A review: flexible devices for nerve stimulation

Abstract

Nerve stimulation technology utilizing electricity, magnetism, light, and ultrasound has found extensive applications in biotechnology and medical fields. Neurostimulation devices serve as the crucial interface between biological tissue and the external environment, posing a bottleneck in the advancement of neurostimulation technology. Ensuring safety and stability is essential for their future applications. Traditional rigid devices often elicit significant immune responses due to the mechanical mismatch between their materials and biological tissues. Consequently, there is a growing demand for flexible nerve stimulation devices that offer enhanced treatment efficacy while minimizing irritation to the human body. This review provides a comprehensive summary of the historical development and recent advancements in flexible devices utilizing four neurostimulation techniques: electrical stimulation, magnetic stimulation, optic stimulation, and ultrasonic stimulation. It highlights their potential for high biocompatibility, low power consumption, wireless operation, and superior stability. The aim is to offer valuable insights and guidance for the future development and application of flexible neurostimulation devices.

Keywords

Nerve stimulation / flexible devices / electrical stimulation / magnetic stimulation / optic stimulation / ultrasonic stimulation

References

[1] Woods GA,Hong G.Bioinspired materials for in vivo bioelectronic neural interfaces.Matter2020;3:1087-113 PMCID:PMC7583599

[2] Song E,Rogers JA.Barrier materials for flexible bioelectronic implants with chronic stability - current approaches and future directions.APL Mater2019;7:050902

[3] Song E,Won SM,Rogers JA.Materials for flexible bioelectronic systems as chronic neural interfaces.Nat Mater2020;19:590-603

[4] Kim DH,Amsden JJ.Dissolvable films of silk fibroin for ultrathin conformal bio-integrated electronics.Nature Mater2010;9:511-7 PMCID:PMC3034223

[5] Ressler KJ.Targeting abnormal neural circuits in mood and anxiety disorders: from the laboratory to the clinic.Nat Neurosci2007;10:1116-24 PMCID:PMC2444035

[6] Wells JD,Jansen ED,Mahadevan-Jansen A.Application of infrared light for in vivo neural stimulation.J Biomed Opt2005;10:064003

[7] Legon W,Opitz A.Transcranial focused ultrasound modulates the activity of primary somatosensory cortex in humans.Nat Neurosci2014;17:322-9

[8] Liang L,Cai P.Highly specific differentiation of MSCs into neurons directed by local electrical stimuli triggered wirelessly by electromagnetic induction nanogenerator.Nano Energy2022;100:107483

[9] Palanker D,Huie P.Design of a high-resolution optoelectronic retinal prosthesis.J Neural Eng2005;2:S105-20

[10] Zhang T,Wang Z.Piezoelectric ultrasound energy - harvesting device for deep brain stimulation and analgesia applications.Sci Adv2022;8:eabk0159 PMCID:PMC9012468

[11] Bonmassar G,Freeman DK,Fried SI.Microscopic magnetic stimulation of neural tissue.Nat Commun2012;3:921 PMCID:PMC3621430

[12] Rand D,Lubin G.Direct electrical neurostimulation with organic pigment photocapacitors.Adv Mater2018;30:1707292

[13] Jiang Y,Luo X.Neural stimulation in vitro and in vivo by photoacoustic nanotransducers.Matter2021;4:654-74

[14] Cogan SF.Neural stimulation and recording electrodes.Annu Rev Biomed Eng2008;10:275-309

[15] Schwalb JM.The history and future of deep brain stimulation.Neurotherapeutics2008;5:3-13 PMCID:PMC5084122

[16] Kellaway P.The part played by electric fish in the early history of bioelectricity and electrotherapy.Bull Hist Med1946;20:112-137

[17] Sackeim HA.Modern electroconvulsive therapy: vastly improved yet greatly underused.JAMA Psychiatry2017;74:779-80

[18] Benabid AL,Louveau A,de Rougemont J.Combined (thalamotomy and stimulation) stereotactic surgery of the VIM thalamic nucleus for bilateral parkinson disease.Stereotact Funct Neurosurg1987;50:344-6

[19] Chen XL,Xu GL.Deep brain stimulation.Intervent Neurol2013;1:200-12 PMCID:PMC4031775

[20] Elkin BS,Morrison B III.Age-dependent regional mechanical properties of the rat hippocampus and cortex.J Biomech Eng2010;132:011010

