1128\/JCM.43.6.2709-2717.2005","article-title":"Transfer and evaluation of an automated, low-cost real-time reverse transcription-PCR test for diagnosis and monitoring of human immunodeficiency virus type 1 infection in a West African resource-limited setting","volume":"43","author":"Rouet","year":"2005","journal-title":"J. Clin. Microbiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1038\/nm0703-847","article-title":"Transmission, acute HIV-1 infection and the quest for strategies to prevent infection","volume":"9","author":"Pope","year":"2003","journal-title":"Nat. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1056\/NEJMra1011874","article-title":"Acute HIV-1 infection","volume":"364","author":"Cohen","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1056\/NEJM199104043241405","article-title":"Transient high levels of viremia in patients with primary human immunodeficiency virus type 1 infection","volume":"324","author":"Daar","year":"1991","journal-title":"N. Engl. J. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1001\/jama.1997.03550010072043","article-title":"Acute primary HIV infection","volume":"278","author":"Quinn","year":"1997","journal-title":"JAMA"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2553","DOI":"10.1002\/smll.201202195","article-title":"Acute on-chip hiv detection through label-free electrical sensing of viral nano-lysate","volume":"9","author":"Shafiee","year":"2013","journal-title":"Small"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Agbana, T., Nijman, P., Hoeber, M., van Grootheest, D., van Diepen, A., van Lieshout, L., Diehl, J.-C., Verhaegen, M., and Vdovine, G. (2020, January 3). Detection of Schistosoma haematobium using lensless imaging and flow cytometry, a proof of principle study. Proceedings of the Optical Diagnostics and Sensing XX: Toward Point-of-Care Diagnostics, San Francisco, CA, USA.","DOI":"10.1117\/12.2545220"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Chen, Y.-C., Kuo, C.-S., Wang, Z.-Z., Lei, H.-Y., Yang, C.-H., and Huang, C.-H. (2020, January 3). Lens-free holographic microscopy for complete blood analysis on a chip. Proceedings of the Optical Diagnostics and Sensing XX: Toward Point-of-Care Diagnostics, San Francisco, CA, USA.","DOI":"10.1117\/12.2543132"}],"container-title":["Sensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8220\/21\/5\/1819\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:33:32Z","timestamp":1760160812000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8220\/21\/5\/1819"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,5]]},"references-count":62,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["s21051819"],"URL":"https:\/\/doi.org\/10.3390\/s21051819","relation":{},"ISSN":["1424-8220"],"issn-type":[{"value":"1424-8220","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,5]]}}}