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


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.


  1. Iyer, S.M. et al. Virally mediated optogenetic excitation and inhibition of pain in freely moving nontransgenic mice. Nat. Biotechnol. 32, 274–278 (2014).

    CAS  Article  Google Scholar 

  2. Towne, C., Montgomery, K.L., Iyer, S.M., Deisseroth, K. & Delp, S.L. Optogenetic control of targeted peripheral axons in freely moving animals. PLoS One 8, e72691 (2013).

    CAS  Article  Google Scholar 

  3. Daou, I. et al. Remote optogenetic activation and sensitization of pain pathways in freely moving mice. J. Neurosci. 33, 18631–18640 (2013).

    CAS  Article  Google Scholar 

  4. Kozai, T.D. et al. Ultrasmall implantable composite microelectrodes with bioactive surfaces for chronic neural interfaces. Nat. Mater. 11, 1065–1073 (2012).

    CAS  Article  Google Scholar 

  5. Sparta, D.R. et al. Construction of implantable optical fibers for long-term optogenetic manipulation of neural circuits. Nat. Protoc. 7, 12–23 (2012).

    CAS  Article  Google Scholar 

  6. Jang, K.I. et al. Rugged and breathable forms of stretchable electronics with adherent composite substrates for transcutaneous monitoring. Nat. Commun. 5, 4779 (2014).

    CAS  Article  Google Scholar 

  7. Kim, D.H. et al. Epidermal electronics. Science 333, 838–843 (2011).

    CAS  Article  Google Scholar 

  8. Kim, T.I. et al. Injectable, cellular-scale optoelectronics with applications for wireless optogenetics. Science 340, 211–216 (2013).

    CAS  Article  Google Scholar 

  9. Xu, S. et al. Soft microfluidic assemblies of sensors, circuits, and radios for the skin. Science 344, 70–74 (2014).

    CAS  Article  Google Scholar 

  10. Montgomery, K.L. et al. Wirelessly powered, fully internal optogenetics for brain, spinal and peripheral circuits in mice. Nat. Methods 12, 969–974 (2015).

    CAS  Article  Google Scholar 

  11. Folcher, M. et al. Mind-controlled transgene expression by a wireless-powered optogenetic designer cell implant. Nat. Commun. 5, 5392 (2014).

    CAS  Article  Google Scholar 

  12. Harrington, R.F. Time-Harmonic Electromagnetic Fields (Wiley-IEEE Press, 2001).

  13. IEEE Standard for Safety Levels with Respect to Human Exposure to Radio Frequency Electromagnetic Fields, 3 kHz to 300 GHz, IEEE Standard C95.1-2005 (Institute of Electronic and Electrical Engineers, 2005).

  14. da Silva, S. et al. Proper formation of whisker barrelettes requires periphery-derived Smad4-dependent TGF-beta signaling. Proc. Natl. Acad. Sci. USA 108, 3395–3400 (2011).

    CAS  Article  Google Scholar 

  15. Hasegawa, H., Abbott, S., Han, B.X., Qi, Y. & Wang, F. Analyzing somatosensory axon projections with the sensory neuron-specific Advillin gene. J. Neurosci. 27, 14404–14414 (2007).

    CAS  Article  Google Scholar 

  16. Fink, D.J. et al. Gene therapy for pain: results of a phase I clinical trial. Ann. Neurol. 70, 207–212 (2011).

    CAS  Article  Google Scholar 

  17. Fink, D.J. & Wolfe, D. Gene therapy for pain: a perspective. Pain Manag. 1, 379–381 (2011).

    Article  Google Scholar 

  18. Miyazato, M. et al. Suppression of detrusor-sphincter dyssynergia by herpes simplex virus vector mediated gene delivery of glutamic acid decarboxylase in spinal cord injured rats. J. Urol. 184, 1204–1210 (2010).

    CAS  Article  Google Scholar 

  19. Yokoyama, H. et al. Gene therapy for bladder overactivity and nociception with herpes simplex virus vectors expressing preproenkephalin. Hum. Gene Ther. 20, 63–71 (2009).

    CAS  Article  Google Scholar 

  20. Pleticha, J. et al. Preclinical toxicity evaluation of AAV for pain: evidence from human AAV studies and from the pharmacology of analgesic drugs. Mol. Pain 10, 54 (2014).

    Article  Google Scholar 

  21. Agarwal, N., Offermanns, S. & Kuner, R. Conditional gene deletion in primary nociceptive neurons of trigeminal ganglia and dorsal root ganglia. Genesis 38, 122–129 (2004).

    CAS  Article  Google Scholar 

  22. Mishra, S.K., Tisel, S.M., Orestes, P., Bhangoo, S.K. & Hoon, M.A. TRPV1-lineage neurons are required for thermal sensation. EMBO J. 30, 582–593 (2011).

    CAS  Article  Google Scholar 

  23. Madisen, L. et al. A toolbox of Cre-dependent optogenetic transgenic mice for light-induced activation and silencing. Nat. Neurosci. 15, 793–802 (2012).

    CAS  Article  Google Scholar 

  24. Bennett, G.J. & Xie, Y.K. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 33, 87–107 (1988).

    CAS  Article  Google Scholar 

  25. Harrison, M. et al. Vertebral landmarks for the identification of spinal cord segments in the mouse. Neuroimage 68, 22–29 (2013).

    Article  Google Scholar 

  26. Golden, J.P. et al. Dopamine-dependent compensation maintains motor behavior in mice with developmental ablation of dopaminergic neurons. J. Neurosci. 33, 17095–17107 (2013).

    CAS  Article  Google Scholar 

  27. Montana, M.C. et al. The metabotropic glutamate receptor subtype 5 antagonist fenobam is analgesic and has improved in vivo selectivity compared with the prototypical antagonist 2-methyl-6-(phenylethynyl)-pyridine. J. Pharmacol. Exp. Ther. 330, 834–843 (2009).

    CAS  Article  Google Scholar 

  28. Golden, J.P. et al. RET signaling is required for survival and normal function of nonpeptidergic nociceptors. J. Neurosci. 30, 3983–3994 (2010).

    CAS  Article  Google Scholar 

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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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Authors and Affiliations



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).

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