Action Potential Monitoring Using Neuronanorobots: Neuroelectric Nanosensors
Abstract
Neuronanorobotics, a key future medical technology that can enable the preservation of human brain information, requires appropriate nanosensors. Action potentials encode the most resource-intensive functional brain data. This paper presents a theoretical design for electrical nanosensors intended for use in neuronanorobots to provide non-destructive, in vivo, continuous, real-time, single-spike monitoring of action potentials initiated and processed within the ~86 x 109 neurons of the human brain as intermediated through the ~2.4 x 1014 human brain synapses. The proposed ~3375 nm3 FET-based neuroelectric nanosensors could detect action potentials with a temporal resolution of at least 0.1 ms, enough for waveform characterization even at the highest human neuron firing rates of 800 Hz. Keywords: Human brain information, nanorobot, nanorobotics, neuronanorobot, neuronanoroboticsReferences
Azevedo F.A., et al. Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled-up primate brain. J Comp Neurol. 2009; 513(5):532–41p.
Martins N.R.B., Erlhagen, W., Freitas, R.A. Jr. Non-destructive whole-brain monitoring using nanorobots: Neural electrical data rate requirements. Intl. J. Machine Consciousness. 2012; 4:109–40p.
IBM (2008) IBM Seeks to Build the Computer of the Future Based on Insights from the Brain. IBM News Room. 20 Nov 2008.
Website: https://www-03.ibm.com/press/us/en/pressrelease/26123.wss
Wilson H.R. Simplifed Dynamics of Human and Mammalian Neocortical Neurons. Journal of Theoretical Biology. 1999; 200 (4): 375–88p.
Contreras, D. (2004) Electrophysiological classes of neocortical neurons. Neural Networks 2004; 17(5–6) 633–46p.
Naundorf B., et al. Unique features of action potential initiation in cortical neurons. Nature 2006; 440: 1060–3p.
Freitas R.A. Jr. Nanomedicine, Volume I: Basic Capabilities. Landes Bioscience, Georgetown, TX. 1999.
Freitas R.A. Jr. Exploratory Design in Medical Nanotechnology: A Mechanical Artificial Red Cell. Artif. Cells, Blood Subst., and Immobil. Biotech. 1998; 26:411–30p.
Freitas R.A. Jr. Nanomedicine, Volume IIA: Biocompatibility. Landes Bioscience, Georgetown, TX. 2003.
Morris K. Macrodoctor, come meet the nanodoctors. Lancet. 2001; 357: 778p.
Astier Y., et al. Protein components for nanodevices. Current Opinion in Chemical Biology. 2005; 9(6): 576–84p.
Patel G.M., et al. Nanorobot: A versatile tool in nanomedicine. Journal of Drug Targeting. 2006; 14(2): 63–7p.
Park H.H., et al. Rise of the nanomachine: The evolution of a revolution in medicine. Nanomedicine 2007; 2(4): 425–39p.
Popov A.M., et al. Biocompatibility and applications of carbon nanotubes in medical nanorobots. International Journal of Nanomedicine. 2007; 2(3): 361–72p.
Martel S., et al. Flagellated magnetotactic bacteria as controlled MRI-trackable propulsion and steering systems for medical nanorobots operating in the human microvasculature. International Journal of Robotics Research. 2009; 28(4): 571–582p.
Mallouk T.E., Sen, A. Powering nanorobots. Scientific American 2009; 300(5): 72–77p.
Kostarelos K.Nanorobots for medicine: How close are we? Nanomedicine (Lond). 2010; 5(3):341–2p.
Mavroides D., Ferreira A. NanoRobotics: Current Approaches and Techniques. Springer, New York. 2011.
Freitas R.A. Progress in Nanomedicine and Medical Nanorobotics. Rieth M, Schommers W, eds., Handbook of Theoretical and Computational Nanotechnology, 6 (Bioinformatics, Nanomedicine, and Drug Design), American Scientific Publishers, Stevenson Ranch, CA; (2006a); 619–72p.
Freitas R.A. Jr. Comprehensive Nanorobotic Control of Human Morbidity and Aging. in Fahy, G.M., et al. The Future of Aging: Pathways to Human Life Extension, Springer, New York. 2010; 685–805p.