[21] Wu X.Polymer-based flexible bioelectronics.Sci Bull2019;64:634-40

[22] Lai HY,Lin CT.Design, simulation and experimental validation of a novel flexible neural probe for deep brain stimulation and multichannel recording.J Neural Eng2012;9:036001

[23] Wurth S,Raspopovic S.Long-term usability and bio-integration of polyimide-based intra-neural stimulating electrodes.Biomaterials2017;122:114-29

[24] Fujie T,Liu H.Engineered nanomembranes for directing cellular organization toward flexible biodevices.Nano Lett2013;13:3185-92

[25] Xiang Z,Xue N.Ultra-thin flexible polyimide neural probe embedded in a dissolvable maltose-coated microneedle.J Micromech Microeng2014;24:065015

[26] Minev IR,Hirsch A.Electronic dura mater for long-term multimodal neural interfaces.Science2015;347:159-63

[27] Zhu M,Li S.Flexible electrodes for in vivo and in vitro electrophysiological signal recording.Adv Healthc Mater2021;10:2100646

[28] David-Pur M,Beit-Yaakov G,Hanein Y.All-carbon-nanotube flexible multi-electrode array for neuronal recording and stimulation.Biomed Microdevices2014;16:43-53 PMCID:PMC3921458

[29] Vitale F,Aazhang B,Pasquali M.Neural stimulation and recording with bidirectional, soft carbon nanotube fiber microelectrodes.ACS Nano2015;9:4465-74

[30] Mccallum GA,Qiu C.Chronic interfacing with the autonomic nervous system using carbon nanotube (CNT) yarn electrodes.Sci Rep2017;7:11723 PMCID:PMC5601469

[31] Tang R,Liu B.Towards an artificial peripheral nerve: liquid metal-based fluidic cuff electrodes for long-term nerve stimulation and recording.Biosens Bioelectron2022;216:114600

[32] Fan X,Sun H,Liu R.Polyelectrolyte-based conductive hydrogels: from theory to applications.Soft Sci2022;2:10

[33] Cong Y.Hydrogel - tissue interface interactions for implantable flexible bioelectronics.Langmuir2022;38:11503-13

[34] Kim SD,Lee S.Injectable and tissue-conformable conductive hydrogel for MRI-compatible brain-interfacing electrodes.Soft Sci2023;3:18

[35] Zhang J,Xue Y.Engineering electrodes with robust conducting hydrogel coating for neural recording and modulation.Adv Mater2023;35:2209324

[36] Nguyen TK,Ashok A.Wide bandgap semiconductor nanomembranes as a long-term biointerface for flexible, implanted neuromodulator.Proc Natl Acad Sci U S A2022;119:e2203287119 PMCID:PMC9388084

[37] Lin JC.A new IEEE standard for safety levels with respect to human exposure to radio-frequency radiation.IEEE Antennas Propag Mag2006;48:157-9

[38] Fotopoulou K.Wireless power transfer in loosely coupled links: coil misalignment model.IEEE Trans Magn2011;47:416-30

[39] Freeman DK,Kumar P.A sub-millimeter, inductively powered neural stimulator.Front Neurosci2017;11:659 PMCID:PMC5712043

[40] Maeng LY,Mu M.Behavioral validation of a wireless low-power neurostimulation technology in a conditioned place preference task.J Neural Eng2019;16:026022 PMCID:PMC6765399

[41] Singer A,Lewis E.Magnetoelectric materials for miniature, wireless neural stimulation at therapeutic frequencies.Neuron2020;107:631-43.e5 PMCID:PMC7818389

[42] Yu Z,Alrashdan FT.MagNI: a magnetoelectrically powered and controlled wireless neurostimulating implant.IEEE Trans Biomed Circuits Syst2020;14:1241-52 PMCID:PMC8712272

[43] Chen JC,Yu Z.A wireless millimetric magnetoelectric implant for the endovascular stimulation of peripheral nerves.Nat Biomed Eng2022;6:706-16 PMCID:PMC9213237

[44] Guduru R,Hong J.Magnetoelectric ‘spin’ on stimulating the brain.Nanomedicine2015;10:2051-61 PMCID:PMC4910966

[45] Kozielski KL,Gilbert HB.Nonresonant powering of injectable nanoelectrodes enables wireless deep brain stimulation in freely moving mice.Sci Adv2021;7:eabc4189 PMCID:PMC7806222

[46] Han F,Zhai Y.Strategy for designing a cell scaffold to enable wireless electrical stimulation for enhanced neuronal differentiation of stem cells.Adv Healthc Mater2021;10:2100027

