Closed-Loop Sensing and Actuation for Gastrointestinal Capsule Systems

University Of Maryland, College Park, College Park MD

Investigators

Abstract

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.