Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

An ingestible device for gastric electrophysiology

Nature Electronics (2024)Cite this article

Subjects

Abstract

The ability to record high-quality electrophysiology data from the gastrointestinal tract and enteric nervous system is of use in understanding a variety of disorders and improving healthcare via early diagnosis. However, such measurements remain challenging because electrodes must be implanted surgically or worn on the skin, which results in a trade-off between signal quality and invasiveness. Here we report an ingestible device for gastric electrophysiology. The non-invasive system, which is termed multimodal electrophysiology via ingestible, gastric, untethered tracking (MiGUT), consists of encapsulated electronics and a sensing electrode ribbon that unrolls in the stomach following delivery to make contact with the mucosa. The device then records and wirelessly transmits biopotential signals to an external receiver. We show that the device can record electrical signals—including the gastric slow wave, respiration signal and heart signal—in a large animal model and can monitor slow wave activity in freely moving and feeding animals.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: MiGUT device overview.
Fig. 2: Design and in vivo evaluation of MiGUT system for multi-day, high-quality recordings.
Fig. 3: Acute recordings in an anaesthetized animal using MiGUT device.
Fig. 4: Validation of MiGUT measurements.
Fig. 5: High-resolution measurements in an ambulating animal using MiGUT device.
Fig. 6: Multi-day measurements in an ambulating animal using MiGUT device.

Similar content being viewed by others

Data availability

The data that supports the findings of this study are available at https://github.com/adamgierlach/MiGUT_data_repository.

Code availability

The code that supports the findings of this study is available at https://github.com/adamgierlach/MiGUT_data_repository.

References

  1. Furness, J. B. The enteric nervous system and neurogastroenterology. Nat. Rev. Gastroenterol. Hepatol. 9, 286–294 (2012).

    Article  Google Scholar 

  2. Spencer, N. J. & Hu, H. Enteric nervous system: sensory transduction, neural circuits and gastrointestinal motility. Nat. Rev. Gastroenterol. Hepatol. 17, 338–351 (2020).

    Article  Google Scholar 

  3. Camilleri, M. et al. Gastroparesis. Nat. Rev. Dis. Prim. 4, 41 (2018).

    Article  Google Scholar 

  4. Grover, M., Farrugia, G. & Stanghellini, V. Gastroparesis: a turning point in understanding and treatment. Gut 68, 2238–2250 (2019).

    Article  Google Scholar 

  5. Mahadeva, S. Epidemiology of functional dyspepsia: a global perspective. World J. Gastroenterol. 12, 2661 (2006).

    Article  Google Scholar 

  6. Travagli, R. A., Browning, K. N. & Camilleri, M. Parkinson disease and the gut: new insights into pathogenesis and clinical relevance. Nat. Rev. Gastroenterol. Hepatol. 17, 673–685 (2020).

    Article  Google Scholar 

  7. Jones, J. D., Rahmani, E., Garcia, E. & Jacobs, J. P. Gastrointestinal symptoms are predictive of trajectories of cognitive functioning in de novo Parkinson’s disease. Parkinsonism Relat. Disord. 72, 7–12 (2020).

    Article  Google Scholar 

  8. Warnecke, T., Schäfer, K.-H., Claus, I., Del Tredici, K. & Jost, W. H. Gastrointestinal involvement in Parkinson’s disease: pathophysiology, diagnosis, and management. npj Parkinsons Dis. 8, 31 (2022).

    Article  Google Scholar 

  9. Hsiao, E. Y. Gastrointestinal issues in autism spectrum disorder. Harv. Rev. Psychiatry 22, 104–111 (2014).

    Article  Google Scholar 

  10. Saurman, V., Margolis, K. G. & Luna, R. A. Autism spectrum disorder as a brain-gut-microbiome axis disorder. Dig. Dis. Sci. 65, 818–828 (2020).

    Article  Google Scholar 

  11. Farajidavar, A. Bioelectronics for mapping gut activity. Brain Res. 1693, 169–173 (2018).

    Article  Google Scholar 

  12. O’Grady, G. et al. Methods for high-resolution electrical mapping in the gastrointestinal tract. IEEE Rev. Biomed. Eng. 12, 287–302 (2019).

