There is a need for biological sensing and diagnostics tools with sensitivity compared to existing state-of-the-art technologies without complicated assays, sample preparation, and bulky equipment. Our platform technology, IRIS offers kinetic analysis of biomolecular binding and detection of proteins, nucleic acids, and individual biological nanoparticles in a simple assay format and with high sensitivity. We have shown that low-cost and disposable sensor chips and microfluidic cartridges compatible with this optical sensing technology can be manufactured using standard Si processing techniques.

We present a multiplexed label-free platform for diagnosis integrating multiple tests for antigens and antibodies onto a single platform and thus enhancing reliability and specificity while reducing cost and complexity.

We present biological imaging and sensing methods based on optical resonance and interference. In fluorescence microscopy, our nanoscale imaging capability sheds light onto conformational changes of DNA, DNA-protein complexes and polymer coatings on a solid surface. Interference measurements on a layered substrate yield a label-free sensing platform for protein binding in a high-throughput micro-array format.

Summary: Because increasing numbers of HIV vaccine candidates are being tested globally, it is essential to differentiate vaccine- from virus-induced antibodies. Most of the currently tested vaccines contain multiple viral components. As a result, many vaccine recipients give positive results in FDA-licensed HIV serodetection tests. We have identified conserved sequences in Env-gp41 and Gag-p6, which are recognized soon after infection but are not included in most HIV vaccine candidates. A new HIV serodetection assay, the HIV-SELECTEST, was established that distinguishes between vaccine-induced antibodies and seroconversion due to true HIV infections. It is important to make this assay globally relevant, because many clinical trials are conducted around the world where most HIV infections are due to non-B subtype HIV-1. Therefore, the current study examined the reactivity of plasma samples from >3000 infections with diverse HIV subtypes worldwide. The HIV-SELECTEST performed at >99% specificity and sensitivity. Both recent and established infections with clades A, B, C, D, E, F, G, J, and CRFs were detected. Antibodies elicited by other vaccinations or infections endemic to the clinical trial sites did not react in this assay. Therefore, HIV-SELECTEST could be an important differential diagnostic tool for HIV vaccine trials, blood banks, and population screening worldwide.

ABSTRACT All current human immunodeficiency virus (HIV) vaccine candidates contain multiple viral components and elicit antibodies that react positively in licensed HIV diagnostic tests, which contain similar viral products. Thus, vaccine trial participants could be falsely diagnosed as infected with HIV. Additionally, uninfected, seropositive vaccinees may encounter long-term social and economic harms. Moreover, this also interferes with early detection of true HIV infections during preventive HIV vaccine trials. An HIV-seropositive test result among uninfected vaccine trial participants is a major public health concern for volunteers who want to participate in future HIV vaccine trials. Based on the increased number of HIV vaccines being tested globally, it is essential to differentiate vaccine- from virus-induced antibodies. Using a whole-HIV-genome phage display library, we identified conserved sequences in Env-gp41 and Gag-p6 which are recognized soon after infection, do not contain protective epitopes, and are not part of most current HIV vaccines. We established a new HIV serodetection assay based on these peptides. To date, this assay, termed HIV-SELECTEST, demonstrates >99% specificity and sensitivity. Importantly, in testing of plasma samples from multiple HIV vaccine trials, uninfected trial participants scored negative, while all intercurrent infections were detected within 1 to 3 months of HIV infection. The new HIV-SELECTEST is a simple but robust diagnostic tool for easy implementation in HIV vaccine trials and blood banks worldwide.

Most of the HIV-1 vaccines under development contain multiple viral genes or proteins. As a result, many vaccinerecipients react positive in licensed HIV-1 detection assays. This will have negative impact on future efficacy trials of prophylactic HIV vaccines that require early detection of intercurrent HIV infections. It will also exclude all vaccinees from blood/plasma donations, and may contribute to other social harms. Therefore, it is important to design new strategies for vaccine trial participants that will clearly discriminate between vaccine-induced antibodies and true HIV-1 infection. We identified new HIV-1 epitopes that: 1) Do not contain important neutralizing or CTL epitopes, and can be omitted from future HIV vaccine candidates, 2) Recognized by antibodies from early HIV infected individuals, 3) Highly conserved among HIV-1 clades and subtypes. Using Phage Display libraries constructed from whole HIV-1 genome, combined with panning over antibodies from early seroconvertors, we identified new immunodominant epitopes, in the gp41 intracytoplasmic tail and in p6, which conform to the above criteria.