An ingestible self-propelling device for intestinal reanimation.

Postoperative ileus (POI) is the leading cause of prolonged hospital stay after abdominal surgery and is characterized by a functional paralysis of the digestive tract, leading to symptoms such as constipation, vomiting, and functional obstruction. Current treatments are mainly supportive and inefficacious and yield acute side effects. Although electrical stimulation studies have demonstrated encouraging pacing and entraining of the intestinal slow waves, no devices exist today to enable targeted intestinal reanimation. Here, we developed an ingestible self-propelling device for intestinal reanimation (INSPIRE) capable of restoring peristalsis through luminal electrical stimulation. Optimizing mechanical, material, and electrical design parameters, we validated optimal deployment, intestinal electrical luminal contact, self-propelling capability, safety, and degradation of the device in ex vivo and in vivo swine models. We compared the INSPIRE's effect on motility in models of normal and depressed motility and chemically induced ileus. Intestinal contraction improved by 44% in anesthetized animals and up to 140% in chemically induced ileus cases. In addition, passage time decreased from, on average, 8.6 days in controls to 2.5 days with the INSPIRE device, demonstrating significant improvement in motility. Luminal electrical stimulation of the intestine via the INSPIRE efficaciously restored peristaltic activity. This noninvasive option offers a promising solution for the treatment of ileus and other motility disorders.

Secure and Stable Wireless Communication for an Ingestible Device.

Wireless communication enables an ingestible device to send sensor information and support external on-demand operation while in the gastrointestinal (GI) tract. However, it is challenging to maintain stable wireless communication with an ingestible device that travels inside the dynamic GI environment as this environment easily detunes the antenna and decreases the antenna gain. In this paper, we propose an air-gap based antenna solution to stabilize the antenna gain inside this dynamic environment. By surrounding a chip antenna with 1 ~ 2 mms of air, the antenna is isolated from the environment, recovering its antenna gain and the received signal strength by 12 dB or more according to our in vitro and in vivo evaluation in swine. The air gap makes margin for the high path loss, enabling stable wireless communication at 2.4 GHz that allows users to easily access their ingestible devices by using mobile devices with Bluetooth Low Energy (BLE). On the other hand, the data sent or received over the wireless medium is vulnerable to being eavesdropped on by nearby devices other than authorized users. Therefore, we also propose a lightweight security protocol. The proposed protocol is implemented in low energy without compromising the security level thanks to the base protocol of symmetric challenge-response and Speck, the cipher that is optimized for software implementation.

Bioinspired, ingestible electroceutical capsules for hunger-regulating hormone modulation.

The gut-brain axis, which is mediated via enteric and central neurohormonal signaling, is known to regulate a broad set of physiological functions from feeding to emotional behavior. Various pharmaceuticals and surgical interventions, such as motility agents and bariatric surgery, are used to modulate this axis. Such approaches, however, are associated with off-target effects or post-procedure recovery time and expose patients to substantial risks. Electrical stimulation has also been used to attempt to modulate the gut-brain axis with greater spatial and temporal resolution. Electrical stimulation of the gastrointestinal (GI) tract, however, has generally required invasive intervention for electrode placement on serosal tissue. Stimulating mucosal tissue remains challenging because of the presence of gastric and intestinal fluid, which can influence the effectiveness of local luminal stimulation. Here, we report the development of a bioinspired ingestible fluid-wicking capsule for active stimulation and hormone modulation (FLASH) capable of rapidly wicking fluid and locally stimulating mucosal tissue, resulting in systemic modulation of an orexigenic GI hormone. Drawing inspiration from Moloch horridus, the "thorny devil" lizard with water-wicking skin, we developed a capsule surface capable of displacing fluid. We characterized the stimulation parameters for modulation of various GI hormones in a porcine model and applied these parameters to an ingestible capsule system. FLASH can be orally administered to modulate GI hormones and is safely excreted with no adverse effects in porcine models. We anticipate that this device could be used to treat metabolic, GI, and neuropsychiatric disorders noninvasively with minimal off-target effects.

Encapsulation of Gas Sensors to Operate in the Gastrointestinal Tract for Continuous Monitoring.

Recent advances in ingestible sensors have enabled in situ detection of gastrointestinal (GI) biomarkers which shows great potential in shifting the paradigm of diagnosing GI and systemic diseases. However, the humid, acidic gastric environment is extremely harsh to electrically powered sensors, which limits their capacity for long term, continuous monitoring. Here, we propose an encapsulation approach for a gas sensor integrated into a nasogastric (NG) tube that overcomes chemical corrosion, electrical short, and mechanical collision in a gastric environment to enable continuous gaseous biomarkers monitoring. The coating effects on the sensitivity, signal latency, and repeatability are investigated. Our long-term continuous monitoring in vitro results show that the proposed coating method enables the gas sensors to function reliably and consistently in the simulated GI environment for more than 1 week. The encapsulation is composed of Polycaprolactone (PCL) to protect against mechanical scratching and Parylene C to prevent a sensor from chemical corrosion and electrical short. The average life-time of the sensor with 10 micrometers Parylene coating is about 3.6 days. Increasing the coating thickness to 20 micrometers results in 10.0 days. In terms of repeatability, 10 micrometers and 20 micrometers Parylene C coated sensors have a standard deviation of 1.30% and 2.10% for its within sensor response, and 5.19% and 3.06% between sensors respectively.

Implantable system for chronotherapy.

Diurnal variation in enzymes, hormones, and other biological mediators has long been recognized in mammalian physiology. Developments in pharmacobiology over the past few decades have shown that timing drug delivery can enhance drug efficacy. Here, we report the development of a battery-free, refillable, subcutaneous, and trocar-compatible implantable system that facilitates chronotherapy by enabling tight control over the timing of drug administration in response to external mechanical actuation. The external wearable system is coupled to a mobile app to facilitate control over dosing time. Using this system, we show the efficacy of bromocriptine on glycemic control in a diabetic rat model. We also demonstrate that antihypertensives can be delivered through this device, which could have clinical applications given the recognized diurnal variation of hypertension-related complications. We anticipate that implants capable of chronotherapy will have a substantial impact on our capacity to enhance treatment effectiveness for a broad range of chronic conditions.