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:

Viscoelastic surface electrode arrays to interface with viscoelastic tissues

Nature Nanotechnology volume 16, pages 1019–1029 (2021)Cite this article

Subjects

Abstract

Living tissues are non-linearly elastic materials that exhibit viscoelasticity and plasticity. Man-made, implantable bioelectronic arrays mainly rely on rigid or elastic encapsulation materials and stiff films of ductile metals that can be manipulated with microscopic precision to offer reliable electrical properties. In this study, we have engineered a surface microelectrode array that replaces the traditional encapsulation and conductive components with viscoelastic materials. Our array overcomes previous limitations in matching the stiffness and relaxation behaviour of soft biological tissues by using hydrogels as the outer layers. We have introduced a hydrogel-based conductor made from an ionically conductive alginate matrix enhanced with carbon nanomaterials, which provide electrical percolation even at low loading fractions. Our combination of conducting and insulating viscoelastic materials, with top-down manufacturing, allows for the fabrication of electrode arrays compatible with standard electrophysiology platforms. Our arrays intimately conform to the convoluted surface of the heart or brain cortex and offer promising bioengineering applications for recording and stimulation.

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: Alginate hydrogels match the viscoelastic properties of mammalian tissues and conform to complex substrates.
Fig. 2: Alginate hydrogels can be tuned to optimize compatibility with both astrocytes, neurons and a coculture.
Fig. 3: Viscoelastic electronics formed from an alginate matrix with electrically active carbon-based fillers.
Fig. 4: Fabrication of highly flexible and stretchable viscoelastic encapsulation layers.
Fig. 5: Device characterization and in vitro validation of the fully viscoelastic devices.
Fig. 6: In vivo validation of the fully viscoelastic device for stimulation and for recording, even under extreme deformation.

Similar content being viewed by others

Data availability

The data sets generated during and/or analysed during the current study are available from the corresponding author upon reasonable request. Figure 6 has associated raw data (the electrocorticography recordings), shown in Supplementary Fig. 28, and the raw files are available upon request.

Code availability

The code associated with the work of this manuscript is available at https://doi.org/10.7910/DVN/8K77QG (ref. 43).

References

  1. Tolstosheeva, E. et al. A multi-channel, flex-rigid ECoG microelectrode array for visual cortical interfacing. Sensors (Basel) 15, 832–854 (2015).

    Article  Google Scholar 

  2. Luan, L. et al. Ultraflexible nanoelectronic probes form reliable, glial scar–free neural integration. Sci. Adv. 3, e1601966 (2017).

    Article  Google Scholar 

  3. Tybrandt, K. et al. High-density stretchable electrode grids for chronic neural recording. Adv. Mater. 30, e1706520 (2018).

    Article  Google Scholar 

  4. Konerding, W. S., Froriep, U. P., Kral, A. & Baumhoff, P. New thin-film surface electrode array enables brain mapping with high spatial acuity in rodents. Sci. Rep. 8, 1–14 (2018).

    Article  CAS  Google Scholar 

  5. Lacour, S. P., Courtine, G. & Guck, J. Materials and technologies for soft implantable neuroprostheses. Nat. Rev. Mater. 1, 16063 (2016).

    Article  CAS  Google Scholar 

  6. Minev, I. R. et al. Electronic dura mater for long-term multimodal neural interfaces. Science 347, 159–163 (2015).

    Article  CAS  Google Scholar 

  7. Chaudhuri, O. et al. Extracellular matrix stiffness and composition jointly regulate the induction of malignant phenotypes in mammary epithelium. Nat. Mater. 13, 970–978 (2014).

    Article  CAS  Google Scholar 

  8. Budday, S. et al. Region- and loading-specific finite viscoelasticity of human brain tissue. Proc. Appl. Math. Mech. 18, 3–4 (2018).

    Article  Google Scholar 

  9. Wang, Z., Golob, M. J. & Chesler, N. C. in Viscoelastic and Viscoplastic Materials (InTech: 2016); https://doi.org/10.5772/64169

  10. Boyle, N. G. & Shivkumar, K. Epicardial interventions in electrophysiology. Circulation 126, 1752–1769 (2012).

    Article  Google Scholar 

  11. Chaudhuri, O. et al. Substrate stress relaxation regulates cell spreading. Nat. Commun. 6, 6365 (2015).

    Article  CAS  Google Scholar 

  12. Chaudhuri, O. et al. Hydrogels with tunable stress relaxation regulate stem cell fate and activity. Nat. Mater. 15, 326–334 (2016).

