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Capacitively coupled arrays of multiplexed flexible silicon transistors for long-term cardiac electrophysiology

Nature Biomedical Engineering volume 1, Article number: 0038 (2017) Cite this article

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An Erratum to this article was published on 09 March 2017

Abstract

Advanced capabilities in electrical recording are essential for the treatment of heart-rhythm diseases. The most advanced technologies use flexible integrated electronics; however, the penetration of biological fluids into the underlying electronics and any ensuing electrochemical reactions pose significant safety risks. Here, we show that an ultrathin, leakage-free, biocompatible dielectric layer can completely seal an underlying array of flexible electronics while allowing for electrophysiological measurements through capacitive coupling between tissue and the electronics, without the need for direct metal contact. The resulting current-leakage levels and operational lifetimes are, respectively, four orders of magnitude smaller and between two and three orders of magnitude longer than those of other flexible-electronics technologies. Systematic electro­physiological studies with normal, paced and arrhythmic conditions in Langendorff hearts highlight the capabilities of the capacitive-coupling approach. These advances provide realistic pathways towards the broad applicability of biocompatible, flexible electronic implants.

Tools for spatially mapping electrical activity on the surface of the heart are critically important to experimental cardiac electrophysiology and clinical therapy. The earliest reported systems involved microelectrode arrays on flat, rigid substrates, with a focus on recording cardiac excitation in cultured cardiomyocytes and on mapping signal propagation across planar cardiac slices1–5. More recent technologies exploit flexible arrays, in formats ranging from sheets to baskets, balloons, ‘socks’ and integumentary membranes, with the ability to integrate directly across large areas of the epicardium and endocardium in beating hearts6–10. The most sophisticated platforms of this type include an underlying backplane of thin, flexible active electronics for local signal amplification and multiplexed addressing11,12. This latter feature is critically important because it enables scaling to high-density, high-speed measurements, in regimes that lie far beyond those accessible with simple, passively addressed systems without integrated electronics. The measurement interface associated with all such cases relies on thin electrode pads in direct physical contact with the tissue, where electrical signals transport through via openings to the underlying electronics. Although this approach has some important modes of use, bio-fluids can readily penetrate through the types of polycrystalline metal films used for the electrodes. Resultant leakage currents from the electronics can cause potentially lethal events such as ventricular fibrillation and cardiovascular collapse13,14; they also lead to degradation of the Si electronics and catastrophic failure of the measurement hardware. Moreover, electrochemical reactions with the electrolyte at the metal/tissue interface lead to bio-corrosion of the metal15. Consequently, devices with such designs are inherently unsuitable for human use, even in surgical contexts or other acute applications. Similar considerations prevent their application in any class of implant16–18.

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Figure 1: Capacitively coupled silicon nanomembrane transistors (covered by a thermal SiO2 layer) as amplified sensing nodes in an actively multiplexed flexible electronic system for high-resolution electrophysiological mapping.
Figure 2: In vitro assessment of electrical performance.
Figure 3: High-density cardiac electrophysiological mapping on ex vivo rabbit heart models.
Figure 4: Comparison of electrical mapping with optical fluorescence recording.
Figure 5: Study of ventricular fibrillation.

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Acknowledgements

This work is supported by the NIH grants R01 HL115415, R01 HL114395 and R21 HL112278, and through the Frederick Seitz Materials Research Laboratory and Center for Microanalysis of Materials at the University of Illinois at Urbana-Champaign. We would like to thank the Micro and Nanotechnology Laboratory and the School of Chemical Sciences Machine Shop at the University of Illinois for help on the device fabrication. J.Z. acknowledges support from a Louis J. Larson Fellowship, Swiegert Fellowship, and H. C. Ting Fellowship from the University of Illinois, Urbana-Champaign. M.T. and J.V. acknowledge the support from the National Science Foundation award CCF 1422914. C.-H.C. and J.V. acknowledge the support from the Army Research Office award W911NF-14-1-0173.

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Author notes

  1. Hui Fang, Ki Jun Yu and Christopher Gloschat: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Electrical and Computer Engineering, Northeastern University, Boston, 02115, Massachusetts, USA

    Hui Fang

  2. Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, 61801, Illinois, USA

    Hui Fang, Ki Jun Yu, Zijian Yang, Enming Song, Jianing Zhao, Sang Min Won, Siyi Xu, Yiding Zhong, Seung Won Han, Dong Xu, Seo Woo Choi & John A. Rogers

  3. Frederick Seitz Materials Research Laboratory, University of Illinois at Urbana-Champaign, Urbana, 61801, Illinois, USA

    Hui Fang, Ki Jun Yu, Zijian Yang, Enming Song, Jianing Zhao, Sang Min Won, Siyi Xu, Yiding Zhong, Seung Won Han, Dong Xu, Seo Woo Choi & John A. Rogers

  4. School of Electrical and Electronic Engineering, Yonsei University, Seoul, 03722, Republic of Korea

    Ki Jun Yu

  5. Department of Biomedical Engineering, The George Washington University, Washington, 20052, DC, USA

    Christopher Gloschat, Matthew Kay & Igor R. Efimov

  6. Department of Biomedical Engineering, Duke University, Durham, 27708, North Carolina, USA

    Chia-Han Chiang, Michael Trumpis & Jonathan Viventi

  7. Department of Mechanical Engineering and Department of Civil and Environmental Engineering, Northwestern University, Evanston, 60208, Illinois, USA

    Yeguang Xue & Yonggang Huang

  8. Department of Bioengineering, University of California San Diego, La Jolla, 92093, California, USA

    Gert Cauwenberghs

  9. Center for Bio-Integrated Electronics, Northwestern University, Evanston, 60208, Illinois, USA

    John A. Rogers

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Contributions

H.F., K.J.Y., C.G., Z.Y., I.R.E. and J.A.R. designed the research; H.F., K.J.Y., Z.Y., E.S., C.-H.C., J.Z., S.X., S.M.W., Y.Z., S.W.H., D.X. and S.W.C. fabricated the devices and electronics; H.F., C.G., Z.Y. and J.Z. carried out animal experiments; H.F., K.J.Y., C.G., Z.Y., C.-H.C., J.Z., M.T., J.V., G.C. and M.K. performed data analysis; H.F., Z.Y., Y.X. and Y.H. contributed to mechanical simulations; H.F., K.J.Y., C.G., Z.Y., I.R.E. and J.A.R. co-wrote the manuscript.

Corresponding authors

Correspondence to Igor R. Efimov or John A. Rogers.

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Supplementary information

Supplementary Information

Supplementary notes and figures. (PDF 2974 kb)

Supplementary Video 1

A flexible capacitively coupled sensing electronic system on a Langendorff-perfused rabbit heart model. (MP4 4793 kb)

Supplementary Video 2

Voltage data from all electrodes, illustrating the activation pattern of the heart during sinus rhythm. (MP4 6160 kb)

Supplementary Video 3

Voltage data from all electrodes, illustrating the paced activation pattern moving from the apex to the base. (MP4 5493 kb)

Supplementary Video 4

Voltage data from all electrodes, illustrating the activation pattern of the heart during ventricular fibrillation. (MP4 14134 kb)

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Fang, H., Yu, K., Gloschat, C. et al. Capacitively coupled arrays of multiplexed flexible silicon transistors for long-term cardiac electrophysiology. Nat Biomed Eng 1, 0038 (2017). https://doi.org/10.1038/s41551-017-0038

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