Review Article

Neural recording and modulation technologies

  • Nature Reviews Materials 2, Article number: 16093 (2017)
  • doi:10.1038/natrevmats.2016.93
  • Download Citation
Published online:

Abstract

In the mammalian nervous system, billions of neurons connected by quadrillions of synapses exchange electrical, chemical and mechanical signals. Disruptions to this network manifest as neurological or psychiatric conditions. Despite decades of neuroscience research, our ability to treat or even to understand these conditions is limited by the capability of tools to probe the signalling complexity of the nervous system. Although orders of magnitude smaller and computationally faster than neurons, conventional substrate-bound electronics do not recapitulate the chemical and mechanical properties of neural tissue. This mismatch results in a foreign-body response and the encapsulation of devices by glial scars, suggesting that the design of an interface between the nervous system and a synthetic sensor requires additional materials innovation. Advances in genetic tools for manipulating neural activity have fuelled the demand for devices that are capable of simultaneously recording and controlling individual neurons at unprecedented scales. Recently, flexible organic electronics and bio- and nanomaterials have been developed for multifunctional and minimally invasive probes for long-term interaction with the nervous system. In this Review, we discuss the design lessons from the quarter-century-old field of neural engineering, highlight recent materials-driven progress in neural probes and look at emergent directions inspired by the principles of neural transduction.

  • Subscribe to Nature Reviews Materials for full access:

    $59

    Subscribe

Additional access options:

Already a subscriber?  Log in  now or  Register  for online access.

References

  1. 1.

    et al. Projected number of people with Parkinson disease in the most populous nations, 2005 through 2030. Neurology 68, 384–386 (2007).

  2. 2.

    , & The cost burden of multiple sclerosis in the United States: a systematic review of the literature. J. Med. Econ. 16, 639–647 (2013).

  3. 3.

    et al. The economic burden of depression in the United States: how did it change between 1990 and 2000? J. Clin. Psychiatry 64, 1465–1475 (2003).

  4. 4.

    & Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med. 3, e442 (2006).

  5. 5.

    Reflex control of immunity. Nat. Rev. Immunol. 9, 418–428 (2009).

  6. 6.

    , & Principles of Neural Science 4th edn (McGraw-Hill Medical, 2000).

  7. 7.

    et al. Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled-up primate brain. J. Comp. Neurol. 513, 532–541 (2009).

  8. 8.

    Glia: listening and talking to the synapse. Nat. Rev. Neurosci. 2, 185–193 (2001).

  9. 9.

    The mystery and magic of glia: a perspective on their roles in health and disease. Neuron 60, 430–440 (2008).

  10. 10.

    et al. Aging and the human neocortex. Exp. Gerontol. 38, 95–99 (2003).

  11. 11.

    , & Acid-sensing ion channels in pain and disease. Nat. Rev. Neurosci. 14, 461–471 (2013).

  12. 12.

    et al. ThermoTRP channels and beyond: mechanisms of temperature sensation. Nat. Rev. Neurosci. 4, 529–539 (2003).

  13. 13.

    , & Lessons from peppers and peppermint: the molecular logic of thermosensation. Curr. Opin. Neurobiol. 13, 487–492 (2003).

  14. 14.

    , & Molecular mechanisms of mechanotransduction in mammalian sensory neurons. Nat. Rev. Neurosci. 12, 139–153 (2011).

  15. 15.

    Long-term recording from single neurons in brain of unrestrained mammals. Science 127, 469–470 (1958). This article is the first report of a chronic recording of isolated action potentials in the brain of a freely moving mammal (a ground squirrel).

  16. 16.

    & Patch clamp techniques for studying ionic channels in excitable membranes. Annu. Rev. Physiol. 46, 455–472 (1984).

  17. 17.

    , , , & A silicon-based, three-dimensional neural interface: manufacturing processes for an intracortical electrode array. IEEE Trans. Biomed. Eng. 38, 758–768 (1991). This article presents an early conceptual demonstration of the Utah array.

  18. 18.

    , , , & Performance of planar multisite microprobes in recording extracellular single-unit intracortical activity. IEEE Trans. Biomed. Eng. 35, 719–732 (1988). In this article, Michigan probes were applied to record neural activity.

  19. 19.

    , & The stereotrode: a new technique for simultaneous isolation of several single units in the central nervous system from multiple unit records. J. Neurosci. Methods 8, 391–397 (1983).

  20. 20.

    , , & Tetrodes markedly improve the reliability and yield of multiple single-unit isolation from multi-unit recordings in cat striate cortex. J. Neurosci. Methods 63, 43–54 (1995). Combining four microwires into a tetrode arrangement was shown to yield superior identification of isolated action potentials.