    Article  Google Scholar 

  13. Rubehn, B., Bosman, C., Oostenveld, R., Fries, P. & Stieglitz, T. A MEMS-based flexible multichannel ECoG-electrode array. J. Neural Eng. 6, 036003 (2009).

    Article  Google Scholar 

  14. Bramini, M. et al. Interfacing graphene-based materials with neural cells. Front. Syst. Neurosci. 12, https://doi.org/10.3389/fnsys.2018.00012 (2018).

  15. Kostarelos, K. & Novoselov, K. S. Graphene devices for life. Nat. Nanotechnol. 9, 744–745 (2014).

    Article  CAS  Google Scholar 

  16. Martín, C., Kostarelos, K., Prato, M. & Bianco, A. Biocompatibility and biodegradability of 2D materials: graphene and beyond. Chem. Commun. 55, 5540–5546 (2019).

    Article  Google Scholar 

  17. Pampaloni, N. P., Giugliano, M., Scaini, D., Ballerini, L. & Rauti, R. Advances in nano neuroscience: from nanomaterials to nanotools. Front. Neurosci. 12, 953 (2019).

    Article  Google Scholar 

  18. Lu, B. et al. Pure PEDOT:PSS hydrogels. Nat. Commun. 10, 1043 (2019).

    Article  Google Scholar 

  19. Liu, Y. et al. Morphing electronics enable neuromodulation in growing tissue. Nat. Biotechnol. 38, 1031–1036 (2020).

    Article  CAS  Google Scholar 

  20. Yuan, X., Wei, Y., Chen, S., Wang, P. & Liu, L. Bio-based graphene/sodium alginate aerogels for strain sensors. RSC Adv. 6, 64056–64064 (2016).

    Article  CAS  Google Scholar 

  21. Golafshan, N., Kharaziha, M. & Fathi, M. Tough and conductive hybrid graphene-PVA: alginate fibrous scaffolds for engineering neural construct. Carbon 111, 752–763 (2017).

    Article  CAS  Google Scholar 

  22. Lin, X. et al. A viscoelastic adhesive epicardial patch for treating myocardial infarction. Nat. Biomed. Eng. 3, 632–643 (2019).

    Article  CAS  Google Scholar 

  23. Son, D. et al. An integrated self-healable electronic skin system fabricated via dynamic reconstruction of a nanostructured conducting network. Nat. Nanotechnol. 13, 1057–1065 (2018).

    Article  CAS  Google Scholar 

  24. Masvidal-Codina, E. et al. High-resolution mapping of infraslow cortical brain activity enabled by graphene microtransistors. Nat. Mater. 18, 280–288 (2019).

    Article  CAS  Google Scholar 

  25. Green, R. Elastic and conductive hydrogel electrodes. Nat. Biomed. Eng. 3, 9–10 (2019).

    Article  Google Scholar 

  26. Choi, S. et al. Highly conductive, stretchable and biocompatible Ag–Au core–sheath nanowire composite for wearable and implantable bioelectronics. Nat. Nanotechnol. 13, 1048–1056 (2018).

    Article  CAS  Google Scholar 

  27. Lee, S. et al. Ultrasoft electronics to monitor dynamically pulsing cardiomyocytes. Nat. Nanotechnol. 14, 156–160 (2019).

    Article  CAS  Google Scholar 

  28. Lee, K. Y. & Mooney, D. J. Alginate: properties and biomedical applications. Prog. Polym. Sci. 37, 106–126 (2012).

    Article  CAS  Google Scholar 

  29. Sun, J. Y. et al. Highly stretchable and tough hydrogels. Nature 489, 133–136 (2012).

    Article  CAS  Google Scholar 

  30. Kang, J. et al. Tough and water-insensitive self-healing elastomer for robust electronic skin. Adv. Mater. 30, e1706846 (2018).