Freitas R.A. Jr. Clottocytes: artificial mechanical platelets. Institute for Molecular Manufacturing; Report No. 18, June 2000.
Freitas R.A. Jr. Nanodentistry. J. Amer. Dent. Assoc. 2000b; 131: 1559–66p.
Freitas R.A. Jr. Microbivores: Artificial Mechanical Phagocytes using Digest and Discharge Protocol. J. Evol. Technol. 2005; 14(Apr):1–52p.
Freitas R.A. Jr. Pharmacytes: An Ideal Vehicle for Targeted Drug Delivery. J. Nanosci. Nanotechnol. 2006: 2769–75p.
Freitas R.A. Jr. The Ideal Gene Delivery Vector: Chromallocytes, Cell Repair Nanorobots for Chromosome Replacement Therapy. J. Evol. Technol. 2007; 16: 1–97p.
Gorelik J. Ion channels in small cells and subcellular structures can be studied with a smart patch-clamp system. Biophys J. 2002; 83(6):3296–303p.
Freitas R.A. Jr., Phoenix, C.J. (2002). Vasculoid: A personal nanomedical appliance to replace human blood. J. Evol. Technol. 11(April):1–139p.
Sporns O., et al. The Human Connectome: A Structural Description of the Human Brain. PLoS Comput Biol 2005; 1(4).
Lu J.Q., (2009) 3-D hyperintegration and packaging technologies for micro-nano systems. Proc. IEEE. 2009; 97(1): 18–30p.
Anderson J.R., et al. The Viking viewer for connectomics: scalable multi-user annotation and summarization of large volume data sets. J Microscopy: 2011; 241: 13–28p.
Kleinfeld D., et al. Large-scale automated histology in the pursuit of connectomes. Journal of Neuroscience 2011; 31(45), 16,125–38p.
Seung H. S. Neuroscience: Towards functional connectomics. Nature. 2011; 471, 170–172p.
Seo D., et al. Neural Dust: An Ultrasonic, Low Power Solution for Chronic Brain-Machine Interfaces. arXiv, 2013, arxiv.org/abs/1307.2196.
Hogg T., Sretavan D.W. Controlling tiny multi-scale robots for nerve repair. In Proc. of the 20th Natl. Conf. on Artificial Intelligence (AAAI 2005), 2005; 1286–91p.
Hogg T., Coordinating Microscopic Robots in Viscous Fluids. Auton Agents Multi-Agent Syst. 2007; 14: 271–305p.
Freitas R.A. Jr. Computational Tasks in Medical Nanorobotics. Eshaghian-Wilner MM, ed., Bio-inspired and Nano-scale Integrated Computing. John Wiley & Sons, NY, 2009; 391–428p.
Freitas R.A. Jr., Merkle R.C. Nanofactory Collaboration. June 2006.
Freitas R.A. Jr., Merkle R.C. Kinematic Self-Replicating Machines. Landes Bioscience. Georgetown, TX. 2004.
Freitas R.A., Mavroidis, C., Ferreira A. NanoRobotics: Current Approaches and Techniques. Springer. 2013.
Kandel E.R., et al. Principles of Neural Science. New York. 4 Edn McGraw Hill. 2000.
Johnson, G.A., et al. Waxholm Space: An image-based reference for coordinating mouse brain research. NeuroImage, 2010; 53(2): 365p.
Fiala J.C., Harris K.M. Extending unbiased stereology of brain ultrastructure to three-dimensional volumes. J Am Med Inform Assoc. 2001 Jan-Feb; 8(1):1–16p.
Wolters Kluwer Health: Lippincott Williams & Wilkins (2012, August 20). High-definition fiber tractography is major advance in brain imaging. Science Daily. Retrieved July 4, 2013, from http://www.sciencedaily.com /releases/2012/08/120820121050.htm.
Fernandez-Miranda, J.C., et al. High-definition fiber tractography of the human brain: neuroanatomical validation and neurosurgical applications. Neurosurgery. 2012 Aug; 71(2):430–53p.
General Electric Phoenix Nanoatom S. 2013.
Website:http://www.ge-mcs.com/en/radiography-x-ray/ct-computed-tomography/nanotom-s.html
Tkachuk A, et al. X-ray computed tomography in Zernike phase contrast mode at 8 keV with 50 nm resolution using Cu rotation anode X-ray source. Zeitschrift für Kristallographie. 2007; 222(11) 650–5p.
