Design and manufacturing challenges of optogenetic neural interfaces: a review

Optogenetics is a relatively new technology to achieve cell-type specific neuromodulation with millisecond-scale temporal precision. Optogenetic tools are being developed to address neuroscience challenges, and to improve the knowledge about brain networks, with the ultimate aim of catalyzing new treatments for brain disorders and diseases. To reach this ambitious goal the implementation of mature and reliable engineered tools is required. The success of optogenetics relies on optical tools that can deliver light into the neural tissue. Objective/Approach: Here, the design and manufacturing approaches available to the scientific community are reviewed, and current challenges to accomplish appropriate scalable, multimodal and wireless optical devices are discussed. SIGNIFICANCE Overall, this review aims at presenting a helpful guidance to the engineering and design of optical microsystems for optogenetic applications.

[1]  J. Y. Sim,et al.  Wireless Optofluidic Systems for Programmable In Vivo Pharmacology and Optogenetics , 2015, Cell.

[2]  Weihua Pei,et al.  A fiber-based implantable multi-optrode array with contiguous optical and electrical sites , 2013, Journal of neural engineering.

[3]  J. Weiland,et al.  Visual performance using a retinal prosthesis in three subjects with retinitis pigmentosa. , 2007, American journal of ophthalmology.

[4]  O. Paul,et al.  Miniaturized 3×3 optical fiber array for optogenetics with integrated 460 nm light sources and flexible electrical interconnection , 2015, 2015 28th IEEE International Conference on Micro Electro Mechanical Systems (MEMS).

[5]  A. J. Perrin.  High-Speed Imaging Reveals Neurophysiological Links to Behavior in an Animal Model of Depression , 2002 .

[6]  Patrick Degenaar,et al.  Optobionic vision—a new genetically enhanced light on retinal prosthesis , 2009, Journal of neural engineering.

[7]  Jing Wang,et al.  Integrated device for combined optical neuromodulation and electrical recording for chronic in vivo applications , 2012, Journal of neural engineering.

[8]  Mohamad Sawan,et al.  Design and Implementation Challenges of Microelectrode Arrays: A Review , 2013 .

[9]  Patrick Degenaar,et al.  A New Individually Addressable Micro-LED Array for Photogenetic Neural Stimulation , 2010, IEEE Transactions on Biomedical Circuits and Systems.

[10]  David J. Anderson,et al.  Optogenetics, Sex, and Violence in the Brain: Implications for Psychiatry , 2012, Biological Psychiatry.

[11]  J. Assad,et al.  Multipoint-Emitting Optical Fibers for Spatially Addressable In Vivo Optogenetics , 2014, Neuron.

[12]  Emilio Bizzi,et al.  Polymer Fiber Probes Enable Optical Control of Spinal Cord and Muscle Function In Vivo , 2014 .

[13]  A. Zorzos,et al.  Multiwaveguide implantable probe for light delivery to sets of distributed brain targets. , 2010, Optics letters.

[14]  Suzie Dufour,et al.  Optrodes for combined optogenetics and electrophysiology in live animals , 2015, Neurophotonics.

[15]  A. Benabid.  Deep brain stimulation for Parkinson’s disease , 2003, Current Opinion in Neurobiology.

[16]  Jacob G. Bernstein,et al.  Optogenetic tools for analyzing the neural circuits of behavior , 2011, Trends in Cognitive Sciences.

[17]  Harald Giessen,et al.  Ultra-compact on-chip LED collimation optics by 3D femtosecond direct laser writing. , 2016, Optics letters.

[18]  Kunal J. Paralikar,et al.  Collagenase-Aided Intracortical Microelectrode Array Insertion: Effects on Insertion Force and Recording Performance , 2008, IEEE Transactions on Biomedical Engineering.

[19]  Robert Puers,et al.  An interconnect for out-of-plane assembled biomedical probe arrays , 2008 .

[20]  Andrei Faraon,et al.  Visible array waveguide gratings for applications of optical neural probes , 2015, Photonics West - Biomedical Optics.

[21]  김성준,et al.  Neural stimulation and recording electrode array and method of manufacturing the same , 2012 .