    Article  Google Scholar 

  31. Tondera, C. et al. Highly conductive, stretchable, and cell-adhesive hydrogel by nanoclay doping. Small 15, 1901406 (2019).

    Article  Google Scholar 

  32. Kim, N. et al. Elastic conducting polymer composites in thermoelectric modules. Nat. Commun. 11, 1424 (2020).

    Article  Google Scholar 

  33. Wang, Y. et al. A highly stretchable, transparent, and conductive polymer. Sci. Adv. 3, e1602076 (2017).

    Article  Google Scholar 

  34. Feig, V. R., Tran, H., Lee, M. & Bao, Z. Mechanically tunable conductive interpenetrating network hydrogels that mimic the elastic moduli of biological tissue. Nat. Commun. 9, 2740 (2018).

    Article  Google Scholar 

  35. Vicente, J., Costa, P., Lanceros-Mendez, S., Abete, J. M. & Iturrospe, A. Electromechanical properties of PVDF-based polymers reinforced with nanocarbonaceous fillers for pressure sensing applications. Materials (Basel) 12, 3545 (2019).

    Article  CAS  Google Scholar 

  36. Chen, Z. et al. Three-dimensional flexible and conductive interconnected graphene networks grown by chemical vapour deposition. Nat. Mater. 10, 424–428 (2011).

    Article  CAS  Google Scholar 

  37. Bhagavatheswaran, E. S. et al. Construction of an interconnected nanostructured carbon black network: development of highly stretchable and robust elastomeric conductors. J. Phys. Chem. C. 119, 21723–21731 (2015).

    Article  CAS  Google Scholar 

  38. Haggenmueller, R., Gommans, H. H., Rinzler, A. G., Fischer, J. E. & Winey, K. I. Aligned single-wall carbon nanotubes in composites by melt processing methods. Chem. Phys. Lett. 330, 219–225 (2000).

    Article  CAS  Google Scholar 

  39. Chen, Y. et al. A skin-inspired stretchable, self-healing and electro-conductive hydrogel with a synergistic triple network for wearable strain sensors applied in human-motion detection. Nanomaterials 9, 1737 (2019).

    Article  CAS  Google Scholar 

  40. Doney, E. et al. 3D printing of preclinical X-ray computed tomographic data sets. J. Vis. Exp. 22, e50250 (2013).

    Google Scholar 

  41. Rowley, J. A., Madlambayan, G. & Mooney, D. J. Alginate hydrogels as synthetic extracellular matrix materials. Biomaterials 20, 45–53 (1999).

    Article  CAS  Google Scholar 

  42. Topsoe, H. Geometric Factors in Four Point Resistivity Measurement. Bulletin No. 472-13 (IISERKOL, 1966). http://four-point-probes.com/haldor-topsoe-geometric-factors-in-four-point-resistivity-measurement/

  43. Tringides, C. & Vachicouras, N. Impedance spectra and cyclic voltammetry analysis. Harvard Dataverse, V1 (2021); https://doi.org/10.7910/DVN/8K77QG

Download references

Acknowledgements

The authors thank T. Sirota and P. Machado, both at the Wyss Institute, Boston Massachusetts, for their help with 3D printing and the machining of moulds, respectively. This work was supported in part by the Center for Nanoscale Systems at Harvard University, which is a member of the National Nanotechnology Infrastructure Network, which is supported by the National Science Foundation under award no. 1541959. We thank the Weitz lab for the use of their rheometer, which is funded by the Materials Research Science and Engineering Center of Harvard University under National Science Foundation award no. DMR 14-20570. This work was supported by an NSF GRFP to C.M.T., as well as funding for C.M.T. through an NIH grant awarded to D.J.M. (RO1DE013033), NSF MRSEC award DMR 14-20570 and funding by the Wyss Institute for Biologically Inspired Engineering at Harvard University. I.d.L. was supported by the National Cancer Institute of the National Institutes of Health under award no. U01CA214369. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. H.W. gratefully acknowledges funding support from the Wyss Technology Development Fellowship. B.R.S. is supported by the National Institute of Dental and Craniofacial Research (R01DE013349) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (P2CHD086843). A.E.-A. received funding for this work from the European Union’s Horizon 2020 research and innovation programme through a Marie Sklodowska-Curie grant agreement no. 798504 (MECHANOSITY). K.K., C.C. and Y.S. were mainly funded by the EPSRC Programme Grant 2D-Health (EP/P00119X/1). C.C. acknowledges support by the EPSRC (EP/N010345/1). N.V., A.T., F.F. and S.P.L. were funded by the Bertarelli Foundation, the Wyss Center Geneva and SNSF Sinergia grant no. CRSII5_183519.

