A wireless millimetre-scale implantable neural stimulator with ultrasonically powered bidirectional communication

Abstract

Clinically approved neural stimulators are limited by battery requirements, as well as by their large size compared with the stimulation targets. Here, we describe a wireless, leadless and battery-free implantable neural stimulator that is 1.7 mm3 and that incorporates a piezoceramic transducer, an energy-storage capacitor and an integrated circuit. An ultrasonic link and a hand-held external transceiver provide the stimulator with power and bidirectional communication. The stimulation protocols were wirelessly encoded on the fly, reducing power consumption and on-chip memory, and enabling protocol complexity with a high temporal resolution and low-latency feedback. Uplink data indicating whether stimulation occurs are encoded by the stimulator through backscatter modulation and are demodulated at the external transceiver. When embedded in ex vivo porcine tissue, the integrated circuit efficiently harvested ultrasonic power, decoded downlink data for the stimulation parameters and generated current-controlled stimulation pulses. When cuff-mounted and acutely implanted onto the sciatic nerve of anaesthetized rats, the device conferred repeatable stimulation across a range of physiological responses. The miniaturized neural stimulator may facilitate closed-loop neurostimulation for therapeutic interventions.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: Overview of the StimDust wireless neural stimulator system.
Fig. 2: Block diagram of the StimDust system.
Fig. 3: Fabrication of StimDust.
Fig. 4: StimDust demonstrated dynamic programmability, backscatter uplink communication and operation at 55 mm depth through ex vivo porcine tissue.
Fig. 5: The StimDust mote operated at an intensity of 7.8% of the safety limit (ISPTA derated) for diagnostic ultrasound, and with a wide mote angle range.
Fig. 6: In vivo performance—mote, backscatter and the evoked neural response waveforms for fully implanted mote.
Fig. 7: Precise control of evoked neural response achieved by varying stimulation current or stimulation pulse width.

Data availability

The main data supporting the results in this study are available within the paper and its Supplementary Information. Raw preprocessed data for Figs. 47 and Supplementary Figs. 39 are provided at https://doi.org/10.6084/m9.figshare.11719611.

Code availability

The computer code used for analysing data is provided at https://github.com/maharbizgroup/StimDust.

References

  1. 1.

    Michelson, R. P. Electrical stimulation of the human cochlea: a preliminary report. Arch. Otolaryngol. 93, 317–323 (1971).

  2. 2.

    Birmingham, K. et al. Bioelectronic medicines: a research roadmap. Nat. Rev. Drug Discov. 13, 399–400 (2014).

  3. 3.

    Plachta, D. T. T. et al. Blood pressure control with selective vagal nerve stimulation and minimal side effects. J. Neural Eng. 11, 036011 (2014).

  4. 4.

    Koopman, F. A. et al. Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis. Proc. Natl Acad. Sci. USA 113, 8284–8289 (2016).

  5. 5.

    Bruns, T. M., Weber, D. J. & Gaunt, R. A. Microstimulation of afferents in the sacral dorsal root ganglia can evoke reflex bladder activity. Neurourol. Urodyn. 34, 65–71 (2015).

  6. 6.

    Zimmerman, L. L., Rice, I. C., Berger, M. B. & Bruns, T. M. Tibial nerve stimulation to drive genital sexual arousal in an anesthetized female rat. J. Sex. Med. 15, 296–303 (2018).

  7. 7.

    Bonaz, B., Sinniger, V. & Pellissier, S. The vagus nerve in the neuro-immune axis: implications in the pathology of the gastrointestinal tract. Front. Immunol. 8, 1452 (2017).

  8. 8.

    Tan, D. W. et al. A neural interface provides long-term stable natural touch perception. Sci. Transl. Med. 6, 257ra138 (2014).

  9. 9.

    Ajiboye, A. B. et al. Restoration of reaching and grasping movements through brain-controlled muscle stimulation in a person with tetraplegia: a proof-of-concept demonstration. Lancet 389, 1821–1830 (2017).

  10. 10.

    Chakravarthy, K., Nava, A., Christo, P. J. & Williams, K. Review of recent advances in peripheral nerve stimulation (PNS). Curr. Pain Headache Rep. 20, 60 (2016).

  11. 11.

    Benabid, A. L. et al. Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus. Lancet 337, 403–406 (1991).

  12. 12.

    Widge, A. S., Malone, D. A. & Dougherty, D. D. Closing the loop on deep brain stimulation for treatment-resistant depression. Front. Neurosci. 12, 175 (2018).

