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Location-aware ingestible microdevices for wireless monitoring of gastrointestinal dynamics

Nature Electronics volume 6, pages 242–256 (2023)Cite this article

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Abstract

Localization and tracking of ingestible microdevices in the gastrointestinal (GI) tract is valuable for the diagnosis and treatment of GI disorders. Such systems require a large field-of-view of tracking, high spatiotemporal resolution, wirelessly operated microdevices and a non-obstructive field generator that is safe to use in practical settings. However, the capabilities of current systems remain limited. Here, we report three dimensional (3D) localization and tracking of wireless ingestible microdevices in the GI tract of large animals in real time and with millimetre-scale resolution. This is achieved by generating 3D magnetic field gradients in the GI field-of-view using high-efficiency planar electromagnetic coils that encode each spatial point with a distinct magnetic field magnitude. The field magnitude is measured and transmitted by the miniaturized, low-power and wireless microdevices to decode their location as they travel through the GI tract. This system could be useful for quantitative assessment of the GI transit-time, precision targeting of therapeutic interventions and minimally invasive procedures.

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Fig. 1: System overview.
Fig. 2: iMAG device architecture and characterization.
Fig. 3: Magnetic-field-gradient generation and characterization.
Fig. 4: In vivo localization of iMAG in the GI tract under acute and chronic conditions.
Fig. 5: Application of iMAG in FI and magnetic label tracking.

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Data availability

The data that support the findings of this study are available from the corresponding authors upon reasonable request.

Code availability

Codes used in this study are available from the corresponding authors upon request.

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Acknowledgements

We acknowledge the contribution of Standard Technology Inc. (FL) in the assembly of gradient coils. We are grateful to the members of MICS Lab (Caltech) for insightful comments and discussions. This research was funded in part by the National Science Foundation under grant 1823036 (A.E. and M.G.S.); in part by the Rothenberg Innovation Initiative under grant 101170 (A.E. and M.G.S.); in part by the Heritage Medical Research Institute under grant 150901 (A.E. and M.G.S.); and in part by a grant from the Karl van Tassel (1925) Career Development Professorship, the Department of Mechanical Engineering at MIT (G.T.). K.B.R. was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH) under award no. F32DK122762 and the Division of Engineering at New York University, Abu Dhabi.

Author information

Author notes

  1. These authors contributed equally: Saransh Sharma, Khalil B. Ramadi.

  2. These authors jointly supervised this work: Mikhail G. Shapiro, Giovanni Traverso, Azita Emami.

Authors and Affiliations

  1. Department of Electrical Engineering, California Institute of Technology, Pasadena, CA, USA

    Saransh Sharma, Nikhil H. Poole, Fatemeh Aghlmand & Azita Emami

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

    Khalil B. Ramadi, Keiko Ishida, Johannes Kuosmanen, Josh Jenkins & Giovanni Traverso

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

    Khalil B. Ramadi, Shriya S. Srinivasan & Giovanni Traverso

  4. Division of Engineering, New York University Abu Dhabi, Abu Dhabi, UAE

    Khalil B. Ramadi

  5. Tandon School of Engineering, New York University, New York, NY, USA

    Khalil B. Ramadi

  6. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA

    Shriya S. Srinivasan

  7. Department of Chemical Engineering, California Institute of Technology, Pasadena, CA, USA

    Margaret B. Swift & Mikhail G. Shapiro

  8. Andrew and Peggy Cherng Department of Medical Engineering, California Institute of Technology, Pasadena, CA, USA

    Mikhail G. Shapiro & Azita Emami

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Contributions

S.S., K.B.R., N.H.P., S.S.S., M.G.S., G.T. and A.E. conceived and designed the research. S.S. designed and assembled the iMAG devices, EM coils for gradient generation and all the electronics. S.S. performed all the in vitro characterization and localization experiments. K.B.R., S.S. and S.S.S. performed the in vivo characterization and localization experiments. N.H.P. and S.S. programmed the nRF chipset on iMAG and the receiver. S.S. performed all the data processing. K.I., J.K. and J.J. helped during the in vivo experiments. F.A. helped with the iMAG PCB design. M.B.S. helped during the in vitro characterization. S.S. wrote the manuscript, with input from all the other authors. M.G.S., G.T. and A.E. supervised the research.

Corresponding authors

Correspondence to Saransh Sharma, Giovanni Traverso or Azita Emami.

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Competing interests

S.S., M.G.S. and A.E. have joint US patents (20,210,137,412 and 11,457,835 B2) on the localization and magnetic-field generation concepts. M.G.S. and A.E. are founding members of Tychon Technologies. All the other authors declare no competing interests.

