Advancing an accessible, high-throughput and multiplex islet autoantibody test with self-collected capillary dried blood spots for regulatory clearance

Project Summary Type 1 diabetes, a chronic autoimmune disorder that affects millions of Americans is characterized by the progressive destruction of the insulin-producing islet cells of the pancreas, resulting in life-long dependency on insulin therapy. Many people with type 1 diabetes are diagnosed with life-threatening diabetic ketoacidosis and develop a panoply of perilous complications affecting every organ over their shortened life spans. Testing for the presence of anti-islet autoantibody biomarkers in blood accurately predicts whether individuals are at risk for developing type 1 diabetes. Autoantibody screening programs have been shown to support interventions that reduce the rates of diabetic ketoacidosis and they help identify eligible candidates for new interventions that may delay or prevent the onset of type 1 diabetes. However, no current testing method exists that combines accuracy, speed, scalability, and the ability to collect samples at home. In application is a follow-on to Enable Biosciences Phase 2 NIDDK SBIR Award R44DK111005 Phase 2B application we are seeking NIDDK support for the process of FDA clearance and comprehensive quality system implementation of our unique dried blood spot test for T1D autoantibodies based on our innovative patented Antibody Detection by Agglutination-PCR (ADAP) technology. ADAP is highly sensitive and ultra-specific and has been repeatedly validated as a top-performing T1D autoantibody assay in blinded peer-reviewed published clinical studies. In Specific Aim 1, we will develop a comprehensive quality system to allow for reliable and high-quality manufacturing of test components to be used for the FDA study. Reagents, materials, protocols, and document control systems will be developed and documented in compliance with FDA requirements. In Specific Aim 2, we will perform standard laboratory analytical validation of the assay, determining the reproducibility, limit of blank, limit of detection and limit of quantification, as well as performing interference analysis by spiking in common adulterants into test samples. In Specific Aim 3, we will perform our clinical validation in collaboration with nationwide and, if needed, global clinical specimen collection sites to establish non-inferiority with the predicate device. . For this