[22]  Karl Deisseroth,et al.  Optetrode: a multichannel readout for optogenetic control in freely moving mice , 2011, Nature Neuroscience.

[23]  Edward S Boyden,et al.  Virally delivered channelrhodopsin-2 safely and effectively restores visual function in multiple mouse models of blindness. , 2011, Molecular therapy : the journal of the American Society of Gene Therapy.

[24]  Nicholas G Hatsopoulos,et al.  The science of neural interface systems. , 2009, Annual review of neuroscience.

[25]  Karl Deisseroth,et al.  High-Speed Imaging Reveals Neurophysiological Links to Behavior in an Animal Model of Depression , 2007, Science.

[26]  Willy Wong,et al.  A novel method for removal of deep brain stimulation artifact from electroencephalography , 2014, Journal of Neuroscience Methods.

[27]  Blake S. Wilson,et al.  Cochlear implants: A remarkable past and a brilliant future , 2008, Hearing Research.

[28]  X.L. Chen,et al.  Deep Brain Stimulation , 2013, Interventional Neurology.

[29]  Steffen B. E. Wolff,et al.  A polymer-based neural microimplant for optogenetic applications: design and first in vivo study. , 2013, Lab on a chip.

[30]  Edward S Boyden,et al.  Three-dimensional multiwaveguide probe array for light delivery to distributed brain circuits. , 2012, Optics letters.

[31]  Euisik Yoon,et al.  A 16-site neural probe integrated with a waveguide for optical stimulation , 2010, 2010 IEEE 23rd International Conference on Micro Electro Mechanical Systems (MEMS).

[32]  G. Buzsáki,et al.  Fiberless multicolor neural optoelectrode for in vivo circuit analysis , 2016, Scientific Reports.

[33]  R. Marc,et al.  Optogenetics for Retinal Disorders , 2014, Journal of ophthalmic & vision research.

[34]  Elena M. Vazey,et al.  New tricks for old dogmas: Optogenetic and designer receptor insights for Parkinson's disease , 2013, Brain Research.

[35]  Martin Garwicz,et al.  Authenticity, Depression, and Deep Brain Stimulation , 2011, Front. Integr. Neurosci..

[36]  Christina M. Tringides,et al.  Multifunctional fibers for simultaneous optical, electrical and chemical interrogation of neural circuits in vivo , 2015, Nature Biotechnology.

[37]  Jakob Voigts,et al.  The flexDrive: an ultra-light implant for optical control and highly parallel chronic recording of neuronal ensembles in freely moving mice , 2013, Front. Syst. Neurosci..

[38]  G. Buzsáki,et al.  Monolithically Integrated μLEDs on Silicon Neural Probes for High-Resolution Optogenetic Studies in Behaving Animals , 2015, Neuron.

[39]  L. Miller,et al.  Optimal spacing of surface electrode arrays for brain–machine interface applications , 2010, Journal of neural engineering.

[40]  K. Mathieson,et al.  Thermal and optical characterization of micro-LED probes for in vivo optogenetic neural stimulation. , 2013, Optics letters.

[41]  Babak Ziaie,et al.  A self-assembled 3D microelectrode array , 2010 .

[42]  A. Benabid,et al.  Brain stimulation: current applications and future prospects , 2001 .

[43]  Xue Han,et al.  Prosthetic systems for therapeutic optical activation and silencing of genetically targeted neurons , 2008, SPIE BiOS.

[44]  Lief E. Fenno,et al.  The Microbial Opsin Family of Optogenetic Tools , 2011, Cell.

[45]  M. Morrell,et al.  Intracranial stimulation therapy for epilepsy , 2009, Neurotherapeutics.

[46]  J. Mink,et al.  Deep brain stimulation. , 2006, Annual review of neuroscience.

[47]  Florian Solzbacher,et al.  Fabrication of compliant high aspect ratio silicon microelectrode arrays using micro-wire electrical discharge machining , 2009 .

[48]  Mary Kay Lobo,et al.  Potential Utility of Optogenetics in the Study of Depression , 2012, Biological Psychiatry.

[49]  P. Tresco,et al.  Response of brain tissue to chronically implanted neural electrodes , 2005, Journal of Neuroscience Methods.

