Researchers are increasingly discovering that the gastrointestinal (GI) system is essential for our overall well-being. Although its primary roles revolve around digestion, the GI system also plays a part in the creation of hormones, immune cells, and even neurotransmitters that can influence mood and cognitive function. Consequently, the GI tract harbors numerous biomarkers that can be advantageous in recognizing, tracking, and addressing ailments—ranging from short-chain fatty acids that signify metabolic syndrome to cytokines that act as indicators of inflammation.

However, there is currently no technology available that can conveniently profile this metabolic and molecular data from the GI tract. Conventional assessment methods involve either fecal analysis or biopsy, which are invasive, costly, and cannot provide real-time profiling throughout the GI tract.

Now, a group of engineers from Caltech has created an innovative capsule named PillTrek, capable of measuring pH, temperature, and a variety of different biomarkers. It includes straightforward, affordable sensors within a compact wireless electrochemical workstation that utilizes low-energy electronics. PillTrek is diminutive, with a diameter of 7 millimeters and a length of 25 millimeters, making it smaller than commercially available capsule cameras used in endoscopy, yet competent in executing a range of electrochemical assessments.

“We engineered this pill to be a highly adaptable platform,” states Wei Gao, a professor of medical engineering at Caltech and a Heritage Medical Research Institute Investigator. “From the perspective of electrochemical sensing, it is exceptionally potent. It can assess metabolites, ions, hormones such as serotonin and dopamine, and possibly even proteins, all within the gut, which presents a complex environment.”

The researchers outline the capsule in a new publication in the journal Nature Electronics. The primary authors of the publication are Jihong Min, a postdoctoral scholar fellow in medical engineering at Caltech, and Hyunah Ahn, a visitor in medical engineering at Caltech and graduate student at the Korea Advanced Institute of Science and Technology (KAIST).

As a proof of concept, PillTrek was utilized in the investigation to measure pH and temperature, along with fluctuating levels of glucose and the neurotransmitter serotonin in animal models.

Gao emphasizes that the electrochemical workstation integrated into the capsule is adaptable. Various sensors could readily be interchanged to facilitate the measurement of different parameters within the gut. His team previously developed a method for 3D printing affordable sensors on sheets of plastic substrate. This approach can be employed to produce the sensors for PillTrek en masse.

Regarding future plans, Gao mentions that he is collaborating with co-author Azita Emami, the Andrew and Peggy Cherng Professor of Electrical Engineering and Medical Engineering at Caltech and director of the Center for Sensing to Intelligence, to explore wireless power transfer and smaller electronic components that would further miniaturize PillTrek and reduce power consumption.

Additional authors of the paper include Heather Lukas (MS ’21), Xiaotian Ma, Rinni Bhansali, Sung-Hyuk Sunwoo, Canran Wang (MS ’23), Yadong Xu, Dickson R. Yao, and Gwangmook Kim from Caltech, as well as Zhaoping Li and Tzung K. Hsiai from the David Geffen School of Medicine at UCLA and Hee-Tae Jung from KAIST.

This research was funded by several organizations, including the National Science Foundation, the National Institutes of Health, the American Cancer Society, the Army Research Office, the US Army Medical Research Acquisition Activity, the National Research Foundation of Korea, the Heritage Medical Research Institute, and the KAIST-UC Berkeley-VNU Global Climate Change Research Center. The team also received significant assistance and resources from the Kavli Nanoscience Institute at Caltech.