  13. 13.

    Santacruz, S. R., Rich, E. L., Wallis, J. D. & Carmena, J. M. Caudate microstimulation increases value of specific choices. Curr. Biol. 27, 3375–3383 (2017).

  14. 14.

    Venkatraman, S. & Carmena, J. M. Active sensing of target location encoded by cortical microstimulation. IEEE Trans. Neural Syst. Rehabil. Eng. 19, 317–324 (2011).

  15. 15.

    Dadarlat, M. C., O’Doherty, J. E. & Sabes, P. N. A learning-based approach to artificial sensory feedback leads to optimal integration. Nat. Neurosci. 18, 138–144 (2015).

  16. 16.

    Medtronic Activa PC Multi-program Neurostimulator Implant Manual 37601 (Medtronic, 2010).

  17. 17.

    Medtronic Intellis Rechargeable Neurostimulator Implant Manual 97715 M946871A001 (Medtronic, 2012).

  18. 18.

    NeuroPace RNS System User Manual 1015882 (NeuroPace, 2015).

  19. 19.

    Christie, B. P. et al. “Long-term stability of stimulating spiral nerve cuff electrodes on human peripheral nerves”. J. Neuroeng. Rehabil. 14, 70 (2017).

  20. 20.

    Tan, D. W., Schiefer, M. A., Keith, M. W., Anderson, J. R. & Tyler, D. J. Stability and selectivity of a chronic, multi-contact cuff electrode for sensory stimulation in human amputees. J. Neural Eng. 12, 026002 (2015).

  21. 21.

    Ortiz-catalan, M., Håkansson, B. & Brånemark, R. An osseointegrated human-machine gateway for long-term sensory feedback and motor control of artificial limbs. Sci. Transl. Med. 6, 257re6 (2014).

  22. 22.

    Moro, E. Neurosurgery: complications of DBS surgery-insights from large databases. Nat. Rev. Neurol. 12, 617–618 (2016).

  23. 23.

    Kuntaegowdanahalli, S. S. et al. Mechanical fatigue resistance of an implantable branched lead system for a distributed set of longitudinal intrafascicular electrodes. J. Neural Eng. 14, 066014 (2017).

  24. 24.

    Wang, Y., Vaddiraju, S., Gu, B., Papadimitrakopoulos, F. & Burgess, D. J. Foreign body reaction to implantable biosensors: effects of tissue trauma and implant size. J. Diabetes Sci. Technol. 9, 966–977 (2015).

  25. 25.

    Patrick, J. F. & Clark, G. M. The Nucleus 22-channel cochlear implant system. Ear Hear. 12, 269–271 (1991).

  26. 26.

    Zeng, F.-G., Rebscher, S., Harrison, W., Xiaoan, S. & Feng, H. Cochlear implants: system design, integration, and evaluation. IEEE Rev. Biomed. Eng. 1, 115–142 (2008).

  27. 27.

    Cochlear implant comparison chart. Cochlear Implant HELP https://cochlearimplanthelp.files.wordpress.com/2018/02/cochlearimplantcomparisonchart_v7-0b.pdf (2018).

  28. 28.

    Tanabe, Y. et al. High-performance wireless powering for peripheral nerve neuromodulation systems. PLoS ONE 12, e0186698 (2017).

  29. 29.

    Freeman, D. K. et al. A sub-millimeter, inductively powered neural stimulator. Front. Neurosci. 11, 659 (2017).

  30. 30.

    Lee, H. M., Kwon, K. Y., Li, W. & Ghovanloo, M. A power-efficient switched-capacitor stimulating system for electrical/optical deep brain stimulation. IEEE J. Solid-St. Circ. 50, 360–374 (2015).

  31. 31.

    Lee, B. et al. An implantable peripheral nerve recording and stimulation system for experiments on freely moving animal subjects. Sci. Rep. 8, 6115 (2018).

  32. 32.

    Lin, Y. P. et al. A battery-less, implantable neuro-electronic interface for studying the mechanisms of deep brain stimulation in rat models. IEEE Trans. Biomed. Circ. Syst. 10, 98–112 (2016).

  33. 33.

    Seo, D., Carmena, J. M., Rabaey, J. M., Alon, E. & Maharbiz, M. M. Neural dust: an ultrasonic, low power solution for chronic brain-machine interfaces. Preprint at https://arxiv.org/abs/1307.2196 (2013).

  34. 34.

    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).

  35. 35.

