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:

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

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.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

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.

Similar content being viewed by others

References

  1. Thomas, C., Springer, P., Loeb, G., Berwald-Netter, Y. & Okun, L. A miniature microelectrode array to monitor the bioelectric activity of cultured cells. Exp. Cell Res. 74, 61–66 (1972).

    Article  Google Scholar 

  2. Pertsov, A. M., Davidenko, J. M., Salomonsz, R., Baxter, W. T. & Jalife, J. Spiral waves of excitation underlie reentrant activity in isolated cardiac muscle. Circ. Res. 72, 631–650 (1993).

    Article  CAS  Google Scholar 

  3. Sprössler, C., Denyer, M., Britland, S., Knoll, W. & Offenhäusser, A. Electrical recordings from rat cardiac muscle cells using field-effect transistors. Phys. Rev. E 60, 2171–2176 (1999).

    Article  Google Scholar 

  4. Camelliti, P. et al. Adult human heart slices are a multicellular system suitable for electrophysiological and pharmacological studies. J. Mol. Cell. Cardiol. 51, 390–398 (2011).

    Article  CAS  Google Scholar 

  5. Huys, R. et al. Single-cell recording and stimulation with a 16k micro-nail electrode array integrated on a 0.18 μm CMOS chip. Lab Chip 12, 1274–1280 (2012).

    Article  CAS  Google Scholar 

  6. Zhang, X., Tai, J., Park, J. & Tai, Y.-C. Flexible MEA for adult zebrafish ECG recording covering both ventricle and atrium. In Proc. IEEE 27th Int. Conf. Micro Electro Mechanical Systems (MEMS) 841-844 (IEEE, 2014).

  7. Friedman, P. A. Novel mapping techniques for cardiac electrophysiology. Heart 87, 575–582 (2002).

    Article  Google Scholar 

  8. Kim, D.-H. et al. Materials for multifunctional balloon catheters with capabilities in cardiac electrophysiological mapping and ablation therapy. Nat. Mater. 10, 316–323 (2011).

    Article  CAS  Google Scholar 

  9. Kim, D.-H. et al. Electronic sensor and actuator webs for large-area complex geometry cardiac mapping and therapy. Proc. Natl Acad. Sci. USA 109, 19910–19915 (2012).

    Article  CAS  Google Scholar 

  10. Xu, L. et al. 3D multifunctional integumentary membranes for spatiotemporal cardiac measurements and stimulation across the entire epicardium. Nat. Commun. 5, 3329 (2014).

    Article  Google Scholar 

  11. Viventi, J. et al. A conformal, bio-interfaced class of silicon electronics for mapping cardiac electrophysiology. Sci. Transl. Med. 2, 24ra22 (2010).

    Article  Google Scholar 

  12. Viventi, J. et al. Flexible, foldable, actively multiplexed, high-density electrode array for mapping brain activity in vivo. Nat. Neurosci. 14, 1599–1605 (2011).

    Article  CAS  Google Scholar 

  13. Laks, M. M., Arzbaecher, R., Bailey, J. J., Geselowitz, D. B. & Berson, A. S. Recommendations for safe current limits for electrocardiographs a statement for healthcare professionals from the Committee on Electrocardiography, American Heart Association. Circulation 93, 837–839 (1996).

    Article  CAS  Google Scholar 

  14. Swerdlow, C. D. et al. Cardiovascular collapse caused by electrocardiographically silent 60-Hz intracardiac leakage current implications for electrical safety. Circulation 99, 2559–2564 (1999).

    Article  CAS  Google Scholar 

  15. Beech, I. B. & Sunner, J. Biocorrosion: towards understanding interactions between biofilms and metals. Curr. Opin. Biotechnol. 15, 181–186 (2004).

    Article  CAS  Google Scholar 

  16. Bowman, L. & Meindl, J. D. The packaging of implantable integrated sensors. IEEE Trans. Biomed. Eng. 33, 248–255 (1986).

    Article  CAS  Google Scholar 

  17. Liu, X. et al. Stability of the interface between neural tissue and chronically implanted intracortical microelectrodes. IEEE Trans. Rehab. Eng. 7, 315–326 (1999).