[50]  Bin Fan,et al.  Micro-lens-coupled LED neural stimulator for optogenetics , 2015, 2015 IEEE Biomedical Circuits and Systems Conference (BioCAS).

[51]  K. Deisseroth,et al.  Circuit-breakers: optical technologies for probing neural signals and systems , 2007, Nature Reviews Neuroscience.

[52]  G. Buzsáki,et al.  An implantable neural probe with monolithically integrated dielectric waveguide and recording electrodes for optogenetics applications , 2013, Journal of neural engineering.

[53]  I. Ulbert,et al.  CMOS-Based High-Density Silicon Microprobe Arrays for Electronic Depth Control in Intracortical Neural Recording–Characterization and Application , 2012, Journal of Microelectromechanical Systems.

[54]  Jared P. Ness,et al.  Graphene-based carbon-layered electrode array technology for neural imaging and optogenetic applications , 2014, Nature Communications.

[55]  Patrick Ruther,et al.  Let There Be Light—Optoprobes for Neural Implants , 2017, Proceedings of the IEEE.

[56]  Yei Hwan Jung,et al.  Injectable, Cellular-Scale Optoelectronics with Applications for Wireless Optogenetics , 2013, Science.

[57]  Suzie Dufour,et al.  A Multimodal Micro-Optrode Combining Field and Single Unit Recording, Multispectral Detection and Photolabeling Capabilities , 2013, PloS one.

[58]  Tri Giang Phan,et al.  Fabricating low cost and high performance elastomer lenses using hanging droplets. , 2014, Biomedical optics express.

[59]  Dheeraj S. Roy,et al.  Memory retrieval by activating engram cells in mouse models of early Alzheimer’s disease , 2016, Nature.

[60]  K. Wise,et al.  In vivo optical modulation of neural signals using monolithically integrated two-dimensional neural probe arrays , 2015, Scientific Reports.

[61]  Karl Deisseroth,et al.  Recent advances in optogenetics and pharmacogenetics , 2013, Brain Research.

[62]  Shin-Yuan Chen,et al.  N-of-1 trial following deep brain stimulation in a patient with obsessive–compulsive disorder , 2012 .

[63]  Karl Deisseroth,et al.  Genetic Reactivation of Cone Photoreceptors Restores Visual Responses in Retinitis Pigmentosa , 2010, Science.

[64]  S. B. Goncalves,et al.  Flexible three-dimensional microelectrode array for neural applications , 2014 .

[65]  Luis de Lecea,et al.  Optogenetic investigation of neural circuits in vivo. , 2011, Trends in molecular medicine.

[66]  John A Rogers,et al.  Soft, stretchable, fully implantable miniaturized optoelectronic systems for wireless optogenetics , 2015, Nature Biotechnology.

[67]  Anatol C. Kreitzer,et al.  Regulation of parkinsonian motor behaviours by optogenetic control of basal ganglia circuitry , 2010, Nature.

[68]  F. Solzbacher,et al.  A 3D glass optrode array for optical neural stimulation , 2012, Biomedical optics express.

[69]  N. Alpert,et al.  A functional neuroimaging investigation of deep brain stimulation in patients with obsessive-compulsive disorder. , 2006, Journal of neurosurgery.

[70]  Attila Losonczy,et al.  Multi‐array silicon probes with integrated optical fibers: light‐assisted perturbation and recording of local neural circuits in the behaving animal , 2010, The European journal of neuroscience.

[71]  I. Ozden,et al.  Transparent intracortical microprobe array for simultaneous spatiotemporal optical stimulation and multichannel electrical recording , 2015, Nature Methods.

[72]  Wen Li,et al.  Opto-μECoG Array: A Hybrid Neural Interface With Transparent μECoG Electrode Array and Integrated LEDs for Optogenetics , 2013, IEEE Transactions on Biomedical Circuits and Systems.

[73]  M. Dawson,et al.  Visible-Light Communications Using a CMOS-Controlled Micro-Light- Emitting-Diode Array , 2012, Journal of Lightwave Technology.

[74]  Karl Deisseroth,et al.  Closed-Loop and Activity-Guided Optogenetic Control , 2015, Neuron.