    Seo, D. et al. Wireless recording in the peripheral nervous system with ultrasonic neural dust. Neuron 91, 529–539 (2016).

  36. 36.

    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-St. Circ. 50, 1741–1753 (2015).

  37. 37.

    Luo, Y. S. et al. Ultrasonic power/data telemetry and neural stimulator with OOK-PM signaling. IEEE Trans. Circ. Syst. II 60, 827–831 (2013).

  38. 38.

    Charthad, J. et al. A mm-sized wireless implantable device for electrical stimulation of peripheral nerves. IEEE Trans. Biomed. Circ. Syst. 12, 257–270 (2018).

  39. 39.

    Thimot, J. & Shepard, K. L. Bioelectronic devices: wirelessly powered implants. Nat. Biomed. Eng. 1, 0051 (2017).

  40. 40.

    Information for Manufacturers Seeking Marketing Clearance of Diagnostic Ultrasound Systems and Transducers 1–64 (FDA, 2008); https://www.fda.gov/downloads/UCM070911.pdf

  41. 41.

    Piech, D. K., Kay, J. E., Boser, B. E. & Maharbiz, M. M. Rodent wearable ultrasound system for wireless neural recording. In Proc. 39th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (eds Park, K.-S. et al.) 221–225 (IEEE, 2017).

  42. 42.

    Johnson, B. C. et al. StimDust: a 6.5mm3, wireless ultrasonic peripheral nerve stimulator with 82% peak chip efficiency. In Proc. Custom Integrated Circuits Conference (eds Tam, K. et al.) 8–11 (IEEE, 2018).

  43. 43.

    Johnson, B. C. et al. An implantable 700μW 64-channel neuromodulation IC for simultaneous recording and stimulation with rapid artifact recovery. In Proc. 2017 Symposium on VLSI Circuits (eds Tomita, Y. et al.) C48–C49 (IEEE, 2017).

  44. 44.

    Weitz, A. C., Behrend, M. R., Humayun, M. S., Chow, R. H. & Weiland, J. D. Interphase gap decreases electrical stimulation threshold of retinal ganglion cells. In Proc. 33rd Annual International Conference of the IEEE Engineering in Medicine and Biology Society (eds Lovell, N. et al.) 6725–6728) (IEEE, 2011).

  45. 45.

    Weitz, A. C. et al. Interphase gap as a means to reduce electrical stimulation thresholds for epiretinal prostheses. J. Neural Eng. 11, 016007 (2014).

  46. 46.

    Grill, W. M. & Mortimer, J. T. Inversion of the current-distance relationship by transient depolarization. IEEE Trans. Biomed. Eng. 44, 1–9 (1997).

  47. 47.

    Maciejasz, P. et al. Delaying discharge after the stimulus significantly decreases muscle activation thresholds with small impact on the selectivity: an in vivo study using TIME. Med. Biol. Eng. Comput. 53, 371–379 (2015).

  48. 48.

    van den Honert, C. & Mortimer, J. T. The response of the myelinated nerve fiber to short duration biphasic stimulating currents. Ann. Biomed. Eng. 7, 117–125 (1979).

  49. 49.

    Gorman, P. H. & Mortimer, J. T. The effect of stimulus parameters on the recruitment characteristics of direct nerve stimulation. IEEE Trans. Biomed. Eng. 30, 407–414 (1983).

  50. 50.

    Stanslaski, S. et al. Design and validation of a fully implantable, chronic, closed-loop neuromodulation device with concurrent sensing and stimulation. IEEE Trans. Neural Syst. Rehabil. Eng. 20, 410–421 (2012).

  51. 51.

    Sooksood, K., Stieglitz, T. & Ortmanns, M. An experimental study on passive charge balancing. Adv. Radio Sci. 7, 197–200 (2009).

  52. 52.

    Ayaz, M. et al. Sexual dependency of rat sciatic nerve fiber conduction velocity distributions. Int. J. Neurosci. 117, 1537–1549 (2007).

  53. 53.

    Celichowski, J. Mechanisms underlying the regulation of motor unit contraction in the skeletal muscle. J. Physiol. Pharmacol. 51, 17–33 (2000).

  54. 54.

    Bhadra, N., Bhadra, N., Kilgore, K. & Gustafson, K. J. High frequency electrical conduction block of the pudendal nerve. J. Neural Eng. 3, 180–187 (2006).

  55. 55.