Biswal, B.B., et al. Toward discovery science of human brain function. Proceedings of the National Academy of Sciences 2010; 107(10): 4734–40p.
Nishimoto S., et al. Reconstructing Visual Experiences from Brain Activity Evoked by Natural Movies. Current Biology. 2011; 21: 1641–6p.
Hayworth K.J., et al. Automating the collection of ultrathin serial sections for large volume TEM reconstructions. Microscopy and Microanalysis 2006; 12 (Suppl 2): 86–7p.
Anderson J. M., et al. Physiology and Function of the Tight Junction. Cold Spring Harbor Perspectives in Biology. 2009; 1(2), 2584p.
Hayworth K.J. Electron imaging technology for whole brain neural circuit mapping; International Journal of Machine Consciousness. 2012; 4(1):87–108p.
Helmstaedter M., et al. High-accuracy neurite reconstruction for high-throughput neuroanatomy. Nat Neurosci 2011; 14:1081–8p.
Livet J., et al. Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system. Nature 2007; 450 (7166): 56–62p.
Lichtman J., et al. A technicolour approach to the connectome. Nature Reviews Neuroscience. 2008; 9 (6): 417–422p.
Zador A.M., et al. Sequencing the Connectome. PLoS Biol. 2012; 10(10): e1001411p.
Withers P.J. X-ray nanotomography, Materials today. 2007; 10(12): 26–34p.
Helmholtz Association New microscope reveals ultrastructure of cells. Public Release: 19 Nov 2010 http://www.eurekalert.org/pub_releases/2010-11/haog-nmr111910.php
Bock D.D., et al. Network anatomy and in vivo physiology of visual cortical neurons. Nature. 2011;471:177–82p.
Allen Brain Atlas. Website: ©2014 Allen Institute for Brain Science. Allen Human Brain Atlas.
Available from: http://human.brain-map.org/.
Hawrylycz M.J. An anatomically comprehensive atlas of the adult human brain transcriptome. Nature. 2012; 489, 391–9p.
Allen Mouse Atlas. Website: ©2013 Allen Institute for Brain Science. Allen Developing Mouse Brain Atlas. Available from: http://developingmouse.brain-map.org.
Chung K., Deisseroth, K. CLARITY for mapping the nervous system. Nature Methods.2013; 10(6), 508–513p.
Chung K., et al. Structural and molecular interrogation of intact biological systems; Nature 2013; 497: 332–337p.
White, J.G., et al. The structure of the nervous system of the nematode Caenorhabditis elegans. Phil Trans R Soc Lond B. 1986; 314: 1–340p.
Cheng D., et al. Relative and Absolute Quantification of Postsynaptic Density Proteome Isolated from Rat Forebrain and Cerebellum. Molecular & Cellular Proteomics. 2006; 5:1158–70p.
Varshney L.R., et al. Structural Properties of the Caenorhabditis elegans Neuronal Network, PLoS Comput Biol. 2011 February; 7(2).
Bumbarger D.J., et al. System-wide Rewiring Underlies Behavioral Differences in Predatory and Bacterial-Feeding Nematodes. Cell. 2013; 152(1): 109–19p.
Kaynig V., et al. Large-Scale Automatic Reconstruction of Neuronal Processes from Electron Microscopy. Medical image analysis. 2013; 16(1).
Amunts K., et al. BigBrain: An Ultrahigh-Resolution 3D Human Brain. Model Science. June 2013; 340(6139): 1472–5p.
OCP -Open Connectome Project. 2014. Website: http://www.openconnectomeproject.org
Black J.E., et al. Learning causes synaptogenesis, whereas motor activity causes angiogenesis, in cerebellar cortex of adult rats. Proc. Nati. Acad. Sci. USA, 87: 5568–72p.
Bliss, T.V., et al. Collingridge A synaptic model of memory: long-term potentiation in the hippocampus. Nature 1993; 361: 31–39p.
Kandel E.R. The molecular biology of memory storage: A dialogue between gene and synapses. Science. 2001; 294(5544): 1030–8p.
Liu X., et al. Optogenetic stimulation of a hippocampal engram activates fear memory recall. Nature. 2012; 484, 381–385.
