A team of Northwestern University scientists spanning disciplines have developed new technology that could lead to the creation of a rapid point-of-care test for HIV infection competitive with traditional lab-based HIV testing in a fraction of the time and without the need for a stressful wait while results are processed or confirmed in a clinical laboratory.
HIV-diagnostic technology traditionally relied on the detection of HIV-specific antibodies that form several weeks after infection. This has limited their use in early detection, complicating patient care and HIV prevention efforts. Newer tests that detect both HIV antibodies and the p24 antigen (an earlier marker of HIV infection) are now the gold standard for diagnosis, but require clinical labs to run results, contributing to longer processing times, higher costs and the need for multiple patient visits.
The technology described in a study published today (April 2) in the journal Biosensors and Bioelectronics uses a nanomechanical platform and tiny cantilevers to detect multiple HIV antigens at high sensitivity in a matter of minutes. These silicon cantilevers are cheap and easy to mass produce and can be readily equipped with a digital readout. Built into a solar-powered device, this technology could be taken to hard-to-reach parts of the world where early detection remains a challenge to deliver fast interventions to vulnerable populations without waiting for a lab.
“We hope this technology will lead to the development of new point-of-care diagnostics for HIV to improve patient health and help bring an end to this epidemic,” said Northwestern virologist and co-author of the study, Judd F. Hultquist.
After proving its efficacy in testing for both the SARS-CoV-2 virus that causes COVID-19, and now HIV, the team is confident that the biosensor will continue to prove effective when testing for additional diseases. A potential next target, they say, could be measles, another infection in desperate need of point-of-care interventions as cases rise across multiple U.S. states.
The team was led by co-corresponding authors Vinayak Dravid, a materials engineer, Hultquist, a virologist, and co-author Gajendra Shekhawat, a micro- and nanofabrication expert in the Dravid Lab.
“When we first developed the microcantilever technology 20 years ago, I realized that this technology is so generally applicable,” Dravid said. “It is a very powerful tool that depends on three basic things: sensitivity, antigen-antibody affinity and specificity. This is where HIV comes in, because HIV is so pernicious that it mutates so there is no unique antibody. We had to figure out how to overcome that challenge.”
Beginning with pure samples of the p24 antigen, the team applied layers of antibodies onto each “finger” of the gold-coated microcantilever to measure how strongly p24 bonded to the surface, which would cause the cantilever to bend a measurable and quantifiable amount.
After this proof-of-concept, the team introduced human blood samples, which are much more complex than purified samples. The sensor continued to bend only in samples where p24 was present, demonstrating high specificity.
Finally, the scientists added two antibodies to different “fingers” of the microcantilever to more broadly cover all HIV subtypes. Even in very low concentrations, the test accurately responded when antigens specific to HIV were introduced.
“To account for HIV’s genetic diversity, we functionalized the test for HIV using broadly cross-reactive antibodies (ANT-152 and C65690M),” Shekhawat said. “This allowed accurate detection across diverse HIV-1 subtypes, ensuring reliability in global settings.”
To streamline diagnostics and enable immediate medical care, the team envisions developing a point-of-care test simultaneously detecting HIV, hepatitis B and hepatitis C antigens, acknowledging the higher prevalence of hepatitis co-infections in people living with HIV that can lead to severe liver complications if left untreated.
Dravid is the Abraham Harris Professor of Materials Science and Engineering at the McCormick School of Engineering and a faculty affiliate of the Paula M. Trienens Institute for Sustainability and Energy. He is also the founding director of the Northwestern University Atomic and Nanoscale Characterization (NUANCE) Center as well as the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource, and also serves as the associate director for global programs at the International Institute of Nanotechnology.
Hultquist is an assistant professor of medicine at Northwestern University Feinberg School of Medicine and serves as the associate director for the Center for Pathogen Genomics and Microbial Evolution in the Havey Institute for Global Health. He specializes in translational research of infectious diseases and host-pathogen interactions.
Shekhawat is a research professor of materials science and engineering at McCormick, researching semiconductor microfabrication, integration of sensors with synthetic biology and biomaterials and nanoscale characterization.
The research was supported by an award from the National Institutes of Health-funded Third Coast Center for AIDS Research (P30AI117943), as well as through NIH funding for the HIV Accessory & Regulatory Complexes Center (U54 AI170792) and NIH funding for HIV research (R01AI176599, R01AI167778, R01AI150455, R01AI165236, R01AI150998, R21 AI174864, and R56AI174877).
Vinayak Dravid, Gajendra Shekhawat, Judd Hultquist and Northwestern have financial interests (equities, royalties) in the reported research.