    Winther-Jensen, B. et al. In vivo comparison of the charge densities required to evoke motor responses using novel annular penetrating microelectrodes. Front. Neurosci. 9, 265 (2015).

  56. 56.

    Khalifa, A. et al. The microbead: a highly miniaturized wirelessly powered implantable neural stimulating system. IEEE Trans. Biomed. Circ. Syst. 12, 521–531 (2018).

  57. 57.

    Sato, Y., Mizutani, K., Wakatsuki, N. & Nakamura, T. Design for an aspherical acoustic Fresnel lens with phase continuity. Jpn. J. Appl. Phys. 47, 4354–4359 (2008).

  58. 58.

    Sanchis, L., Yánez, A., Galindo, P. L., Pizarro, J. & Pastor, J. M. Three-dimensional acoustic lenses with axial symmetry. Appl. Phys. Lett. 97, 054103 (2010).

  59. 59.

    Håkansson, A., Sánchez-Dehesa, J. & Sanchis, L. Acoustic lens design by genetic algorithms. Phys. Rev. B 70, 214302 (2004).

  60. 60.

    Kothapalli, S. V. V. N. et al. A convenient, reliable, and fast acoustic pressure field measurement method for magnetic resonance-guided high-intensity focused ultrasound systems with phased array transducers. J. Ther. Ultrasound 6, 5 (2018).

  61. 61.

    Fan, T. et al. Acoustic characterization of high intensity focused ultrasound field generated from a transmitter with large aperture. AIP Conf. Proc. 1821, 180002 (2017).

  62. 62.

    Seo, D. et al. Ultrasonic beamforming system for interrogating multiple implantable sensors. In Proc. 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (eds Patton, J. et al.) 1–4 (IEEE, 2015).

  63. 63.

    Naples, G. G., Mortimer, J. T., Scheiner, A. & Sweeney, J. D. A spiral nerve cuff electrode for peripheral nerve stimulation. IEEE Trans. Biomed. Eng. 35, 905–916 (1988).

  64. 64.

    Cowley, A. W. Helical electrode for nerve stimulation. US patent 8,478,428 (2013).

  65. 65.

    Tarver, W. B., George, R. E., Maschino, S. E., Holder, L. K. & Wernicke, J. F. Clinical experience with a helical bipolar stimulating lead. Pacing Clin. Electrophysiol. 15, 1545–1556 (1992).

  66. 66.

    Tyler, D. J. & Durand, D. M. Functionally selective peripheral nerve stimulation with a flat interface nerve electrode. IEEE Trans. Neural Syst. Rehabil. Eng. 10, 294–303 (2002).

  67. 67.

    Schiefer, M. A., Polasek, K. H., Triolo, R. J., Pinault, G. C. J. & Tyler, D. J. Selective stimulation of the human femoral nerve with a flat interface nerve electrode. J. Neural Eng. 7, 026006 (2010).

  68. 68.

    Stieglitz, T., Beutel, H. & Meyer, J. U. A flexible, light-weight multichannel sieve electrode with integrated cables for interfacing regenerating peripheral nerves. Sens. Actuat. A 60, 240–243 (1997).

  69. 69.

    Rijnbeek, E. H., Eleveld, N. & Olthuis, W. Update on peripheral nerve electrodes for closed-loop neuroprosthetics. Front. Neurosci. 12, 350 (2018).

  70. 70.

    Boretius, T. et al. A transverse intrafascicular multichannel electrode (TIME) to interface with the peripheral nerve. Biosens. Bioelectron. 26, 62–69 (2010).

  71. 71.

    Alexandrov, A. V. et al. Ultrasound-enhanced systemic thrombolysis for acute ischemic stroke. N. Engl. J. Med. 351, 2170–2178 (2004).

  72. 72.

    Baron, C., Aubry, J. F., Tanter, M., Meairs, S. & Fink, M. Simulation of intracranial acoustic fields in clinical trials of sonothrombolysis. Ultrasound Med. Biol. 35, 1148–1158 (2009).

  73. 73.

    Green, R. A. et al. Integrated electrode and high density feedthrough system for chip-scale implantable devices. Biomaterials 34, 6109–6118 (2013).

  74. 74.

    Ordonez, J. S., Schuettler, M., Ortmanns, M. & Stieglitz, T. A 232-channel retinal vision prosthesis with a miniaturized hermetic package. In Proc. 34th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (eds Lovell, N. et al.) 2796–2799 (IEEE, 2012).

  75. 75.

