EAGER: Gut-Nav: A Gut Navigator for Real-Time Diagnostic Reporting on Gastro-Intestinal Health

微电子和纳米电子领域的最新进展使得能够开发用于诊断和治疗疾病的患者友好系统。它们还绕过了侵入性样本提取和劳动密集型实验室分析的需要。沿着这些路线，该提案展示了具有传感器和集成电子组件的胶囊微系统，用于监测和无线共享胰腺健康的诊断。传感器将通过标准光刻工艺制造，并与对胰腺分泌物敏感的生物材料集成。选择的两种生物材料将是（i）与胰腺细胞分泌的microRNA标记物结合的单链microRNA（核糖核酸）序列;和（ii）可以被胰淀粉酶、蛋白酶和脂肪酶消化的天然来源的大分子（例如淀粉、多肽和甘油三酯）的薄膜。这些生物材料将与封装在可摄取胶囊内的基于电容和阻抗的电传感器连接。胶囊骨架将使用生物相容性聚合物进行3D打印。当传感器暴露于肠道中的胰腺分泌物时，它们将实时收集诊断数据并将其无线传输到连接的设备。利用这些技术的传感系统的制造可以提供关于分析物阵列的位置特定数据，以更好地理解触发疾病过程的复杂生物相互作用。这一知识将导致有效的早期检测策略，胰腺健康和其他病理性疾病的肠道。除了共同指导和培训一名研究生外，这种胶囊技术及其与电影《奇妙的航行》的相似之处将被用来捕捉公众的想象力，作为许多刺激和教育推广活动的基础。这项研究旨在展示一种可摄入的无线胶囊系统，能够原位检测胃肠道中的酶和microRNA生物标志物，用于胰腺健康监测。胶囊技术确实存在，但目前还没有可摄取的技术，允许感测肠道内靶向区域内的特定生物分子分析物。胰腺癌表现为胰腺分泌物的化学和生物分子变化。然而，这些分泌物很难进入，因为它们通过胰管排入十二指肠，目前还没有有效指示胰腺癌早期阶段的方法。申报器械涉及材料降解的阻抗和电容感应或电极上的标记探针功能化，以响应分析物暴露和特定反应。这些材料由天然来源的大分子组成，如淀粉、多肽和甘油三酯，它们以薄膜的形式沉积，分别被胰淀粉酶、蛋白酶和脂肪酶消化。探针是在电极表面上功能化的单链microRNA序列，其结合胰腺细胞分泌的microRNA标记物。上述电信号通过组件网络读取和传输，包括模数转换器、蓝牙低功耗芯片、低功耗定时器集成电路和锂聚合物电池。该包装由3D打印的生物相容性胶囊组成，具有用于保留在特定pH值下溶解的聚合物的微网结构，从而允许GI定位靶向。该工具代表了基于聚合物涂层生物降解、生物标志物检测、微电子集成和封装的传感系统的基础。所开发的系统可作为各种其他传感应用的平台，并为设计更小的可摄取或可植入系统铺平了道路，用于体内的各个部分。

Recent advancements in the field of micro- and nano-electronics have enabled the development of patient-friendly systems, for diagnostics and treatment of diseases. They also bypass the need for invasive sample extraction and labor-intensive laboratory analysis. Along these lines, this proposal demonstrates a capsule-microsystem with sensors and integrated electronic components for monitoring and wirelessly sharing the diagnostics on pancreatic health. The sensors will be fabricated by standard lithographic processes and integrated with bio-materials, sensitive to the pancreatic secretions. The two biomaterials of choice will be (i) single-strand microRNA (Ribo-Nucleic Acid) sequences that bind to microRNA markers secreted by pancreatic cells; and (ii) thin films of naturally-derived macromolecules, such as starch, polypeptides, and triglycerides, that can be digested by pancreatic amylase, protease, and lipase. These biomaterials will be interfaced with capacitance and impedance based electrical sensors, encapsulated within the ingestible capsule. The capsule skeleton will be 3D printed with a bio-compatible polymer. As the sensors are exposed to pancreatic secretions in the gut, they will collected diagnostic data in real-time and transmit it wirelessly to the connected devices. The fabrication of sensing systems utilizing these technologies can provide location specific data on an array of analytes for a better understanding of the complex biological interactions triggering a disease process. This knowledge will lead to effective early detection strategies for the pancreatic health and other pathological disorders of the gut. In addition to co-advising and training one graduate student, this capsule technology and its parallels to the film the Fantastic Voyage will be used to capture general public's imagination, serving as a basis for many stimulating and educational outreach activities. The proposed research aims to demonstrate an ingestible wireless capsule system capable of in situ sensing of enzyme and microRNA biomarkers in the gastrointestinal tract for pancreatic health monitoring. Capsule technologies do exist, but no ingestible technology is currently available that allows for sensing of specific biomolecular analytes within targeted regions within the gut. Pancreatic adenocarcinoma manifests in the form of chemical and biomolecular changes in pancreatic secretions. However, these secretions are difficult to access as they are emptied into the duodenum via the pancreatic duct, and there is currently no method for effectively indicating early stages of pancreatic adenocarcinoma. The proposed device involves impedance and capacitive sensing of material degradation or marker probe functionalization over electrodes in response to analyte exposure and specific reactivity. The materials consist of naturally-derived macromolecules, such as starch, polypeptides, and triglycerides, that have been deposited in the form of thin films that are digested by pancreatic amylases, proteases, and lipases, respectively. The probes are single-strand microRNA sequences functionalized on an electrode surface that bind to microRNA markers secreted by pancreatic cells. The electrical signals described above are read and transmitted via a network of components, including an analog-to-digital converter, a Bluetooth low-energy chip, a low power timer integrated circuit, and a lithium polymer battery. The packaging consists of a 3D-printed biocompatible capsule, with micromesh structures for retaining polymers that dissolve at a specified pH, thereby allowing for GI location targeting. This tool represents a foundation for sensing systems based on the biodegradation of polymer coatings, biomarker detection, microelectronics integration, and packaging. The developed system serves as a platform for a variety of other sensing applications and paves the way for the design of smaller ingestible or implantable systems for use in various segments within the body.