Microfluidic Immunoassay for Enabling In Vivo Gastrointestinal Diagnostics

描述(申请人提供)：痛点和建议的解决方案：胃肠道(GI)疾病，如炎症性肠道疾病和结直肠癌，将显著受益于病变部位的蛋白质生物标记物诊断。这是因为传统的成像方法，如超声波、核磁共振和X射线计算机断层扫描，不能评估这种分子水平的信息。虽然免疫分析技术能够在体外定量疾病生物标记物，但目前的分析技术太大，无法用于在体内评估胃肠道健康。因此，该项目的目标是开发一种可以缩小到胶囊大小的微型诊断分析方法。技术创新：最初的微流控检测将专注于检测 作为肠道出血模型生物标志物的血红蛋白。微流控装置将被设计成在一个完全自主的微流控系统中进行微型规模的电化学免疫分析。本项目的具体目标如下：(1)设计一种检测血红蛋白的电化学酶联免疫吸附试验，并在模拟肠液的条件下进行优化。(2)设计了一种基于毛细管驱动流的小型化、自主式微流控一步法检测蛋白质生物标志物的装置。(3)利用人体肠液对平台进行验证和优化。这项技术的更广泛影响：在短期内，该平台可以与内窥镜相结合，允许在内窥镜检查期间直接分析胃肠道，或者作为长期目标，它可以被整合到基于胶囊的活体诊断设备中，从而允许定期采集胃肠道液体样本。尤其是后一个目标，可能导致一种筛选胃肠道生物标志物的微创手段，从而为患者，甚至健康人提供全面的胃肠道健康评估。此外，作为一种即时翻译应用，这种平台可以扩展到涉及血清携带的生物标志物的护理点(POC)诊断，例如用于乳糜泻的抗TTG2，或用于急性心肌梗死的心肌肌钙蛋白I和T。培训潜力：拟议的培训计划为我提供了一个机会，利用我目前在流体动力学、纳米技术和传感器开发方面的科学背景，同时扩展我的技能集，包括微流体、表面图案化和修改、设备制造和生物工程-所有这些都将对实现我未来的职业目标至关重要，即领导一个利用纳米材料探测生物系统的学术实验室。此外，该项目还提供了与不同领域的专家合作的独特机会，包括生物化学、生物工程、微流体学、胃肠病学和放射学。通过这些互动，我不仅将扩大我的知识面，还将扩大我的学术网络，建立跨学科的联系，并促进未来的合作。

DESCRIPTION (provided by applicant): Pain Point and Proposed Solution: Gastrointestinal (GI) diseases, such as inflammatory bowel disease and colorectal cancer, would significantly benefit from protein-biomarker diagnostics at the site of a lesion. This is because conventional imaging methods such as ultrasound, MRI, and x-ray computed tomography cannot assess this molecular-level information. While immunoassay technologies are capable of quantifying disease biomarkers in vitro, current assay technologies are too large to be utilized for the assessment of gastrointestinal health, in vivo. Therefore, the objective of this project is to develop a miniaturized, diagnostics assay, which can be scaled down to capsule-sized dimensions. Technological Innovation: The initial microfluidic assay will focus on the detection of hemoglobin as a model biomarker for intestinal bleeding. The microfluidic device will be engineered to perform electrochemical immunoassays on a miniaturized scale within a fully autonomous microfluidic system. The specific aims of the project are the following: (1) Design an electrochemical ELISA for hemoglobin, and optimize under conditions that mimic intestinal fluid. (2) Design a miniaturized and autonomous microfluidic device, based on capillary- driven flow, for one-step detection of this protein biomarker. (3) Validate and optimize the platform using human intestinal fluid. Broader Impacts of the Technology: In the near-term, this platform could be coupled with an endoscope, allowing for direct analysis of the GI tract during endoscopy, or as a long-term objective, it could be incorporated into a capsule-based in vivo diagnostic device, allowing for periodic sampling of fluid along the gastrointestinal tract. This latter objective, in particular, could lead to a minimally invasive means of screening for a panel of gastrointestinal biomarkers, thereby providing a thorough assessment of gastrointestinal health for patients, and even healthy individuals. Further, as an immediately translational application, such a platform could be extended to point-of-care (POC) diagnostics involving serum-borne biomarkers, such as anti-TTG2 for celiac disease, or cardiac troponins I and T for acute myocardial infarction. Training Potential: The proposed training plan provides an opportunity for me to leverage my current scientific background in fluid dynamics, nanotechnology and sensor development, while expanding my skill set to include microfluidics, surface patterning and modification, device fabrication, and bioengineering - all of which will be essential for achieving my future career goal of leading an academic lab that utilizes nanomaterials to probe biological systems. In addition, the project provides a unique opportunity to work in collaboration with experts across a variety of fields, including biochemistry, bioengineering, microfluidics, gastroenterology, and radiology. Through these interactions, I will expand not only my breadth of knowledge, but also my academic network, building contacts across disciplines, and enabling future collaborations.