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

基本信息

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
项目类别：
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&apos 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

项目摘要

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（由申请人提供）：本申请是一项针对护理点设备的可行性研究，用于对最常见的自身抗体进行快速多重分析，这些抗体表明罹患 1 型糖尿病 (T1D) 的风险很高，T1D 是一种由自身免疫系统破坏引起的自身免疫性疾病。产生胰岛素和调节身体能量代谢所需的细胞虽然与更常见的 2 型糖尿病分类，但实际上，它们在病因学、诊断、代谢、流行病学等方面是不同的疾病。目前尚无已知的治疗方法，但人们对筛查和早期检测的兴趣日益浓厚，以便在未来更好地控制和预防青少年中的疾病，每年每 10,000 名成人中就有 18 至 20 例 T1D 病例。据认为，T1D 占所有糖尿病确诊病例的 5%，而且与 2 型糖尿病相比，1 型糖尿病造成的费用不成比例地高。妊娠期可导致 5% 至 10% 的妊娠出现严重的出生缺陷，而 15% 至 20% 的妊娠则可能导致自然流产。1D 病常常无法确诊，因为其症状难以确定，而且患者通常只会在出现急性症状后才寻求治疗。目前用于早期识别 T1D 风险的最佳特征生物标志物是胰岛细胞自身抗体 (ICA)，它不适当地针对垂死的胰腺细胞释放的细胞内蛋白质。 ICA 不被认为是因果关系，而是对未检测到的 T 细胞杀死胰岛 β 细胞而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，ICA 提供了一种循环生物标志物。警惕 T1D 风险升高。特别是，针对胰岛素、IA-1、GAD65 和 ZnT8 蛋白的自身抗体是 T1D 高风险的标志，并且存在的 ICA 越多，风险就越高。这一阶段的可行性研究旨在开发一个快速点。 -护理诊断平台（EOSCAPE-T1D），可以同时测量医生的多个ICA水平¿办公室、实验室、诊所和医院缺乏训练有素的工作人员，目前的 ICA 诊断非常复杂，需要较长的等待时间、大量的实验室设备、经过专门培训的技术人员，并且通常需要放射性同位素。封闭式盒式护理点诊断，改编自申请组织的 EOSCAPE-HIV 平台，该平台开创了一套高性能核酸检测新技术，且每次结果的成本较低。 EOSCAPE-HIV 于 2009 年 9 月被 NIAID 选择开发，用于在未来的 HIV 疫苗试验中区分真正的感染和疫苗诱导的血清阳性，目前正进入开发的验证和确认阶段。流体致动器和盒架构具有新颖的镧系元素时间分辨福斯特共振能量转移检测，用于 T1D 自身抗体的同质多重检测。