Development of An Implantable Optrode for Optogenetic Stimulation_Journal of Biomedical Engineering

Authors：

YUESen ^1,2,4 , YUANMingjun ^1,2,4 , ZHANGYunpeng ¹ , WANGXiyuan ³ ,  WANGShouyan ¹

1. Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China;
2. Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences, Changchun 130033, China;
3. Shandong Agricultural University, Taian 271018, China;
4. University of Chinese Academy of Sciences, Beijing 100049, China;

Corresponding author：

WANGShouyan, Email: swang@sibet.ac.cn

Keywords：

optogenetics; neural stimulation; optrode

DOI：

10.7507/1001-5515.20160057

Video：

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In this study, an implantable optrode was developed for optogenetics stimulation of neural population in nuclei or multi-sites in neural circuits. The optrode was composed of base layer, micro-light emitting diode (LED) and coating layer. The base layer was a 150 μm thick polyimide substrate on which copper wires and contacts were fabricated by flexible printed circuit board processes. The micro-LED was soldered on the contacts using SnBi. Parylene-C was deposited over the optrode as the coating layer using a vacuum vapor deposition system. The optical output power was tested by optical power meter and the insulating property was tested using saline in the experiment. The stimulation function of the optrode was demonstrated through animal experiment. The width of the optrode was 500 μm and the maximum thickness of the optrode was 310 μm at the LED position. The thickness of the parylene coating layer was about 1 μm. The maximum optical output power of optrode was 9.31 mW and the effective illumination area was a 3.03 mm² spherical cap at 650 μm deep in brain tissue. The optrode was still functional after 14 days in physiological saline. Conventional copper electrodes were used to verify the efficacy of the optrode for stimulation and robust spiking activities of the expressing Channelrhodopsin-2 neurons in the entire cortex of a mouce were recorded. Obvious behavior change happened when light stimulation was applied to the expressing Channelrhodopsin-2 neurons in the secondary motor cortex of the mice. The optrode has the characteristics of large effective illumination range, flexible in implantation and long-term implantable, which provide neural population in nuclei research a new tool.

Citation： YUESen, YUANMingjun, ZHANGYunpeng, WANGXiyuan, WANGShouyan. Development of An Implantable Optrode for Optogenetic Stimulation. Journal of Biomedical Engineering, 2016, 33(2): 337-342, 367. doi: 10.7507/1001-5515.20160057 Copy

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1. WARDEN M R, CARDIN J A, DEISSEROTH K. Optical neural interfaces[J]. Ann Rev biomed Eng, 2014, 16:103-129.
2. 陈宜张.光遗传学研究[J].科学(上海), 2014, 66(4):21-26.
3. Editorial. Method of the Year 2010[J]. Nat Methods, 2011, 8(1):1.
4. ADAMANTIDIS A R, ZHANG Feng, ARAVANIS A M, et al. Neural substrates of awakening probed with optogenetic control of hypocretin neurons[J]. Nature, 2007, 450(7168):420-424.
5. ARAVANIS A M, WANG Liping, ZHANG Feng, et al. An optical neural interface:in vivo control of rodent motor cortex with integrated fiberoptic and optogenetic technology[J]. J Neural Eng, 2007, 4(3):S143-S156.
6. ZHANG Feng, GRADINARU V, ADAMANTIDIS A R, et al. Optogenetic interrogation of neural circuits:technology for probing mammalian brain structures[J]. Nat Protoc, 2010, 5(3):439-456.
7. WU Fan, STARK E, IM M, et al. An implantable neural probe with monolithically integrated dielectric waveguide and recording electrodes for optogenetics applications[J]. J Neural Eng, 2013, 10(5):056012.
8. KANNO S, LEE S, HARASHIMA T, et al. Multiple optical stimulation to neuron using Si opto-neural probe with multiple optical waveguides and metal-cover for optogenetics[C]//35th Annual International Conference of the IEEE EMBS. Osaka:2013:253-256.
9. ZHANG J, LAIWALLA F, KIM J A, et al. A microelectrode array incorporating an optical waveguide device for stimulation and spatiotemporal electrical recording of neural activity[C]//Engineering in Medicine and Biology Society (EMBC). Minneapolis:2009:2046-2049.
10. HIRA R, HONKURA N, NOGUCHI J, et al. Transcranial optogenetic stimulation for functional mapping of the motor cortex[J]. J Neurosci Methods, 2009, 179(2):258-263.
11. WARDEN M R, SELIMBEYOGLU A, MIRZABEKOV J J, et al. A prefrontal cortex-brainstem neuronal projection that controls response to behavioural challenge[J]. Nature, 2012, 492(7429):428-432.
12. WITTEN I B, STEINBERG E E, LEE S Y, et al. Recombinase-driver rat lines:tools, techniques, and optogenetic application to dopamine-mediated reinforcement[J]. Neuron, 2011, 72(5):721-733.
13. KIM T I, MCCALL J G, JUNG Y H, et al. Injectable, cellular-scale optoelectronics with applications for wireless optogenetics[J]. Science, 2013, 340(6129):211-216.
14. KWON K Y, KHOMENKO A, HAQ M, et al. Integrated slanted microneedle-LED array for optogenetics[C]//201335th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC). Osaka:2013:249-252.
15. CAO H, GU Ling, MOHANTY S K, et al. An integrated μLED optrode for optogenetic stimulation and electrical recording[J]. IEEE Trans Biomed Eng, 2013, 60(1):225-229.
16. SMITH K S, VIRKUD A, DEISSEROTH K, et al. Reversible online control of habitual behavior by optogenetic perturbation of medial prefrontal cortex[J]. Proc Natl Acad Sci U S A, 2012, 109(46):18932-18937.
17. ZALOCUSKY K, DEISSEROTH K. Optogenetics in the behaving rat:integration of diverse new technologies in a vital animal model[J]. Optogenetics, 2013, 1:1-17.
18. 周洪波, 李刚, 张华, 等.简易低成本柔性神经微电极制作方法[J].光学精密工程, 2007, 15(7):1056-1063.
19. 芮岳峰, 王亚军, 刘景全, 等.基于Parylene的柔性生物微电极阵列的制作[J].纳米技术与精密工程, 2011, 09(5):422-426.

Journal of Biomedical Engineering

Development of An Implantable Optrode for Optogenetic Stimulation

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