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病人友好的系统得以开发，用于疾病的诊断和治疗。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。沿着这些思路，这项提议展示了一个胶囊-微系统，带有传感器和集成的电子元件，用于监测和无线共享胰腺健康诊断。传感器将通过标准的光刻工艺制造，并与对胰腺分泌物敏感的生物材料集成。这两种生物材料将是(I)与胰腺细胞分泌的microRNA标志物结合的单链microRNA(核糖核酸)序列；以及(Ii)可被胰腺淀粉酶、蛋白酶和脂肪酶消化的天然衍生大分子的薄膜，如淀粉、多肽和甘油三酯。这些生物材料将与基于电容和阻抗的电子传感器接口，封装在可摄入的胶囊中。胶囊骨架将用一种生物兼容聚合物进行3D打印。当传感器接触到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。利用这些技术制造传感系统可以提供一系列分析物的特定位置数据，以便更好地了解触发疾病过程的复杂生物相互作用。这些知识将导致对胰腺健康和其他肠道病理疾病的有效早期检测策略。除了共同为一名研究生提供咨询和培训外，这项胶囊技术及其与电影《奇幻之旅》的相似之处将被用来激发普通公众的想象力，作为许多刺激和教育推广活动的基础。这项拟议的研究旨在展示一种可摄取的无线胶囊系统，该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来检测肠道内目标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改变。然而，这些分泌物很难获得，因为它们通过胰管排空到十二指肠，目前还没有方法有效地指示胰腺癌的早期阶段。建议的设备包括对材料降解的阻抗和电容传感，或者电极上的标记探针功能化，以响应分析物暴露和特定的反应性。这些材料由自然衍生的大分子组成，如淀粉、多肽和甘油三酯，这些大分子以薄膜的形式沉积，分别被胰淀粉酶、蛋白酶和脂肪酶消化。这些探针是单链microRNA序列，作用于电极表面，与胰腺细胞分泌的microRNA标记物结合。上述电信号通过包括模数转换器、蓝牙低能量芯片、低功率定时器集成电路和锂聚合物电池的组件网络来读取和传输。该包装由3D打印的生物兼容胶囊组成，具有微网结构，用于保留在指定pH下溶解的聚合物，从而允许GI定位。该工具为基于聚合物涂层的生物降解、生物标志物检测、微电子集成和包装的传感系统奠定了基础。开发的系统作为各种其他传感应用的平台，并为设计更小的可摄取或植入系统铺平了道路，用于人体内的不同部分。

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.