Nanoengineers have developed a self-powered device capable of measuring and transmitting data on the glucose level in the small intestine. The capsule, which can be swallowed, could be used to deliver real-time information on critical metabolites in the human body, suggest the teams led by Joseph Wang and Patrick P. Mercier from the University of California San Diego, La Jolla, USA, who designed and tested the device in a porcine model .
Inside the Gastrointestinal Tract
Exploring the body from the inside is a powerful way to investigate diseases. Gastroscopes and enteroscopes have made it possible to inspect the walls of the stomach and bowels for lesions and alterations. Ingestible capsules incorporating light sources, cameras, batteries, and transmitters, can give us a lively picture of what happens at the walls of the digestive tract. However, cameras only provide snapshots of the body at a given time. Identifying the dynamics of metabolism needs sensors that transmit real-time data from the location of interest, but direct metabolic measurements are difficult.
Metabolic data of the small intestine are usually acquired indirectly, via stool or breath tests, and glucose concentration is usually obtained from the blood. In contrast, the capsule developed by Wang, Mercier, and their teams for the first time measures and transmits real-time data on the dynamics of the glucose level, while it passes the small intestine. This three to five meters long intestine section before the large intestine poses two main challenges for the development of encapsulated sensors: the power supply and the pH environment for the sensing electrodes.
Combined Power Generator and Sensor
Ingestible capsules usually rely on batteries to power their sensors and transmit data. However, batteries increase the size of the capsule and only supply energy for a certain amount of time. In addition, they contain a toxic element that could leak if the case breaks. The researchers, therefore, focused on biofuel cells, which generate electric energy from metabolites such as glucose or lactate. The glucose biofuel cell they developed had a dual function: not only did it provide the energy for operation and transmission, it also performed the sensing itself.
Glucose biofuel cells generate power from the glucose oxidase reaction. This reaction needs a neutral pH, which means that the electrodes had to be protected from the acidic environment of the stomach. Three layers of a pH-responsive enteric coating were used as a cover, keeping the sensor intact in the stomach, put dissolving in the pH-neutral environment of the small intestine, thereby exposing the electrodes. The rest of the electronics, including a microchip and antenna, remained encapsulated in a stable 3D-printed shell made of silicone and polyurethane.
The electrodes themselves were made of a nickel foam coated with carbon nanotubes and immobilized enzymes. For the anode, the researchers devised a glucose oxidation reaction using glucose oxidase and a mediator, while bilirubin oxidase and a mediator performed the reduction of oxygen. The generated voltage was then converted into a frequency signal, which could be transmitted through an integrated loop-based antenna.
To test the device, the researchers used a porcine model. They fed a pig under anesthesia with the capsule (by intubation) and kept the (woken) animal fasting. Fourteen hours later, when the capsule had entered the small intestine, the pig was anesthetized again, and fed with glucose solutions of various concentrations, roughly comparable to the intake of zero, one, two, or three two-gram glucose candy drops in a large glass of water.
The boluses led to clear responses in the receiver. Blood glucose was also measured in parallel, using a conventional method. While the capsule measured stepwise changes, reflecting the bolus arrivals in the small intestine, blood glucose levels increased continuously. This means that monitoring both concentrations could be used to pinpoint difficulties in sugar absorption. “There are no other ways to comfortably measure real-time intestinal glucose concentrations,” the researchers state.
For future developments, the researchers envision integrating even more sensors in this self-powered circuit, for example, to track pH, oxygen, or other metabolites and drugs. However, several parameters must be tested first. For example, it is unclear what happens when the pig is awake and solid food is present, since solid parts may block the electrodes and decrease their response.
The dimensions of the device also need fine-tuning. With its size of more than two and a half centimeters in length and almost one centimeter in diameter, the capsule is hard to swallow and may even lead to complications when traveling through the digestive tract.
 Ernesto De la Paz, Nikhil Harsha Maganti, Alexander Trifonov, Itthipon Jeerapan, Kuldeep Mahato, Lu Yin, Thitaporn Sonsa-ard, Nicolas Ma, Won Jung, Ryan Burns, Amir Zarrinpar, Joseph Wang, Patrick P. Mercier, A self-powered ingestible wireless biosensing system for real-time in situ monitoring of gastrointestinal tract metabolites, Nat. Commun. 2022. https://doi.org/10.1038/s41467-022-35074-y
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