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Fully implantable optoelectronic systems for battery-free, multimodal operation in neuroscience research

Nature Electronics volume 1, pages 652–660 (2018)Cite this article

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Abstract

Recently developed ultrasmall, fully implantable devices for optogenetic neuromodulation eliminate the physical tethers associated with conventional set-ups and avoid the bulky head-stages and batteries found in alternative wireless technologies. The resulting systems allow behavioural studies without motion constraints and enable experiments in a range of environments and contexts, such as social interactions. However, these devices are purely passive in their electronic design, thereby precluding any form of active control or programmability; independent operation of multiple devices, or of multiple active components in a single device, is, in particular, impossible. Here we report optoelectronic systems that, through developments in integrated circuit and antenna design, provide low-power operation, and position- and angle-independent wireless power harvesting, with full user-programmability over individual devices and collections of them. Furthermore, these integrated platforms have sizes and weights that are not significantly larger than those of previous, passive systems. Our results qualitatively expand options in output stabilization, intensity control and multimodal operation, with broad potential applications in neuroscience research and, in particular, the precise dissection of neural circuit function during unconstrained behavioural studies.

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Fig. 1: Digitally controlled multimodal optogenetic implants.
Fig. 2: Electronic and optical characterization.
Fig. 3: Advanced multimodal operation.
Fig. 4: Implantation and operational capabilities.
Fig. 5: MRI and CT imaging results of the bilateral multi µ-ILED device.

Data availability

The data that support the plots within this paper and other findings of this study are available from the corresponding author upon reasonable request.

References

  1. Boyden, E. S., Zhang, F., Bamberg, E., Nagel, G. & Deisseroth, K. Millisecond-timescale, genetically targeted optical control of neural activity. Nat. Neurosci. 8, 1263–1268 (2005).

    Article  Google Scholar 

  2. Deisseroth, K. Optogenetics. Nat. Methods 8, 26–29 (2011).

    Article  Google Scholar 

  3. Park, S. I. et al. Soft, stretchable, fully implantable miniaturized optoelectronic systems for wireless optogenetics. Nat. Biotechnol. 33, 1280–1286 (2015).

    Article  Google Scholar 

  4. Pisanello, F. et al. Multipoint-emitting optical fibers for spatially addressable in vivo optogenetics. Neuron 82, 1245–1254 (2014).

    Article  Google Scholar 

  5. Yizhar, O., Fenno, L. E., Davidson, T. J., Mogri, M. & Deisseroth, K. Optogenetics in neural systems. Neuron 71, 9–34 (2011).

    Article  Google Scholar 

  6. Chen, R., Canales, A. & Anikeeva, P. Neural recording and modulation technologies. Nat. Rev. Mater. 2, 16093 (2017).

    Article  Google Scholar 

  7. Shin, G. et al. Flexible near-field wireless optoelectronics as subdermal implants for broad applications in optogenetics. Neuron 93, 509–521 (2017). e503.

    Article  Google Scholar 

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

    Article  Google Scholar 

  9. Park, S. I. et al. Stretchable multichannel antennas in soft wireless optoelectronic implants for optogenetics. Proc. Natl Acad. Sci. USA 113, E8169–E8177 (2016).

    Article  Google Scholar 

  10. Ho, J. S. et al. Self-tracking energy transfer for neural stimulation in untethered mice. Phys. Rev. Appl. 4, 024001 (2015).

    Article  Google Scholar 

  11. Gutruf, P. & Rogers, J. A. Implantable, wireless device platforms for neuroscience research. Curr. Opin. Neurobiol. 50, 42–49 (2018).

    Article  Google Scholar 

  12. Klapoetke, N. C. et al. Independent optical excitation of distinct neural populations. Nat. Methods 11, 338–346 (2014).

    Article  Google Scholar 

  13. Akerboom, J. et al. Genetically encoded calcium indicators for multi-color neural activity imaging and combination with optogenetics. Front. Mol. Neurosci. https://doi.org/10.3389/fnmol.2013.00002 (2013).

  14. Harvey, C. D., Collman, F., Dombeck, D. A. & Tank, D. W. Intracellular dynamics of hippocampal place cells during virtual navigation. Nature 461, 941–946 (2009).

    Article  Google Scholar 

  15. Tye, K. M. et al. Amygdala circuitry mediating reversible and bidirectional control of anxiety. Nature 471, 358–362 (2011).

    Article  Google Scholar 

  16. Hight, A. E. et al. Superior temporal resolution of Chronos versus channelrhodopsin-2 in an optogenetic model of the auditory brainstem implant. Hear. Res. 322, 235–241 (2015).

    Article  Google Scholar 

  17. Gerlai, R. A small fish with a big future: zebrafish in behavioral neuroscience. Rev. Neurosci. 22, 3–4 (2011).

    Article  Google Scholar 

  18. Yartsev, M. M. & Ulanovsky, N. Representation of three-dimensional space in the hippocampus of flying bats. Science 340, 367–372 (2013).

    Article  Google Scholar 

  19. Lu, L. et al. Wireless optoelectronic photometers for monitoring neuronal dynamics in the deep brain. Proc. Natl Acad. Sci. USA 115, E1374–E1383 (2018).

    Article  Google Scholar 

  20. Samineni, V. K. et al. Fully implantable, battery-free wireless optoelectronic devices for spinal optogenetics. Pain 158, 2108–2116 (2017).

