Engineering researchers have developed a battery-free, pill-shaped, ingestible biosensor system designed for continuous monitoring of the gut environment. It gives scientists the ability to monitor gut metabolites in real time, which was previously not possible. This feat of technological integration could open a new understanding of the composition of gut metabolites, which have significant implications for human health as a whole.
The work, led by engineers from the University of California San Diego, appears in the December issue of the journal nature communication.
The ingestible, biofuel-powered sensor facilitates in situ access to the small intestine, facilitating glucose monitoring and providing continuous results. These measurements are a critical component in tracking overall gastrointestinal health, are an important factor in studying diet, diagnosing and treating various diseases, preventing obesity, and more.
“In our experiments, the battery-free biosensor technology continuously monitored glucose levels in the small intestine of pigs 14 hours after ingestion, providing measurements every five seconds for two to five hours,” said Ernesto De La Paz Andres, a graduate student in nanotechnology at UC San Diego and one of the first co-authors of the publication. “Our next step is to reduce the size of the pills from the current 2.6cm length to make them easier for people to swallow.”
Older methods of directly monitoring the interior of the small intestine can cause significant patient discomfort while producing only brief, single data records of a constantly changing environment. In contrast, this biosensor provides access to continuous data readings over time. The platform could also be used to develop new ways to study the microbiome of the small intestine. The “smart pill” approach could lead to simpler and cheaper ways to monitor the small intestine, which could result in significant cost savings in the future.
“Currently, the way to take fluid in your stomach and intestines is to do an endoscopy, where a doctor inserts a catheter down your throat and into your gastrointestinal tract,” said Patrick Mercier, a professor of electrical and computer engineering at UC San Diego, who led the team along with nanoengineering professor Joseph Wang. Wang and Mercier co-direct the UC San Diego Center for Wearable Sensors. “By combining the ultra-low-power circuit and wireless technologies from my lab with glucose-powered fuel cells and state-of-the-art electrochemical sensing from the lab of Joseph Wang, professor of nanoengineering at UC San Diego, we have the opportunity to create new modalities for the understanding what happens in the small intestine,” Mercier said.
Instead of a battery, this “smart pill” is powered by a non-toxic fuel cell that runs on glucose.
“With our battery-free smart pill approach, we have the ability to monitor the small intestine for much longer than just a moment,” Wang said. “We also plan to add additional sensors to the system. Our goal is to develop a sensory platform for the gut that allows collecting many different types of information over longer periods of time. We’re working to show that there’s so much opportunity to find out what’s really going on in the small intestine. I hope that this type of information will be helpful in better understanding the role of changes in the environment of the small intestine in health and disease.”
A smarter way to measure critical gut activity
About 20% of us will suffer from gastrointestinal disorders at some point in our lives. These may include inflammatory bowel disease (IBD), diabetes or obesity, all of which are caused in part by the dysfunction of the gut processes that involve the absorption or digestion of gut metabolites. Such diseases impose significant costs on the economy and put a strain on healthcare systems. Therefore, access to information from the relevant sections of the gastrointestinal tract is quite high.
However, there are significant challenges in developing ingestible sensors like the new smart pill system being developed at UC San Diego.
“It has proven difficult to develop an ingestible device that is equipped with the necessary sensors and electronics to perform a wireless readout and that does not require batteries,” Wang said.
To meet these specs, the team landed on a self-sufficient glucose-biofuel biosensor integrated into a circuit that performs energy harvesting, biosensing, and wireless telemetry using an energy-to-frequency conversion scheme that mimics the magnetic communication of the human body uses.
The unique battery-free operation is enabled by the team’s glucose biofuel cell (BFC) to harvest power during operation while simultaneously measuring changing glucose concentrations. Its energy-efficient magnetic Human Body Communication (mHBC) system operates in the 40-200 MHz range to receive the time-resolved transmitted signals.
“It uses the glucose present in the gut as a biofuel to power the device,” Mercier said. “Getting all of this to work with ultra-low-power electronics and with a stable but small glucose biofuel cell were major technical challenges that were addressed here.”
The Proof-of-Concept Smart Pill measures 2.6 cm in length and 0.9 cm in diameter. So far, small intestine data collection has only been performed in pigs, which have a gastrointestinal tract similar in size to humans.
After getting promising results in these experiments, the researchers now plan to increase the number of sensors available in the pills. This allows even more chemical parameters in the intestine to be monitored. They also plan to further miniaturize the sensors and electronic circuitry to match what is currently available in the smart pill market.
“Given that the gastrointestinal tract exhibits dynamic changes in pH, temperature, and oxygen concentration, future work envisions the integration of additional sensor modalities to account for these differences,” said De La Paz Andres.
This project is a UC San Diego intercampus collaboration involving researchers from the Department of Electrical and Computer Engineering and the Department of Nanoengineering at the UC San Diego Jacobs School of Engineering; the UC San Diego Center for Wearable Sensors; the UC San Diego Center for Microbiome Innovation; the Department of Gastroenterology at UC San Diego Health; and the VA San Diego Healthcare System.
The study was co-authored by Nikhil Harsha Maganti, Department of Electrical and Computer Engineering, UC San Diego, along with De La Paz, Mercier, and Wang; Alexander Trifonov, Itthipon Jeerapan, Kuldeep Mahato, Lu Yin, Thitaporn Sonsa-ard, Nicolas Ma, and Won Jung, Department of Nanoengineering, UC San Diego; Ryan Burns, Department of Electrical and Computer Engineering, UC San Diego; and Amir Zarrinpar, Department of Gastroenterology and Center for Microbiome Innovation, UC San Diego and VA San Diego Healthcare System.
This research was supported by the UC San Diego Center for Wearable Sensors (CWS).