  21. 21.

    & Miniature motorized microdrive and commutator system for chronic neural recording in small animals. J. Neurosci. Methods 112, 83–84 (2001).

  22. 22.

    et al. Switching on and off fear by distinct neuronal circuits. Nature 454, 600–606 (2008).

  23. 23.

    & Reactivation of hippocampal ensemble memories during sleep. Science 265, 676–679 (1994).

  24. 24.

    et al. Neurotrophic electrode: method of assembly and implantation into human motor speech cortex. J. Neurosci. Methods 174, 168–176 (2008).

  25. 25.

    et al. Neuronal ensemble control of prosthetic devices by a human with tetraplegia. Nature 442, 164–171 (2006). This article demonstrates the use of neural signals from the brain of a patient with tetraplegia to control a prosthetic arm.

  26. 26.

    et al. High-frequency network oscillation in the hippocampus. Science 256, 1025–1027 (1992).

  27. 27.

    Silicon microsystems for neuroscience and neural prostheses. IEEE Eng. Med. Biol. Mag. 24, 22–29 (2005).

  28. 28.

    et al. Ultra-high-density in vivo neural probes. Conf. Proc. IEEE Eng. Med. Biol. Soc. 2032–2035 (2014).

  29. 29.

    & Materials for microfabricated implantable devices: a review. Lab Chip 15, 4256–4272 (2015).

  30. 30.

    Brain–machine interfaces to restore motor function and probe neural circuits. Nat. Rev. Neurosci. 4, 417–422 (2003).

  31. 31.

    Connecting cortex to machines: recent advances in brain interfaces. Nat. Neurosci. 5, 1085–1088 (2002).

  32. 32.

    et al. Reach and grasp by people with tetraplegia using a neurally controlled robotic arm. Nature 485, 372–375 (2012).

  33. 33.

    , , & Toward a comparison of microelectrodes for acute and chronic recordings. Brain Res. 1282, 183–200 (2009).

  34. 34.

    , & Response of brain tissue to chronically implanted neural electrodes. J. Neurosci. Methods 148, 1–18 (2005). A comprehensive review article that summarized the biological failure modes seen in chronically implanted neural probes.

  35. 35.

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

  36. 36.

    et al. Brain tissue responses to neural implants impact signal sensitivity and intervention strategies. ACS Chem. Neurosci. 6, 48–67 (2015).

  37. 37.

    , , & Biomechanical analysis of silicon microelectrode-induced strain in the brain. J. Neural Eng. 2, 81–89 (2005).

  38. 38.

    , & The density difference between tissue and neural probes is a key factor for glial scarring. Sci. Rep. 3, 2942 (2013).

  39. 39.

    et al. Brain responses to micro-machined silicon devices. Brain Res. 983, 23–35 (2003).

  40. 40.

    et al. The impact of chronic blood–brain barrier breach on intracortical electrode function. Biomaterials 34, 4703–4713 (2013).

  41. 41.

    et al. Evaluation of MEMS materials of construction for implantable medical devices. Biomaterials 23, 2737–2750 (2002).

  42. 42.

    et al. Nanoporous gold as a neural interface coating: effects of topography, surface chemistry, and feature size. ACS Appl. Mater. Interfaces 7, 7093–7100 (2015).

  43. 43.

    & Dexamethasone-coated neural probes elicit attenuated inflammatory response and neuronal loss compared to uncoated neural probes. Brain Res. 1148, 15–27 (2007).

  44. 44.

    et al. Surface immobilization of neural adhesion molecule L1 for improving the biocompatibility of chronic neural probes: in vitro characterization. Acta Biomater. 4, 1208–1217 (2008).

  45. 45.

    et al. Soft materials in neuroengineering for hard problems in neuroscience. Neuron 86, 175–186 (2015).

  46. 46.

    et al. Organic electrode coatings for next-generation neural interfaces. Front. Neuroeng. 7, 15 (2014).

  47. 47.

    , , , & Conducting polymers on hydrogel-coated neural electrode provide sensitive neural recordings in auditory cortex. Acta Biomater. 6, 57–62 (2010).

  48. 48.

    , & Cell attachment functionality of bioactive conducting polymers for neural interfaces. Biomaterials 30, 3637–3644 (2009).

  49. 49.

    et al. Flexible, foldable, actively multiplexed, high-density electrode array for mapping brain activity in vivo. Nat. Neurosci. 14, 1599–1605 (2011).

  50. 50.

    et al. 3D Parylene sheath neural probe for chronic recordings. J. Neural Eng. 10, 045002 (2013).

  51. 51.

    et al. Novel flexible Parylene neural probe with 3D sheath structure for enhancing tissue integration. Lab Chip 13, 554–561 (2012).

