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State-of-the-Art Technology on Highly Miniaturized Free-Floating Neural Implants

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Handbook of Neuroengineering

Abstract

Wirelessly powered implants are being developed to interface with nerves and neurons in the brain. They often rely on microelectrode arrays which are limited by their ability to cover large cortical surface areas and long-term stability because of their physical size and rigid configuration. Yet some clinical and research applications prioritize a distributed neural interface over one that offers high resolution. One solution to make a scalable, fully specifiable, electrical stimulation/recording possible is to disconnect the electrodes from the base so that they can be arbitrarily placed freely in the nervous system. This chapter provides an overview of the latest work on highly miniaturized wirelessly powered floating neural implants with an in-depth look at the smallest stimulating implant to date and a discussion on future directions/limitations.

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Abbreviations

CNS:

Central nervous system

FCC:

Federal Communications Commission

FDMA:

Frequency division multiple access

FOM:

Figure of merit

IMD:

Implantable medical device

MEA:

Microelectrode array

MIM:

Metal-insulator-metal

PCE:

Power conversion efficiency

Pcell:

Parameterized cell

PNS:

Peripheral nervous system

PTE:

Power transfer efficiency

SAR:

Specific absorption limit

References

  1. Agarwal, K., Jegadeesan, R., Guo, Y.-X., Thakor, N.V.: Wireless power transfer strategies for implantable bioelectronics. IEEE Rev. Biomed. Eng. 10, 136–161 (2017)

    Google Scholar 

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

    Google Scholar 

  3. Dinis, H., Colmiais, I., Mendes, P.: Extending the limits of wireless power transfer to miniaturized implantable electronic devices. Micromachines 8(12), 359 (2017)

    Google Scholar 

  4. Karumbaiah, L., Saxena, T., Carlson, D., Patil, K., Patkar, R., Gaupp, E.A., Betancur, M., Stanley, G.B., Carin, L., Bellamkonda, R.V.: Relationship between intracortical electrode design and chronic recording function. Biomaterials 34(33), 8061–8074 (2013)

    Google Scholar 

  5. Polikov, V.S., Tresco, P.A., Reichert, W.M.: Response of brain tissue to chronically implanted neural electrodes. J. Neurosci. Methods 148(1) 1–18 (2005)

    Google Scholar 

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

    Google Scholar 

  7. Cavuto, M.L., Constandinou, T.G.: Investigation of insertion method to achieve chronic recording stability of a semi-rigid implantable neural probe. In: 2019 9th International IEEE/EMBS Conference on Neural Engineering (NER), pp. 665–669. IEEE (2019)

    Google Scholar 

  8. Musk, E., et al.: An integrated brain-machine interface platform with thousands of channels, BioRxiv, p. 703801 (2019)

    Google Scholar 

  9. Lee, S., Wang, H., Wang, J., Shi, Q., Yen, S.-C., Thakor, N.V., Lee, C.: Battery-free neuromodulator for peripheral nerve direct stimulation. Nano Energy 50, 148–158 (2018)

    Google Scholar 

  10. Charthad, J., Weber, M.J., Chang, T.C., Arbabian, A.: A mm-sized implantable medical device (IMD) with ultrasonic power transfer and a hybrid bi-directional data link. IEEE J. Solid-State Circuits 50(8), 1741–1753 (2015)

    Google Scholar 

  11. Seo, D., Carmena, J.M., Rabaey, J.M., Maharbiz, M.M., Alon, E.: Model validation of untethered, ultrasonic neural dust motes for cortical recording. J. Neurosci. Methods 244, 114–122 (2015)

    Google Scholar 

  12. Basaeri, H., Christensen, D.B., Roundy, S.: A review of acoustic power transfer for bio-medical implants. Smart Mater. Struct. 25(12), 123001 (2016)

    Google Scholar 

  13. Sodagar, A.M., Perlin, G.E., Yao, Y., Najafi, K., Wise, K.D.: An implantable 64-channel wireless microsystem for single-unit neural recording. IEEE J. Solid-State Circuits 44(9), 2591–2604 (2009)

    Google Scholar 

  14. Troyk, P., Bredeson, S., Cogan, S., Romero-Ortega, M., Suh, S., Hu, Z., Kanneganti, A., Granja-Vazquez, R., Seifert, J., Bak, M.: In-vivo tests of a 16-channel implantable wireless neural stimulator. In: 2015 7th International IEEE/EMBS Conference on Neural Engineering (NER), pp. 474–477. IEEE (2015)

