Principal Investigator (Last, First): Hall, Drew A. ABSTRACT The world?s population requires affordable and reliable diagnosis for effective healthcare. Infectious diseases such as human immunodeficiency virus, Zika virus, Dengue Fever, and Ebola virus represent significant global health threats, yet the frequent and pervasive testing required for full control or universal eradication remain out of reach in many settings due to the costs and limitations of current technologies. While modern diagnostics are becoming increasingly more sensitive and great gains have been made in portability and affordability, no single technique provides an ideal mix of sensitivity, specificity, and the ability to simultaneously diagnose multiple diseases. Thus, the healthcare system remains fragmented and must maintain several types of tests and testing platforms. While this remains feasible in the developed world, it is nearly impossible in many remote and resource limited settings. We propose a method for simultaneous point-of-care (POC) disease diagnosis based on electrochemical detection of pathogen directed host responses. This immune profile, or immunosignature (IMS), is a measurement of the profile of circulating antibodies in an individual at a specific time. This profile changes in response to disease. In the case of infection, it provides an evaluation of the host?s response similar to an enzyme linked immunosorbent assay (ELISA), rather than a direct measure of the pathogen itself. There are ~1 billion different antibodies circulating in the blood at any time, and when an infection occurs (or another disease that presents new antigens), a subset of antibodies will be amplified by up to 1011 fold. As such, Immunosignaturing not only has higher sensitivity and specificity than current immunodiagnostics, but is disease agnostic: it is a multidimensional evaluation of the humeral immune system as a whole, and thus can be used to detect and identify any disease with a significant antibody response (even retrospectively), from less than a pinprick of blood. Existing fluorescent-based Immunosignaturing technology remains expensive ($100 per sample) and laboratory bound. We hypothesize that the Immunosignaturing method may be adapted to an electrochemical sensing technique that would dramatically lower production costs, increase scalability, and portability by piggybacking on the annual advancements in the multibillion-dollar semiconductor industry. In this two year effort, we aim to lay the groundwork for a low-cost POC diagnostic platform that could ultimately allow the simultaneous diagnosis of a significant portion of the global burden of disease. Abstract

Public Health Relevance

Principal Investigator (Last, First): Hall, Drew A. NARRATIVE Access to effective healthcare is a universal need for all of the nearly seven billion people worldwide. Infections such as human immunodeficiency virus (HIV), Zika virus, Dengue Fever, and Ebola virus represent significant and imminent global health threats, yet the pervasive testing required for full control or universal eradication remain out of reach to many health systems given the costs and limitations of current technologies. We hypothesize that this pressing need can be addressed using semiconductor-based electrochemical biosensor technology coupled with high-density in-situ synthesized peptide arrays for rapid, immunosignature based point- of-care diagnostics. Project Narrative

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Exploratory/Developmental Grants (R21)
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Instrumentation and Systems Development Study Section (ISD)
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Gondre-Lewis, Timothy A
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University of California, San Diego
Engineering (All Types)
Schools of Arts and Sciences
La Jolla
United States
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Sun, Alexander C; Alvarez-Fontecilla, Enrique; Venkatesh, A G et al. (2018) High-Density Redox Amplified Coulostatic Discharge-Based Biosensor Array. IEEE J Solid-State Circuits 53:2054-2064