  52. 52.

    et al. Electronic dura mater for long-term multimodal neural interfaces. Science 347, 159–163 (2015).

  53. 53.

    et al. Concurrent recordings of bladder afferents from multiple nerves using a microfabricated PDMS microchannel electrode array. Lab Chip 12, 2540–2551 (2012).

  54. 54.

    et al. Flexible and stretchable micro-electrodes for in vitro and in vivo neural interfaces. Med. Biol. Eng. Comput. 48, 945–954 (2010).

  55. 55.

    et al. Microchannel-based regenerative scaffold for chronic peripheral nerve interfacing in amputees. Biomaterials 41, 151–165 (2015).

  56. 56.

    et al. A regenerative microchannel neural interface for recording from and stimulating peripheral axons in vivo. J. Neural Eng. 9, 016010 (2012).

  57. 57.

    et al. Fabrication of responsive, softening neural interfaces. Adv. Funct. Mater. 22, 3470–3479 (2012).

  58. 58.

    , , & Stimuli-responsive polymer nanocomposites inspired by the sea cucumber dermis. Science 319, 1370–1374 (2008).

  59. 59.

    et al. Flexible and stretchable electronics for biointegrated devices. Annu. Rev. Biomed. Eng. 14, 113–128 (2012).

  60. 60.

    , & Materials and mechanics for stretchable electronics. Science 327, 1603–1607 (2010).

  61. 61.

    et al. Epidermal electronics. Science 333, 838–343 (2011). A pioneering application of flexible and stretchable microcontact-printed electronics for biological sensing.

  62. 62.

    et al. Waterproof AlInGaP optoelectronics on stretchable substrates with applications in biomedicine and robotics. Nat. Mater. 9, 929–937 (2010).

  63. 63.

    et al. Fractal design concepts for stretchable electronics. Nat. Commun. 5, 3266 (2014).

  64. 64.

    et al. Multifunctional fibers for simultaneous optical, electrical and chemical interrogation of neural circuits in vivo. Nat. Biotechnol. 33, 277–284 (2015).

  65. 65.

    et al. Ultrasmall implantable composite microelectrodes with bioactive surfaces for chronic neural interfaces. Nat. Mater. 11, 1065–1073 (2012).

  66. 66.

    , , & A carbon-fiber electrode array for long-term neural recording. J. Neural Eng. 10, 046016 (2013).

  67. 67.

    et al. Neural stimulation and recording with bidirectional, soft carbon nanotube fiber microelectrodes. ACS Nano 9, 4465–4474 (2015).

  68. 68.

    Organic bioelectronics: a new era for organic electronics. Biochim. Biophys. Acta 1830, 4286–4287 (2013).

  69. 69.

    et al. A transparent organic transistor structure for bidirectional stimulation and recording of primary neurons. Nat. Mater. 12, 672–680 (2013).

  70. 70.

    et al. Degradation of organic solar cells due to air exposure. Sol. Energy Mater. Sol. Cells 90, 3520–3530 (2006).

  71. 71.

    , , , & PEDOT: Principles and Applications of an Intrinsically Conductive Polymer (CRC Press, 2010).

  72. 72.

    et al. Chronic neural recordings using silicon microelectrode arrays electrochemically deposited with a poly(3,4 ethylenedioxythiophene) (PEDOT) film. J. Neural Eng. 3, 59–70 (2006).

  73. 73.

    et al. Poly(3,4 ethylenedioxythiophene) (PEDOT) polymer coatings facilitate smaller neural recording electrodes. J. Neural Eng. 8, 014001 (2011).

  74. 74.

    et al. In vivo recordings of brain activity using organic transistors. Nat. Commun. 4, 1575 (2013).

  75. 75.

    et al. NeuroGrid: recording action potentials from the surface of the brain. Nat. Neurosci. 18, 310–315 (2015).

  76. 76.

    et al. Biologically compatible neural interface to safely couple nanocoated electrodes to the surface of the brain. ACS Nano 7, 3887–3895 (2013).

  77. 77.

    et al. Polymer fiber probes enable optical control of spinal cord and muscle function in vivo. Adv. Funct. Mater. 24, 6594–6600 (2014).

  78. 78.

    et al. A skin-inspired organic digital mechanoreceptor. Science 350, 313–316 (2015).

  79. 79.

    et al. Electromechanical cardioplasty using a wrapped elasto-conductive epicardial mesh. Sci. Transl. Med. 8, 344ra86 (2016).

  80. 80.

    et al. Highly stretchable electric circuits from a composite material of silver nanoparticles and elastomeric fibres. Nat. Nanotechnol. 7, 803–809 (2012).