    Xie, X. et al. Long-term reliability of Al2O3 and parylene C bilayer encapsulated Utah electrode array based neural interfaces for chronic implantation. J. Neural Eng. 11, 026016 (2014).

  76. 76.

    Shen, K. & Maharbiz, M. M. Ceramic packages for acoustically coupled neural implants. In Proc. 9th International IEEE/EMBS Conference on Neural Engineering, (eds Carmena, J. et al.) 847–850 (IEEE, 2019).

  77. 77.

    Fang, H. et al. Ultrathin, transferred layers of thermally grown silicon dioxide as biofluid barriers for biointegrated flexible electronic systems. Proc. Natl Acad. Sci. USA 113, 11682–11687 (2016).

  78. 78.

    Diaz-Botia, C. A. et al. A silicon carbide array for electrocorticography and peripheral nerve recording. J. Neural Eng. 14, 056006 (2017).

  79. 79.

    Hsieh, C.-L., Grange, R., Pu, Y. & Psaltis, D. Characterization of the cytotoxicity and imaging properties of second-harmonic nanoparticles. In Proc. SPIE 7759, Biosensing III (eds Mohseni, H. & Razeghi, M.) 77590T (2010).

  80. 80.

    Takenaka, T. Lead-free piezo-ceramics. In Advanced Piezoelectric Materials (ed. Uchino, K.) 130–170 (Elsevier, 2010).

  81. 81.

    Venkatraman, S. et al. In vitro and in vivo evaluation of PEDOT microelectrodes for neural stimulation and recording. IEEE Trans. Neural Syst. Rehabil. Eng. 19, 307–316 (2011).

  82. 82.

    Schander, A. et al. In-vitro evaluation of the long-term stability of PEDOT:PSS coated microelectrodes for chronic recording and electrical stimulation of neurons. In Proc. 2016 38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (eds Patton, J. et al.) 6174–6177 (IEEE, 2016).

  83. 83.

    Ganji, M., Tanaka, A., Gilja, V., Halgren, E. & Dayeh, S. A. Scaling effects on the electrochemical stimulation performance of Au, Pt, and PEDOT:PSS electrocorticography arrays. Adv. Funct. Mater. 27, 1703019 (2017).

  84. 84.

    Cogan, S. F., Troyk, P. R., Ehrlich, J. & Plante, T. D. In vitro comparison of the charge-injection limits of activated iridium oxide (AIROF) and platinum-iridium microelectrodes. IEEE Trans. Biomed. Eng. 52, 1612–1614 (2005).

  85. 85.

    VNS Therapy System Implantation Procedure 26-0007-7200/1 (Cyberonics, 2010).

  86. 86.

    Yuan, Y., Hao, H., Wen, X., Mo, X. & Li, L. Fatigue test of helical nervous electrodes and weak point analysis of helical nervous electrodes design. In Proc. 2013 35th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (eds Lovell, N. et al.) 6159–6162 (IEEE, 2013).

  87. 87.

    Advancing DBS Therapy with Vercise DBS Directional Lead. NM-305626-AB_SEP2015 (Boston Scientific, 2015).

  88. 88.

    Petrossians, A., Whalen III, J. J., Weiland, J. D. & Mansfeld, F. Electrodeposition and characterization of thin-film platinum-iridium alloys for biological interfaces. J. Electrochem. Soc. 158, D269–D276 (2011).

  89. 89.

    Boehler, C., Stieglitz, T. & Asplund, M. Nanostructured platinum grass enables superior impedance reduction for neural microelectrodes. Biomaterials 67, 346–353 (2015).

  90. 90.

    Boehler, C., Oberueber, F., Schlabach, S., Stieglitz, T. & Asplund, M. Long-term stable adhesion for conducting polymers in biomedical applications: IrOx and nanostructured platinum solve the chronic challenge. ACS Appl. Mater. Inter. 9, 189–197 (2017).

  91. 91.

    Pranti, A. S., Schander, A., Bödecker, A. & Lang, W. PEDOT: PSS coating on gold microelectrodes with excellent stability and high charge injection capacity for chronic neural interfaces. Sens. Actuat. B 275, 382–393 (2018).

  92. 92.

    Fullerton, G. D. & Zagzebski, J. A. (eds) Medical physics of CT and Ultrasound: Tissue Imaging and Characterization (American Association of Physicists in Medicine, 1980).

  93. 93.