Fuhrmann G., et al. Coding of Temporal Information by Activity-Dependent Synapses The Journal of Neurophysiology. January 2002; 87(1): 140–8p.
Rollenhagen A., Lübke J.H.R. The morphology of excitatory central synapses: from structure to function, Cell Tissue Res. 2006; 326: 221–37p.
Rollenhagen A., et al. Structural determinants of transmission at large hippocampal mossy fiber synapses. J. Neurosci. 2007; 26; 27(39): 10434–44p.
Sabatini B.L., Regehr W.G. Timing of neurotransmission at fast synapses in the mammalian brain. Nature. 1996; 384:170–2p.
Südhof T.C. The synaptic vesicle cycle. Annual Review of Neuroscience 2004; 27: 509–47p.
Polavieja G. G., et al. Stimulus History Reliably Shapes Action Potential Waveforms of Cortical Neurons. J Neurosci. 2005 Jun 8; 25(23):5657–65p.
Kole M.H., et al. Action potential generation requires a high sodium channel density in the axon initial segment. Nat Neurosci. 2008; 178–86p.
Sanford L. He axon hillock and the initial segment; The Journal of Cell Biology, 1968; 38, 193–201p.
Palmer, L.M., Stuart, G.J. Site of Action Potential Initiation in Layer 5 Pyramidal Neurons. The Journal of Neuroscience, February 8, 2006, 26(6):1854–63p.
Colbert, C.M., et al. Axonal Action-Potential Initiation and Na+ Channel Densities in the Soma and Axon Initial Segment of Subicular Pyramidal Neurons. J Neurosci. 1996; 16(21): 6676–86p.
Clark B.A., et al. The site of action potential initiation in cerebellar purkinje neurone. Nature Neuroscience. 2005; 8: 137–9p.
Connors B.W., Gutnick, M.J. (). Intrinsic firing patterns of diverse neocortical neurons. Trends in Neuroscience. 1990; 13(3), 99–104p.
Tateno T., et al. Threshold Firing Frequency–Current Relationships of Neurons in Rat Somatosensory Cortex: Type 1 and Type 2 Dynamics; JN Physiol. 2004; 92(4): 2283–94p.
Steriade M. Neocortical Cell Classes Are Flexible Entities. Nature Reviews Neuroscience. 2004; 5: 121–134p.
Steriade M., et al. Dynamic properties of corticothalamic neurons and local cortical interneurons generating fast rhythmic (30-40 Hz) spike burst. Journal of Neurophysiology. 1998; 79(1), 483–490p.
Wang X. J. Fast burst firing and short-term synaptic plasticity: A model of neocortical chattering neurons. Neuroscience. 1999; 89(2):347–62p.
Rubel E.W., Parks, T.N. Organization and development of brain stem auditory nuclei of the chicken: tonotopic organization of n. magnocellularis and n. laminaris. J Comp Neurol. 1975; 164:411–33p.
Berry M.J., et al. Refractoriness and neural precision. J Neurosci; 1998; 18 (6): 2200–11p.
VanRullen R., Thorpe S.J. Rate Coding vs Temporal Order Coding: What the Retinal Ganglion Cells tell the Visual Cortex. Neural Comput. 2001; 13(6): 1255–83p.
Kuznetsova M.S., et al. Adaptation of Firing Rate and Spike Timing Precision in the Avian Cochlear Nucleus; J Neurosci. 2008; 28(46): 1190615p.
Fields D.M., Weissburg M.J. Rapid firing rates from mechanosensory neurons in copepod antennules. J Comp Physiol A. 2004; 190: 877–82p. DOI 10.1007/s00359-004-0543-2.
Cressman J.R. Jr, et al. The influence of sodium and potassium dynamics on excitability, seizures, and the stability of persistent states: I. Single neuron dynamics. J Comput Neurosci. 2009; 26(2):159–70p.
Fettiplace R. et al. The thickness, composition and structure of some lipid bilayers and natural membranes. The Journal of Membrane Biology. 1971; 5(3): 277–296p.
Clever H.L. The Hydrated Hydronium Ion. J. Chem. Ed. 1963; 637–41p.
Israelachvili J.N. Intermolecular and Surface Forces. Academic Press, NY. 2 Edn. 1992.
