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Soft, stretchable, fully implantable miniaturized optoelectronic systems for wireless optogenetics

Abstract

Optogenetics allows rapid, temporally specific control of neuronal activity by targeted expression and activation of light-sensitive proteins. Implementation typically requires remote light sources and fiber-optic delivery schemes that impose considerable physical constraints on natural behaviors. In this report we bypass these limitations using technologies that combine thin, mechanically soft neural interfaces with fully implantable, stretchable wireless radio power and control systems. The resulting devices achieve optogenetic modulation of the spinal cord and peripheral nervous system. This is demonstrated with two form factors; stretchable film appliqués that interface directly with peripheral nerves, and flexible filaments that insert into the narrow confines of the spinal epidural space. These soft, thin devices are minimally invasive, and histological tests suggest they can be used in chronic studies. We demonstrate the power of this technology by modulating peripheral and spinal pain circuitry, providing evidence for the potential widespread use of these devices in research and future clinical applications of optogenetics outside the brain.

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Figure 1: Miniaturized, fully implantable, soft optoelectronic systems for wireless optogenetics.
Figure 2: Electrical and mechanical characteristics of the stretchable optoelectronics systems.
Figure 3: Electrophysiological and anatomical characterization of ChR2 expression in Advillin-ChR2 mice.
Figure 4: Wireless activation of ChR2 expressed in nociceptive pathways results in spontaneous pain behaviors and place aversion.

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Acknowledgements

This work was supported by a US National Institutes of Health (NIH) Director's Transformative Research Award (NS081707) to R.W.G., J.A.R. and M.R.B. D.S.B. was supported by an NIH Ruth L. Kirschstein F31 Predoctoral Fellowship (1F31NS078852). C.D.M. was supported by a Howard Hughes Medical Institute (HHMI) Medical Research Fellowship. B.A.C. was supported by a W.M. Keck Fellowship in Molecular Medicine and TR32 GM108539. M.Y.P. was supported by T32 GM007067. S.D. was supported by NS076324. Illustrations created by J. Sinn-Hanlon and P. Focken, University of Illinois. The authors appreciate the gifts of heterozygous SNS-cre mice from R. Kuner (University of Heidelberg), heterozygous TrpV1-cre mice from M. Hoon (NIH/National Institute of Dental and Craniofacial Research) and heterozygous Advillin-cre mice from F. Wang (Duke University). We would also like to think R.E. Schmidt for the expertise he provided in neuropathological examination of tissue.

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Contributions

S.I.P. designed wireless optoelectronic systems, fabricated devices, tested devices, made wireless measurements, conducted simulations of wireless performance, designed experiments, generated figures, wrote and edited the manuscript. D.S.B. designed sciatic nerve devices, implanted devices, tested mice behavior, designed experiments, performed immunostaining, generated figures, wrote and edited the manuscript. G.S. designed and fabricated spinal cord devices, tested devices, generated figures, wrote and edited the manuscript. C.D.M. designed spinal cord devices, implanted devices, tested mice in behavior, designed experiments, performed immunostaining, generated figures, wrote and edited the manuscript. B.A.C. performed immunostaining and quantification, electrophysiology experiments, generated figures. H.U.C. and K.N.N. fabricated devices and tested devices. M.Y.P. performed surgical procedures, behavioral studies and electrophysiology, generated figures and edited the manuscript. S.D. performed experiments, implanted devices, generated figures. S.J.O., J.Y. and K.-I.J. made contributions to fabrication and testing of devices. V.K.S. performed experiments, immunostaining and generated figures. M.N. performed immunostaining and quantification of slides, as well as mouse breeding. J.G.G.-R. performed experiments and generated figures. S.K.V. performed immunostaining and mouse breeding. S.S.S. performed immunostaining and mouse breeding. K.M.W. performed immunostaining. J.S.H. made contributions to fabrication and testing of devices. R.X., T.P. and Y.H. performed mechanical simulations of device tolerance levels. T.K. designed and tested wireless optoelectronic systems for sciatic nerve. M.C.M. designed experiments and generated figures. J.P.G. performed immunostaining, generated figures, performed behavioral experiments, helped develop epidural implants and edited the manuscript. M.R.B. designed experiments. R.W.G. and J.A.R. oversaw all experiments and data analysis, designed experiments and devices, wrote and edited the manuscript.

Corresponding authors

Correspondence to Robert W Gereau IV or John A Rogers.

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The authors declare no competing financial interests.

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Supplementary Notes 1–8; Supplementary Figures 1–22; Supplementary Tables 1–2 (PDF 4753 kb)

Supplementary Movie 1 (MP4 3437 kb)

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Park, S., Brenner, D., Shin, G. et al. Soft, stretchable, fully implantable miniaturized optoelectronic systems for wireless optogenetics. Nat Biotechnol 33, 1280–1286 (2015). https://doi.org/10.1038/nbt.3415

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