    Google Scholar 

  15. Xie, X., Rieth, L., Williams, L., Negi, S., Bhandari, R., Caldwell, R., Sharma, R., Tathireddy, P., Solzbacher, F.: Long-term reliability of al2o3 and parylene c bilayer encapsulated utah electrode array based neural interfaces for chronic implantation. J. Neural Eng. 11(2), 026016 (2014)

    Google Scholar 

  16. Ha, S., Akinin, A., Park, J., Kim, C., Wang, H., Maier, C., Cauwenberghs, G., Mercier, P.P.: A 16-channel wireless neural interfacing soc with rf-powered energy-replenishing adiabatic stimulation. In: VLSI Circuits, pp. C106–C107 (2015)

    Google Scholar 

  17. Schwarz, D.A., Lebedev, M.A., Hanson, T.L., Dimitrov, D.F., Lehew, G., Meloy, J., Rajangam, S., Subramanian, V., Ifft, P.J., Li, Z.: Chronic, wireless recordings of large-scale brain activity in freely moving rhesus monkeys. Nat. Methods, 11(6), 670–676 (2014)

    Google Scholar 

  18. Borton, D.A., Yin, M., Aceros, J., Nurmikko, A.: An implantable wireless neural interface for recording cortical circuit dynamics in moving primates. J. Neural Eng. 10(2), 026010 (2013)

    Google Scholar 

  19. Dvorak, I., Holden, A.V.: Mathematical Approaches to Brain Functioning Diagnostics. Manchester University Press, Manchester (1991)

    Google Scholar 

  20. Grill, W.M., Norman, S.E., Bellamkonda, R.V.: Implanted neural interfaces: biochallenges and engineered solutions. Annu. Rev. Biomed. Eng. 11, 1–24 (2009)

    Google Scholar 

  21. Campbell, A., Wu, C.: Chronically implanted intracranial electrodes: tissue reaction and electrical changes. Micromachines 9(9), 430 (2018)

    Google Scholar 

  22. Bressler, S.L., Menon, V., Large-scale brain networks in cognition: emerging methods and principles. Trends Cogn. Sci. 14(6), 277–290 (2010)

    Google Scholar 

  23. Alivisatos, A.P., Chun, M., Church, G.M., Greenspan, R.J., Roukes, M.L., Yuste, R.: The brain activity map project and the challenge of functional connectomics. Neuron 74(6), 970–974 (2012)

    Google Scholar 

  24. Eckhorn, R., Reitboeck, H.J., Arndt, M., Dicke, P.: Feature linking via synchronization among distributed assemblies: simulations of results from cat visual cortex. Neural Comput. 2(3), 293–307 (1990)

    Google Scholar 

  25. Seeley, W.W., Crawford, R.K., Zhou, J., Miller, B.L., Greicius, M.D.: Neurodegenerative diseases target large-scale human brain networks. Neuron 62(1), 42–52 (2009)

    Google Scholar 

  26. Tabot, G.A., Dammann, J.F., Berg, J.A., Tenore, F.V., Boback, J.L., Vogelstein, R.J., Bensmaia, S.J.: Restoring the sense of touch with a prosthetic hand through a brain interface. Proc. Natl. Acad. Sci. 110, 18279–18284 (2013)

    Google Scholar 

  27. Plachta, D.T., Gierthmuehlen, M., Cota, O., Espinosa, N., Boeser, F., Herrera, T.C., Stieglitz, T., Zentner, J.: Blood pressure control with selective vagal nerve stimulation and minimal side effects. J. Neural Eng. 11(3), 036011 (2014)

    Google Scholar 

  28. Yoo, P.B., Liu, H., Hincapie, J.G., Ruble, S.B., Hamann, J.J., Grill, W.M.: Modulation of heart rate by temporally patterned vagus nerve stimulation in the anesthetized dog. Physiol. Rep. 4(2), e12689 (2016)

    Google Scholar 

  29. Angle, M.R., Kong, Y.: Neural-interface probe and methods of packaging the same, 25 June 2019, US Patent 10,327,655

    Google Scholar 

  30. Obaid, A., Hanna, M.-E., Wu, Y.-W., Kollo, M., Racz, R., Angle, M.R., Müller, J., Brackbill, N., Wray, W., Franke, F., et al.: Massively parallel microwire arrays integrated with CMOS chips for neural recording. Sci. Adv. 6(12), eaay2789 (2020)

    Google Scholar 

  31. Guitchounts, G., Cox, D.: 64-channel carbon fiber electrode arrays for chronic electrophysiology. Sci. Rep. 10(1), 1–9 (2020)