    Article  CAS  Google Scholar 

  18. Bazaka, K. & Jacob, M. V. Implantable devices: issues and challenges. Electronics 2, 1–34 (2012).

    Article  Google Scholar 

  19. Someya, T. et al. Conformable, flexible, large-area networks of pressure and thermal sensors with organic transistor active matrixes. Proc. Natl Acad. Sci. USA 102, 12321–12325 (2005).

    Article  CAS  Google Scholar 

  20. Lacour, S. P., Jones, J., Wagner, S., Li, T. & Suo, Z. Stretchable interconnects for elastic electronic surfaces. Proc. IEEE 93, 1459–1467 (2005).

    Article  CAS  Google Scholar 

  21. Tian, B. et al. Three-dimensional, flexible nanoscale field-effect transistors as localized bioprobes. Science 329, 830–834 (2010).

    Article  CAS  Google Scholar 

  22. Takei, K. et al. Nanowire active-matrix circuitry for low-voltage macroscale artificial skin. Nat. Mater. 9, 821–826 (2010).

    Article  CAS  Google Scholar 

  23. Schwartz, G. et al. Flexible polymer transistors with high pressure sensitivity for application in electronic skin and health monitoring. Nat. Commun. 4, 1859 (2013).

    Article  Google Scholar 

  24. Wu, W., Wen, X. & Wang, Z. L. Taxel-addressable matrix of vertical-nanowire piezotronic transistors for active and adaptive tactile imaging. Science 340, 952–957 (2013).

    Article  CAS  Google Scholar 

  25. Khodagholy, D. et al. NeuroGrid: recording action potentials from the surface of the brain. Nat. Neurosci. 18, 310–315 (2015).

    Article  CAS  Google Scholar 

  26. Fromherz, P., Offenhäusser, A., Vetter, T. & Weis, J. A neuron-silicon junction: a Retzius cell of the leech on an insulated-gate field-effect transistor. Science 252, 1290–1293 (1991).

    Article  CAS  Google Scholar 

  27. Zeck, G. & Fromherz, P. Noninvasive neuroelectronic interfacing with synaptically connected snail neurons immobilized on a semiconductor chip. Proc. Natl Acad. Sci. USA 98, 10457–10462 (2001).

    Article  CAS  Google Scholar 

  28. Chi, Y. M., Jung, T.-P. & Cauwenberghs, G. Dry-contact and noncontact biopotential electrodes: methodological review. IEEE Rev. Biomed. Eng. 3, 106–119 (2010).

    Article  Google Scholar 

  29. Spira, M. E. & Hai, A. Multi-electrode array technologies for neuroscience and cardiology. Nat. Nanotech. 8, 83–94 (2013).

    Article  CAS  Google Scholar 

  30. Berdondini, L. et al. Active pixel sensor array for high spatio-temporal resolution electrophysiological recordings from single cell to large scale neuronal networks. Lab Chip 9, 2644–2651 (2009).

    Article  CAS  Google Scholar 

  31. Eversmann, B. et al. A 128× 128 CMOS biosensor array for extracellular recording of neural activity. IEEE J. Solid-State Circ. 38, 2306–2317 (2003).

    Article  Google Scholar 

  32. Bakkum, D. J. et al. Tracking axonal action potential propagation on a high-density microelectrode array across hundreds of sites. Nat. Commun. 4, 21821 (2013).

    Article  Google Scholar 

  33. Byers, C. L., Beazell, J. W., Schulman, J. H. & Rostami, A. Hermetically sealed ceramic and metal package for electronic devices implantable in living bodies. US patent US4991582 A (1991).

  34. Zeng, F.-G., Rebscher, S., Harrison, W., Sun, X. & Feng, H. Cochlear implants: system design, integration, and evaluation. IEEE Rev. Biomed. Eng. 1, 115–142 (2008).

    Article  Google Scholar 

  35. Sillay, K. A., Larson, P. S. & Starr, P. A. Deep brain stimulator hardware-related infections: incidence and management in a large series. Neurosurgery 62, 360–367 (2008).

    Article  Google Scholar 

  36. Jeong, J. W. et al. Capacitive epidermal electronics for electrically safe, long-term electrophysiological measurements. Adv. Health. Mater. 3, 642–648 (2014).

    Article  CAS  Google Scholar 

  37. Duan, X. et al. Quantification of the affinities and kinetics of protein interactions using silicon nanowire biosensors. Nat. Nanotech. 7, 401–407 (2012).

