A self-powered ingestible wireless biosensing system for real-time in situ monitoring of gastrointestinal tract metabolites

Gastrointestinal (GI) disorders affect a significant portion of the population, leading to substantial healthcare costs. Metabolites derived from the gut microbiota play a crucial role in various physiological processes and diseases, including inflammatory bowel disease (IBD), diabetes, and obesity. Current methods for monitoring small intestinal metabolites are invasive or provide non-real-time analysis. Miniaturized ingestible devices offer a promising solution for accessing the gut microbiota and monitoring biomarkers in situ. Previous research has demonstrated the use of ingestible devices for various applications, such as imaging, endoscopy, temperature monitoring, and biomarker detection. However, a battery-free, self-powered system for real-time metabolite monitoring in the small intestine has been lacking. This research addresses this gap by developing a novel ingestible biosensing system.

The study extensively reviews existing technologies for gastrointestinal monitoring, highlighting the limitations of invasive procedures and non-real-time methods like stool tests, endoscopic fluid collection, and breath testing. It also discusses the progress made in miniaturized ingestible devices, including those used for imaging, endoscopy, and the monitoring of various physiological parameters. The review emphasizes the need for a self-powered, real-time system capable of monitoring metabolites directly within the small intestine, a critical area currently underserved by existing technologies. The authors highlight the significance of accessing real-time data on small intestinal metabolite dynamics for improved understanding of GI health and disease.

The researchers designed a custom microchip that operates directly from the biofuel cell (BFC), avoiding the need for bulky DC-DC converters. The chip utilizes a voltage-to-frequency conversion scheme for wireless transmission via magnetic human body communication (mHBC). The BFC, acting as both power source and glucose sensor, is integrated into a miniature capsule. Electrochemical studies were performed to assess the BFC performance at various pH levels and oxygen concentrations, reflecting the conditions within the small intestine. The response to glucose was tested in different solutions and the impact of temperature variation was assessed. The biocompatibility of the system was evaluated by testing the sensor's response in artificial intestinal fluid containing biofouling agents. The pH-responsive coating was optimized to protect the BFC during its passage through the stomach. The in vitro glucose sensing performance was evaluated using a flow system that mimicked the physiological conditions in the GI tract. In vivo testing was conducted using a porcine model. The capsule's location was tracked via X-ray imaging. Blood glucose levels were also measured to validate the capsule's readings. The authors detailed the materials and reagents used, the chip manufacturing process, capsule fabrication, electrode fabrication, encapsulation process for the flow system and in situ experiments, wireless signal acquisition, and the animal in situ experimental procedures. Ethical considerations and statistical methods are also described.

The custom microchip operates with an average power consumption of 0.4 µW, enabling wireless transmission using mHBC. The glucose BFC exhibited a linear response to increasing glucose concentrations and its performance was affected by pH and oxygen levels, showing sensitivity to changes in the intestinal environment. In vitro tests showed excellent stability and reversibility of the BFC sensor, with a limit of detection of 4.656 mM and a dynamic range of 3–90 mM. Minimal cross-reactivity was observed with interfering compounds, and the sensor showed resilience to biofouling. In vivo testing in a porcine model demonstrated the system's ability to monitor intestinal glucose levels in real-time, with responses correlating with changes in blood glucose levels following oral glucose administration. The system successfully distinguished between different glucose dosages and responded to the dilution of glucose by glucose-free saline. The study showed that the device can operate under different glucose concentrations and presence of other compounds in the intestine.

This research successfully demonstrated a self-powered, battery-free ingestible biosensing capsule for in situ real-time intestinal glucose monitoring. The system addresses several challenges associated with ingestible devices such as battery elimination, miniaturization, signal transmission, and protection against harsh biological environments. The in vitro and in vivo results validated the system's sensitivity, stability, and ability to provide reliable measurements in a physiological setting. The ability to continuously monitor intestinal glucose has significant implications for diagnosing and managing various conditions related to glucose metabolism and absorption. This platform can be expanded to monitor other biomarkers such as pH, oxygen, electrolytes, and drugs, offering a comprehensive view of the gut environment and fostering advancement in the diagnosis and treatment of related diseases.

This study successfully demonstrated a self-powered, battery-free ingestible biosensing system for real-time in situ monitoring of intestinal glucose. The system's ability to operate wirelessly and resist biofouling makes it a significant advancement in the field of ingestible diagnostics. Future work could focus on miniaturizing the device, integrating additional sensors to monitor a wider range of biomarkers, and conducting further in vivo studies to validate the system's long-term performance in diverse populations.

The study was limited to glucose monitoring in a porcine model and the effects of solid food were not extensively explored. The sampling rate used in the in vivo studies might be higher than necessary. Further research is required to assess the device's long-term performance and its applicability in diverse populations and clinical settings.