  81. 81.

    , , & Conducting-polymer nanotubes improve electrical properties, mechanical adhesion, neural attachment, and neurite outgrowth of neural electrodes. Small 6, 421–429 (2010).

  82. 82.

    & Nanomaterial-enabled stretchable conductors: strategies, materials and devices. Adv. Mater. 27, 1480–1511 (2015).

  83. 83.

    Percolation and conduction. Rev. Mod. Phys. 45, 574–588 (1973).

  84. 84.

    et al. Scalable coating and properties of transparent, flexible, silver nanowire electrodes. ACS Nano 4, 2955–2963 (2010).

  85. 85.

    & Deep brain stimulation. Annu. Rev. Neurosci. 29, 229–257 (2006).

  86. 86.

    et al. Spinal cord stimulation for chronic, intractable pain: superiority of “multi-channel” devices. Pain 44, 119–130 (1991).

  87. 87.

    & Deep brain stimulation for treatment-resistant depression. Am. J. Psychiatry 167, 1437–1444 (2010).

  88. 88.

    Neural stimulation and recording electrodes. Annu. Rev. Biomed. Eng. 10, 275–309 (2008).

  89. 89.

    , , & Translational principles of deep brain stimulation. Nat. Rev. Neurosci. 8, 623–635 (2007).

  90. 90.

    et al. Optetrode: a multichannel readout for optogenetic control in freely moving mice. Nat. Neurosci. 15, 163–170 (2011).

  91. 91.

    , , , , & Millisecond-timescale, genetically targeted optical control of neural activity. Nat. Neurosci. 8, 1263–1268 (2005). ChR2, a microbial opsin, is used to control neural activity with millisecond optical pulses for the first time, marking the invention of optogenetics.

  92. 92.

    et al. Optogenetic control of heart muscle in vitro and in vivo. Nat. Methods 7, 897–900 (2010).

  93. 93.

    et al. Direct optical activation of skeletal muscle fibres efficiently controls muscle contraction and attenuates denervation atrophy. Nat. Commun. 6, 8506 (2015).

  94. 94.

    et al. Beyond the brain: optogenetic control in the spinal cord and peripheral nervous system. Sci. Transl. Med. 8, 337rv5 (2016).

  95. 95.

    et al. Channelrhodopsin 2, a directly light-gated cation-selective membrane channel. Proc. Natl Acad. Sci. USA 100, 13940–13945 (2003).

  96. 96.

    et al. The microbial opsin family of optogenetic tools. Cell 147, 1446–1457 (2011).

  97. 97.

    et al. Multimodal fast optical interrogation of neural circuitry. Nature 446, 633–639 (2007).

  98. 98.

    , , , & Optogenetics in neural systems. Neuron 71, 9–34 (2011).

  99. 99.

    et al. Independent optical excitation of distinct neural populations. Nat. Methods 11, 338–346 (2014).

  100. 100.

    et al. Integrated device for optical stimulation and spatiotemporal electrical recording of neural activity in light-sensitized brain tissue. J. Neural Eng. 6, 055007 (2009).

  101. 101.

    et al. Multi-array silicon probes with integrated optical fibers: light-assisted perturbation and recording of local neural circuits in the behaving animal. Eur. J. Neurosci. 31, 2279–2291 (2010).

  102. 102.

    , & Optogenetic identification of striatal projection neuron subtypes during in vivo recordings. Brain Res. 1511, 21–32 (2013).

  103. 103.

    Buzsá et al. Tools for probing local circuits: high-density silicon probes combined with optogenetics. Neuron 86, 92–105 (2015).

  104. 104.

    et al. Monolithically integrated μLEDs on silicon neural probes for high-resolution optogenetic studies in behaving animals. Neuron 88, 1136–1148 (2015).

  105. 105.

    , , & Transparent intracortical microprobe array for simultaneous spatiotemporal optical stimulation and multichannel electrical recording. Nat. Methods 12, 1157–1162 (2015).

  106. 106.

    et al. Transparent and flexible low noise graphene electrodes for simultaneous electrophysiology and neuroimaging. Nat. Commun. 5, 5259 (2014).

  107. 107.

    , , , & A polymer-based neural microimplant for optogenetic applications: design and first in vivo study. Lab Chip 13, 579–588 (2013).

  108. 108.

    et al. Injectable, cellular-scale optoelectronics with applications for wireless optogenetics. Science 340, 211–216 (2013).

  109. 109.

    et al. Restoring voluntary control of locomotion after paralyzing spinal cord injury. Science 336, 1182–1185 (2012).

  110. 110.