    Article  Google Scholar 

  13. Keller, J. et al. Advances in the diagnosis and classification of gastric and intestinal motility disorders. Nat. Rev. Gastroenterol. Hepatol. 15, 291–308 (2018).

    Article  Google Scholar 

  14. Sanders, K. M., Koh, S. D. & Ward, S. M. Interstitial cells of Cajal as pacemakers in the gastrointestinal tract. Annu. Rev. Physiol. 68, 307–343 (2006).

    Article  Google Scholar 

  15. Alvarez, W. The electrogastrogram and what it shows. J. Am. Med. Assoc. 78, 1116 (1922).

    Article  Google Scholar 

  16. Lammers, W. J. E. P., Stephen, B., Arafat, K. & Manefield, G. W. High resolution electrical mapping in the gastrointestinal system: initial results. Neurogastroenterol. Motil. 8, 207–216 (1996).

    Article  Google Scholar 

  17. Angeli, T. R. et al. High-resolution electrical mapping of porcine gastric slow-wave propagation from the mucosal surface. Neurogastroenterol. Motil. 29, e13010 (2017).

    Article  Google Scholar 

  18. Paskaranandavadivel, N. et al. Ambulatory gastric mucosal slow wave recording for chronic experimental studies. In 39th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) 755–758 (IEEE, 2017); https://doi.org/10.1109/EMBC.2017.8036934

  19. Paskaranandavadivel, N. et al. Multi-day, multi-sensor ambulatory monitoring of gastric electrical activity. Physiol. Meas. 40, 025011 (2019).

    Article  Google Scholar 

  20. Gharibans, A. A. et al. Artifact rejection methodology enables continuous, noninvasive measurement of gastric myoelectric activity in ambulatory subjects. Sci. Rep. 8, 5019 (2018).

    Article  Google Scholar 

  21. Steiger, C. et al. Ingestible electronics for diagnostics and therapy. Nat. Rev. Mater. 4, 83–98 (2019).

    Article  Google Scholar 

  22. Yang, S.-Y. et al. Powering implantable and ingestible electronics. Adv. Funct. Mater. 31, 2009289 (2021).

    Article  Google Scholar 

  23. Kalantar-Zadeh, K. et al. A human pilot trial of ingestible electronic capsules capable of sensing different gases in the gut. Nat. Electron. 1, 79–87 (2018).

    Article  Google Scholar 

  24. De la Paz, E. et al. A self-powered ingestible wireless biosensing system for real-time in situ monitoring of gastrointestinal tract metabolites. Nat. Commun. 13, 7405 (2022).

    Article  Google Scholar 

  25. Koziolek, M. et al. Intragastric pH and pressure profiles after intake of the high-caloric, high-fat meal as used for food effect studies. J. Control. Release 220, 71–78 (2015).

    Article  Google Scholar 

  26. Sarker, S., Jones, R., Chow, G. & Terry, B. Design of a soft, self-uncoiling stent for extended retention of drug delivery in the small intestine. In Proc. 2021 Design of Medical Devices Conference V001T12A010 (ASME, 2021); https://doi.org/10.1115/DMD2021-1063

  27. Schostek, S. et al. Pre-clinical study on a telemetric gastric sensor for recognition of acute upper gastrointestinal bleeding: the “HemoPill monitor”. Surg. Endosc. 34, 888–898 (2020).

    Article  Google Scholar 

  28. Hutten, G. J., van Thuijl, H. F., van Bellegem, A. C. M., van Eykern, L. A. & van Aalderen, W. M. C. A literature review of the methodology of EMG recordings of the diaphragm. J. Electromyogr. Kinesiol. 20, 185–190 (2010).

    Article  Google Scholar 

  29. Lokin, J. L., Dulger, S., Glas, G. J. & Horn, J. Transesophageal versus surface electromyography of the diaphragm in ventilated subjects. Respir. Care 65, 1309–1314 (2020).

