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

项目摘要 1型糖尿病是一种影响数百万美国人的慢性自身免疫性疾病，其特征是： 胰腺产生胰岛素的胰岛细胞的逐渐破坏，导致终身 依赖胰岛素治疗。许多1型糖尿病患者被诊断为危及生命的糖尿病。 糖尿病酮症酸中毒，并发展出一系列危险的并发症，影响他们的每个器官。 缩短寿命。准确检测血液中抗胰岛自身抗体生物标志物的存在 预测个体是否有患1型糖尿病的风险。自身抗体筛查项目 已被证明支持降低糖尿病酮症酸中毒率的干预措施， 为可能延迟或预防1型糖尿病发作的新干预措施确定合格的候选人。 然而，目前还不存在将准确性、速度、可扩展性和以下能力结合在一起的测试方法： 在家采集样本。 在应用中是启用生物科学第2阶段NIDDK SBIR奖R44 DK 111005的后续产品 2B阶段申请我们正在寻求NIDDK对FDA批准过程的支持， 全面的质量体系实施我们独特的T1 D自身抗体干血斑检测 基于我们的创新专利抗体检测凝集-PCR（ADAP）技术。ADAP 具有高度敏感性和超特异性，已被反复验证为最佳T1 D 在盲态同行评审的已发表临床研究中进行自身抗体测定。 在具体目标1中，我们将开发一个全面的质量体系，以实现可靠和高质量的产品。 用于FDA研究的试验组件的生产。试剂、材料、方案和 将按照FDA的要求开发和记录文件控制系统。 在具体目标2中，我们将对检测试剂盒进行标准实验室分析验证， 重现性、空白限、检测限和定量限，以及 通过将常见掺杂物加标到供试品中进行干扰分析。 在具体目标3中，我们将与全国合作进行临床验证，如果需要， 全球临床样本采集中心，以确定与同品种器械的非劣效性。 .为此

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