    & DREADDs (designer receptors exclusively activated by designer drugs): chemogenetic tools with therapeutic utility. Annu. Rev. Pharmacol. Toxicol. 55, 399–417 (2015). This comprehensive review describes powerful chemogenetic approaches to targeted neuromodulation with DREADDs (designer receptors exclusively activated by designer drugs).

  111. 111.

    et al. Wireless optofluidic systems for programmable in vivo pharmacology and optogenetics. Cell 162, 662–674 (2015).

  112. 112.

    et al. A minimally invasive 64 channel wireless μECoG implant. IEEE J. Solid-State Circuits 50, 344–359 (2015).

  113. 113.

    et al. Wirelessly powered, fully internal optogenetics for brain, spinal and peripheral circuits in mice. Nat. Methods 12, 969–974 (2015).

  114. 114.

    et al. Soft, stretchable, fully implantable miniaturized optoelectronic systems for wireless optogenetics. Nat. Biotechnol. 33, 1280–1286 (2015).

  115. 115.

    et al. Model validation of untethered, ultrasonic neural dust motes for cortical recording. J. Neurosci. Methods 244, 114–122 (2015).

  116. 116.

    et al. Wireless recording in the peripheral nervous system with ultrasonic neural dust. Neuron 91, 529–539 (2016). The first in vivo validation of neural dust motes.

  117. 117.

    & Multi-electrode array technologies for neuroscience and cardiology. Nat. Nanotechnol. 8, 83–94 (2013).

  118. 118.

    et al. Multisite electrophysiological recordings by self-assembled loose-patch-like junctions between cultured hippocampal neurons and mushroom-shaped microelectrodes. Sci. Rep. 6, 27110 (2016).

  119. 119.

    et al. Subcellular neural probes from single-crystal gold nanowires. ACS Nano 8, 8182–8189 (2014).

  120. 120.

    et al. Vertical nanowire electrode arrays as a scalable platform for intracellular interfacing to neuronal circuits. Nat. Nanotechnol. 7, 180–184 (2012).

  121. 121.

    et al. Intracellular recording of action potentials by nanopillar electroporation. Nat. Nanotechnol. 7, 185–190 (2012).

  122. 122.

    et al. Iridium oxide nanotube electrodes for sensitive and prolonged intracellular measurement of action potentials. Nat. Commun. 5, 3206 (2014).

  123. 123.

    & Fusion of biomimetic stealth probes into lipid bilayer cores. Proc. Natl Acad. Sci. USA 107, 5815–5820 (2010).

  124. 124.

    et al. Detection, stimulation, and inhibition of neuronal signals with high-density nanowire transistor arrays. Science 313, 1100–1104 (2006).

  125. 125.

    & Synthetic nanoelectronic probes for biological cells and tissues. Annu. Rev. Anal. Chem. 6, 31–51 (2013).

  126. 126.

    et al. Intracellular recordings of action potentials by an extracellular nanoscale field-effect transistor. Nat. Nanotechnol. 7, 174–179 (2012).

  127. 127.

    et al. Three-dimensional, flexible nanoscale field-effect transistors as localized bioprobes. Science 329, 830–834 (2010).

  128. 128.

    et al. Syringe-injectable electronics. Nat. Nanotechnol. 10, 629–636 (2015).

  129. 129.

    et al. Three-dimensional macroporous nanoelectronic networks as minimally invasive brain probes. Nat. Mater. 14, 1286–1292 (2015).

  130. 130.

    et al. Stable long-term chronic brain mapping at the single-neuron level. Nat. Methods 13, 875–882 (2016). A pioneering demonstration of long-term recordings using microstructured electrode meshes with a negligible tissue response.

  131. 131.

    & Nanomaterial-enabled neural stimulation. Front. Neurosci. 10, 69 (2016).

  132. 132.

    , & Multifunctional magnetic nanoparticles: design, synthesis, and biomedical applications. Acc. Chem. Res. 42, 1097–1107 (2009).

  133. 133.

    et al. Gold nanostructures: engineering their plasmonic properties for biomedical applications. Chem. Soc. Rev. 35, 1084–1094 (2006).

  134. 134.

    et al. Neuromodulation: present and emerging methods. Front. Neuroeng. 7, 27, (2014).

  135. 135.

    et al. Application of infrared light for in vivo neural stimulation. J. Biomed. Opt. 10, 064003 (2005).

  136. 136.

    et al. Optogenetics in neural systems. Neuron 71, 9–34 (2011).

  137. 137.

    et al. An optical neural interface: in vivo control of rodent motor cortex with integrated fiberoptic and optogenetic technology. J. Neural Eng. 4, S143–S156 (2007).

  138. 138.

    Genetically encoded optical indicators for the analysis of neuronal circuits. Nat. Rev. Neurosci. 13, 687–700 (2012).