    Article  Google Scholar 

  30. Sanger, G. J. & Furness, J. B. Ghrelin and motilin receptors as drug targets for gastrointestinal disorders. Nat. Rev. Gastroenterol. Hepatol. 13, 38–48 (2016).

    Article  Google Scholar 

  31. Hopkins, S. Clinical toleration and safety of azithromycin. Am. J. Med. 91, S40–S45 (1991).

    Article  Google Scholar 

  32. Gharibans, A. A. et al. Gastric dysfunction in patients with chronic nausea and vomiting syndromes defined by a noninvasive gastric mapping device. Sci. Transl. Med. 14, eabq3544 (2022).

    Article  Google Scholar 

  33. Ray, T. R. et al. Bio-integrated wearable systems: a comprehensive review. Chem. Rev. 119, 5461–5533 (2019).

    Article  Google Scholar 

  34. Vujic, A. et al. Gut-brain computer interfacing (GBCI): wearable monitoring of gastric myoelectric activity. In 41st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) 5886–5889 (IEEE, 2019); https://doi.org/10.1109/EMBC.2019.8856568

  35. Obioha, C. et al. Effect of body mass index on the sensitivity of magnetogastrogram and electrogastrogram. J. Gastroenterol. Hepatol. Res. 2, 513–519 (2013).

    Google Scholar 

  36. Abramson, A. et al. Ingestible transiently anchoring electronics for microstimulation and conductive signaling. Sci. Adv. 6, eaaz0127 (2020).

    Article  Google Scholar 

  37. Kong, Y. L. et al. 3D‐printed gastric resident electronics. Adv. Mater. Technol. 4, 1800490 (2019).

    Article  Google Scholar 

  38. Abid, A. et al. Wireless power transfer to millimeter-sized gastrointestinal electronics validated in a swine model. Sci. Rep. 7, 46745 (2017).

    Article  Google Scholar 

  39. Javan-Khoshkholgh, A., Sassoon, J. C. & Farajidavar, A. A wireless rechargeable implantable system for monitoring and pacing the gut in small animals. In 2019 IEEE Biomedical Circuits and Systems Conference (BioCAS) 1–4 (IEEE, 2019); https://doi.org/10.1109/BIOCAS.2019.8919125

  40. Yuk, H., Wu, J. & Zhao, X. Hydrogel interfaces for merging humans and machines. Nat. Rev. Mater. 7, 935–952 (2022).

    Article  Google Scholar 

  41. Ramadi, K. B., Srinivasan, S. S. & Traverso, G. Electroceuticals in the gastrointestinal tract. Trends Pharmacol. Sci. 41, 960–976 (2020).

    Article  Google Scholar 

  42. Li, C. et al. Design of biodegradable, implantable devices towards clinical translation. Nat. Rev. Mater. 5, 61–81 (2020).

    Article  Google Scholar 

  43. Abramson, A. et al. An ingestible self-orienting system for oral delivery of macromolecules. Science 363, 611–615 (2019).

    Article  Google Scholar 

Download references

Acknowledgements

We are grateful for discussions with R. Langer and the numerous members of the Traverso, Langer and Chandrakasan Laboratories. We are also grateful to G. Liu for suggesting names and acronyms for the MiGUT device. We thank V. E. Fulford, Alar Illustration, for work in Fig. 1. This work was in part supported by the following grants including a grant from Novo Nordisk, Karl van Tassel (1925) Career Development Professorship, the Department of Mechanical Engineering, Massachusetts Institute of Technology (MIT) and the Division of Gastroenterology, Brigham and Women’s Hospital. The research was funded in part by the Advanced Research Projects Agency for Health (ARPA-H) under Award Number D24AC00040-00. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Advanced Research Projects Agency for Health. A.G. is supported by the Natural Science and Engineering Research Council of Canada Postgraduate Scholarship-Doctoral and a Takeda Fellowship, MIT. P.S. was supported by a Rotary Global Grant scholarship. S.-Y.Y. was supported in part by a Mathworks Fellowship, MIT. S.O. is supported by the National Institute of Diabetes and Digestive and Kidney Diseases award 1T32DK135449-01.

