SBIR Phase I: 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 is the development of a tool to accelerate the discovery of new autoantibody biomarkers for the early detection and personalized treatment of human diseases. Autoantibody biomarkers are broadly used to diagnose a variety of conditions, such as autoimmune disorders, infectious diseases and cancers. However, the limited reproducibility, cost and sensitivity of current autoantibody profiling methods frustrate the discovery of new biomarkers to improve management of these diseases. A cost-effective autoantibody profiling platform that is highly sensitive and robust could reveal changes in the autoantibody repertoire that might have been missed by current methods. Such a tool would serve as an invaluable pipeline for the discovery of new biomarkers, augmenting the ability to detect, treat and understand numerous diseases. In the $7.4 Billion/yr biomarker discovery array market, the proposed tool, sold as a service or as micro-arrays kits for client use, meets must-have needs of several customers, including biopharmaceutical companies seeking for new disease targets, improving clinical trials and academic groups pursuing better understanding of human biology. This SBIR Phase I project proposes to develop a highly multiplexed and sensitive autoantibody biomarker profiling tool to expedite biomarker discovery. The proposed approach uses agglutination-PCR, a novel technique developed at UC Berkeley and Stanford. Agglutination-PCR detects autoantibodies in the solution-phase to ensure proper folding of antigen probes while leveraging the sensitivity and multiplex power of standard qPCR instruments. This project employs an innovative synthetic strategy to prepare and optimize a large panel of probes at low cost. While a traditional synthetic route would take up to 3 months, the proposed strategy could reduce the time down to one week. In addition, the probe library for autoantibody detection will be validated using banked serum/plasma from healthy patients or patients with systemic lupus erythematosus (SLE). This experiment will serve as a powerful proof-of-principle, as SLE displays many distinct autoantibodies that are challenging to detect with other methods. The analytical sensitivity and reproducibility of the proposed product will be compared to standard protein microarrays. The platform will be tested to ensure reproducibility and ease-of-use. The probe library and protocols will function as a minimum viable product and the prototype for applications in other diseases.