  139. 139.

    et al. In vivo three-photon microscopy of subcortical structures within an intact mouse brain. Nat. Photonics 7, 205–209 (2013).

  140. 140.

    & in SPAWDA 2015, Symp. Piezoelectricity Acoust. Waves Device Appl. 102–105 (SPAWDA, 2015).

  141. 141.

    & A review of low-intensity transcranial focused ultrasound for clinical applications. Curr. Behav. Neurosci. Rep. 2, 60–66 (2015).

  142. 142.

    et al. Transcranial focused ultrasound modulates the activity of primary somatosensory cortex in humans. Nat. Neurosci. 17, 322–329 (2014). Focused ultrasound is used for non-invasive neuromodulation in the cortex of human subjects.

  143. 143.

    et al. Functional ultrasound imaging of the brain. Nat. Methods 8, 662–664 (2011).

  144. 144.

    & RF magnetic field penetration, phase shift and power dissipation in biological tissue: implications for NMR imaging. Phys. Med. Biol. 23, 630–643 (1978).

  145. 145.

    , & Frequency/depth-penetration considerations in hyperthermia by magnetically induced currents. Electron. Lett. 16, 358–359 (1980).

  146. 146.

    Transcranial magnetic stimulation: a primer. Neuron 55, 187–199 (2007).

  147. 147.

    , & Electric field depth–focality tradeoff in transcranial magnetic stimulation: simulation comparison of 50 coil designs. Brain Stimul. 6, 1–13 (2013).

  148. 148.

    , & Applications of fMRI in translational medicine and clinical practice. Nat. Rev. Neurosci. 7, 732–744 (2006).

  149. 149.

    et al. Ultrafast ultrasound localization microscopy for deep super-resolution vascular imaging. Nature 527, 499–502 (2015).

  150. 150.

    et al. A magnetic switch for the control of cell death signalling in in vitro and in vivo systems. Nat. Mater. 11, 1038–1043 (2012).

  151. 151.

    et al. Magnetic nanoparticles for ultrafast mechanical control of inner ear hair cells. ACS Nano 8, 6590–6598 (2014).

  152. 152.

    , , & Progress in applications of magnetic nanoparticles in biomedicine. J. Phys. D: Appl. Phys. 42, 224001 (2009).

  153. 153.

    et al. Magneto-electric nanoparticles to enable field-controlled high-specificity drug delivery to eradicate ovarian cancer cells. Sci. Rep. 3, 2953 (2013).

  154. 154.

    et al. Remote switching of cellular activity and cell signaling using light in conjunction with quantum dots. Biomed. Opt. Express 3, 447–454 (2012).

  155. 155.

    et al. Nanoscale engineering of a cellular interface with semiconductor nanoparticle films for photoelectric stimulation of neurons. Nano Lett. 7, 513–519 (2007).

  156. 156.

    et al. Electric field modulation of semiconductor quantum dot photoluminescence: insights into the design of robust voltage-sensitive cellular imaging probes. Nano Lett. 15, 6848–6854 (2015).

  157. 157.

    & Optical strategies for sensing neuronal voltage using quantum dots and other semiconductor nanocrystals. ACS Nano 7, 4601–4609 (2013).

  158. 158.

    , & Probing the cytotoxicity of semiconductor quantum dots. Nano Lett. 4, 11–18 (2004).

  159. 159.

    et al. Gold nanoparticles in biology: beyond toxicity to cellular imaging. Acc. Chem. Res. 41, 1721–1730 (2008).

  160. 160.

    et al. Photothermal inhibition of neural activity with near-infrared-sensitive nanotransducers. ACS Nano 8, 8040–8049 (2014).

  161. 161.

    Carvalho- et al. Photosensitivity of neurons enabled by cell-targeted gold nanoparticles. Neuron 86, 207–217 (2015).

  162. 162.

    et al. Gold nanoparticle-assisted all optical localized stimulation and monitoring of Ca2+ signaling in neurons. Sci. Rep. 6, 20619 (2016).

  163. 163.

    et al. Thermosensitive ion channel activation in single neuronal cells by using surface-engineered plasmonic nanoparticles. Angew. Chem. Int. Ed. 54, 11725–11729 (2015).

  164. 164.

    , & Optical detection of brain cell activity using plasmonic gold nanoparticles. Nano Lett. 9, 519–524 (2009).

  165. 165.

    et al. Effects of geometry and composition on charge-induced plasmonic shifts in gold nanoparticles. J. Phys. Chem. C. 112, 7309–7317 (2008).

  166. 166.

    et al. Nanometre-scale thermometry in a living cell. Nature 500, 54–58 (2013).

