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Continuous biochemical profiling of the gastrointestinal tract using an integrated smart capsule

Nature Electronics volume 8, pages 844–855 (2025)Cite this article

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Abstract

The gastrointestinal tract contains a wealth of chemical information that can be used to decipher the health of the digestive and nervous systems. Traditional methods of analysis, such as faecal analysis and biopsies, are invasive, costly and incapable of providing real-time metabolic and hormone profiling across the gastrointestinal tract. Commercial ingestible capsule sensors have been developed, but only monitor basic markers, such as pH and pressure, neglecting detailed chemical analysis. Here we report an integrated smart capsule that can simultaneously detect a spectrum of biochemical markers, including electrolytes, metabolites and hormones. The capsule, which is termed PillTrek, is 7 mm in diameter and 25 mm in length, and houses a miniaturized wireless electrochemical workstation capable of executing a range of electrochemical measurement techniques (potentiometry, amperometry, voltammetry and impedimetry), allowing it to interface with a variety of electrochemical sensors and detect various parameters in the gut. Using an array of sensors (serotonin, glucose, pH, ionic strength and temperature), we illustrate the capabilities of the system in vitro and in vivo in animal studies involving rat and rabbit models, monitoring the dynamic profile of these crucial biomarkers and their responsiveness to different dietary intakes.

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Fig. 1: PillTrek, a capsule electrochemical platform for continuous, multiplexed GI fluid analysis.
Fig. 2: Electrochemical sensor array of PillTrek for multiplexed detection of GI biomarkers.
Fig. 3: The system integration of PillTrek for prolonged wireless operation in the GI tract.
Fig. 4: In vitro evaluation of PillTrek for assessing the dietary influences on GI biomarker levels in rats.
Fig. 5: In vivo validation of PillTrek for real-time multimodal monitoring of GI biomarkers in rabbits.

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Data availability

The data that supports the findings of this study are available from the corresponding authors on reasonable request. Source data are provided with this paper.

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Acknowledgements

This project was supported by the National Science Foundation grant no. 2145802, National Institutes of Health grant nos. R01HL155815 and R21DK13266, American Cancer Society Research Scholar grant no. RSG-21-181-01-CTPS, Army Research Office grant no. W911NF-23-1-0041, US Army Medical Research Acquisition Activity grant no. HT9425-24-1-0249, National Research Foundation of Korea grant no. RS-2024-00411904 and Heritage Medical Research Institute (all to W.G.). We gratefully acknowledge critical support and infrastructure provided for this work by the Kavli Nanoscience Institute at Caltech. J.M. acknowledges fellowship support from the National Institutes of Health Training grant (no. T32EB023858). H.A. and H.-T.J. acknowledge the support from the KAIST-UC Berkeley-VNU Climate Change Research Center grant no. 2021K1A4A8A01079356. Lemberg (Austria) helped with porting code.

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Author notes

  1. These authors contributed equally: Jihong Min, Hyunah Ahn.

Authors and Affiliations

  1. Andrew and Peggy Cherng Department of Medical Engineering, Division of Engineering and Applied Science, California Institute of Technology, Pasadena, CA, USA

    Jihong Min, Hyunah Ahn, Heather Lukas, Xiaotian Ma, Rinni Bhansali, Sung-Hyuk Sunwoo, Canran Wang, Yadong Xu, Dickson R. Yao, Gwangmook Kim, Azita Emami & Wei Gao

  2. Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea

    Hyunah Ahn & Hee-Tae Jung

  3. Division of Clinical Nutrition, David Geffen School of Medicine, University of California, Los Angeles, CA, USA

    Zhaoping Li

  4. Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA

    Tzung K. Hsiai

  5. Department of Electrical Engineering, Division of Engineering and Applied Science, California Institute of Technology, Pasadena, CA, USA

    Azita Emami

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Contributions

W.G. and J.M. initiated the concept of and designed the studies. W.G. supervised the work. J.M. and H.A. led the experiments and collected the overall data. H.L., R.B. and G.K. contributed to sensor characterization and validation. X.M., S.-H.S., C.W., Y.X. and D.R.Y contributed to the animal studies. Z.L., T.K.H., A.E. and H.-T.J. contributed to the study design. All authors contributed to the data analysis and provided the feedback on the paper.

Corresponding authors

Correspondence to Hee-Tae Jung or Wei Gao.

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The authors declare no competing interests.

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Nature Electronics thanks Rabia Yazicigil and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary Notes 1 and 2, Figs. 1–41, Tables 1–5, Videos 1 and 2 and Refs. 1–12.

Reporting Summary

Supplementary Video 1

PillTrek performing multiparametric measurements while moving through a phantom intestine model.

Supplementary Video 2

PillTrek with protective cap repeatedly contacting rabbit intestinal tissue.

Source data

Source Data Figs. 2–5

Source data for sensor characterization studies in Fig. 2. Source data for electronic system characterization studies in Fig. 3. Source data for ex-vivo rat studies in Fig. 4. Source data for in vivo rabbit studies in Fig. 5.

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Min, J., Ahn, H., Lukas, H. et al. Continuous biochemical profiling of the gastrointestinal tract using an integrated smart capsule. Nat Electron 8, 844–855 (2025). https://doi.org/10.1038/s41928-025-01407-0

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