Rapidly Adaptable and Mass-Producible Microscopic Chiplets for Minimally-Instrumented Respiratory Viral Screening

Project Summary Objective: Respiratory viral infections affect millions of individuals each year. Conducting frequent widespread viral screening tests can curb outbreaks by quickly identifying infectious persons. Unfortunately, no screening diagnostic platform exists with the capacity to test hundreds of millions of people daily during a pandemic. This proposal is the first step in developing a novel viral screening test to fill this gap. The assay will consist of microscopic circuits containing field effect transistors with antigen-specific receptors that are sensitive to particular viruses. These chiplets - barely visible to the human eye - will be powered by light and will transmit data using a light emitting diode, such that a few can be mixed into an extracted sample and illuminated with a handheld device to yield immediate results. This diagnostic will be scalable and inexpensive; millions of tiny chiplets can be fabricated simultaneously. It will be minimally instrumented; an ordinary cellphone with a strobe flash and camera will interface with the chips. It will be flexible, rapidly adaptable, and multiplexable; receptors specific to different or emerging viruses could be immobilized on distinct circuits, allowing multiple diseases to be detected simultaneously in a single patient sample. This diagnostic will thus be unmatched as a mass producible, simple to use, adaptable, and high throughput tool for frequent and widespread virus screening. Specific aims: The proposed diagnostic will be developed by pursuing the following specific aims. 1. Integrate biological field effect transistors into the existing optical wireless integrated circuit platform. 2. Develop a multiplexed detection scheme for interacting with optical wireless integrated circuits. 3. Demonstrate the test's feasibility in a clinically relevant quantitative range using mock clinical specimens. Career development plan and career goals: Dr. Matthew Campbell (Ph.D., P.E.) is a postdoctoral researcher in the School of Engineering and Applied Science at the University of Pennsylvania, where his work is focused on fabricating microelectromechanical systems. The proposed K25 career development award will apply his nanofabrication skills toward biosensor development and extend his training and exposure into two new domains: (1) biomedical experimentation, and (2) medical biology. This proposal contains a cohesive mentorship and didactic strategy centered on these areas to accelerate his trajectory toward research independence. Completion of this multifaceted training plan will position Dr. Campbell with the cross-disciplinary skills and expertise necessary to become a leading investigator in the field of biomedical sensing diagnostics. Mentors and environment: Dr. Campbell is enthusiastically supported by the university and his strong mentoring team. His primary mentor is an expert in micromanufacturing (Prof. Igor Bargatin (Ph.D.)), and his co- mentors bring extensive experience in microscopic circuits (Prof. Marc Miskin (Ph.D.)), field effect transistor sensors (Prof. Charlie Johnson (Ph.D.) and Prof. Haim Bau (Ph.D.)), and viral respiratory tract infections (Prof. Ronald Collman (M.D.). This group will provide the ideal training situation for Dr. Campbell to develop this assay.