  167. 167.

    et al. Modulation of nitrogen vacancy charge state and fluorescence in nanodiamonds using electrochemical potential. Proc. Natl Acad. Sci. USA 113, 3938–3943 (2016).

  168. 168.

    et al. Optical magnetic detection of single-neuron action potentials using quantum defects in diamond. Preprint at (2016).

  169. 169.

    et al. Illuminating cell signaling with near-infrared light-responsive nanomaterials. ACS Nano. 10, 3881–3885 (2016).

  170. 170.

    et al. Near-infrared photoactivatable control of Ca2+ signaling and optogenetic immunomodulation. eLife 4, e10024 (2015).

  171. 171.

    et al. Sonogenetics is a non-invasive approach to activating neurons in Caenorhabditis elegans. Nat. Commun. 6, 8264 (2015).

  172. 172.

    et al. Piezoelectric nanoparticle-assisted wireless neuronal stimulation. ACS Nano 9, 7678–7689 (2015).

  173. 173.

    Remote control of cellular behaviour with magnetic nanoparticles. Nat. Nanotechnol. 3, 139–143 (2008).

  174. 174.

    Cellular mechanotransduction: putting all the pieces together again. FASEB. J. 20, 811–827 (2006).

  175. 175.

    et al. A mechanogenetic toolkit for interrogating cell signaling in space and time. Cell 165, 1507–1518 (2016).

  176. 176.

    et al. Selective activation of mechanosensitive ion channels using magnetic particles. J. R. Soc. Interface 5, 855–863 (2008).

  177. 177.

    et al. Spatiotemporal control of microtubule nucleation and assembly using magnetic nanoparticles. Nat. Nanotechnol. 8, 199–205 (2013).

  178. 178.

    et al. Biofunctionalized magnetic-vortex microdiscs for targeted cancer-cell destruction. Nat. Mater. 9, 165–171 (2010).

  179. 179.

    et al. Nanomagnetic actuation of receptor-mediated signal transduction. Nat. Nanotechnol. 3, 36–40 (2008).

  180. 180.

    , & Simple models for dynamic hysteresis loop calculations of magnetic single-domain nanoparticles: application to magnetic hyperthermia optimization. J. Appl. Phys. 109, 083921 (2011).

  181. 181.

    et al. Wireless magnetothermal deep brain stimulation. Science 347, 1477–1480 (2015).

  182. 182.

    et al. Remote control of ion channels and neurons through magnetic-field heating of nanoparticles. Nat. Nanotechnol. 5, 602–606 (2010). The first application of MNP heating to regulate intracellular calcium with AMFs.

  183. 183.

    et al. Radio-wave heating of iron oxide nanoparticles can regulate plasma glucose in mice. Science 336, 604–608 (2012).

  184. 184.

    et al. Externally controlled on demand release of anti-HIV drug using magneto-electric nanoparticles as carriers. Nat. Commun. 4, 1707 (2013).

  185. 185.

    et al. Magnetoelectric ‘spin’ on stimulating the brain. Nanomedicine 10, 2051–2061 (2015).

  186. 186.

    et al. Recent advances in magnetic nanoparticle-based multi-modal imaging. Chem. Soc. Rev. 44, 4501–4516 (2015).

  187. 187.

    , & Environmentally responsive MRI contrast agents. Chem. Commun. (Camb.) 49, 9704–9721 (2013).

  188. 188.

    et al. Calcium-sensitive MRI contrast agents based on superparamagnetic iron oxide nanoparticles and calmodulin. Proc. Natl Acad. Sci. USA 103, 14707–14712 (2006).

  189. 189.

    et al. Dynamic imaging with MRI contrast agents: quantitative considerations. Magn. Reson. Imaging 24, 449–462 (2006).

  190. 190.

    et al. Magnetic nanosensors optimized for rapid and reversible self-assembly. Chem. Commun. (Camb.) 50, 3595–3598 (2014).

  191. 191.

    , , , & Molecular-level functional magnetic resonance imaging of dopaminergic signaling. Science 344, 533–535 (2014).

  192. 192.

    et al. Magnetically multiplexed heating of single domain nanoparticles. Appl. Phys. Lett. 104, 213103 (2014).

  193. 193.

    et al. Selective release of multiple DNA oligonucleotides from gold nanorods. ACS Nano 3, 80–86 (2008).

  194. 194.

    et al. High-performance ferrite nanoparticles through nonaqueous redox phase tuning. Nano Lett. 16, 1345–1351 (2016).

  195. 195.

    & Modern methods for delivery of drugs across the blood–brain barrier. Adv. Drug Deliv. Rev. 64, 640–665 (2012).