[75]  Jing Wang,et al.  A coaxial optrode as multifunction write-read probe for optogenetic studies in non-human primates , 2013, Journal of Neuroscience Methods.

[76]  R. Buckner,et al.  Mapping brain networks in awake mice using combined optical neural control and fMRI. , 2011, Journal of neurophysiology.

[77]  Kensall D. Wise,et al.  A dual-shank neural probe integrated with double waveguides on each shank for optogenetic applications , 2011, 2011 Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[78]  B. Connors,et al.  Integrated device for optical stimulation and spatiotemporal electrical recording of neural activity in light-sensitized brain tissue , 2009, Journal of neural engineering.

[79]  E. Boyden.  Optogenetics and the future of neuroscience , 2015, Nature Neuroscience.

[80]  O. Yizhar.  Optogenetic Insights into Social Behavior Function , 2012, Biological Psychiatry.

[81]  T. Murphy,et al.  Automated light-based mapping of motor cortex by photoactivation of channelrhodopsin-2 transgenic mice , 2009, Nature Methods.

[82]  Patrick Ruther,et al.  High-density probe with integrated thin-film micro light emitting diodes (μLEDs) for optogenetic applications , 2016, 2016 IEEE 29th International Conference on Micro Electro Mechanical Systems (MEMS).

[83]  Christoph Stippich,et al.  Motor cortex stimulation for long-term relief of chronic neuropathic pain: A 10 year experience , 2006, Pain.

[84]  M. Gelabert-González,et al.  [Deep brain stimulation in Parkinson's disease]. , 2013, Revista de neurologia.

[85]  P. Albert,et al.  Light up your life: optogenetics for depression? , 2014, Journal of psychiatry & neuroscience : JPN.

[86]  Jan M. Rabaey,et al.  Reliable Next-Generation Cortical Interfaces for Chronic Brain–Machine Interfaces and Neuroscience , 2017, Proceedings of the IEEE.

[87]  Edward S Boyden,et al.  Processes for design, construction and utilisation of arrays of light-emitting diodes and light-emitting diode-coupled optical fibres for multi-site brain light delivery. , 2015, Journal of engineering.

[88]  Patrick Degenaar,et al.  Multi-site optical excitation using ChR2 and micro-LED array , 2010, Journal of neural engineering.

[89]  M. Deschenes,et al.  A microprobe for parallel optical and electrical recordings from single neurons in vivo , 2011, Nature Methods.

[90]  Ilan Lampl,et al.  Optopatcher—An electrode holder for simultaneous intracellular patch-clamp recording and optical manipulation , 2013, Journal of Neuroscience Methods.

[91]  A. Lozano,et al.  Deep Brain Stimulation for Treatment-Resistant Depression , 2005, Neuron.

[92]  Edward S Boyden,et al.  Optogenetics and Translational Medicine , 2013, Science Translational Medicine.

[93]  Feng Zhang,et al.  Molecular Tools and Approaches for Optogenetics , 2012, Biological Psychiatry.

[94]  O. Paul,et al.  GaN-based micro-LED arrays on flexible substrates for optical cochlear implants , 2014 .

[95]  José Higino Correia,et al.  Fabrication and mechanical characterization of long and different penetrating length neural microelectrode arrays , 2015 .

[96]  Murtaza Z Mogri,et al.  Targeting and Readout Strategies for Fast Optical Neural Control In Vitro and In Vivo , 2007, The Journal of Neuroscience.

[97]  D. S. Freedman,et al.  Chronic tissue response to untethered microelectrode implants in the rat brain and spinal cord , 2015, Journal of neural engineering.

[98]  Michael X. Cohen,et al.  Deep Brain Stimulation to Reward Circuitry Alleviates Anhedonia in Refractory Major Depression , 2008, Neuropsychopharmacology.

[99]  J. C. Middlebrooks,et al.  Cochlear implants: the view from the brain , 2005, Current Opinion in Neurobiology.

[100]  Olivier Marre,et al.  Targeting channelrhodopsin-2 to ON-bipolar cells with vitreally administered AAV Restores ON and OFF visual responses in blind mice. , 2015, Molecular therapy : the journal of the American Society of Gene Therapy.