    Google Scholar 

  32. Lopez, C.M., Putzeys, J., Raducanu, B.C., Ballini, M., Wang, S., Andrei, A., Rochus, V., Vandebriel, R., Severi, S., Van Hoof, C., et al.: A neural probe with up to 966 electrodes and up to 384 configurable channels in 0.13 μm SOI CMOS. IEEE Trans. Biomed. Circuits Syst. 11(3), 510–522 (2017)

    Google Scholar 

  33. Steinmetz, N.A., Koch, C., Harris, K.D., Carandini, M.: Challenges and opportunities for large-scale electrophysiology with neuropixels probes. Curr. Opin. Neurobiol. 50, 92–100 (2018)

    Google Scholar 

  34. Zhou, T., Hong, G., Fu, T.-M., Yang, X., Schuhmann, T.G., Viveros, R.D., Lieber, C.M.: Syringe-injectable mesh electronics integrate seamlessly with minimal chronic immune response in the brain. Proc. Natl. Acad. Sci. 114(23), 5894–5899 (2017)

    Google Scholar 

  35. Liu, J.: Syringe injectable electronics. In: Biomimetics Through Nanoelectronics, pp. 65–93. Springer, Cham (2018)

    Google Scholar 

  36. Lyu, H., Wang, J., La, J.-H., Chung, J.M., Babakhani, A.: An energy-efficient wirelessly powered millimeter-scale neurostimulator implant based on systematic codesign of an inductive loop antenna and a custom rectifier. IEEE Trans. Biomed. Circuits Syst. 99, 1–13 (2018)

    Google Scholar 

  37. Tanabe, Y., Ho, J.S., Liu, J., Liao, S.-Y., Zhen, Z., Hsu, S., Shuto, C., Zhu, Z.-Y., Ma, A., Vassos, C., et al.: High-performance wireless powering for peripheral nerve neuromodulation systems. PloS One 12(10), e0186698 (2017)

    Google Scholar 

  38. Montgomery, K.L., Yeh, A.J., Ho, J.S., Tsao, V., Iyer, S.M., Grosenick, L., Ferenczi, E.A., Tanabe, Y., Deisseroth, K., Delp, S.L., et al.: Wirelessly powered, fully internal optogenetics for brain, spinal and peripheral circuits in mice. Nat. Methods 12(10), 969 (2015)

    Google Scholar 

  39. Charthad, J., Chang, T.C., Liu, Z., Sawaby, A., Weber, M.J., Baker, S., Gore, F., Felt, S.A., Arbabian, A.: A mm-sized wireless implantable device for electrical stimulation of peripheral nerves. IEEE Trans. Biomed. Circuits Syst. 12(2), 257–270 (2018)

    Google Scholar 

  40. Piech, D.K., Johnson, B.C., Shen, K., Ghanbari, M.M., Li, K.Y., Neely, R.M., Kay, J.E., Carmena, J.M., Maharbiz, M.M., Muller, R.: Stimdust: a 2.2 mm3, precision wireless neural stimulator with ultrasonic power and communication, arXiv preprint arXiv:1807.07590 (2018)

    Google Scholar 

  41. Cho, S.-H., Xue, N., Cauller, L., Rosellini, W., Lee, J.-B.: A su-8-based fully integrated biocompatible inductively powered wireless neurostimulator. J. Microelectromech. Syst. 22(1), 170–176 (2013)

    Google Scholar 

  42. Freeman, D.K., O’Brien, J.M., Kumar, P., Daniels, B., Irion, R.A., Shraytah, L., Ingersoll, B.K., Magyar, A.P., Czarnecki, A., Wheeler, J.: A sub-millimeter, inductively powered neural stimulator. Front. Neurosci. 11, 659 (2017)

    Google Scholar 

  43. Lim, J., Moon, E., Barrow, M., Nason, S.R., Patel, P.R., Patil, P.G., Oh, S., Lee, I., Kim, H.-S., Sylvester, D., et al.: 26.9 a 0.19× 0.17 mm 2 wireless neural recording IC for motor prediction with near-infrared-based power and data telemetry. In: 2020 IEEE International Solid-State Circuits Conference-(ISSCC), pp. 416–418. IEEE (2020)

    Google Scholar 

  44. Singer, A., Dutta, S., Lewis, E., Chen, Z., Chen, J.C., Verma, N., Avants, B., Feldman, A.K., O’Malley, J., Beierlein, M., et al.: Magnetoelectric materials for miniature, wireless neural stimulation at therapeutic frequencies. Neuron 107, 631–643.e5 (2020)

    Google Scholar 

  45. Yeon, P., Mirbozorgi, S.A., Lim, J., Ghovanloo, M.: Feasibility study on active back telemetry and power transmission through an inductive link for millimeter-sized biomedical implants. IEEE Trans. Biomed. Circuits Syst. 11(6), 1366–1376 (2017)

