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

通过同质 FRE 进行快速多重即时糖尿病自身抗体检测

• 批准号: 8545839
• 负责人: ANDREW M ARSHAM
• 金额: $ 29.52万
• 依托单位: WAVE 80 BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-14 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8545839
• 关键词: Acceleration; Accounting; Acute; Adult; Algorithms; Antibodies; Antigens; Architecture; Autoantibodies; Autoimmune Diseases; Beta Cell; Binding; Biological Assay; Biological Markers; Blood Circulation; Blood capillaries; Blood specimen; Cells; Chemistry; Clinics and Hospitals; Complex; Conceptions; Congenital Abnormality; Detection; Development; Devices; Diabetes Mellitus; Diabetes autoantibodies; Diagnosis; Disease; Early Diagnosis; Early identification; Energy Metabolism; Energy Transfer; Engineering; Epidemiology; Equipment; Etiology; Feasibility Studies; First Pregnancy Trimester; Freeze Drying; Future; Glutamate Decarboxylase; HIV; HIV vaccine; Hyperglycemia; Immunochemistry; Infection; Insulin; Insulin-Dependent Diabetes Mellitus; Islet Cell; Islets of Langerhans; Label; Laboratories; Lanthanoid Series Elements; Lead; Measures; Metabolism; Methods; Modeling; National Institute of Allergy and Infectious Disease; Non-Insulin-Dependent Diabetes Mellitus; Nucleic Acid Amplification Tests; Optics; Pancreas; Patients; Performance; Phase; Physicians' Offices; Pregnancy; Process; Property; Protein Isoforms; Proteins; Radioisotopes; Reagent; Research Infrastructure; Resolution; Risk; Running; Sampling; Signal Transduction; Solutions; Spontaneous abortion; Staging; Symptoms; System; Systems Development; T-Lymphocyte; Testing; Time; Training; Vaccines; Whole Blood; Work; Youth; base; capillary; care seeking; cell killing; computerized data processing; cost; cost effective; disorder control; disorder prevention; fluorophore; high risk; innovation; instrumentation; insulinoma; interest; new technology; novel; patient population; point of care; point-of-care diagnostics; programs; reaction rate; response; screening; verification and validation

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.

描述（由应用程序提供）：此应用是针对护理设备的可行性研究，用于对最常见的自身抗体的快速多路复用分析，这表明开发1糖尿病类型（T1D）的高风险，这是一种由胰岛素产生胰岛素并调节人体能量的细胞所带来的自身免疫性疾病，这是一种自身免疫性疾病。虽然将更为常见的2糖尿病归类为实际目的，但它们是基于病因，诊断，代谢，流行病学和治疗的独特疾病。没有已知的治愈方法，但是对筛查和早期发现的兴趣正在增加，以便将来可以更好地控制疾病和预防。在年轻人中，新的T1D案例的速度为每年每10,000人中的18至20。在成年人中，T1D被认为占所有糖尿病诊断病例的5％，与2型相比，归因于1Diabetes类型的成本占不成比例的。概念前的T1D控制不善，在孕期，可能会导致5％至10％的怀孕，并在15％至20％的怀孕20％中造成重大出生缺陷。 T1D经常无法诊断，因为其症状很难确定，并且患者通常只在高血糖发作后不久就寻求护理急性症状。当前最适合早期鉴定T1D风险的生物标志物是胰岛细胞自动抗体（ICA），它们不适当地靶向从垂死的胰腺细胞中释放出来的细胞内蛋白。 ICA被认为不是因果关系，而是通过未发现的T细胞杀死胰岛β细胞来释放到循环中的抗原的反应。换句话说，当灾难性疾病过程已经在进行中，但无法检测到，ICA提供了一种循环生物标志物，以提醒临床医生升高T1D风险。在 特别是针对蛋白质胰岛素，IA-1，GAD65和ZNT8的自身抗体是高T1D风险的标志，并且存在更多的ICA，风险越高。这项I阶段的可行性研究旨在开发一个快速的护理诊断平台（Eoscape-T1D），该平台可以轻松地测量医生，实验室，诊所和医院的多个ICAS的水平，并具有最低培训的员工，几乎没有其他基础设施。当前的ICA诊断很复杂，需要长时间的等待时间，广泛的实验室设备，经过专门训练的技术以及通常放射性的同位素。 Eoscape-T1D是根据应用程序组织的Eoscape-HIV平台进行改编的封闭式护理诊断点，该平台率领一套新技术，用于高性能的核酸测试，其价格低廉。 NIAID在2009年9月选择了Eoscape-HIV进行开发，用于区分未来的HIV疫苗试验中的真实感染和疫苗诱导的促阳性，现在正在进入开发的验证和验证阶段。 Eoscape-T1D将结合专有的微富集性执行器和墨盒结构与新型的灯笼型时间分析，解决了用于T1D自动抗体的均质多路复用测定的Forster共振能量转移检测。