[101]  E. Bamberg,et al.  Optogenetic stimulation of the auditory pathway. , 2014, The Journal of clinical investigation.

[102]  Stephen A. Allsop,et al.  Optogenetic insights on the relationship between anxiety-related behaviors and social deficits , 2014, Front. Behav. Neurosci..

[103]  Stephen A. Allsop,et al.  Optogenetic insights on the relationship between anxiety-related behaviors and social deficits , 2014, Front. Behav. Neurosci..

[104]  J. Henderson,et al.  A 12-Month Prospective Study of Gasserian Ganglion Stimulation for Trigeminal Neuropathic Pain , 2007, Stereotactic and Functional Neurosurgery.

[105]  Lei Yao,et al.  A low-profile three-dimensional neural probe array using a silicon lead transfer structure , 2013 .

[106]  K. Djupsund,et al.  Flexible polyimide microelectrode array for in vivo recordings and current source density analysis. , 2007, Biosensors & bioelectronics.

[107]  B. Trimmer,et al.  Flexible parylene-based microelectrode arrays for high resolution EMG recordings in freely moving small animals , 2011, Journal of Neuroscience Methods.

[108]  K. Deisseroth,et al.  Millisecond-timescale, genetically targeted optical control of neural activity , 2005, Nature Neuroscience.

[109]  WA Martin,et al.  ECG artifact due to deep brain stimulation , 2003, The Lancet.

[110]  Yasushi Miyashita,et al.  A glass-coated tungsten microelectrode enclosing optical fibers for optogenetic exploration in primate deep brain structures , 2012, Journal of Neuroscience Methods.

[111]  Eran Stark,et al.  Diode probes for spatiotemporal optical control of multiple neurons in freely moving animals. , 2012, Journal of neurophysiology.

[112]  M. Merzenich,et al.  A multielectrode implant device for the cerebral cortex , 1999, Journal of Neuroscience Methods.

[113]  K D Wise,et al.  An Ultra Compact Integrated Front End for Wireless Neural Recording Microsystems , 2010, Journal of Microelectromechanical Systems.

[114]  V. Nevolin,et al.  SUBSTRATES FOR EPITAXY OF GALLIUM NITRIDE: NEW MATERIALS AND TECHNIQUES , 2008 .

[115]  S. Nakanishi,et al.  Spatio‐temporal control of neural activity in vivo using fluorescence microendoscopy , 2012, The European journal of neuroscience.

[116]  G. Clark,et al.  Characterization of a 3D optrode array for infrared neural stimulation , 2012, Biomedical optics express.

[117]  A. Schwartz,et al.  High-performance neuroprosthetic control by an individual with tetraplegia , 2013, The Lancet.

[118]  Ben A. Duffy,et al.  MRI compatible optrodes for simultaneous LFP and optogenetic fMRI investigation of seizure-like afterdischarges , 2015, NeuroImage.

[119]  Maysam Ghovanloo,et al.  A wireless slanted optrode array with integrated micro leds for optogenetics , 2014, 2014 IEEE 27th International Conference on Micro Electro Mechanical Systems (MEMS).

[120]  Jessica A. Cardin,et al.  Noninvasive optical inhibition with a red-shifted microbial rhodopsin , 2014, Nature Neuroscience.

[121]  José Higino Correia,et al.  Measurement and statistical analysis toward reproducibility validation of AZ4562 cylindrical microlenses obtained by reflow , 2014 .

[122]  John P. Donoghue,et al.  Bridging the Brain to the World: A Perspective on Neural Interface Systems , 2008, Neuron.

[123]  K. Mathieson,et al.  Depth-specific optogenetic control in vivo with a scalable, high-density μLED neural probe , 2016, Scientific Reports.

[124]  Wim Vanduffel,et al.  Optogenetics in primates: a shining future? , 2013, Trends in genetics : TIG.

[125]  T. Dick,et al.  Light-Induced Rescue of Breathing after Spinal Cord Injury , 2008, The Journal of Neuroscience.

[126]  Hung Cao,et al.  An Integrated μLED Optrode for Optogenetic Stimulation and Electrical Recording , 2013, IEEE Transactions on Biomedical Engineering.