[47] Tang B,Wang L.Harnessing cell dynamic responses on magnetoelectric nanocomposite films to promote osteogenic differentiation.ACS Appl Mater Interfaces2018;10:7841-51

[48] Zhang Y,Xiao Z.Magnetoelectric nanoparticles incorporated biomimetic matrix for wireless electrical stimulation and nerve regeneration.Adv Healthc Mater2021;10:2100695

[49] Qi F,Shuai Y.Magnetic-driven wireless electrical stimulation in a scaffold.Compos B Eng2022;237:109864

[50] Goetz G,Cizmar T. Holographic display system for photovoltaic retinal prosthesis. Invest Ophthalmol Vis Sci 2013;54:352. Available from: https://iovs.arvojournals.org/article.aspx?articleid=2148311. [Last accessed on 27 Nov 2023]

[51] Chen ZC,Bhuckory MB. Optically configurable confinement of electric field with photovoltaic retinal prosthesis. Invest Ophthalmol Vis Sci 2021;62:3166. Available from: https://iovs.arvojournals.org/article.aspx?articleid=2776270. [Last accessed on 27 Nov 2023]

[52] Chenais NAL,Ghezzi D.Photovoltaic retinal prosthesis restores high-resolution responses to single-pixel stimulation in blind retinas.Commun Mater2021;2:28

[53] Loudin JD,Vijayraghavan K.Optoelectronic retinal prosthesis: system design and performance.J Neural Eng2007;4:S72

[54] Mathieson K,Goetz G.Photovoltaic retinal prosthesis with high pixel density.Nature Photon2012;6:391-7 PMCID:PMC3462820

[55] Boinagrov D,Goetz G.Photovoltaic pixels for neural stimulation: circuit models and performance.IEEE Trans Biomed Circuits Syst2016;10:85-97 PMCID:PMC6497060

[56] Lei X,Flores TA. Photovoltaic subretinal prosthesis with pixel sizes down to 40 um. Invest Ophthalmol Vis Sci 2017;58:4269. Available from: https://iovs.arvojournals.org/article.aspx?articleid=2641379. [Last accessed on 27 Nov 2023]

[57] Bhuckory MB,Shin A. 3-dimensional subretinal prosthesis with single-cell resolution. Invest Ophthalmol Vi Sci 2022;63:4516-F0303. Available from: https://iovs.arvojournals.org/article.aspx?articleid=2782016. [Last accessed on 27 Nov 2023]

[58] Wang BY,Bhuckory M.Electronic photoreceptors enable prosthetic visual acuity matching the natural resolution in rats.Nat Commun2022;13:6627 PMCID:PMC9636145

[59] Silverå Ejneby M,Gicevičius M.Extracellular photovoltage clamp using conducting polymer-modified organic photocapacitors.Adv Mater Technol2020;5:1900860

[60] Silverå Ejneby M,Ferrero JJ.Chronic electrical stimulation of peripheral nerves via deep-red light transduced by an implanted organic photocapacitor.Nat Biomed Eng2022;6:741-53

[61] Menz MD,Khuri-Yakub PT.Precise neural stimulation in the retina using focused ultrasound.J Neurosci2013;33:4550-60 PMCID:PMC6704938

[62] Seo D,Shen K.Wireless recording in the peripheral nervous system with ultrasonic neural dust.Neuron2016;91:529-39

[63] Marketing clearance of diagnostic ultrasound systems and transducers. Guidance for industry and food and drug administration staff. Available from: https://www.fda.gov/media/71100/download. [Last accessed on 27 Nov 2023]

[64] Wang X,Liu J.Direct-current nanogenerator driven by ultrasonic waves.Science2007;316:102-5

[65] Ciofani G,D’Alessandro D.Enhancement of neurite outgrowth in neuronal-like cells following boron nitride nanotube-mediated stimulation.ACS Nano2010;4:6267-77

[66] Marino A,Hou Y.Piezoelectric nanoparticle-assisted wireless neuronal stimulation.ACS Nano2015;9:7678-89 PMCID:PMC9003232

[67] Piech DK,Shen K.A wireless millimetre-scale implantable neural stimulator with ultrasonically powered bidirectional communication.Nat Biomed Eng2020;4:207-22

[68] Shi Q,Lee C.MEMS based broadband piezoelectric ultrasonic energy harvester (PUEH) for enabling self-powered implantable biomedical devices.Sci Rep2016;6:24946 PMCID:PMC4844957