    Article  Google Scholar 

  21. Wang, L., Jacques, S. L. & Zheng, L. MCML—Monte Carlo modeling of light transport in multi-layered tissues. Comput. Methods Programs Biomed. 47, 131–146 (1995).

    Article  Google Scholar 

  22. Keijzer, M., Jacques, S. L., Prahl, S. A. & Welch, A. J. Light distributions in artery tissue: Monte Carlo simulations for finite‐diameter laser beams. Lasers Surg. Med. 9, 148–154 (1989).

    Article  Google Scholar 

  23. Yaroslavsky, A. et al. Optical properties of selected native and coagulated human brain tissues in vitro in the visible and near infrared spectral range. Phys. Med. Biol. 47, 2059 (2002).

    Article  Google Scholar 

  24. Yona, G., Meitav, N., Kahn, I. & Shoham, S. Realistic numerical and analytical modeling of light scattering in brain tissue for optogenetic applications. eNeuro 3, ENEURO.0059-0015.2015 (2016).

    Article  Google Scholar 

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Acknowledgements

We acknowledge support from the Center for Bio-Integrated Electronics at Northwestern University. C.R.H. is supported by Cancer Center Support Grant P30 CA060553 from the National Cancer Institute awarded to the Robert H. Lurie Comprehensive Cancer Center. Z.X. acknowledges support from the National Natural Science Foundation of China (grant number 11402134). Y.H. acknowledges support from the National Science Foundation (grant numbers 1400169, 1534120 and 1635443).

Author information

Authors and Affiliations

  1. Center for Bio-Integrated Electronics at the Simpson Querrey Institute for BioNanotechnology and the Department of Materials Science and Engineering, Northwestern University, Evanston, IL, USA

    Philipp Gutruf, Chun-Ju Su, Siddharth R. Krishnan & Tyler Ray

  2. Department of Biomedical Engineering, Bioscience Research Laboratories, University of Arizona, Tucson, AZ, USA

    Philipp Gutruf

  3. Functional Material and Microsystems Research Group and Micro Nano Research Facility, RMIT University, Melbourne, Victoria, Australia

    Vaishnavi Krishnamurthi

  4. CREOL, The College of Optics and Photonics, University of Central Florida, Orlando, FL, USA

    Abraham Vázquez-Guardado & Debashis Chanda

  5. NanoScience Technology Center, University of Central Florida, Orlando, FL, USA

    Abraham Vázquez-Guardado & Debashis Chanda

  6. Department of Civil and Environmental Engineering, Mechanical Engineering, and Materials Science and Engineering, Northwestern University, Evanston, IL, USA

    Zhaoqian Xie & Yonggang Huang

  7. Department of Materials Science and Engineering Frederick Seitz Materials Research Laboratory University of Illinois at Urbana-Champaign, Urbana, IL, USA

    Anthony Banks

  8. Key Laboratory of C&PC Structures of the Ministry of Education, Southeast University, Nanjing, China

    Yeshou Xu

  9. Center for Advanced Molecular Imaging, Radiology, and Biomedical Engineering, Northwestern University, Evanston, IL, USA

    Chad R. Haney

  10. Center for Advanced Molecular Imaging, Northwestern University, Evanston, IL, USA

    Emily A. Waters

  11. Developmental Therapeutics Core, Northwestern University, Evanston, IL, USA

    Irawati Kandela

  12. Department of Biomedical Engineering McCormick School of Engineering and Applied Science, Northwestern University, Evanston, IL, USA

    John P. Leshock

  13. Departments of Materials Science and Engineering, Biomedical Engineering, Chemistry, Neurological Surgery, Mechanical Engineering, Electrical Engineering and Computer Science Simpson Querrey Institute & Feinberg Medical School, Northwestern University, Evanston, IL, USA

    John A. Rogers

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  1. Philipp Gutruf
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  15. Debashis Chanda
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Contributions

P.G., A.V.-G., Z.X. and J.A.R. designed research. P.G., V.K., A.V-G., Z.X., A.B., C.-J.S., Y.X., C.R.H., E.A.W., I.K., S.R.K, T.R. and J.P.L. performed research. P.G., A.V.-G., Z.X., C.R.H., E.A.W., I.K., Y.H., D.C. and J.A.R. analysed data. P.G. and J.A.R. wrote the paper.

Corresponding author

Correspondence to John A. Rogers.

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Supplementary information

Supplementary Information

Supplementary Figures 1–14

Reporting Summary

Supplementary Video 1

Demonstration of output intensity modulation. The program increases intensity from OFF to full intensity and terminates with an indicator flash.

Supplementary Video 2

Demonstration of output modulation using one-way communication. Remotely selected programs include: State 1, sequential blinking of all four LEDs; State 2, alternate blinking of left and right shank; State 3, blinking of LED1; State 4, blinking of LED2; State 5, blinking of LED3; State 6, blinking of LED4 and subsequent reset to State 1.

Supplementary Video 3

Demonstration of individual control over device functionality of multiple devices in one experimental environment.

Supplementary Video 4

Freely moving mouse with constant-intensity device implanted and active.

Supplementary Video 5

Bilateral optogenetic implant operating inside a 7 tesla small animal MRI​.

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Gutruf, P., Krishnamurthi, V., Vázquez-Guardado, A. et al. Fully implantable optoelectronic systems for battery-free, multimodal operation in neuroscience research. Nat Electron 1, 652–660 (2018). https://doi.org/10.1038/s41928-018-0175-0

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