    Article  CAS  Google Scholar 

  38. Fattahi, P., Yang, G., Kim, G. & Abidian, M. R. A review of organic and inorganic biomaterials for neural interfaces. Adv. Mater. 26, 1846–1885 (2014).

    Article  CAS  Google Scholar 

  39. Langendorff, O. Untersuchungen am überlebenden Säugethierherzen. Pflügers Archiv Eur. J. Physiol. 61, 291–332 (1895).

    Article  Google Scholar 

  40. Efimov, I. R., Nikolski, V. P. & Salama, G. Optical imaging of the heart. Circ. Res. 95, 21–33 (2004).

    Article  CAS  Google Scholar 

  41. Bossaert, L. Fibrillation and defibrillation of the heart. Br. J. Anaesth. 79, 203–213 (1997).

    Article  CAS  Google Scholar 

  42. Efimov, I. R., Cheng, Y., Van Wagoner, D. R., Mazgalev, T. & Tchou, P. J. Virtual electrode-induced phase singularity a basic mechanism of defibrillation failure. Circ. Res. 82, 918–925 (1998).

    Article  CAS  Google Scholar 

  43. Rogers, J. M. Combined phase singularity and wavefront analysis for optical maps of ventricular fibrillation. IEEE Trans. Biomed. Eng. 51, 56–65 (2004).

    Article  Google Scholar 

  44. Narayan, S. M. et al. Treatment of atrial fibrillation by the ablation of localized sources: CONFIRM (conventional ablation for atrial fibrillation with or without focal impulse and rotor modulation) trial. J. Am. Coll. Cardiol. 60, 628–636 (2012).

    Article  Google Scholar 

  45. Lim, H. S. et al. Noninvasive mapping to guide atrial fibrillation ablation. Cardiac Electrophysiol. Clinics 7, 89–98 (2015).

    Article  Google Scholar 

  46. Bray, M. A., Lin, S. F., Aliev, R. R., Roth, B. J. & Wikswo, J. P. Experimental and theoretical analysis of phase singularity dynamics in cardiac tissue. J. Cardiovasc. Electrophysiol. 12, 716–722 (2001).

    Article  CAS  Google Scholar 

  47. Onuki, Y., Bhardwaj, U., Papadimitrakopoulos, F. & Burgess, D. J. A review of the biocompatibility of implantable devices: current challenges to overcome foreign body response. J. Diabetes Sci. Technol. 2, 1003–1015 (2008).

    Article  Google Scholar 

  48. Ward, W. K. A review of the foreign-body response to subcutaneously-implanted devices: the role of macrophages and cytokines in biofouling and fibrosis. J. Diabetes Sci. Technol. 2, 768–777 (2008).

    Article  Google Scholar 

  49. Morais, J. M., Papadimitrakopoulos, F. & Burgess, D. J. Biomaterials/tissue interactions: possible solutions to overcome foreign body response. AAPS J. 12, 188–196 (2010).

    Article  CAS  Google Scholar 

  50. Vegas, A. J. et al. Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates. Nat. Biotechnol. 34, 345–352 (2016).

    Article  CAS  Google Scholar 

  51. Hibbitt, H., Karlsson, B. & Sorensen, P. Abaqus analysis user’s manual v.6.10 (Dassault Systèmes Simulia Corp, 2011).

    Google Scholar 

  52. Shi, Y., Rogers, J. A., Gao, C. & Huang, Y. Multiple neutral axes in bending of a multiple-layer beam with extremely different elastic properties. J. Appl. Mech. 81, 114501 (2014).

    Article  Google Scholar 

  53. Li, L. et al. Integrated flexible chalcogenide glass photonic devices. Nat. Photon. 8, 643–649 (2014).

    Article  CAS  Google Scholar 

  54. Su, Y., Li, S., Li, R. & Dagdeviren, C. Splitting of neutral mechanical plane of conformal, multilayer piezoelectric mechanical energy harvester. Appl. Phys. Lett. 107, 041905 (2015).

    Article  Google Scholar 

  55. Fang, H. et al. Dataset for ‘Capacitively coupled arrays of multiplexed flexible silicon transistors for long-term cardiac electrophysiology’. figsharehttps://figshare.com/s/961786fcede5a8703ec5 (2017).

Download references

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.

Author information

Authors and Affiliations

Authors

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.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

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)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41551-017-0038

This article is cited by

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