[69] Yang Z,Wang H,Tan J.Harvesting ultrasonic energy using 1-3 piezoelectric composites.Smart Mater Struct2015;24:075029

[70] Jiang L,Chen R.Flexible piezoelectric ultrasonic energy harvester array for bio-implantable wireless generator.Nano Energy2019;56:216-24 PMCID:PMC6717511

[71] Jiang L,Chen R.Ultrasound-induced wireless energy harvesting for potential retinal electrical stimulation application.Adv Funct Mater2019;29:1902522

[72] Jiang L,Zeng Y.Flexible ultrasound-induced retinal stimulating piezo-arrays for biomimetic visual prostheses.Nat Commun2022;13:3853 PMCID:PMC9253314

[73] Jiang L,Yang Y.Photoacoustic and piezo-ultrasound hybrid-induced energy transfer for 3D twining wireless multifunctional implants.Energy Environ Sci2021;14:1490-505

[74] Chen P,Wan X.Ultrasound-driven electrical stimulation of peripheral nerves based on implantable piezoelectric thin film nanogenerators.Nano Energy2021;86:106123

[75] Das R,Le TT.Biodegradable nanofiber bone-tissue scaffold as remotely-controlled and self-powering electrical stimulator.Nano Energy2020;76:105028

[76] Chen P,Wan X.Wireless electrical stimulation of the vagus nerves by ultrasound-responsive programmable hydrogel nanogenerators for anti-inflammatory therapy in sepsis.Nano Energy2021;89:106327

[77] Xu Z,Mo X.Electrostatic assembly of laminated transparent piezoelectrets for epidermal and implantable electronics.Nano Energy2021;89:106450

[78] Wan X,Xu Z.Hybrid-piezoelectret based highly efficient ultrasonic energy harvester for implantable electronics.Adv Funct Mater2022;32:2200589

[79] Tofts PS.The distribution of induced currents in magnetic stimulation of the nervous system.Phys Med Biol1990;35:1119-28

[80] Bagherzadeh H,Lu H,Yang Y.High-performance magnetic-core coils for targeted rodent brain stimulations.BME Front2022;2022:9854846 PMCID:PMC10521704

[81] Klomjai W,Lackmy-Vallée A.Basic principles of transcranial magnetic stimulation (TMS) and repetitive TMS (rTMS).Ann Phys Rehabil Med2015;58:208-13

[82] Deng ZD,Peterchev AV.Electric field depth-focality tradeoff in transcranial magnetic stimulation: simulation comparison of 50 coil designs.Brain Stimul2013;6:1-13 PMCID:PMC3568257

[83] Roth Y,Levkovitz Y.Three-dimensional distribution of the electric field induced in the brain by transcranial magnetic stimulation using figure-8 and deep H-coils.J Clin Neurophysiol2007;24:31-8

[84] Wilson SA,Thickbroom GW.Spatial differences in the sites of direct and indirect activation of corticospinal neurones by magnetic stimulation.Electroencephalogr Clin Neurophysiol1996;101:255-61

[85] Di Lazzaro V,Meglio M.Direct demonstration of the effect of lorazepam on the excitability of the human motor cortex.Clin Neurophysiol2000;111:794-9

[86] Pascual-Leone A,Wassermann EM.Responses to rapid-rate transcranial magnetic stimulation of the human motor cortex.Brain1994;117:847-58

[87] Chen R,Gerloff C.Depression of motor cortex excitability by low-frequency transcranial magnetic stimulation.Neurology1997;48:1398-403

[88] Huang YZ,Rounis E,Rothwell JC.Theta burst stimulation of the human motor cortex.Neuron2005;45:201-6

[89] Hamada M,Terao Y.Quadro-pulse stimulation is more effective than paired-pulse stimulation for plasticity induction of the human motor cortex.Clin Neurophysiol2007;118:2672-82

[90] Khedr EM,Rothwell J.Effects of low frequency and low intensity repetitive paired pulse stimulation of the primary motor cortex.Clin Neurophysiol2004;115:1259-63

[91] Park HJ,Kaltenbach JA,Manzoor NF.Activation of the central nervous system induced by micro-magnetic stimulation.Nat Commun2013;4:2463 PMCID:PMC3845906

[92] Khalifa A,Zhou TX.The development of microfabricated solenoids with magnetic cores for micromagnetic neural stimulation.Microsyst Nanoeng2021;7:91 PMCID:PMC8589949