Author information

Authors and Affiliations

  1. Harvard Program in Biophysics, Harvard University, Cambridge, MA, USA

    Christina M. Tringides

  2. Harvard–MIT Division in Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA

    Christina M. Tringides

  3. Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA, USA

    Christina M. Tringides, Irene de Lázaro, Hua Wang, Bo Ri Seo, Alberto Elosegui-Artola & David J. Mooney

  4. Laboratory for Soft Bioelectronic Interfaces, Institute of Microengineering, Institute of Bioengineering, Centre for Neuroprosthetics, École Polytechnique Fédérale de Lausanne, Geneva, Switzerland

    Nicolas Vachicouras, Alix Trouillet, Florian Fallegger & Stéphanie P. Lacour

  5. John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA

    Irene de Lázaro, Hua Wang, Bo Ri Seo, Alberto Elosegui-Artola & David J. Mooney

  6. Institute for Bioengineering of Catalonia, Barcelona, Spain

    Alberto Elosegui-Artola

  7. Department of Chemistry, The University of Manchester, Manchester, UK

    Yuyoung Shin & Cinzia Casiraghi

  8. Nanomedicine Lab, National Graphene Institute and Faculty of Biology, Medicine & Health, The University of Manchester, Manchester, UK

    Kostas Kostarelos

  9. Catalan Institute of Nanoscience and Nanotechnology (ICN2), Bellaterra, Barcelona, Spain

    Kostas Kostarelos

Authors
  1. Christina M. Tringides
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nicolas Vachicouras
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Irene de Lázaro
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hua Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alix Trouillet
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bo Ri Seo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Alberto Elosegui-Artola
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Florian Fallegger
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yuyoung Shin
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Cinzia Casiraghi
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Kostas Kostarelos
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Stéphanie P. Lacour
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. David J. Mooney
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

C.M.T. and D.J.M. conceived the work and designed the experiments. C.M.T. characterized all the materials and developed the conductive gels, as well as fabricated and characterized all the devices. Y.S., C.C. and K.K. synthesized and provided the graphene material. C.M.T. and H.W. developed and synthesized the PEVM. C.M.T. and A.E.-A. made the material for the alginate gels for the in vitro studies. C.M.T. and I.d.L. carried out the cardiac in vivo recordings, and C.M.T., I.d.L. and B.R.S. conducted the muscular stimulation experiments. F.F. supplied the connectors, F.F. and A.T. performed the neural in vivo recordings, and A.T. analysed the electrocorticography data. C.M.T. and N.V. conducted all the data analysis. C.M.T. and D.J.M. wrote the manuscript, and C.M.T., D.J.M. and S.P.L. discussed the results. All authors contributed to the writing and editing of the manuscript.

Corresponding author

Correspondence to David J. Mooney.

Ethics declarations

Competing interests

C.M.T. and D.J.M. are inventors on a patent submitted over the viscoelastic conductors and viscoelastic arrays described in this work. C.C. is an inventor on US patent 10421875B2, which covers the graphene materials used in these studies. All the remaining authors declare no competing interests.

Additional information

Peer review information Nature Nanotechnology thanks Rylie Green, Bozhi Tian and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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

Supplementary information

Supplementary Information

Supplementary Figs. 1–29, Material 1 and Tables 1 and 2.

Reporting Summary

Supplementary Video 1

Device stimulating the mouse hindlimb, with two toes responding.

Supplementary Video 2

Device stimulating the mouse hindlimb, with foot responding.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tringides, C.M., Vachicouras, N., de Lázaro, I. et al. Viscoelastic surface electrode arrays to interface with viscoelastic tissues. Nat. Nanotechnol. 16, 1019–1029 (2021). https://doi.org/10.1038/s41565-021-00926-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41565-021-00926-z

This article is cited by

Search

Advanced search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research