Lehr L., et al. Electron Solvation in Finite Systems: Femtosecond Dynamics of Iodide-(Water). Anion Clusters. Science. 23 April 1999; 284: 635–8p.
Dubach J. et al. Abstract 1879: Novel Intracellular Sodium Nanosensors to Study Sodium Dynamics in Cardiomyocytes. Circulation. 2008; 118: 399p.
Berg H.C., et al. Physics of Chemoreception. Biophysical Journal 1977; (20):193–219p.
Li Y., Gregory S. Diffusion of ions in sea water and in deep-sea sediments. Geochimica et Cosmochimica Acta. 1974 (38): 703–14p.
Gadani, D.H., et al. Effect of salinity on the dielectric properties of water. Indian J. Pure Appl. Phys. 2012; (50): 405–10p.
Nano Med Labs Nano Patch-Clamp (NPC): Development of a High-Throughput System Based On Planar Patch-Clamp. 15 July 2010. Website: http://www.nanomed.unige.it/Projects/NPC.htm
Electronic Bio Sciences. High performance single ion channel recordings at a low cost. 2013.
Website: http://www.electronicbio.com.
Novak P., et al. Nanoscale-Targeted Patch-Clamp Recordings of Functional Presynaptic Ion Channels. Neuron. 2013; 79: 1067–77p.
Electronic BioSciences. 2014. Website: www.electronicbio.com/Nanopatch/
Veitinger S. The Patch-Clamp Technique: An Introduction. Website:http://www.leica-microsystems.com/science-lab/the-patch-clamp-technique2011/
DeFelice L.J. Introduction to Membrane Noise. Plenum Press, New York. 1981.
Lauger P. Current noise generated by electrogenic ion pumps. Eur Biophys J. 1984; 11(2): 117–28p.
Hô N., Destexhe A. Synaptic background activity enhances the responsiveness of neocortical pyramidal neurons. J. Neurophysiol. 2000; 84, 1488p.
Li C., et al. Chaos in a three-neuron hysteresis hopfield-type neural networks. Physics Letters A, 2001; 285: 368–72p.
Gerstner W., Kistler W.M. Spiking Neuron Models: Single Neurons, Populations, Plasticity, Cambridge University Press. August 2002.
Brunetti, R., et al. Shot noise in single open ion channels: A computational approach based on atomistic simulations. Journal of Computational Electronics. 2007; 6(1): 391–394p.
Serletis D., et al. Complexity in neuronal noise depends on network interconnectivity. Ann Biomed Eng. 2011; 39(6): 1768–78p.
Birn, R.M., () The role of physiological noise in resting-state functional connectivity. Neuroimage. 2012; 62(2), 864–870p.doi: 10.1016/j. neuroimage. 2012.01.016.
Weaver J.C., Astumian R.D. The Response of Living Cells to Very Weak Electric Fields: The Thermal Noise Limit. Science. 1990; 247:459–62p.
Homes C. C., et al. Optical Response of High-Dielectric-Constant Perovskite-Related Oxide. Science. 27 July 2001; 293: 673–6p.
Gutman G.A., et al. Nomenclature and Molecular Relationships of Voltage-Gated Potassium Channels. Pharmacol Rev. 2005; 57: 473–508p.
Kole M.H., et al. Axon Initial Segment Kv1 Channels Control Axonal Action Potential Waveform and Synaptic Efficacy. Neuron. 2007 Aug 16; 55(4):633–47p.
Colley B.S. et al. TRKB increases Kv1.3 ion channel half-life and surface expression; Neuroscience. 2007; 144(2): 531–46.
Smyth J.W., Shaw R.M. Forward trafficking of ion channels: What the clinician needs to know. Heart Rhythm. 2010; (8):1135–40p.
Angelides K.J. et al. Distribution and lateral mobility of voltage-dependent sodium channels in neurons. J. Cell Biol. 1988; 106: 1911–25p.
De Vittorio M. et al. Nanotechnology and Neuroscience: Nano-electronic-13 Photonic and Mechanical Neuronal Interfacing. Springer. 2014.
Cohen-Karni T., et al. Synthetically Encoded Ultrashort-Channel Nanowire Transistors for Fast, Pointlike Cellular Signal Detection. Nano Lett. 2012; 12; 2639−44p.
