This application is a feasibility study for a point of care device for rapid multiplexed analysis of the most common auto-antibodies that indicate high risk for developing type 1diabetes (T1D), an autoimmune disorder caused by destruction of the cells required to produce insulin and regulate the body's energy metabolism. While classified with the much more common type 2 diabetes, for practical purposes they are distinct diseases on the basis of etiology, diagnosis, metabolism, epidemiology, and treatment. There is no known cure, but interest is increasing in screening and early detection to enable better disease control and prevention in the future. Among youth the rate of new cases of T1D is between 18 and 20 per 10,000 each year. In adults, T1D is thought to account for as much as 5 percent of all diagnosed cases of diabetes, and the costs attributed to type 1diabetes compared to type 2 are disproportionately high. Poorly controlled T1D before conception and during the first trimester can cause major birth defects in 5 percent to 10 percent of pregnancies and spontaneous abortions in15 percent to 20 percent of pregnancies. T1D often goes undiagnosed because its symptoms are difficult to pinpoint, and patients generally only seek care for acute symptoms soon after the onset of hyperglycemia. The best characterized current biomarkers for early identification of T1D risk are islet cell auto-antibodies (ICA) which inappropriately target intracellular proteins released from dying pancreatic cells. ICAs are not thought to be causal but rather to be a response to antigens released into circulation by undetected T-cell killing of pancreatic islet beta cells. In other words, when the causal disease process is already underway but undetectable, ICAs provide a circulating biomarker to alert clinicians to elevated T1D risk. In particular, auto-antibodies against the proteins insulin, IA-1, GAD65, and ZnT8 are hallmarks of high T1D risk, and the more ICAs are present, the higher the risk. This Phase I feasibility study seeks to develop a fast point-of-care diagnostic platform (the EOSCAPE-T1D) which can simultaneously measure the levels of multiple ICAs in doctors? offices, labs, clinics, and hospitals with minimally trained staff and little to no other infrastructure. Current ICA diagnostis are complex, and require long wait times, extensive laboratory equipment, specially trained technicians, and often radioactive isotopes. The EOSCAPE-T1D is an enclosed cartridge point of care diagnostic adapted from the applicant organization's EOSCAPE-HIV platform, which pioneered a suite of new technologies for high-performance nucleic acid testing with a low cost-per-result. The EOSCAPE-HIV was chosen for development in September 2009 by NIAID for use in differentiating between true infection and vaccine-induced seropositivity in future HIV vaccine trials and is now entering the verification and validation stage of development. The EOSCAPE-T1D will combine proprietary micro-fluidic actuators and cartridge architecture with novel lanthanide time resolved Forster resonance energy transfer detection for a homogeneous multiplexed assay for T1D auto-antibodies.