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Extended data

Extended Data Fig. 1 Coil embodiments for different use-cases.

a, The flat-spiral Z-coil is shown and is made using several loops of copper wire beginning from an inner diameter of 26 cm and extending to an outer diameter of 60 cm. Using different diameters of the copper wire, different embodiments of the Z-coil (and similarly the X and Y coils) can be realized. b, Gradient profiles generated by the Z-coil of Embodiment-1 carrying 15 A of d.c. current. The prototype used in this work is an implementation of Embodiment-1. c, Gradient profiles generated by the Z-coil of Embodiment-2 carrying 350 mA of d.c. current. The gradient in Embodiment-2 is only 5x lower than the gradient in Embodiment-1, while the d.c. current is 43x lower. d, This is achieved by using a much smaller diameter of the copper wire for Embodiment-2 that results in ≈9x increase in the number of turns that can be fitted in the same coil footprint. The 350 mA of current leads to only 0.25 W of heat (corresponding to <0.1 °C increase in the surface temperature of the coils) for a measurement done every minute, which is sufficient for monitoring the GI transit-time and motility. For applications requiring a higher sampling rate (maximum achievable 3.3 Hz by the current system), thermal insulators can be used around the coils to alleviate the heating. The 7.5 mm of mean position resolution for Embodiment-2 is acceptable for localization in the GI tract. The total weight of the coils in Embodiment-2 and the required battery for powering the coils is suitable for portable prototypes such as jackets or backpacks.

Extended Data Fig. 2 Localization error of iMAG as a function of distance from the coils.

a, The spatial error while localizing a single iMAG relative to the gradient coils is plotted for Z = 6 cm plane. The X, Y and Z errors (shown below the coil-setup) are close to the lower error-bound of the system (≈1 mm). b, The spatial errors are plotted for Z = 12 cm plane and the errors in most regions of the FOV are in 1–2 mm range. The transition to the higher error-bound of the system (≈5 mm) is visible at the boundary panes of the FOV. c, The spatial errors are plotted for Z = 18 cm plane and the presence of the higher error-bound of the system (yellow regions) is more prominent at the boundary planes of the FOV compared to the Z = 12 cm plane. The FOV ends at Z = 20 cm and the remaining half of the 40x40x40cm3 FOV is covered by the other set of the gradient coils shown in Fig. 4a.

Extended Data Fig. 3 X-Ray scans for fecal incontinence study.

a-r, Consecutive X-ray scans obtained while moving the iMAG (connected to a catheter) out of the anal sphincter in steps of five mm during the fecal incontinence study. Detailed results shown in Fig. 5a–c.

Extended Data Fig. 4 X-ray scans for magnetic label tracking.

a-p, Consecutive X-ray scans obtained while moving the iMAG (connected to a catheter) out of the anal sphincter in steps of five mm during the magnetic label (barium beads) tracking study. Detailed results shown in Fig. 5d–i.

Extended Data Fig. 5 iMAG trajectory compared to the meanders in colon.

a, Pig’s colon shown for comparison. b, iMAG trajectory from the fecal incontinence monitoring study. c, iMAG trajectory from the magnetic label tracking study. The two sharp bends in the rectum are prominently visible (highlighted by green arrows) in (a) and are captured by both the iMAG trajectories shown in (b) and (c). This shows that our technology can distinguish anatomical features for organs that are retroperitoneally fixed in the GI tract, like colon. The trajectory maps in (b) and (c) are created by plotting together all the decoded position coordinates of iMAG using the magnetic field measurements performed by it as it moves along the colon.

Extended Data Fig. 6 iMAG for smart toilets.

a, Front-view of the gradient coils assembly mounted on a toilet seat for continuous GI monitoring. b, Side-view of the toilet seat with the gradient coils. Two iMAG devices are placed in a tank filled with saline solution to demonstrate 3D localization. The experiment is repeated for n = 20 different locations of the iMAG devices in the FOV. c, Error obtained at all the locations is clustered together and plotted. d, Error at each location is plotted separately. Error reported as mean ± s.d.: 1.09 ± 1.29 mm (X), 1.25 ± 1.22 mm (Y), 0.95 ± 1.05 mm (Z). This prototype shows the ability of our technology to be deployed in common human-specific settings.

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Supplementary Figs. 1–15, Table 1 and links to videos for Extended Data Figs. 3 and 4.

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Sharma, S., Ramadi, K.B., Poole, N.H. et al. Location-aware ingestible microdevices for wireless monitoring of gastrointestinal dynamics. Nat Electron 6, 242–256 (2023). https://doi.org/10.1038/s41928-023-00916-0

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