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Review
. 2022;7(11):908-925.
doi: 10.1038/s41578-022-00477-2. Epub 2022 Sep 14.

Mucosa-interfacing electronics

Kewang Nan #  1   2 , Vivian R Feig #  2   3 , Binbin Ying #  1   2 , Julia G Howarth  1 , Ziliang Kang  1   2 , Yiyuan Yang  1 , Giovanni Traverso  1   2
Affiliations
Review

Mucosa-interfacing electronics

Kewang Nan et al. Nat Rev Mater. 2022.

Abstract

The surface mucosa that lines many of our organs houses myriad biometric signals and, therefore, has great potential as a sensor-tissue interface for high-fidelity and long-term biosensing. However, progress is still nascent for mucosa-interfacing electronics owing to challenges with establishing robust sensor-tissue interfaces; device localization, retention and removal; and power and data transfer. This is in sharp contrast to the rapidly advancing field of skin-interfacing electronics, which are replacing traditional hospital visits with minimally invasive, real-time, continuous and untethered biosensing. This Review aims to bridge the gap between skin-interfacing electronics and mucosa-interfacing electronics systems through a comparison of the properties and functions of the skin and internal mucosal surfaces. The major physiological signals accessible through mucosa-lined organs are surveyed and design considerations for the next generation of mucosa-interfacing electronics are outlined based on state-of-the-art developments in bio-integrated electronics. With this Review, we aim to inspire hardware solutions that can serve as a foundation for developing personalized biosensing from the mucosa, a relatively uncharted field with great scientific and clinical potential.

Keywords: Biomedical engineering; Sensors and biosensors.

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Conflict of interest statement

Competing interestsFinancial competing interests for G.T. that may be interpreted as related to the current manuscript 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 and the Defense Advanced Research Projects Agency, 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 the supplementary information. K.N. and G.T. report a patent application (U.S. Provisional Application no. 63/301,491) describing a flexible silicone liquid-metal-filled manometry system. G.T. reports the following patents and/or patent applications: U.S. patent no. 10,149,635 describing ingestible devices for physiological status monitoring, U.S. patent nos. 10,182,985, 10,413,507, 10,517,819, 10,517,820, 10,532,027, 10,596,110, 10,610,482, 10,716,751 and 10,716,752 describing gastric residence structures and materials supporting safe residence and GI transit, U.S. patent nos. 10,693,544 and 10,879,983 describing methods for charging of GI devices through RF transmission, U.S. patent no. 11,207,272 describing a device with gastric anchoring capabilities and the capacity for electrical stimulation and sensing, U.S. Provisional Application patent no. 16/152,785 describing a flexible piezoelectric device that can sense deformation in the GI tract, U.S. Provisional Application patent no. 16/207,647 a gastric resident electronic device, U.S. Provisional Application patent no. 17/470,942 describing a gastric resident system capable of sensing radiation and toxic agents and releasing therapeutics, U.S. Provisional Application patent no. 63/246,761 describing a nasogastric system for biochemical sensing and U.S. Provisional Application patent no. 63/294,902 describing a system for energy harvesting from the GI tract. All other authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Overview of mucosa-interfacing electronics in relation to existing sensors that interact with mucosa and the skin-interfacing electronics.
The key features of existing clinically approved sensors that interact with the mucosa and skin-interfacing electronics are highlighted, as well as the end goal for mucosa-interfacing electronics.
Fig. 2
Fig. 2. Towards mucosa-interfacing electronics.
Schematic of an envisioned mucosa-interfacing electronics system, outlining the main challenges facing mucosa-interfacing electronics devices (right) compared with state-of-the-art skin-interfacing electronics (left). The challenges include aspects related to sensor performance (sensor–tissue interface and encapsulation), sensor deployment (localization, retention and removal) and communication and power supplies. Left image courtesy of J. A. Rogers.
Fig. 3
Fig. 3. Methods for establishing sensor–tissue interfaces with mucosa.
a | Illustration of the structural (left) and materials (right) engineering approaches for establishing robust sensor–tissue interfaces. b | Schematics of various structural engineering approaches that convert plastic materials into stretchable conductors, showing the conductors before and after stretching. The axis shows a range of reported maximum stretchability for each approach. c | Schematic showing the enhancement of the sensor–tissue interface by minimizing the mechanical mismatch with the tissue using a soft hydrogel (right) compared with a sensor–tissue interface with a conventional electrode (left). The insets show the corresponding equivalent circuit diagrams, comprising capacitors (C) and resistors (R). d | Schematic showing the formation of covalent bonds between a conductive hydrogel and tissue to simultaneously realize strong adhesion and low electrical impedance at the sensor–tissue interface. e | Schematics showing the initial hydrogel (left), the fragile swollen state of the hydrogel following fluid uptake (middle) and the swelling-triggered toughening mechanism that involves the diffusion of encapsulated crosslinker molecules in the first polymer network (polymer 1) and then crosslinking of a second polymer network (polymer 2) to enhance the toughness of the hydrogel after fluid uptake (right).
Fig. 4
Fig. 4. Modes of retention on the mucosa.
Different physical and chemical adhesive mechanisms (mucus-adhering (part a), mucus-penetrating (part b), mechanical anchoring (part c) and luminal confinement (part d) strategies) lead to a wide range of average retention times from minutes to months. In general, methods that penetrate or deplete the mucus and interact directly with the underlying mucosa offer longer retention, but at the expense of increased invasiveness. Luminal confinement provides the longest retention.
See this image and copyright information in PMC

References

    1. Classen C. Review of W. F. Bynum and Roy Porter, Medicine and the Five Senses. Cambridge University Press, 1993. 331 pp. J. Hist. Behav. Sci. 1995;31:402–403. doi: 10.1002/1520-6696(199510)31:4<402::AID-JHBS2300310410>3.0.CO;2-F. - DOI
    1. Nelson WG, Rosen A, Pronovost PJ. Reengineering the physical examination for the new millennium? JAMA. 2016;315:2391–2392. doi: 10.1001/jama.2016.4470. - DOI - PubMed
    1. Neuman MR, et al. Advances in medical devices and medical electronics. Proc. IEEE. 2012;100:1537–1550. doi: 10.1109/JPROC.2012.2190684. - DOI
    1. Xu S, Jayaraman A, Rogers JA. Skin sensors are the future of health care. Nature. 2019;571:319–321. doi: 10.1038/d41586-019-02143-0. - DOI - PubMed
    1. Hammock ML, Chortos A, Tee BC-K, Tok JB-H, Bao Z. 25th anniversary article: the evolution of electronic skin (e-skin): a brief history, design considerations, and recent progress. Adv. Mater. 2013;25:5997–6038. doi: 10.1002/adma.201302240. - DOI - PubMed