Closed-Loop Sensing and Actuation for Gastrointestinal Capsule Systems

微创医疗设备由于其在实现早期疾病检测和治疗方面的前所未有的潜力而具有很高的需求，同时减轻了患者的负担。可摄取胶囊系统作为用于微创胃肠道（GI）介入的自主医疗车辆已经受到了极大的关注。最近的进展已经证明了各种功能，包括GI成像、气体传感、病变活检和药物释放，为胶囊系统检测和随后治疗/监测慢性GI相关病理（如炎症性肠病（如克罗恩病、溃疡性结肠炎））铺平了道路。然而，由于开发能够在GI环境中操作的鲁棒传感器技术所固有的挑战以及对应用这种干预的紧凑致动器的要求，很少有系统已经证明了响应于传感器信号的反馈驱动的干预。可摄取系统的小形状因子和功率要求放大了这些挑战。作为回应，这项工作将开发一种可摄取的胶囊，利用闭环操作将微飞镖锚定到由传感器信号触发的胃肠道粘膜中。传感器将旨在检测炎症性疾病状态，致动器释放载药飞镖以治疗疾病。关于知识价值，这种集成胶囊系统将能够有效地检测，干预或进一步监测胃肠道病变。反馈驱动的系统集成将为开发下一代GI驻留医疗设备提供技术平台，以满足日益增长的针对性个性化和非侵入性治疗需求。该项目的更广泛影响在于扩大微创诊断和治疗的范围，以提高公众的可及性，因为它将提高临床诊断和治疗的效率，为患者提供更好的生活质量，并降低与更具侵入性的程序相关的成本。1）开发用于靶向GI诊断和治疗的微型飞镖加载的热机械弹簧致动器。将使用热释放硅弹簧将安装的微型飞镖推进GI粘膜。仿生组织锚定结构设计上的microdarts将有助于附着到胃肠道壁。飞镖将采用微机电系统（MEMS）技术和高精度3D光刻技术制造。基于MEMS的致动器可以批量制造，并且具有紧凑的形状因子，便于它们与其他系统部件集成。2)传感器使能的胃肠道靶向胶囊的系统集成。反馈驱动系统将通过将靶向微传感器和药物释放组件集成到单个胶囊中来开发。pH敏感涂层将允许区域特异性胶囊活化。板载电容传感器将检测局部目标，如炎症标记，并单独触发弹簧致动器，以部署药物洗脱或传感器集成的微型飞镖，分别用于延长治疗或长期监测。弹簧致动器、微型飞镖、电子器件和电源将被集成到具有指定开口的胶囊形包装中，用于与胃肠道壁相互作用。3)体外模型设计和系统验证。胶囊系统的输送、驱动和锚定机制将在模拟台架模型中进行测试。将采用几种不同的台式模型，包括一种由合成组织制成的模型，可以模拟胃肠道的蠕动，另一种简单的模型，使用动物肠道与管道注射溶液模拟胃肠道分泌物。仪器如摄像机或pH和温度探头将与台式模型一起使用。拟议的硅基致动器将通过利用双光子3D打印技术和创造性的蚀刻方法来展示仿生结构，推动紧凑型批量制造致动器的开发并增强其能力。基于pH敏感涂层的区域特定目标将建立在先前研究pH敏感聚合物在可摄入胶囊系统中的作用的基础上。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Minimally invasive medical devices are in high demand due to their unprecedented potential in achieving detection and treatment of diseases at early stages with reduced burden to the patient. Ingestible capsule systems have received significant attention as autonomous medical vehicles for minimally invasive gastrointestinal (GI) tract interventions. Recent advancements have demonstrated a variety of functions including GI imaging, gas sensing, lesion biopsy, and drug release, paving the way for capsule systems to detect and subsequently treat/monitor chronic GI-associated pathologies such as inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis). However, few systems have demonstrated feedback-driven intervention in response to sensor signals due to challenges inherent in developing robust sensor technologies capable of operating in the GI environment and the requirements for compact actuators to apply such interventions. The small form factor and power requirements for ingestible systems amplify these challenges. In response, this work will develop an ingestible capsule utilizing closed-loop operation for anchoring microdarts into the GI mucosa triggered by a sensor signal. The sensors will be aimed at detecting an inflammatory disease state with the actuator releasing medication laden darts to treat the condition. With regard to intellectual merit, this integrated capsule system will enable effective detection, intervention, or further surveillance of GI pathologies. The feedback-driven system integration will provide a technological platform to develop next-generation GI-resident medical devices to meet the growing demand for targeted personalized and non-invasive therapies. The broader impact of this project lies in the goal of expanding the horizon of minimally invasive diagnostics and therapeutics to improve public accessibility, as it will lead to improved efficacy of clinical diagnosis and treatment, provide a better quality of life for patients, and reduce costs associated with more invasive procedures.This effort can be broken down in to three specific aims: 1) Development of microdart-loaded thermomechanical spring actuators for targeted GI diagnostics and treatment. Thermally-released silicon springs will be implemented to propel mounted microdarts into the GI mucosa. Biomimetic tissue-anchoring structures designed on the microdarts will facilitate attachment to the GI tract wall. The darts will be fabricated with both microelectromechanical systems (MEMS) techniques and high precision 3D lithography. The MEMS based actuators can be batch fabricated and possess a compact form factor facilitating their integration with other system components. 2) Systems integration of sensor-enabled GI tract-targeting capsules. The feedback-driven system will be developed by integrating both targeting microsensors and drug-releasing components into a single capsule. A pH-sensitive coating will allow region-specific capsule activation. An onboard capacitive sensor will detect local targets, such as inflammatory markers, and individually trigger spring actuators to deploy drug-eluting or sensor-integrated microdarts for extended therapy or long-term monitoring, respectively. The spring actuators, microdarts, electronics, and power source will be integrated into a capsule-shaped package with designated openings for interaction with the GI tract wall. 3) In vitro model design and system validation. The delivery, actuation, and anchoring mechanisms of the capsule systems will be tested in a simulated benchtop model. Several different benchtop models will be pursued, including one made from synthetic tissue that can mimic peristalsis of the GI tract and another simple model that uses animal intestines with tubing to inject solutions for simulating GI secretions. Instrumentation such as a camera or a pH and temperature probe will be used with the benchtop models. The proposed silicon-based actuator will advance the development of compact batch-fabricated actuators and augmentation of their capabilities by leveraging two-photon 3-D printing technology and creative etching methods to demonstrated biomimetic structures. The region-specific targeting based on pH-sensitive coatings will build on previous work examining the role of pH sensitive polymers for ingestible capsule systems.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.