Caltech’s New Smart Pill Can Read Your Gut Like Never Before

Male Large Intestine Anatomy Close Up — A novel 7 × 25 mm capsule, PillTrek, wirelessly profiles gut chemistry—pH, temperature, metabolites, and neurotransmitters—offering a minimally invasive window into the gut’s vital role in health. Credit: Stock

PillTrek is a mini capsule that senses gut biomarkers in real time. It enables advanced GI diagnostics without invasive methods.

Researchers are gaining a deeper appreciation for the critical role the gastrointestinal (GI) tract plays in maintaining overall health. Beyond its primary responsibilities in digestion, the GI system contributes to the production of hormones, immune cells, and neurotransmitters that influence brain function and emotional well-being.

Because of this, the GI tract contains a wide array of biomarkers that are valuable for diagnosing, tracking, and managing disease—from short-chain fatty acids associated with metabolic syndrome to cytokines linked to inflammation.

However, current technologies fall short when it comes to capturing this biochemical information directly from the GI tract. Existing methods, such as fecal sampling and tissue biopsies, are often invasive, costly, and unable to deliver continuous or comprehensive real-time data throughout the length of the digestive system.

Miniature PillTrek Smart Capsule Shown Next to U.S. Quarter — Caltech’s PillTrek smart capsule measures just 7 millimeters in diameter and 25 millimeters in length, making it smaller than commercially available capsule cameras used for endoscopy but capable of executing a range of electrochemical measurements in the gut. Credit: Jihong Min and Wei Gao

A new solution: PillTrek smart capsule

A group of engineers at Caltech has created a new smart capsule named PillTrek, designed to monitor pH, temperature, and various biomarkers within the gastrointestinal tract. The device contains a compact, wireless electrochemical system built with affordable sensors and powered by low-energy electronics. Measuring just 7 millimeters wide and 25 millimeters long, PillTrek is smaller than typical capsule endoscopy cameras yet equipped to perform a broad array of electrochemical analyses.

3D Printed Biosensor Array Inside Caltech’s PillTrek Capsule — A 3D-printed biosensor array is at the heart of the electrochemical workstation inside Caltech’s PillTrek smart capsule. Credit: Jihong Min and Wei Gao

“We designed this pill to be a very versatile platform,” says Wei Gao, professor of medical engineering at Caltech and a Heritage Medical Research Institute Investigator. “From an electrochemical-sensing point of view, it is very powerful. It has the ability to measure metabolites, ions, hormones such as <span class="glossaryLink" aria-describedby="tt" data-cmtooltip="

serotonin

Serotonin is a neurotransmitter that is widely regarded as a key player in regulating mood, anxiety, and happiness. Chemically derived from tryptophan, serotonin impacts various parts of the body, influencing the functioning of the cardiovascular, renal, immune, and gastrointestinal systems. In the brain, it is primarily associated with feelings of well-being and happiness and is often a target for antidepressant medications like SSRIs (selective serotonin reuptake inhibitors), which help increase serotonin levels in the nervous system. Beyond its role in mood regulation, serotonin also affects sleep patterns, appetite, temperature regulation, and pain perception.

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dopamine

Dopamine is a crucial neurotransmitter involved in many important functions in the brain, particularly those related to pleasure, reward, motivation, and motor control. It plays a central role in the brain's reward system, where it helps reinforce rewarding behaviors by increasing pleasure and satisfaction, making it critical for habit formation and addictive behaviors. Dopamine is also vital for regulating movement, and deficiencies in dopamine production are linked to neurological disorders such as Parkinson's disease. Additionally, dopamine influences various other functions, including mood regulation, learning, and attention, making it a key focus in studies of both mental health and neurodegenerative diseases.

” data-gt-translate-attributes=”[{"attribute":"data-cmtooltip", "format":"html"}]” tabindex=”0″ role=”link”>dopamine, possibly even proteins as well. And all within the gut, which is a complex environment.”

Testing and development of PillTrek

The research team details the development of the capsule in a newly published paper in Nature Electronics. The paper’s lead authors are Jihong Min, a postdoctoral scholar in medical engineer ing at Caltech, and Hyunah Ahn, a visiting researcher at Caltech and graduate student at the Korea Advanced Institute of Science and Technology (<span class="glossaryLink" aria-describedby="tt" data-cmtooltip="

KAIST

KAIST is South Korea’s top science and technology university, renowned for research in robotics, AI, aerospace, and nanomaterials. It is modeled on U.S. technical institutions and emphasizes innovation-driven education.

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To demonstrate its capabilities, PillTrek was tested in animal models, where it successfully measured pH and temperature, along with fluctuations in glucose levels and the <span class="glossaryLink" aria-describedby="tt" data-cmtooltip="

neurotransmitter

A neurotransmitter is a chemical substance that transmits signals across a synapse from one neuron to another in the nervous system. These chemicals play a crucial role in the functioning of the brain and body, influencing everything from mood, sleep, and learning to heart rate, anxiety, and fear. Common neurotransmitters include dopamine, serotonin, acetylcholine, and norepinephrine. They bind to specific receptors on the surface of neurons, triggering various physiological responses and allowing for the communication that underpins all neural activities. Imbalances in neurotransmitter levels can lead to neurological disorders or mental health issues, making them a central focus of study in both medicine and psychology.

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Gao points out that the electrochemical workstation within the capsule is reconfigurable. A variety of different sensors could easily be swapped into place to enable measurements of different parameters in the gut. His team previously developed a technique for 3D printing inexpensive sensors on sheets of plastic substrate. That technique can be used to mass-produce the sensors for PillTrek.

Future directions for miniaturization and impact

In terms of next steps, Gao says that he is working with co-author Azita Emami, the Andrew and Peggy Cherng Professor of Electrical Engineering and Medical Engineering at Caltech, to look into wireless power transfer and smaller electronics that would make PillTrek even smaller and lower power.

“Ingestible capsules have significant potential in diagnosis, monitoring, and management of chronic conditions, but previous devices were very limited in terms of their sensing capabilities, lifetime, and size,” says Emami, who is also director of the Center for Sensing to Intelligence. “This work is an important translational step toward devices that can provide meaningful medical information for patients and physicians.”

Reference: “Continuous biochemical profiling of the gastrointestinal tract using an integrated smart capsule” by Jihong Min, Hyunah Ahn, Heather Lukas, Xiaotian Ma, Rinni Bhansali, Sung-Hyuk Sunwoo, Canran Wang, Yadong Xu, Dickson R. Yao, Gwangmook Kim, Zhaoping Li, Tzung K. Hsiai, Azita Emami, Hee-Tae Jung and Wei Gao, 27 June 2025, Nature Electronics.
DOI: 10.1038/s41928-025-01407-0

The work was supported by funding from the National Science Foundation, the <span class="glossaryLink" aria-describedby="tt" data-cmtooltip="

National Institutes of Health

The National Institutes of Health (NIH) is the primary agency of the United States government responsible for biomedical and public health research. Founded in 1887, it is a part of the U.S. Department of Health and Human Services. The NIH conducts its own scientific research through its Intramural Research Program (IRP) and provides major biomedical research funding to non-NIH research facilities through its Extramural Research Program. With 27 different institutes and centers under its umbrella, the NIH covers a broad spectrum of health-related research, including specific diseases, population health, clinical research, and fundamental biological processes. Its mission is to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability.

” data-gt-translate-attributes=”[{"attribute":"data-cmtooltip", "format":"html"}]” tabindex=”0″ role=”link”>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 critical support and infrastructure from the Kavli Nanoscience Institute at Caltech.

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