Early detection of type 1 diabetes via Exosome Technology with Optoelectronics Lab-on-chip: EXTOL

项目总结 1型糖尿病(T1D)是一种自身免疫性疾病，在美国有160多万人受到影响， 到2050年，预计将有超过500万美国人被诊断出患有T1D。临床T1D之前有一个 自身免疫性β细胞丢失和功能障碍的隐匿期。疾病预测可用于临床试验 目的：结合胰岛自身抗体、遗传标记和代谢标记。然而， 短期内的预测能力，特别是在疾病早期或作为治疗反应的早期标志， 往往是不够的。这导致需要对T1D干预进行更长时间和更广泛的临床试验。小岛- 衍生的外体(或由胰岛β细胞或邻近细胞产生的小细胞外小泡) 胰岛周围环境)可能揭示胰岛细胞功能障碍和胰岛炎症，被认为是有前景的 用于T1D早期检测和监测的生物标志物，但还很少被探索。因此，有一个紧急的 以及尚未满足的识别和表征胰岛来源的外切体以早期检测T1D的需要，特别是 在无症状阶段。我们的总体目标是创建一个完整的外切体分离和分析 用于高通量筛选和鉴定胰岛来源的外切标记的系统 T1D胰岛来源外切体的纯化及特异性检测。拟议工作的基本原理是 筛选胰岛特异的外切体标记，进一步发展一种新的外切体技术 用于快速和特定捕获和分析胰岛的光电子芯片上实验室(EXTOL)系统 T1D中的外体。然后，我们将验证Extol系统并筛选出临床使用的Exosomal标志物 样本来自T1D患者和适当的对照组。这项研究的最终成果是提供一种新的 筛选、鉴定和分析外体标志物的平台，用于快速和特异地检测无症状的 T1D。

PROJECT SUMMARY Type 1 Diabetes (T1D) is an autoimmune disease affecting over 1.6 million people in the United States, and more than 5 million Americans are expected to be diagnosed with T1D by 2050. Clinical T1D is preceded by an occult period of autoimmune beta cell loss and dysfunction. Disease prediction can be performed for clinical trial purposes, with a combination of islet autoantibodies, genetic markers, and metabolic markers. However, the predictive ability in the short term, particularly early in the disease or as an early marker of response to therapy, is often inadequate. This results in needing longer and more extensive clinical trials for T1D interventions. Islet- derived exosomes (or small extracellular vesicles produced by pancreatic beta cells or nearby cells within the peri-islet environment) may reveal beta cell dysfunction and islet inflammation and are believed as promising biomarkers for early detection and monitoring of T1D, but little has been explored yet. Thus, there is an urgent and unmet need to identify and characterize islet-derived exosomes for the early detection of T1D, particularly during the asymptomatic phase. Our overall objective is to create an integrated exosome isolation and analysis system for the high throughput screening and identification of islet-derived exosomal markers with the rapid purification and specific detection of islet-derived exosomes in T1D. The rationale for the proposed work is to screen for pancreatic islet-specific exosomal markers and further develop an Exosome Technology with Optoelectronics Lab-on-chip (EXTOL) system for rapid and specific capturing and analyzing islet-derived exosomes in T1D. Then, we will validate the EXTOL system and screened exosomal markers using clinical samples from T1D patients and appropriate controls. The ultimate product of this study is to provide a new platform to screen, identify, and analyze exosomal markers for rapid and specific detection of asymptomatic T1D.