    Google Scholar 

  46. Ghanbari, M.M., Piech, D.K., Shen, K., Alamouti, S.F., Yalcin, C., Johnson, B.C., Carmena, J.M., Maharbiz, M.M., Muller, R.: A sub-mm ultrasonic free-floating implant for multi-mote neural recording, arXiv preprint arXiv:1905.09386 (2019)

    Google Scholar 

  47. Biederman, W., Yeager, D.J., Narevsky, N., Koralek, A.C., Carmena, J.M., Alon, E., Rabaey, J.M.: A fully-integrated, miniaturized (0.125 mm2) 10.5 μw wireless neural sensor. IEEE J. Solid-State Circuits 48(4), 960–970 (2013)

    Google Scholar 

  48. Leung, V.W., Lee, J., Li, S., Yu, S., Kilfovle, C., Larson, L., Nurmikko, A., Laiwalla, F.: A CMOS distributed sensor system for high-density wireless neural implants for brain-machine interfaces. In: ESSCIRC 2018-IEEE 44th European Solid State Circuits Conference (ESSCIRC), pp. 230–233. IEEE (2018)

    Google Scholar 

  49. Lee, S., Cortese, A.J., Gandhi, A.P., Agger, E.R., McEuen, P.L., Molnar, A.C.: A 250 μm × 57μm microscale opto-electronically transduced electrodes (MOTEs) for neural recording. IEEE Trans. Biomed. Circuits Syst. 12(6), 1256–1266 (2018)

    Google Scholar 

  50. Yeon, P., Mirbozorgi, S.A., Ash, B., Eckhardt, H., Ghovanloo, M.: Fabrication and microassembly of a mm-sized floating probe for a distributed wireless neural interface. Micromachines 7(9), 154 (2016)

    Google Scholar 

  51. Seo, D., Neely, R.M., Shen, K., Singhal, U., Alon, E., Rabaey, J.M., Carmena, J.M., Maharbiz, M.M.: Wireless recording in the peripheral nervous system with ultrasonic neural dust. Neuron 91(3), 529–539 (2016)

    Google Scholar 

  52. Wickens, A., Avants, B., Verma, N., Lewis, E., Chen, J.C., Feldman, A.K., Dutta, S., Chu, J., O’Malley, J., Beierlein, M., et al.: Magnetoelectric materials for miniature, wireless neural stimulation at therapeutic frequencies, bioRxiv, p. 461855 (2018)

    Google Scholar 

  53. Piech, D.K., Johnson, B.C., Shen, K., Ghanbari, M.M., Li, K.Y., Neely, R.M., Kay, J.E., Carmena, J.M., Maharbiz, M.M., Muller, R.: A wireless millimetre-scale implantable neural stimulator with ultrasonically powered bidirectional communication. Nat. Biomed. Eng. 4(2), 207–222 (2020)

    Google Scholar 

  54. Khalifa, A., Liu, Y., Karimi, Y., Wang, Q., Eisape, A., Stanaćević, M., Thakor, N., Bao, Z., Etienne-Cummings, R.: The microbead: a 0.009 mm3 implantable wireless neural stimulator. IEEE Trans. Biomed. Circuits Syst. 13(5), 971–985 (2019)

    Google Scholar 

  55. Ho, J.S., Yeh, A.J., Neofytou, E., Kim, S., Tanabe, Y., Patlolla, B., Beygui, R.E., Poon, A.S.: Wireless power transfer to deep-tissue microimplants. Proc. Natl. Acad. Sci. 111, 7974–7979 (2014)

    Google Scholar 

  56. Maeng, L.Y., Murillo, M.F., Mu, M., Lo, M.-C., de la Rosa, M., O’Brien, J.M., Freeman, D., Widge, A.S.: Behavioral validation of a wireless low-power neurostimulation technology in a conditioned place preference task. J. Neural Eng. 16, 026022 (2019)

    Google Scholar 

  57. Khalifa, A., Karimi, Y., Wang, Q., Garikapati, S., Montlouis, W., Stanaćević, M., Thakor, N., Etienne-Cummings, R.: The microbead: a highly miniaturized wirelessly powered implantable neural stimulating system. IEEE Trans. Biomed. Circuits Syst. 12(3), 521–531 (2018)

    Google Scholar 

  58. Khalifa, A., Zhang, J., Leistner, M., Etienne-Cummings, R.: A compact, low-power, fully analog implantable microstimulator. In: 2016 IEEE International Symposium on Circuits and Systems (ISCAS), pp. 2435–2438 (2016)