  196. 196.

    et al. Transferrin-functionalized nanoparticles lose their targeting capabilities when a biomolecule corona adsorbs on the surface. Nat. Nanotechnol. 8, 137–143 (2013).

  197. 197.

    et al. Rapid formation of plasma protein corona critically affects nanoparticle pathophysiology. Nat. Nanotechnol. 8, 772–781 (2013).

  198. 198.

    et al. Role of cell cycle on the cellular uptake and dilution of nanoparticles in a cell population. Nat. Nanotechnol. 7, 62–68 (2012).

  199. 199.

    et al. Local and reversible blood–brain barrier disruption by noninvasive focused ultrasound at frequencies suitable for trans-skull sonications. Neuroimage 24, 12–20 (2005).

  200. 200.

    et al. Iron oxide nanoparticles as a drug delivery vehicle for MRI monitored magnetic targeting of brain tumors. Biomaterials 29, 487–496 (2008).

  201. 201.

    et al. Post-mortem studies in glioblastoma patients treated with thermotherapy using magnetic nanoparticles. Biomaterials 30, 52–57 (2009).

  202. 202.

    et al. A nanobody-based system using fluorescent proteins as scaffolds for cell-specific gene manipulation. Cell 154, 928–939 (2013).

  203. 203.

    & Remote magnetic orientation of 3D collagen hydrogels for directed neuronal regeneration. Nano Lett. 16, 2567–2573 (2016).

  204. 204.

    , & Injectable hydrogels for central nervous system therapy. Biomed. Mater. 7, 024101 (2012).

  205. 205.

    et al. Biogenic gas nanostructures as ultrasonic molecular reporters. Nat. Nanotechnol. 9, 311–316 (2014).

  206. 206.

    et al. Bidirectional electromagnetic control of the hypothalamus regulates feeding and metabolism. Nature 531, 647–650 (2016).

  207. 207.

    et al. Genetically targeted magnetic control of the nervous system. Nat. Neurosci. 19, 756–761 (2016).

  208. 208.

    & Mineralization in ferritin: an efficient means of iron storage. J. Struct. Biol. 126, 182–194 (1999).

  209. 209.

    Physical limits to magnetogenetics. eLife 5, e17210 (2016).

  210. 210.

    et al. Magnetosomes are cell membrane invaginations organized by the actin-like protein MamK. Science 311, 242–245 (2006).

  211. 211.

    et al. Biosynthesis of magnetic nanostructures in a foreign organism by transfer of bacterial magnetosome gene clusters. Nat. Nanotechnol. 9, 193–197 (2014).

  212. 212.

    et al. Health care costs for patients with chronic spinal cord injury in the veterans health administration. J. Spinal Cord Med. 30, 477–481 (2007).

  213. 213.

    et al. The current and projected economic burden of Parkinson's disease in the United States. Mov. Disord. 28, 311–318 (2013).

  214. 214.

    et al. Direct and indirect pathways of basal ganglia: a critical reappraisal. Nat. Neurosci. 17, 1022–1030 (2014).

  215. 215.

    Motorcircuits in action: specification, connectivity, and function. Neuron 74, 975–989 (2012).

  216. 216.

    Descending motor pathways and the spinal motor systemml: limbic and non-limbic components. Prog. Brain Res. 87, 307–421 (1991).

  217. 217.

    et al. Biostability of micro-photodiode arrays for subretinal implantation. Biomaterials 23, 797–804 (2002).

  218. 218.

    et al. Corrosion of tungsten microelectrodes used in neural recording applications. J. Neurosci. Methods 198, 158–171 (2011).

  219. 219.

    et al. Stability of and inflammatory response to silicon coated with a fluoroalkyl self-assembled monolayer in the central nervous system. J. Biomed. Mater. Res. A. 81, 363–372 (2007).

  220. 220.

    et al. Corrosion behavior of parylene–metal–parylene thin films in saline. ECS Trans 11, 1–6 (2008).

Download references

Acknowledgements

P.A. is supported by the National Science Foundation (NSF) through a CAREER Award, Center for Materials Science and Engineering, Center for Sensorimotor Neural Engineering, National Institutes for Neurological Disorders and Stroke, National Institute of Mental Health, the Defense Advanced Research Projects Agency, Dresselhaus Fund Award, and the Bose Research Grant.

Author information

Affiliations

  1. Department of Materials Science and Engineering, and Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02193, USA.

    • Ritchie Chen
    • , Andres Canales
    •  & Polina Anikeeva

Authors

  1. Search for Ritchie Chen in:

  2. Search for Andres Canales in:

  3. Search for Polina Anikeeva in:

Competing interests

The authors declare no competing interests.

Corresponding author

Correspondence to Polina Anikeeva.