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

通过外泌体技术和光电子芯片实验室早期检测 1 型糖尿病：EXTOL

• 批准号: 10706522
• 负责人: Jason Gaglia
• 金额: $ 73.32万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10706522
• 关键词: Acoustics; Address; Affect; American; Autoimmune; Autoimmune Diseases; Benchmarking; Beta Cell; Biological Assay; Biological Markers; Biology; Cells; Clinical; Clinical Trials; Complement; DNA; Detection; Development; Devices; Diabetes Mellitus; Diagnosis; Disease; Early Diagnosis; Electronics; Engineering; Environment; Expert Systems; Functional disorder; Genetic Markers; Hour; Inflammation; Insulin-Dependent Diabetes Mellitus; Interdisciplinary Study; Intervention; Islets of Langerhans; Label; MALDI-TOF Mass Spectrometry; Machine Learning; Membrane; Membrane Proteins; Metabolic Marker; Methods; MicroRNAs; Microfluidics; Monitor; Nature; Nucleic Acids; Optics; Outcome; Pancreatectomy; Patients; Persons; Phase; Plasma; Proteins; RNA; Research Personnel; Sampling; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Standardization; Structure of beta Cell of islet; System; Systems Analysis; Systems Integration; Technology; United States; Work; biomarker discovery; detection platform; early detection biomarkers; exosome; experimental study; extracellular vesicles; high throughput screening; improved; innovation; islet; islet cell antibody; microRNA biomarkers; photonics; pre-clinical; protein biomarkers; response biomarker; sensor; treatment response

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.

项目摘要 1型糖尿病（T1 D）是一种自身免疫性疾病，在美国影响超过160万人， 预计到2050年将有超过500万美国人被诊断患有T1 D。临床T1 D之前有 自身免疫性β细胞丢失和功能障碍的隐匿期。可进行疾病预测，用于临床试验 胰岛自身抗体、遗传标记物和代谢标记物的组合。但 短期内的预测能力，特别是在疾病早期或作为对治疗反应的早期标志物， 往往是不够的。这导致T1 D干预需要更长时间和更广泛的临床试验。胰岛- 来源的外泌体（或由胰腺β细胞或胰腺内的附近细胞产生的小的细胞外囊泡）。 胰岛周围环境）可以揭示β细胞功能障碍和胰岛炎症， T1 D的早期检测和监测的生物标志物，但很少已经探索。因此，迫切需要 和未满足的需要，以鉴定和表征胰岛来源的外来体，用于T1 D的早期检测，特别是 在无症状阶段。我们的总体目标是建立一个整合的外泌体分离和分析 用快速免疫荧光技术高通量筛选和鉴定胰岛来源的外泌体标志物的系统 纯化和特异性检测T1 D中胰岛来源的外泌体。拟议工作的理由是 筛选胰岛特异性外泌体标志物，并进一步开发外泌体技术， 用于快速和特异性捕获和分析胰岛衍生的光电子芯片实验室（EXTOL）系统 T1 D中的外泌体。然后，我们将验证EXTOL系统，并使用临床试验筛选外泌体标记物。 来自T1 D患者和适当对照的样品。这项研究的最终成果是提供一个新的 筛选、鉴定和分析外泌体标志物的平台，用于快速和特异性检测无症状的 T1D