[93] Boyden ES,Bamberg E,Deisseroth K.Millisecond-timescale, genetically targeted optical control of neural activity.Nat Neurosci2005;8:1263-8

[94] Yang Y,Vázquez-Guardado A.Wireless multilateral devices for optogenetic studies of individual and social behaviors.Nat Neurosci2021;24:1035-45 PMCID:PMC8694284

[95] Rajalingham R,Azadi R,DiCarlo JJ.Chronically implantable LED arrays for behavioral optogenetics in primates.Nat Methods2021;18:1112-6

[96] Wells J,Mariappan K.Optical stimulation of neural tissue in vivo.Opt Lett2005;30:504-6

[97] Wu X,Rommelfanger NJ.Tether-free photothermal deep-brain stimulation in freely behaving mice via wide-field illumination in the near-infrared-II window.Nat Biomed Eng2022;6:754-70 PMCID:PMC9232843

[98] Harvey EN.The effect of high frequency sound waves on heart muscle and other irritable tissues.Am J Physiol1929;91:284-90

[99] Tufail Y,Baldwin N.Transcranial pulsed ultrasound stimulates intact brain circuits.Neuron2010;66:681-94

[100] Yoo SS,Lee JH.Focused ultrasound modulates region-specific brain activity.Neuroimage2011;56:1267-75 PMCID:PMC3342684

[101] Lee W,Park MY.Image-guided focused ultrasound-mediated regional brain stimulation in sheep.Ultrasound Med Biol2016;42:459-70

[102] Dallapiazza RF,Holmberg S.Noninvasive neuromodulation and thalamic mapping with low-intensity focused ultrasound.J Neurosurg2018;128:875-84 PMCID:PMC7032074

[103] Deffieux T,Wattiez N,Pouget P.Low-intensity focused ultrasound modulates monkey visuomotor behavior.Curr Biol2013;23:2430-3

[104] Legon W,Tyshynsky R,Mueller JK.Transcranial focused ultrasound neuromodulation of the human primary motor cortex.Sci Rep2018;8:10007 PMCID:PMC6030101

[105] Panczykowski DM,Friedlander RM.Transcranial focused ultrasound modulates the activity of primary somatosensory cortex in humans.Neurosurgery2014;74:N8-9

[106] Zhang F,Adamantidis A,Deisseroth K.Circuit-breakers: optical technologies for probing neural signals and systems.Nat Rev Neurosci2007;8:577-81

[107] Wagner T,Pascual-Leone A.Noninvasive human brain stimulation.Annu Rev Biomed Eng2007;9:527-65

[108] Dalecki D.Mechanical bioeffects of ultrasound.Annu Rev Biomed Eng2004;6:229-48

[109] Dinno MA,Young SR,Hart J.The significance of membrane changes in the safe and effective use of therapeutic and diagnostic ultrasound.Phys Med Biol1989;34:1543-52

[110] Ye J,Meng L.Ultrasonic control of neural activity through activation of the mechanosensitive channel MscL.Nano Lett2018;18:4148-55

[111] Li J,Zhang T,Zhu B.Recent advancements in ultrasound transducer: from material strategies to biomedical applications.BME Front2022;2022:9764501 PMCID:PMC10521713

[112] Qian X,Thomas BB.Noninvasive ultrasound retinal stimulation for vision restoration at high spatiotemporal resolution.BME Front2022;2022:9829316 PMCID:PMC10521738

[113] Zhang T,Liang H.Transcranial focused ultrasound stimulation of periaqueductal gray for analgesia.IEEE Trans Biomed Eng2022;69:3155-62

[114] Kook G,Oh C.Multifocal skull-compensated transcranial focused ultrasound system for neuromodulation applications based on acoustic holography.Microsyst Nanoeng2023;9:45 PMCID:PMC10085992

[115] Jiang Y,Lan L.Optoacoustic brain stimulation at submillimeter spatial precision.Nat Commun2020;11:881 PMCID:PMC7021819

[116] Shi L,Fernandez FR.Non-genetic photoacoustic stimulation of single neurons by a tapered fiber optoacoustic emitter.Light Sci Appl2021;10:143 PMCID:PMC8277806

[117] Zheng N,Cheng R,Kaplan DL.Photoacoustic carbon nanotubes embedded silk scaffolds for neural stimulation and regeneration.ACS Nano2022;16:2292-305