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.

Activated Metals to Generate Heat for Biomedical Applications.

Delivering heat in vivo could enhance a wide range of biomedical therapeutic and diagnostic technologies, including long-term drug delivery devices and cancer treatments. To date, providing thermal energy is highly power-intensive, rendering it oftentimes inaccessible outside of clinical settings. We developed an in vivo heating method based on the exothermic reaction between liquid-metal-activated aluminum and water. After establishing a method for consistent activation, we characterized the heat generation capabilities with thermal imaging and heat flux measurements. We then demonstrated one application of this reaction: to thermally actuate a gastric resident device made from a shape-memory alloy called Nitinol. Finally, we highlight the advantages and future directions for leveraging this novel in situ heat generation method beyond the showcased example.

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.

Cost-Effective Solution of Remote Photoplethysmography Capable of Real-Time, Multi-Subject Monitoring with Social Distancing.

Recent advances in remote-photoplethysmography (rPPG) have enabled the measurement of heart rate (HR), oxygen saturation (SpO2), and blood pressure (BP) in a fully contactless manner. These techniques are increasingly applied clinically given a desire to minimize exposure to individuals with infectious symptoms. However, accurate rPPG estimation often leads to heavy loading in computation that either limits its real-time capacity or results in a costly setup. Additionally, acquiring rPPG while maintaining protective distance would require high resolution cameras to ensure adequate pixels coverage for the region of interest, increasing computational burden. Here, we propose a cost-effective platform capable of the real-time, continuous, multi-subject monitoring while maintaining social distancing. The platform is composed of a centralized computing unit and multiple low-cost wireless cameras. We demonstrate that the central computing unit is able to simultaneously handle continuous rPPG monitoring of five subjects with social distancing without compromising the frame rate and rPPG accuracy.

In Situ Detection of Gastrointestinal Inflammatory Biomarkers Using Electrochemical Gas Sensors.

More than two decades ago it was discovered that nitric oxide (NO) concentrations in gas aspirated during colonoscopy were more than 100 times higher in patients diagnosed with Ulcerative Colitis (UC) than controls. While this provides a diagnostic opportunity, it has not been possible to perform in situ detection of NO via a non-invasive manner. This work presents the feasibility of in situ detection of NO by means of a capsule-like electrochemical gas sensor. Our in vivo results in a large animal model of intestinal inflammation show that NO can be directly detected at the site of inflammation and that it quickly dissipates to surrounding tissues, demonstrating the importance of in situ detection.

An automated all-in-one system for carbohydrate tracking, glucose monitoring, and insulin delivery.

Glycemic control through titration of insulin dosing remains the mainstay of diabetes mellitus treatment. Insulin therapy is generally divided into dosing with long- and short-acting insulin, where long-acting insulin provides basal coverage and short-acting insulin supports glycemic excursions associated with eating. The dosing of short-acting insulin often involves several steps for the user including blood glucose measurement and integration of potential carbohydrate loads to inform safe and appropriate dosing. The significant burden placed on the user for blood glucose measurement and effective carbohydrate counting can manifest in substantial effects on adherence. Through the application of computer vision, we have developed a smartphone-based system that is able to detect the carbohydrate load of food by simply taking a single image of the food and converting that information into a required insulin dose by incorporating a blood glucose measurement. Moreover, we report the development of comprehensive all-in-one insulin delivery systems that streamline all operations that peripheral devices require for safe insulin administration, which in turn significantly reduces the complexity and time required for titration of insulin. The development of an autonomous system that supports maximum ease and accuracy of insulin dosing will transform our ability to more effectively support patients with diabetes.

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.