    Charles, D., Jhamandas, J., Stein, R. B., Hoffer, J.-A. & Gordon, T. Impedance properties of metal electrodes for chronic recording from mammalian nerves. IEEE Trans. Biomed. Eng. 25, 532–537 (2007).

  94. 94.

    Grill, W. M. & Thomas Mortimer, J. Electrical properties of implant encapsulation tissue. Ann. Biomed. Eng. 22, 23–33 (1994).

  95. 95.

    Spuck, S. et al. Operative and technical complications of vagus nerve stimulator implantation. Oper. Neurosurg. 67, 489–494 (2010).

  96. 96.

    Kabir, S. M. R. et al. Vagus nerve stimulation in children with intractable epilepsy: indications, complications and outcome. Childs Nerv. Syst. 25, 1097–1100 (2009).

  97. 97.

    Fenoy, A. J. & Simpson, R. K. Risks of common complications in deep brain stimulation surgery: management and avoidance. J. Neurosurg. 120, 132–139 (2014).

  98. 98.

    Ramsay, R. E. et al. Vagus nerve stimulation for treatment of partial seizures: 2. safety, side effects, and tolerability. Epilepsia 35, 627–636 (1994).

  99. 99.

    Hassler, C., Boretius, T. & Stieglitz, T. Polymers for neural implants. J. Polym. Sci. B 49, 18–33 (2011).

  100. 100.

    Barrese, J. C. et al. Failure mode analysis of silicon-based intracortical microelectrode arrays in non-human primates. J. Neural Eng. 10, 066014 (2013).

  101. 101.

    Tang, H.-Y., Lu, Y., Fung, S., Horsley, D. A. & Boser, B. E. Integrated ultrasonic system for measuring body-fat composition. In Proc. 2015 IEEE International Solid-State Circuits Conference—Digest of Technical Papers (eds Chandrakasan, A. et al.) 210–212 (IEEE, 2015).

  102. 102.

    Aquaflex Ultrasonic Gel Pad. Parker https://www.parkerlabs.com/aquaflex.asp (accessed 2018).

  103. 103.

    UltraDrape UGPIV Barrier and Securement. Parker https://www.parkerlabs.com/ultradrape.asp (accessed 2019).

  104. 104.

    Casarotto, R. A., Adamowski, J. C., Fallopa, F. & Bacanelli, F. Coupling agents in therapeutic ultrasound: acoustic and thermal behavior. Arch. Phys. Med. Rehabil. 85, 162–165 (2004).

Download references

Acknowledgements

This work was supported in part by the National Institutes of Health NIH grant no. R21EY027570; the Defense Advanced Research Projects Agency (DARPA) BTO grant/contract no. HR011-15-2-0006; the National Science Foundation NSF EAGER grant no. 1551239; the McKnight Foundation Technological Innovations in Neuroscience Award (to M.M.M. and J.M.C.); the Chan Zuckerberg Biohub (to R.M. and M.M.M.); and a NIH Training grant T32 GM008155 (to D.K.P.).

Author information

Affiliations

Authors

Contributions

B.C.J., R.M., M.M.G. and K.Y.L. designed and characterized the IC. D.K.P., J.E.K. and M.M.M. designed and implemented the external transceiver. K.S., D.K.P., M.M.M. and R.M.N. designed and assembled the motes. D.K.P., R.M.N., J.M.C., K.S. and B.C.J. designed and performed the in vivo studies. D.K.P. performed in vitro and ex vivo studies. D.K.P. and B.C.J. conducted data analysis and simulations. All of the authors discussed the results. D.K.P., B.C.J., R.M., M.M.M., J.M.C., K.S. and M.M.G. prepared the manuscript with input from all of the authors.

Corresponding authors

Correspondence to Jose M. Carmena or Michel M. Maharbiz or Rikky Muller.

Ethics declarations

Competing interests

M.M.M., J.M.C., R.M.N. and J.E.K. are members of iota Biosciences, Inc. All of the other authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

41551_2020_518_MOESM3_ESM.mp4

In vivo neural stimulation with a fully implanted wireless StimDust.

Supplementary Information

Supplementary figures, tables and references, and the caption for Supplementary Video 1.

Reporting Summary

Supplementary Video 1

In vivo neural stimulation with a fully implanted wireless StimDust.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Piech, D.K., Johnson, B.C., Shen, K. et al. A wireless millimetre-scale implantable neural stimulator with ultrasonically powered bidirectional communication. Nat Biomed Eng 4, 207–222 (2020). https://doi.org/10.1038/s41551-020-0518-9

Download citation

Further reading