Fast multiplexed point-of-care diabetes autoantibody detection by homogeneous FRE

描述（由申请人提供）：本申请是一项关于点护理设备的可行性研究，该设备用于快速多路分析最常见的自身抗体，这些抗体表明发生1型糖尿病（T1D）的高风险，这是一种自身免疫性疾病，由产生胰岛素和调节身体能量代谢所需的细胞被破坏引起。虽然与更常见的2型糖尿病分类，但实际上它们在病因、诊断、代谢、流行病学和治疗的基础上是不同的疾病。目前还没有已知的治愈方法，但人们对筛查和早期发现的兴趣越来越大，以便在未来更好地控制和预防疾病。在青少年中，每年每万人中有18至20例新发T1D病例。在成人中，T1D被认为占所有糖尿病确诊病例的5%，与2型糖尿病相比，1型糖尿病的成本高得不成比例。妊娠前和妊娠早期控制不良的T1D会导致5% - 10%的孕妇出现严重的出生缺陷，15% - 20%的孕妇会自然流产。T1D通常无法确诊，因为其症状难以确定，患者通常只在高血糖发作后不久才寻求急性症状的治疗。目前最具特征的T1D风险早期识别生物标志物是胰岛细胞自身抗体（ICA），它不恰当地靶向垂死胰腺细胞释放的细胞内蛋白。ICAs不被认为是因果关系，而是对未被发现的t细胞杀死胰岛β细胞释放到循环中的抗原的反应。换句话说，当致病过程已经开始但无法检测到时，ICAs提供了一种循环生物标志物，提醒临床医生T1D风险升高。在

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: Project Narrative Type 1 diabetes is a devastating disease in which the body's immune system destroys its own insulin-producing cells, requiring a lifetime of intensive insulin therapy. Unlike the more common type 2 diabetes, type 1 diabetes is most common in young children. This application focuses on development of a powerful new tool for detecting type 1 diabetes early on, when emerging therapies might be able to change the course of the disease: a blood testing system which is both technologically advanced and suitable for use in settings where at-risk young children are already receiving routine medical care.