Closed-Loop Sensing and Actuation for Gastrointestinal Capsule Systems

胃肠胶囊系统的闭环传感和驱动

• 批准号: 1939236
• 负责人: Reza Ghodssi
• 金额: $ 35万
• 依托单位: University of Maryland, College Park
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1939236&HistoricalAwards=false
• 关键词: Closed; Loop; Sensing; Actuation; Gastrointestinal

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.

微创医疗设备因其在早期阶段检测和治疗疾病并减轻患者负担方面具有前所未有的潜力而受到广泛需求。可摄入胶囊系统作为微创胃肠道干预的自主医疗车辆受到了广泛关注。最近的进展已经证明了多种功能，包括胃肠道成像、气体传感、病变活检和药物释放，为胶囊系统检测并随后治疗/监测慢性胃肠道相关疾病铺平了道路，例如炎症性肠病（例如克罗恩病、溃疡性结肠炎）。然而，由于开发能够在胃肠道环境中运行的强大传感器技术所固有的挑战以及应用此类干预措施的紧凑型执行器的要求，很少有系统能够响应传感器信号而表现出反馈驱动的干预。可摄取系统的小外形尺寸和功率要求加剧了这些挑战。作为回应，这项工作将开发一种可摄入胶囊，利用闭环操作将微镖锚定到由传感器信号触发的胃肠道粘膜中。这些传感器的目的是检测炎症性疾病状态，执行器释放载有药物的飞镖来治疗这种疾病。就智力价值而言，这种集成胶囊系统将能够有效检测、干预或进一步监测胃肠道病理。反馈驱动的系统集成将为开发下一代胃肠道驻留医疗设备提供技术平台，以满足对有针对性的个性化和非侵入性治疗日益增长的需求。该项目更广泛的影响在于扩大微创诊断和治疗的视野，提高公众的可及性，从而提高临床诊断和治疗的功效，为患者提供更好的生活质量，并降低成本这项工作可以分为三个具体目标：1）开发用于有针对性的胃肠道诊断和治疗的微飞镖热机械弹簧致动器。将采用热释放硅弹簧将安装的微镖推入胃肠道粘膜。在微镖上设计的仿生组织锚定结构将有助于附着在胃肠道壁上。这些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 的执行器可以批量制造，并且具有紧凑的外形，有利于与其他系统组件的集成。 2) 具有传感器功能的胃肠道靶向胶囊的系统集成。该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定的胶囊激活。板载电容传感器将检测局部目标，例如炎症标记物，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飞镖，分别用于延长治疗或长期监测。弹簧致动器、微飞镖、电子器件和电源将集成到一个胶囊形封装中，该封装具有指定的开口，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式模型中进行测试。将开发几种不同的台式模型，包括一种由合成组织制成的、可以模拟胃肠道蠕动的模型，以及另一种简单的模型，该模型使用动物肠道和管道注射溶液来模拟胃肠道分泌物。台式型号将使用相机或 pH 和温度探头等仪器。拟议的硅基执行器将通过利用双光子 3D 打印技术和创造性蚀刻方法来演示仿生结构，从而推动紧凑型批量制造执行器的开发并增强其功能。基于 pH 敏感涂层的特定区域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智力优势和更广泛的评估进行评估，被认为值得支持。影响审查标准。

项目成果

Wireless Sensor-Integrated Platform for Localized Dissolved Oxygen Sensing in Bioreactors

用于生物反应器中局部溶解氧传感的无线传感器集成平台

• DOI: 10.1109/jmems.2020.2999089
• 发表时间: 2020-06
• 期刊: Journal of Microelectromechanical Systems
• 影响因子: 2.7
• 作者: Stine, Justin M.;Beardslee, Luke A.;Chu, Sangwook;Liu, Sanwei;Motabar, Dana;Bentley, William E.;Ghodssi, Reza
• 通讯作者: Ghodssi, Reza

Complementary Capillary System Integrated Microneedles for Autonomously Localized Therapeutics Loading

互补毛细管系统集成微针，用于自主定位治疗加载

• DOI: 10.1109/jmems.2020.2999255
• 发表时间: 2020-10
• 期刊: Journal of Microelectromechanical Systems
• 影响因子: 2.7
• 作者: Chu, Sangwook;Uplekar, Nikhil;Liu, Sanwei;Ghodssi, Reza
• 通讯作者: Ghodssi, Reza

Thermomechanical Soft Actuator for Targeted Delivery of Anchoring Drug Deposits to the GI Tract (Adv. Mater. Technol. 2/2023)

用于将锚定药物沉积物靶向输送至胃肠道的热机械软执行器（Adv. Mater. Technol. 2/2023）

• DOI: 10.1002/admt.202370009
• 发表时间: 2023-01
• 期刊: Advanced Materials Technologies
• 影响因子: 6.8
• 作者: Levy, Joshua A.;Straker, Michael A.;Stine, Justin M.;Beardslee, Luke A.;Borbash, Vivian;Ghodssi, Reza
• 通讯作者: Ghodssi, Reza

Hybrid and Passive Tissue-Anchoring Mechanism for Ingestible Resident Devices

用于可摄入居民设备的混合和被动组织锚定机制

• DOI: 10.1109/jmems.2020.2999448
• 发表时间: 2020-06
• 期刊: Journal of Microelectromechanical Systems
• 影响因子: 2.7
• 作者: Liu, Sanwei;Chu, Sangwook;Beardslee, Luke A.;Ghodssi, Reza
• 通讯作者: Ghodssi, Reza