[127]  Chuan-Pu Liu,et al.  Tuning the emitting wavelength of InGaN/GaN superlattices from blue, green to yellow by controlling the size of InGaN quasi-quantum dot , 2006 .

[128]  O. Paul,et al.  Ultracompact optrode with integrated laser diode chips and SU-8 waveguides for optogenetic applications , 2013, 2013 IEEE 26th International Conference on Micro Electro Mechanical Systems (MEMS).

[129]  Tobias Moser,et al.  Optogenetic stimulation of the auditory pathway for research and future prosthetics , 2015, Current Opinion in Neurobiology.

[130]  Mary Kay Lobo,et al.  Antidepressant Effect of Optogenetic Stimulation of the Medial Prefrontal Cortex , 2010, The Journal of Neuroscience.

[131]  K. Cheung.  Implantable microscale neural interfaces , 2007, Biomedical microdevices.

[132]  S. B. Goncalves,et al.  Neural Electrode Array Based on Aluminum: Fabrication and Characterization , 2013, IEEE Sensors Journal.

[133]  G. Feng,et al.  Optogenetic Stimulation of Lateral Orbitofronto-Striatal Pathway Suppresses Compulsive Behaviors , 2013, Science.

[134]  K. Wise,et al.  A Three-Dimensional 64-Site Folded Electrode Array Using Planar Fabrication , 2011, Journal of Microelectromechanical Systems.

[135]  Yong-Jun Kim,et al.  The first neural probe integrated with light source (blue laser diode) for optical stimulation and electrical recording , 2011, 2011 Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[136]  K. Mathieson,et al.  Optogenetic activation of neocortical neurons in vivo with a sapphire-based micro-scale LED probe , 2015, Front. Neural Circuits.

[137]  Tobias Moser,et al.  Considering optogenetic stimulation for cochlear implants , 2015, Hearing Research.

[138]  Jon A. Mukand,et al.  Neuronal ensemble control of prosthetic devices by a human with tetraplegia , 2006, Nature.

[139]  Jiayi Zhang,et al.  Corrigendum: Integrated device for combined optical neuromodulation and electrical recording for chronic in vivo applications (2012 J. Neural Eng. 9 016001) , 2016 .

[140]  Dae-Shik Kim,et al.  Global and local fMRI signals driven by neurons defined optogenetically by type and wiring , 2010, Nature.

[141]  Dirk Trauner,et al.  LiGluR restores visual responses in rodent models of inherited blindness. , 2011, Molecular therapy : the journal of the American Society of Gene Therapy.

[142]  Karl Deisseroth,et al.  Optogenetics in Neural Systems , 2011, Neuron.

[143]  Ramin Pashaie,et al.  Optogenetic Brain Interfaces , 2014, IEEE Reviews in Biomedical Engineering.

[144]  Timothy Denison,et al.  An Implantable Optical Stimulation Delivery System for Actuating an Excitable Biosubstrate , 2011, IEEE Journal of Solid-State Circuits.

[145]  T. Kawano,et al.  Flexible optrode array: Parylene-film waveguide arrays with microelectrodes for optogenetics , 2015, 2015 Transducers - 2015 18th International Conference on Solid-State Sensors, Actuators and Microsystems (TRANSDUCERS).

[146]  Justin C. Williams,et al.  From Optogenetic Technologies to Neuromodulation Therapies , 2013, Science Translational Medicine.

[147]  A. Nurmikko,et al.  Combining Multicore Imaging Fiber With Matrix Addressable Blue/Green LED Arrays for Spatiotemporal Photonic Excitation at Cellular Level , 2008, IEEE Journal of Selected Topics in Quantum Electronics.

[148]  Feng Zhang,et al.  An optical neural interface: in vivo control of rodent motor cortex with integrated fiberoptic and optogenetic technology , 2007, Journal of neural engineering.

[149]  K. Deisseroth.  Optogenetics: 10 years of microbial opsins in neuroscience , 2015, Nature Neuroscience.

[150]  Daryl R Kipke,et al.  Complex impedance spectroscopy for monitoring tissue responses to inserted neural implants , 2007, Journal of neural engineering.