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Viscoelastic surface electrode arrays to interface with viscoelastic tissues

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.

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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.

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).

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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.

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Authors and Affiliations

Authors

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.

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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.

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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.

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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.

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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

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