Tian B., et al. Three-dimensional, flexible nanoscale field-effect transistors as localized bioprobes. Science. 2010; 329(5993): 830–4p.
Chen K., et al. Silicon nanowire field-effect transistor-based biosensors for biomedical diagnosis and cellular recording investigation. Nano Today. 2011; 6(2): 131–54p.
Duan X., et al. Nanoelectronics Meets Biology: From New Nanoscale Devices for Live-Cell Recording to 3D Innervated Tissues; Chem. Asian J. 2013; 8: 2304–4p.
Shimada T., et al. Double-wall carbon nanotube field-effect transistors: Ambipolar transport characteristics. Appl. Phys. Lett. 2004; 84: 2412p.
Duan X., et al. Intracellular recordings of action potentials by an extracellular nanoscale field-effect transistor. Nat Nanotechnol. 2011; 7: 174–9p.
Cao D. et al. Electronic sensitivity of a single-walled carbon nanotube to internal electrolyte composition. Nanotechnology. 2012; 23(8): 85203p.
Yoon I., et al. Intracellular neural recording with pure carbon nanotube probes, PLoS One. 2013;8(6).
Aoki K., et al. Fabrication of glass-coated electrodes with nano and micrometer size by means of dissolution with HF. Electrochimica Acta. 2010; 55(24): 7328–33p.
Cox J.T., et al. Nanoelectrodes: Recent Advances and New Directions. Annu. Rev. Anal. Chem. 2012; 5: 253–72p.
Lambert N.J., et al. A charge parity ammeter, 2014 American Chemical Society, Nano Lett. 2014; 14, 1148−52p.
Fujisawa T. Bidirectional Counting of Single Electrons. Science. 2006; 312(5780): 1634–6p.
Park K., et al. Single Molecule Quantum Confined Stark Effect Measurements of Semiconductor Nanoparticles at Room Temperature. ACS Nano. 2012; 6: 10013–23p.
Tyner K. M., et al. Nanosized Voltmeter” Enables Cellular-Wide Electric Field Mapping. Biophysical Journal. 2007; 93(4), 1163–74p.
Dergan A. Electronic and transport properties of carbon nanotubes. University of Ljubljana. Faculty of Mathematics and Physics. 2010.
Uryu S. Electronic states and quantum transport in double-wall carbon nanotubes. Physical Review B. 2004; 69: 075402p.
Bacsa R.R. Narrow diameter double-wall carbon nanotubes: synthesis, electron microscopy and inelastic light scattering. New Journal of Physics. 2003; 5: 131.1–131.9p
Roman C., et al. Single-Walled Carbon Nanotube Sensor Concepts. Springer Handbook of Nanotechnology. 2010; 403–25p.
Nick C. et al. Three-Dimensional Carbon Nanotube Electrodes for Extracellular Recording of Cardiac Myocytes. Biointerphases. 2012; 7(1–4): 58p.
Liu S., Guo X. Carbon nanomaterials field-effect-transistor-based biosensors. NPG Asia Materials. NPG Asia Materials. 2012; 4: e23p.
Lin C.M. Flexible carbon nanotubes electrode for neural recording. Biosens Bioelectron. 2009; 15; 24(9): 2791–7p.
Mehrabani, S., et al. Hybrid Integrated Label-Free Chemical and Biological Sensors. Sensors. 2014 ; 14 : 5890–928p.
Zhang Y. et al. Cytotoxicity Effects of Graphene and Single-Wall Carbon Nanotubes in Neural Phaeochromocytoma-Derived PC12 Cells. ACS Nano. 2010; 4(6): 3181–6p.
Bosi S., et al. Carbon nanotubes: a promise for nerve tissue engineering? Nanotechnol Rev. 2013; 2(1): 47–57p.
Silva G.A. Shorting neurons with nanotubes. Nature Nanotechnology. 2009; 4, 82–3p.
Voge C.M., Stegemann J.P. Carbon nanotubes in neural interfacing applications. J Neural Eng. 2011; 8p.
Kim W., et al. Hysteresis Caused by Water Molecules in Carbon Nanotube Field-Effect Transistors, Nano Letters. 2003; 3(2):193–8p.
