High throughput Point-of-Care assays for diabetes auto-antibody detection

描述（由申请人提供）：随着糖尿病的日益流行，在早期阶段准确可靠地诊断糖尿病的能力已成为公共卫生的优先事项。T1 D风险的早期识别和自身免疫性的发作为寻求预防或延迟疾病的各种主要正在进行的研究提供了基础。研究人员使用胰岛自身抗体阳性、自身抗体血清转换、遗传易感性生物标志物和β细胞功能测定的组合作为标准来选择发展T1 D的高风险个体。然而，目前用于识别处于风险中的个体的技术是昂贵的， 需要研究实验室的参与，并且可能不适合在建立有效的预防干预措施后进行的公共卫生筛查。需要对个体进行基于人群的筛查，因为大多数T1 D新发病例（约70- 80%）没有受影响的亲属。拟议的合作研究的具体目标是开发一种高通量-护理点（POC）测定平台（可靠，准确，具有成本效益，高度灵敏度和特异性标准化，具有快速周转时间），用于自身免疫性糖尿病诊断和随访的自身抗体检测。我们提出的技术的直接应用将针对开发多路复用的、均质的（无洗涤步骤）传感器阵列，其特异性地用于检测四种胰岛素自身抗体，即胰岛素自身抗体（IAA）、谷氨酸脱羧酶（GAD 65）、IA-2或ICA 512自身抗体和ZnT 8自身抗体。 公共卫生相关性：用于更有效地识别可能有资格进行预防性干预的T1 D风险个体的方法将包括低成本、高通量、准确和预测性的测定和可在护理点水平使用的装置。当预防或延迟T1 D的有效方法可用时，应用这种技术可以促进和加快检测，并且对于确定可以从这种治疗中受益的个人至关重要。

DESCRIPTION (provided by applicant): With the growing prevalence of diabetes, the ability to accurately and reliably diagnose diabetes in its earliest stages has become a public health priority. Early identification of T1D risk and the onset of autoimmunity provide the basis for a variety of major ongoing studies seeking to prevent or delay the disease. Investigators have used a combination of islet autoantibody positivity, autoantibody seroconversion, biomarkers of genetic susceptibility and beta cell functional assays as criteria to select individuals at high rik of developing T1D. However, current technology for identification of at risk individuals is costly, requires participation of research laboratories, and may not be suitable for public health screening that would ensue should effective preventative interventions be established. Population based screening of individuals would be required as the majority of new cases of T1D (~70-80 percent) have no affected relatives. The specific aim of the proposed collaborative research is to develop a high throughput - Point of care (POC) assay platform (reliable, accurate, cost-effective, highly sensitive and specific standardized having rapid turnaround time) for autoantibody detection for autoimmune diabetes diagnosis and follow-up. The immediate application of our proposed technology will be directed towards the development of a multiplexed, homogenous (no wash steps), sensor array specifically for the detection of four insulin auto-antibodies namely, Insulin auto-antibodies (IAA), glutamic acid decarboxylase (GAD65), IA-2 or ICA512 auto-antibodies, and ZnT8 auto-antibodies. PUBLIC HEALTH RELEVANCE: Methods for more efficient identification of individuals at risk of T1D who may be eligible for preventative intervention would include low cost, high-throughput, accurate and predictive assays and devices that could be used at the point of care level. Application of such technologies could facilitate and expedite testing when effective ways to prevent or delay T1D become available and would be essential for identifying individuals who can benefit from such treatments.