This broader impacts of this proposed RAPID proposal is to provide critically enabling measurement science tools to government, industry and academic professionals engaged in mitigating the effects of COVID-19 through work from the NSF Industry-University Cooperative Research Center for Bioanalytic Metrology (CBM). Researchers at Indiana University have developed unique instrumentation to determine the composition of very large particles such as viruses, and they will characterize viruses, vaccine candidates, and antibodies bound to viral particles. Making this unique instrumentation generally available to researchers working on COVID-19 vaccines across the national network of government, industry and academic researchers will quickly address the measurement science problems that will inevitably arise during the race to develop a safe and reproducible vaccine. In parallel, the CBM will address challenges of rapid antibody tests that are not quantitative nor highly sensitive, and typical lab-based methods for determining antibody concentrations are long and cumbersome. Researchers at the University of Notre Dame and Purdue University will develop devices to rapidly quantify the amount of COVID-19 antibodies in patient serum. Such analyses are vital for low-cost examination of antibody levels (and hence immunity) over time. The proposed devices will exploit a combination of innovative antibody capture technology developed at Notre Dame, which provides enhanced signals, and Purdue University’s expertise in the development of point-of-care diagnostic devices. These measurements will be important for investigating the problem of fading immunity and determining if convalescent plasma from a given patient is appropriate for therapeutic studies.
The proposed RAPID research aims to provide fundamental knowledge of the structure of COVID-19 and its elicited antibody response. Analytical and measurement science support of vaccine and biomolecular therapeutic research is notoriously difficult. The molecules in question are often too big and complex for standard characterization methods, and many questions about heterogeneity, stoichiometry and structure cannot easily be answered. Researchers will use advancements in Charge Detection Mass Spectrometry (CDMS) and Ion Mobility Spectrometry (IMS) to study the heterogeneity, stoichiometry, structure and interactions of viral protein assemblies and to provide essential measurements for characterizing newly developed vaccine and therapeutic candidates for COVID-19. The CDMS and IMS tools at the CBM are unique and will allow researchers to directly observe inactivated viruses, 'dummy' viral particles without nucleic acids, bioconjugates containing immunogens on a hapten carrier, oligonucleotides, antibodies complexed to target proteins, and antibodies bound to viral particles. These instruments are starting to revolutionize the analysis of bioconjugations, vaccine development, gene therapies and protein therapeutics. Development of devices for rapidly examining antibody titer will rely on antibody capture in porous membranes that have a long pathlength for sensitive optical detection and a high surface area to volume ratio that enables efficient antibody capture. Device design will exploit expertise in the development of thin strip microfluidic diagnostics. Based on the fluorescence intensity of captured secondary antibodies, these devices will provide a measure of the abundance of different classes of COVID-19 antibodies.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