Author information

Author notes

  1. These authors contributed equally: Siheng Sean You, Adam Gierlach.

Authors and Affiliations

  1. David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA

    Siheng Sean You, Adam Gierlach, Paul Schmidt, George Selsing, Injoo Moon, Keiko Ishida, Josh Jenkins, Wiam A. M. Madani, So-Yoon Yang, Hen-Wei Huang, Stephanie Owyang, Alison Hayward & Giovanni Traverso

  2. Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Siheng Sean You, Paul Schmidt, George Selsing, Injoo Moon, Keiko Ishida, Wiam A. M. Madani, Hen-Wei Huang, Stephanie Owyang, Alison Hayward & Giovanni Traverso

  3. Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, USA

    Adam Gierlach, So-Yoon Yang & Anantha P. Chandrakasan

  4. Materials Chemistry, RWTH Aachen University, Aachen, Germany

    Paul Schmidt

  5. Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA

    Josh Jenkins, Hen-Wei Huang & Giovanni Traverso

  6. Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA

    Alison Hayward

Authors
  1. Siheng Sean You
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Adam Gierlach
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paul Schmidt
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. George Selsing
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Injoo Moon
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Keiko Ishida
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Josh Jenkins
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Wiam A. M. Madani
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. So-Yoon Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Hen-Wei Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Stephanie Owyang
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Alison Hayward
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Anantha P. Chandrakasan
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Giovanni Traverso
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

S.S.Y., A.G., P.S., H.-W.H. and G.T. conceived and designed the research. S.S.Y., A.G., G.S., I.M., P.S. and S.-Y.Y. designed, tested and validated electronics. S.S.Y., A.G., P.S., S.-Y.Y., K.I., W.A.M.M., J.J. and A.H. performed animal experiments. S.S.Y., A.G., G.S. and I.M. wrote device firmware. S.S.Y. and A.G. wrote software to analyse data. S.S.Y., A.G., P.S., S.O. and G.T. interpreted results. S.S.Y., A.G., P.S., A.P.C. and G.T. wrote the paper. All authors reviewed and approved the paper.

Corresponding author

Correspondence to Giovanni Traverso.

Ethics declarations

Competing interests

Financial competing interests for G.T. that may be interpreted as related to the current paper include current and prior funding from Novo Nordisk, Hoffman La Roche, Oracle, Draper Laboratory, MIT Lincoln Laboratory, NIH (NIBIB and NCI), Bill and Melinda Gates Foundation, The Leona M. and Harry B. Helmsley Charitable Trust, Karl van Tassel (1925) Career Development Professor, MIT, the Defense Advanced Research Projects Agency, and the Advanced Research Projects Agency for Health (ARPA-H) as well as employment by the Massachusetts Institute of Technology and Brigham and Women’s Hospital. Personal financial interests include equity/stock (Lyndra Therapeutics, Suono Bio, Vivtex, Celero Systems, Syntis Bio), board of directors member and/or consultant (Lyndra Therapeutics, Novo Nordisk, Suono Bio, Vivtex, Celero Systems, Syntis Bio) and royalties (past and potentially in the future) from licensed and/or optioned intellectual property (Lyndra Therapeutics, Novo Nordisk, Suono Bio, Vivtex, Celero Systems, Syntis Bio, Johns Hopkins, MIT, Mass General Brigham Innovation). Complete details of all relationships for profit and not-for-profit for G.T. can be found in Supplementary Information. The authors S.S.Y., A.G., G.S., S.-Y.Y. and G.T., with R. Langer, report a patent application (US Provisional Patent Application No. 63/589,401) describing the system reported in the paper. The other authors declare no competing interests.

Peer review

Peer review information

Nature Electronics thanks Aydin Farajidavar, Bozhi Tian and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Information

Supplementary Figs. 1–17, Tables 1–4 and a full list of competing interests.

Reporting Summary

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

You, S.S., Gierlach, A., Schmidt, P. et al. An ingestible device for gastric electrophysiology. Nat Electron (2024). https://doi.org/10.1038/s41928-024-01160-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41928-024-01160-w

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing