Transparent neural implantable devices: a comprehensive review of challenges and progress
Source abstract
Abstract
Abstract The key to designing an implantable device lies in condensing the synergistic effects of diagnostic and therapeutic methods in a single tool. In conjunction with the integration of electrophysiology and optical modalities, a transparent neural interface alleviates challenges of conventional metal-based microelectrodes. In this review, the multimodal sensing and stimulation functionalities of recent research are addressed. Next, issues that arise when combining functionalities of conventional metal-based, opaque electrode arrays together with optical modalities—(1) photoelectric artifacts, (2) optical image blocking, and (3) light transmission efficiency—are introduced. Then, an introduction of advancing material candidates for transparent neural interfaces follows with the latest research.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Neuroscience and Neural Engineering · Advanced Memory and Neural Computing · EEG and Brain-Computer Interfaces
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (100+)
Show source-provided references
1. Huang, S., Liu, Y., Zhao, Y., Ren, Z. & Guo, C. F. Flexible electronics: stretchable electrodes and their future. Adv. Funct. Mater. 29, 1805924 (2019).10.1002/adfm.201805924 ↗
2. Shi, J. & Fang, Y. Flexible and implantable microelectrodes for chronically stable neural interfaces. Adv. Mater. 31, 1804895 (2019).10.1002/adma.201804895 ↗
3. Cho, Y., Park, S., Lee, J. & Yu, K. J. Emerging materials and technologies with applications in flexible neural implants: a comprehensive review of current issues with neural devices. Adv. Mater. 33, 2005786 (2021).10.1002/adma.202005786 ↗
4. Hong, G. & Lieber, C. M. Novel electrode technologies for neural recordings. Nat. Rev. Neurosci. 20, 330–345 (2019).10.1038/s41583-019-0140-6 ↗
5. Hejazi, M. A. et al. Hybrid diamond/carbon fiber microelectrodes enable multimodal electrical/chemical neural interfacing. Biomaterials 230, 119648 (2020).10.1016/j.biomaterials.2019.119648 ↗
6. Kim, W. S. et al. Organ-specific, multimodal, wireless optoelectronics for high-throughput phenotyping of peripheral neural pathways. Nat. Commun. 12, 1–10 (2021).10.1038/s41467-020-20314-w ↗
7. He, F. et al. Multimodal mapping of neural activity and cerebral blood flow reveals long-lasting neurovascular dissociations after small-scale strokes. Sci. Adv. 6, eaba1933 (2020).10.1126/sciadv.aba1933 ↗
8. Kang, K., Cho, Y. & Yu, K. J. Novel nano-materials and nano-fabrication techniques for flexible electronic systems. Micromachines 9, 263 (2018).10.3390/mi9060263 ↗
9. Obaid, S. N. et al. Multifunctional flexible biointerfaces for simultaneous colocalized optophysiology and electrophysiology. Adv. Funct. Mater. 30, 1910027 (2020).10.1002/adfm.201910027 ↗
10. Lu, Y. et al. Ultralow impedance graphene microelectrodes with high optical transparency for simultaneous deep two-photon imaging in transgenic mice. Adv. Funct. Mater. 28, 1800002 (2018).10.1002/adfm.201800002 ↗
11. Zhang, Z., Russell, L. E., Packer, A. M., Gauld, O. M. & Häusser, M. Closed-loop all-optical interrogation of neural circuits in vivo. Nat. Methods 15, 1037–1040 (2018).10.1038/s41592-018-0183-z ↗
12. Zou, L. et al. Self-assembled multifunctional neural probes for precise integration of optogenetics and electrophysiology. Nat. Commun. 12, 1–9 (2021).10.1038/s41467-021-26168-0 ↗
13. Zhang, X., Xu, B., Pei, J. & Feng, L. Graphene and graphene-related materials as brain electrode. J. Mater. Chem. B 9, 9485–9496 (2021).10.1039/D1TB01795K ↗
14. Middya, S. et al. Microelectrode arrays for simultaneous electrophysiology and advanced optical microscopy. Adv. Sci. 8, 2004434 (2021).10.1002/advs.202004434 ↗
15. Park, D.-W. et al. Electrical neural stimulation and simultaneous in vivo monitoring with transparent graphene electrode arrays implanted in GCaMP6f mice. ACS Nano 12, 148–157 (2018).10.1021/acsnano.7b04321 ↗
16. Park, D.-W. et al. Fabrication and utility of a transparent graphene neural electrode array for electrophysiology, in vivo imaging, and optogenetics. Nat. Protoc. 11, 2201–2222 (2016).10.1038/nprot.2016.127 ↗
17. Yang, W. & Yuste, R. In vivo imaging of neural activity. Nat. Methods 14, 349–359 (2017).10.1038/nmeth.4230 ↗
18. Seo, J.-W. et al. Artifact-free 2D mapping of neural activity in vivo through transparent gold nanonetwork array. Adv. Funct. Mater. 30, 2000896 (2020).10.1002/adfm.202000896 ↗
19. Kozai, T. D. & Vazquez, A. L. Photoelectric artefact from optogenetics and imaging on microelectrodes and bioelectronics: new challenges and opportunities. J. Mater. Chem. B 3, 4965–4978 (2015).10.1039/C5TB00108K ↗
20. Wang, L.-C. et al. The use of a double-layer platinum black-conducting polymer coating for improvement of neural recording and mitigation of photoelectric artifact. Biosens. Bioelectron. 145, 111661 (2019).10.1016/j.bios.2019.111661 ↗
21. Pisanello, F., Sileo, L. & De Vittorio, M. Micro-and nanotechnologies for optical neural interfaces. Front. Neurosci. 10, 70 (2016).
22. Araki, T. et al. Long-term implantable, flexible, and transparent neural interface based on Ag/Au core–shell nanowires. Adv. Healthc. Mater. 8, 1900130 (2019).10.1002/adhm.201900130 ↗
23. Araki, T. et al. Wireless monitoring using a stretchable and transparent sensor sheet containing metal nanowires. Adv. Mater. 32, 1902684 (2020).10.1002/adma.201902684 ↗
24. Kuzum, D. et al. Transparent and flexible low noise graphene electrodes for simultaneous electrophysiology and neuroimaging. Nat. Commun. 5, 1–10 (2014).10.1038/ncomms6259 ↗
25. Qiang, Y. et al. Transparent arrays of bilayer-nanomesh microelectrodes for simultaneous electrophysiology and two-photon imaging in the brain. Sci. Adv. 4, eaat0626 (2018).10.1126/sciadv.aat0626 ↗
26. Kim, K., Park, Y. G., Hyun, B. G., Choi, M. & Park, J. U. Recent advances in transparent electronics with stretchable forms. Adv. Mater. 31, 1804690 (2019).10.1002/adma.201804690 ↗
27. Zhang, J. et al. Stretchable transparent electrode arrays for simultaneous electrical and optical interrogation of neural circuits in vivo. Nano Lett. 18, 2903–2911 (2018).10.1021/acs.nanolett.8b00087 ↗
28. Park, D.-W. et al. Graphene-based carbon-layered electrode array technology for neural imaging and optogenetic applications. Nat. Commun. 5, 5258 (2014).10.1038/ncomms6258 ↗
29. Kang, H., Jung, S., Jeong, S., Kim, G. & Lee, K. Polymer-metal hybrid transparent electrodes for flexible electronics. Nat. Commun. 6, 1–7 (2015).10.1038/ncomms7503 ↗
30. Hofmann, A. I., Cloutet, E. & Hadziioannou, G. Materials for transparent electrodes: from metal oxides to organic alternatives. Adv. Electron. Mater. 4, 1700412 (2018).10.1002/aelm.201700412 ↗
31. Green, R. & Abidian, M. R. Conducting polymers for neural prosthetic and neural interface applications. Adv. Mater. 27, 7620–7637 (2015).10.1002/adma.201501810 ↗
32. Ye, S., Rathmell, A. R., Chen, Z., Stewart, I. E. & Wiley, B. J. Metal nanowire networks: the next generation of transparent conductors. Adv. Mater. 26, 6670–6687 (2014).10.1002/adma.201402710 ↗
33. Song, C.-H., Han, C. J., Ju, B.-K. & Kim, J.-W. Photoenhanced patterning of metal nanowire networks for fabrication of ultraflexible transparent devices. ACS Appl. Mater. Interfaces 8, 480–489 (2016).10.1021/acsami.5b09386 ↗
34. Jung, E. D. et al. Highly efficient flexible optoelectronic devices using metal nanowire-conducting polymer composite transparent electrode. Electron. Mater. Lett. 11, 906–914 (2015).10.1007/s13391-015-5120-z ↗
35. Schneider, J. et al. Electrohydrodynamic nanodrip printing of high aspect ratio metal grid transparent electrodes. Adv. Funct. Mater. 26, 833–840 (2016).10.1002/adfm.201503705 ↗
36. Gao, T. et al. Hierarchical graphene/metal grid structures for stable, flexible transparent conductors. ACS Nano 9, 5440–5446 (2015).10.1021/acsnano.5b01243 ↗
37. Park, J. H. et al. Flexible and transparent metallic grid electrodes prepared by evaporative assembly. ACS Appl. Mater. Interfaces 6, 12380–12387 (2014).10.1021/am502233y ↗
38. Ginting, R. T., Ovhal, M. M. & Kang, J.-W. A novel design of hybrid transparent electrodes for high performance and ultra-flexible bifunctional electrochromic-supercapacitors. Nano Energy 53, 650–657 (2018).10.1016/j.nanoen.2018.09.016 ↗
39. Won, Y. et al. Annealing-free fabrication of highly oxidation-resistive copper nanowire composite conductors for photovoltaics. NPG Asia Mater. 6, e105 (2014).10.1038/am.2014.36 ↗
40. Park, Y., Chung, T. S., Lee, G. & Rogers, J. A. Materials chemistry of neural interface technologies and recent advances in three-dimensional systems. Chem. Rev. 122, 5277–5316 (2022).10.1021/acs.chemrev.1c00639 ↗
41. Wellman, S. M. et al. A materials roadmap to functional neural interface design. Adv. Funct. Mater. 28, 1701269 (2018).10.1002/adfm.201701269 ↗
42. Fattahi, P., Yang, G., Kim, G. & Abidian, M. R. A review of organic and inorganic biomaterials for neural interfaces. Adv. Mater. 26, 1846–1885 (2014).10.1002/adma.201304496 ↗
43. Ferguson, M., Sharma, D., Ross, D. & Zhao, F. A critical review of microelectrode arrays and strategies for improving neural interfaces. Adv. Healthc. Mater. 8, 1900558 (2019).10.1002/adhm.201900558 ↗
44. Patil, A. C. & Thakor, N. V. Implantable neurotechnologies: a review of micro-and nanoelectrodes for neural recording. Med Biol. Eng. Comput 54, 23–44 (2016).10.1007/s11517-015-1430-4 ↗
45. Lee, W. et al. Integration of organic electrochemical and field-effect transistors for ultraflexible, high temporal resolution electrophysiology arrays. Adv. Mater. 28, 9722–9728 (2016).10.1002/adma.201602237 ↗
46. Fu, T.-M. et al. Stable long-term chronic brain mapping at the single-neuron level. Nat. Methods 13, 875–882 (2016).10.1038/nmeth.3969 ↗
47. He, B., Yang, L., Wilke, C. & Yuan, H. Electrophysiological imaging of brain activity and connectivity-challenges and opportunities. IEEE Trans. Biomed. Eng. 58, 1918–1931 (2011).10.1109/TBME.2011.2139210 ↗
48. Chiang, C.-H. et al. Development of a neural interface for high-definition, long-term recording in rodents and nonhuman primates. Sci. Transl. Med. 12, eaay4682 (2020).10.1126/scitranslmed.aay4682 ↗
49. Jun, J. J. et al. Fully integrated silicon probes for high-density recording of neural activity. Nature 551, 232–236 (2017).10.1038/nature24636 ↗
50. Monai, H. et al. Calcium imaging reveals glial involvement in transcranial direct current stimulation-induced plasticity in mouse brain. Nat. Commun. 7, 1–10 (2016).10.1038/ncomms11100 ↗
51. Gu, X. et al. Long-term optical imaging of neurovascular coupling in mouse cortex using GCaMP6f and intrinsic hemodynamic signals. NeuroImage 165, 251–264 (2018).10.1016/j.neuroimage.2017.09.055 ↗
52. Rao, J., Dragulescu-Andrasi, A. & Yao, H. Fluorescence imaging in vivo: recent advances. Curr. Opin. Biotechnol. 18, 17–25 (2007).10.1016/j.copbio.2007.01.003 ↗
53. Barretto, R. P., Messerschmidt, B. & Schnitzer, M. J. In vivo fluorescence imaging with high-resolution microlenses. Nat. Methods 6, 511–512 (2009).10.1038/nmeth.1339 ↗
54. Chemla, S. & Chavane, F. Voltage-sensitive dye imaging: technique review and models. J. Physiol. Paris 104, 40–50 (2010).10.1016/j.jphysparis.2009.11.009 ↗
55. Brown, C. E., Aminoltejari, K., Erb, H., Winship, I. R. & Murphy, T. H. In vivo voltage-sensitive dye imaging in adult mice reveals that somatosensory maps lost to stroke are replaced over weeks by new structural and functional circuits with prolonged modes of activation within both the peri-infarct zone and distant sites. J. Neurosci. 29, 1719–1734 (2009).10.1523/JNEUROSCI.4249-08.2009 ↗
56. Lam, S. et al. In vivo optical coherence tomography imaging of preinvasive bronchial lesions. Clin. Cancer Res. 14, 2006–2011 (2008).10.1158/1078-0432.CCR-07-4418 ↗
57. Wang, B., Lu, Y. & Yao, X. In vivo optical coherence tomography of stimulus-evoked intrinsic optical signals in mouse retinas. J. Biomed. Opt. 21, 096010 (2016).10.1117/1.JBO.21.9.096010 ↗
58. Hoshi, Y. & Yamada, Y. Overview of diffuse optical tomography and its clinical applications. J. Biomed. Opt. 21, 091312 (2016).10.1117/1.JBO.21.9.091312 ↗
59. Lee, C. W., Cooper, R. J. & Austin, T. Diffuse optical tomography to investigate the newborn brain. Pediatr. Res. 82, 376–386 (2017).10.1038/pr.2017.107 ↗
60. Tang, Q. et al. In vivo voltage-sensitive dye imaging of subcortical brain function. Sci. Rep. 5, 17325 (2015).10.1038/srep17325 ↗
61. Tang, Q. et al. In vivo mesoscopic voltage-sensitive dye imaging of brain activation. Sci. Rep. 6, 25269 (2016).10.1038/srep25269 ↗
62. Civillico, E. F. & Contreras, D. Integration of evoked responses in supragranular cortex studied with optical recordings in vivo. J. Neurophysiol. 96, 336–351 (2006).10.1152/jn.00128.2006 ↗
63. Krasnow, A. M., Ford, M. C., Valdivia, L. E., Wilson, S. W. & Attwell, D. Regulation of developing myelin sheath elongation by oligodendrocyte calcium transients in vivo. Nat. Neurosci. 21, 24–28 (2018).10.1038/s41593-017-0031-y ↗
64. Yang, H. H. et al. Subcellular imaging of voltage and calcium signals reveals neural processing in vivo. Cell 166, 245–257 (2016).10.1016/j.cell.2016.05.031 ↗
65. Senarathna, J. et al. A miniature multi-contrast microscope for functional imaging in freely behaving animals. Nat. Commun. 10, 1–13 (2019).10.1038/s41467-018-07926-z ↗
66. Prasad, A., Chaichi, A., Kelley, D. P., Francis, J. & Gartia, M. R. Current and future functional imaging techniques for post-traumatic stress disorder. RSC Adv. 9, 24568–24594 (2019).10.1039/C9RA03562A ↗
67. Cagnan, H., Denison, T., McIntyre, C. & Brown, P. Emerging technologies for improved deep brain stimulation. Nat. Biotechnol. 37, 1024–1033 (2019).10.1038/s41587-019-0244-6 ↗
68. Krause, M. R., Vieira, P. G., Csorba, B. A., Pilly, P. K. & Pack, C. C. Transcranial alternating current stimulation entrains single-neuron activity in the primate brain. Proc. Natl Acad. Sci. USA 116, 5747–5755 (2019).10.1073/pnas.1815958116 ↗
69. Chen, R. et al. Deep brain optogenetics without intracranial surgery. Nat. Biotechnol. 39, 161–164 (2021).10.1038/s41587-020-0679-9 ↗
70. Chen, S. et al. Near-infrared deep brain stimulation via upconversion nanoparticle–mediated optogenetics. Science 359, 679–684 (2018).10.1126/science.aaq1144 ↗
71. Montgomery, K. L. et al. Wirelessly powered, fully internal optogenetics for brain, spinal and peripheral circuits in mice. Nat. Methods 12, 969–974 (2015).10.1038/nmeth.3536 ↗
72. Lee, H. J., Choi, N., Yoon, E.-S. & Cho, I.-J. MEMS devices for drug delivery. Adv. Drug Del. Rev. 128, 132–147 (2018).10.1016/j.addr.2017.11.003 ↗
73. Lee, J. et al. Flexible, sticky, and biodegradable wireless device for drug delivery to brain tumors. Nat. Commun. 10, 1–9 (2019).10.1038/s41467-019-13198-y ↗
74. Dagdeviren, C. et al. Miniaturized neural system for chronic, local intracerebral drug delivery. Sci. Transl. Med. 10, eaan2742 (2018).10.1126/scitranslmed.aan2742 ↗
75. Diana, M. et al. Rehabilitating the addicted brain with transcranial magnetic stimulation. Nat. Rev. Neurosci. 18, 685–693 (2017).10.1038/nrn.2017.113 ↗
76. Klein, M. M. et al. Transcranial magnetic stimulation of the brain: guidelines for pain treatment research. Pain 156, 1601–1614 (2015).10.1097/j.pain.0000000000000210 ↗
77. Zhao, S. et al. Full activation pattern mapping by simultaneous deep brain stimulation and fMRI with graphene fiber electrodes. Nat. Commun. 11, 1–12 (2020).10.1038/s41467-019-13993-7 ↗
78. Opie, N. L. et al. Focal stimulation of the sheep motor cortex with a chronically implanted minimally invasive electrode array mounted on an endovascular stent. Nat. Biomed. Eng. 2, 907–914 (2018).10.1038/s41551-018-0321-z ↗
79. Vissani, M., Isaias, I. U. & Mazzoni, A. Deep brain stimulation: a review of the open neural engineering challenges. J. Neural Eng. 17, 051002 (2020).10.1088/1741-2552/abb581 ↗
80. Mahmoudi, P., Veladi, H. & Pakdel, F. G. Optogenetics, tools and applications in neurobiology. J. Med. Signals Sens. 7, 71–79 (2017).10.4103/2228-7477.205506 ↗
81. Kim, C. Y. et al. Soft subdermal implant capable of wireless battery charging and programmable controls for applications in optogenetics. Nat. Commun. 12, 1–13 (2021).10.1038/s41467-020-20314-w ↗
82. Wang, L. et al. Ultrasoft and highly stretchable hydrogel optical fibers for in vivo optogenetic modulations. Adv. Opt. Mater. 6, 1800427 (2018).10.1002/adom.201800427 ↗