    Google Scholar 

  59. Poon, A.S., O’Driscoll, S., Meng, T.H.: Optimal frequency for wireless power transmission into dispersive tissue. IEEE Trans. Antennas Propag. 58(5), 1739–1750 (2010)

    Google Scholar 

  60. Khalifa, A., Karimi, Y., Stanaćević, M., Etienne-Cummings, R.: Novel integration and packaging concepts of highly miniaturized inductively powered neural implants. In: Proceedings of the 39th IEEE Engineering in Medicine and Biology Society (EMBC), pp. 234–237 (2017)

    Google Scholar 

  61. Luo, X., Weaver, C.L., Zhou, D.D., Greenberg, R., Cui, X.T.: Highly stable carbon nanotube doped poly (3, 4-ethylenedioxythiophene) for chronic neural stimulation. Biomaterials 32(24), 5551–5557 (2011)

    Google Scholar 

  62. Gerwig, R., Fuchsberger, K., Schroeppel, B., Link, G.S., Heusel, G., Kraushaar, U., Schuhmann, W., Stett, A., Stelzle, M.: PEDOT–CNT composite microelectrodes for recording and electrostimulation applications: fabrication, morphology, and electrical properties. Front. Neuroeng. 5, 8 (2012)

    Google Scholar 

  63. Kolarcik, C.L., Catt, K., Rost, E., Albrecht, I.N., Bourbeau, D., Du, Z., Kozai, T.D., Luo, X., Weber, D.J., Cui, X.T.: Evaluation of poly (3, 4-ethylenedioxythiophene)/carbon nanotube neural electrode coatings for stimulation in the dorsal root ganglion. J. Neural Eng. 12(1), 016008 (2014)

    Google Scholar 

  64. Karimi, Y., Khalifa, A., Montlouis, W., Stanaćević, M., Etienne-Cummings, R.: Coil array design for maximizing wireless power transfer to sub-mm sized implantable devices, pp. 1–4 (2017)

    Google Scholar 

  65. Szarowski, D., Andersen, M., Retterer, S., Spence, A., Isaacson, M., Craighead, H., Turner, J., Shain, W.: Brain responses to micro-machined silicon devices. Brain Res. 983(1–2), 23–35 (2003)

    Google Scholar 

  66. Veiseh, O., Doloff, J.C., Ma, M., Vegas, A.J., Tam, H.H., Bader, A.R., Li, J., Langan, E., Wyckoff, J., Loo, W.S., et al.: Size-and shape-dependent foreign body immune response to materials implanted in rodents and non-human primates. Nat. Mater. 14(6), 643 (2015)

    Google Scholar 

  67. Zaeimbashi, M., Nasrollahpour, M., Khalifa, A., Romano, A., Liang, X., Chen, H., Sun, N., Matyushov, A., Lin, H., Dong, C., et al.: Ultra-compact dual-band smart nems magnetoelectric antennas for simultaneous wireless energy harvesting and magnetic field sensing, bioRxiv (2020)

    Google Scholar 

  68. Sigurdsson, S.A., Yu, Z., Lee, J., Nurmikko, A.: A method for large scale implantation of 3d microdevice ensembles into brain and soft tissue, bioRxiv (2020)

    Google Scholar 

  69. Cortese, A.J., Smart, C.L., Wang, T., Reynolds, M.F., Norris, S.L., Ji, Y., Lee, S., Mok, A., Wu, C., Xia, F., et al.: Microscopic sensors using optical wireless integrated circuits. Proc. Natl. Acad. Sci. 117(17), 9173–9179 (2020)

    Google Scholar 

  70. Khalifa, A., Eisape, A., Coughlin, B., Cash, S.: A simple method for implanting free-floating microdevices into the nervous tissue. J. Neural Eng. 18(4), 045004 (2021)

    Google Scholar 

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Authors and Affiliations

  1. Department of Electrical and Computer Engineering, Johns Hopkins University, Baltimore, MD, USA

    Adam Khalifa & Ralph Etienne-Cummings

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  1. Adam Khalifa
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  2. Ralph Etienne-Cummings
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Correspondence to Adam Khalifa .

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  1. Neuroengineering and Biomedical Instrumentation Laboratory Department of Biomedical Engineering and Department of Electrical and Computer Engineering, Neurology, Johns Hopkins University, Baltimore, MD, USA

    Nitish V. Thakor

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Khalifa, A., Etienne-Cummings, R. (2023). State-of-the-Art Technology on Highly Miniaturized Free-Floating Neural Implants. In: Thakor, N.V. (eds) Handbook of Neuroengineering. Springer, Singapore. https://doi.org/10.1007/978-981-16-5540-1_114

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