SBIR Phase II: Development of an ultrasensitive, high-throughput autoantibody discovery platform using agglutination-PCR

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project will be to develop a platform technology for detecting autoantibody markers for research and clinical diagnostics. Precision medicine requires the development of more powerful bioanalytic technologies to diagnose disease and direct targeted therapies. This platform uses a ligation-based DNA barcoding technology for improved antibody detection with increased analytical sensitivity and multiplex power to detect more at the most clinically useful time. Additionally, as a solution-phase assay, it is able to detect numerous clinically-relevant autoantibodies that are refractory to common techniques like ELISA. This platform has the potential to accelerate the development of lifesaving diagnostics across a broad spectrum of human diseases. This Small Business Innovation Research Phase II project aims to develop the first solution-phase, ultrasensitive and multiplex antibody assay platform for the early detection, monitoring and treatment of human diseases. The Antibody Detection by Agglutination-PCR (ADAP) platform represents a major advancement in multiplex immunoassay testing. Many current multiplex technologies, such as microarrays and bead-based arrays, scale poorly due to cross-analyte interference, and lack the analytical sensitivity to detect crippling diseases at the most favorable time. The Phase I results showed the expanded and validated ADAP technology for the ultrasensitive and multiplex detection of antibody biomarkers. The Phase II objectives are: 1) Validation of the multiplex ADAP assay for clinical diagnostics serving autoimmune connective tissue diseases, thyroid disorders and celiac diseases; 2) High-throughput automation of multiplex ADAP assay technology for clinical diagnostics; 3) Manufacturing of assay reagents and establishment of quality control standards; and 4) Demonstration of the applicability of multiplex ADAP for a broader set of antibodies. The intellectual merit of this project resides in the achievement of 10,000x increased sensitivity, and 20-30% increased specificity at multiplex while having the option to use existing PCR reader platforms to help keep lab capital costs low. 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.