83. Shokoueinejad, M. et al. Progress in the field of micro-electrocorticography. Micromachines 10, 62 (2019).10.3390/mi10010062 ↗
84. Alahi, M. E. E. et al. Recent advancement of electrocorticography (ECoG) electrodes for chronic neural recording/stimulation. Mater. Today Commun. 29, 102853 (2021).10.1016/j.mtcomm.2021.102853 ↗
85. Renz, A. F. et al. Opto‐E‐Dura: a soft, stretchable ECoG array for multimodal, multiscale neuroscience. Adv. Healthc. Mater. 9, 2000814 (2020).10.1002/adhm.202000814 ↗
86. Shin, H. et al. 3D high-density microelectrode array with optical stimulation and drug delivery for investigating neural circuit dynamics. Nat. Commun. 12, 1–18 (2021).10.1038/s41467-020-20763-3 ↗
87. Buzsáki, G. et al. Tools for probing local circuits: high-density silicon probes combined with optogenetics. Neuron 86, 92–105 (2015).10.1016/j.neuron.2015.01.028 ↗
88. Yazdan-Shahmorad, A., Silversmith, D. B., Kharazia, V. & Sabes, P. N. Targeted cortical reorganization using optogenetics in non-human primates. eLife 7, e31034 (2018).10.7554/eLife.31034 ↗
89. Kim, K. et al. Artifact-free and high-temporal-resolution in vivo opto-electrophysiology with microLED optoelectrodes. Nat. Commun. 11, 2063 (2020).10.1038/s41467-020-15769-w ↗
90. Richner, T. J. et al. Optogenetic micro-electrocorticography for modulating and localizing cerebral cortex activity. J. Neural Eng. 11, 016010 (2014).10.1088/1741-2560/11/1/016010 ↗
91. Repina, N. A., Rosenbloom, A., Mukherjee, A., Schaffer, D. V. & Kane, R. S. At light speed: advances in optogenetic systems for regulating cell signaling and behavior. Annu. Rev. Chem. Biomol. Eng. 8, 13–39 (2017).10.1146/annurev-chembioeng-060816-101254 ↗
92. Shirai, F. & Hayashi‐Takagi, A. Optogenetics: applications in psychiatric research. Psychiatry Clin. Neurosci. 71, 363–372 (2017).10.1111/pcn.12516 ↗
93. Montgomery, K. L., Iyer, S. M., Christensen, A. J., Deisseroth, K. & Delp, S. L. Beyond the brain: optogenetic control in the spinal cord and peripheral nervous system. Sci. Transl. Med. 8, 337rv335–337rv335 (2016).10.1126/scitranslmed.aad7577 ↗
94. Cardin, J. A. et al. Targeted optogenetic stimulation and recording of neurons in vivo using cell-type-specific expression of Channelrhodopsin-2. Nat. Protoc. 5, 247–254 (2010).10.1038/nprot.2009.228 ↗
95. Cho, I. H., Shin, H., Lee, H. J. & Cho, I.-J. Effects of fabrication process variation on impedance of neural probe microelectrodes. J. Electr. Eng. Technol. 10, 1138–1143 (2015).10.5370/JEET.2015.10.3.1138 ↗
96. Jang, H. et al. Graphene-based flexible and stretchable electronics. Adv. Mater. 28, 4184–4202 (2016).10.1002/adma.201504245 ↗
97. Bi, Y. G. et al. Ultrathin metal films as the transparent electrode in ITO‐free organic optoelectronic devices. Adv. Opt. Mater. 7, 1800778 (2019).10.1002/adom.201800778 ↗
98. Pang, S., Hernandez, Y., Feng, X. & Mullen, K. Graphene as transparent electrode material for organic electronics. Adv. Mater. 23, 2779–2795 (2011).10.1002/adma.201100304 ↗
99. Biswas, C. & Lee, Y. H. Graphene versus carbon nanotubes in electronic devices. Adv. Funct. Mater. 21, 3806–3826 (2011).10.1002/adfm.201101241 ↗
100. Guan, S., Wang, J. & Fang, Y. Transparent graphene bioelectronics as a new tool for multimodal neural interfaces. Nano Today 26, 13–15 (2019).10.1016/j.nantod.2019.01.003 ↗