Graphene-Based Nanomaterials: From Production to Integration With Modern Tools in Neuroscience

Graphene, a two-dimensional carbon crystal, has emerged as a promising material for sensing and modulating neuronal activity in vitro and in vivo. In this review, we provide a primer for how manufacturing processes to produce graphene and graphene oxide result in materials properties that may be tailored for a variety of applications. We further discuss how graphene may be composited with other bio-compatible materials of interest to make novel hybrid complexes with desired characteristics for bio-interfacing. We then highlight graphene’s ever-widen utility and unique properties that may in the future be multiplexed for cross-modal modulation or interrogation of neuronal network. As the biological effects of graphene are still an area of active investigation, we discuss recent development, with special focus on how surface coatings and surface properties of graphene are relevant to its biological effects. We discuss studies conducted in both non-murine and murine systems, and emphasize the preclinical aspect of graphene’s potential without undermining its tangible clinical implementation.

[1]  Lav R. Varshney,et al.  Structural Properties of the Caenorhabditis elegans Neuronal Network , 2009, PLoS Comput. Biol..

[2]  Thomas M. Higgins,et al.  Scalable production of large quantities of defect-free few-layer graphene by shear exfoliation in liquids. , 2014, Nature materials.

[3]  T. Yen,et al.  Non‐Invasive Synergistic Treatment of Brain Tumors by Targeted Chemotherapeutic Delivery and Amplified Focused Ultrasound‐Hyperthermia Using Magnetic Nanographene Oxide , 2013, Advanced materials.

[4]  Toru Maekawa,et al.  Fluorinated Graphene Oxide; a New Multimodal Material for Biological Applications , 2013, Advanced materials.

[5]  David C. Martin,et al.  Layered carbon nanotube-polyelectrolyte electrodes outperform traditional neural interface materials. , 2009, Nano letters.

[6]  Karl Deisseroth,et al.  Next-generation probes, particles, and proteins for neural interfacing , 2017, Science Advances.

[7]  Ji Won Suk,et al.  Enhancement of the electrical properties of graphene grown by chemical vapor deposition via controlling the effects of polymer residue. , 2013, Nano letters.

[8]  Deepthy Menon,et al.  Differential nano-bio interactions and toxicity effects of pristine versus functionalized graphene. , 2011, Nanoscale.

[9]  Duygu Kuzum,et al.  Ultralow Impedance Graphene Microelectrodes with High Optical Transparency for Simultaneous Deep Two‐Photon Imaging in Transgenic Mice , 2018, Advanced functional materials.

[10]  E. J. Mele,et al.  Photoluminescence and band gap modulation in graphene oxide , 2009 .

[11]  Zhuang Liu,et al.  PEGylated nanographene oxide for delivery of water-insoluble cancer drugs. , 2008, Journal of the American Chemical Society.

[12]  T. B. Kirk,et al.  A polyamidoamne dendrimer functionalized graphene oxide for DOX and MMP-9 shRNA plasmid co-delivery. , 2017, Materials science & engineering. C, Materials for biological applications.

[13]  Andre K. Geim,et al.  The rise of graphene. , 2007, Nature materials.

[14]  Simultaneous nitrogen doping and reduction of graphene oxide. , 2009, Journal of the American Chemical Society.

[15]  Yuan Ping,et al.  Chitosan-functionalized graphene oxide as a nanocarrier for drug and gene delivery. , 2011, Small.

[16]  P. Brown,et al.  Adaptive Deep Brain Stimulation In Advanced Parkinson Disease , 2013, Annals of neurology.

[17]  C. Fan,et al.  Protein corona-mediated mitigation of cytotoxicity of graphene oxide. , 2011, ACS nano.

[18]  Karl Deisseroth,et al.  Integration of optogenetics with complementary methodologies in systems neuroscience , 2017, Nature Reviews Neuroscience.

[19]  Deyu Li,et al.  Impact of Graphene on the Efficacy of Neuron Culture Substrates , 2018, Advanced healthcare materials.

[20]  K. Shroyer,et al.  Dose ranging, expanded acute toxicity and safety pharmacology studies for intravenously administered functionalized graphene nanoparticle formulations. , 2014, Biomaterials.

[21]  Kai Yang,et al.  Surface coating-dependent cytotoxicity and degradation of graphene derivatives: towards the design of non-toxic, degradable nano-graphene. , 2014, Small.

[22]  S. Stankovich,et al.  Synthesis of graphene-based nanosheets via chemical reduction of exfoliated graphite oxide , 2007 .

[23]  R. Leblanc,et al.  Head Groups of Lipids Govern the Interaction and Orientation between Graphene Oxide and Lipids , 2013 .

[24]  Kai Yang,et al.  In vitro and in vivo behaviors of dextran functionalized graphene , 2011 .

[25]  Maurizio Prato,et al.  Single-layer graphene modulates neuronal communication and augments membrane ion currents , 2018, Nature Nanotechnology.

[26]  Travis A. Jarrell,et al.  The Connectome of a Decision-Making Neural Network , 2012, Science.

[27]  K Kostarelos,et al.  Promises, facts and challenges for carbon nanotubes in imaging and therapeutics. , 2009, Nature nanotechnology.

[28]  Guohua Chen,et al.  pH-Responsive chitosan-mediated graphene dispersions. , 2010, Langmuir : the ACS journal of surfaces and colloids.

[29]  Zhuang Liu,et al.  Selective probing and imaging of cells with single walled carbon nanotubes as near-infrared fluorescent molecules. , 2008, Nano letters.

[30]  Carolyn R. Bertozzi,et al.  Copper-free click chemistry for dynamic in vivo imaging , 2007, Proceedings of the National Academy of Sciences.

[31]  Sara Linse,et al.  Understanding the nanoparticle–protein corona using methods to quantify exchange rates and affinities of proteins for nanoparticles , 2007, Proceedings of the National Academy of Sciences.

[32]  Eric R Kandel,et al.  The Biology of Memory: A Forty-Year Perspective , 2009, The Journal of Neuroscience.

[33]  M. Prato,et al.  Microglia Determine Brain Region-Specific Neurotoxic Responses to Chemically Functionalized Carbon Nanotubes. , 2015, ACS nano.

[34]  Eduardo D. Martín,et al.  Thermally reduced graphene is a permissive material for neurons and astrocytes and de novo neurogenesis in the adult olfactory bulb in vivo. , 2016, Biomaterials.

[35]  R. Young,et al.  The real graphene oxide revealed: stripping the oxidative debris from the graphene-like sheets. , 2011, Angewandte Chemie.

[36]  Aaron S. Andalman,et al.  Structural and molecular interrogation of intact biological systems , 2013, Nature.

[37]  Rui Zhang,et al.  Multifunctionalization of graphene and graphene oxide for controlled release and targeted delivery of anticancer drugs. , 2017, American journal of translational research.

[38]  Giada Cellot,et al.  PEDOT:PSS Interfaces Support the Development of Neuronal Synaptic Networks with Reduced Neuroglia Response In vitro , 2016, Front. Neurosci..

[39]  S. Gubin,et al.  Reduced graphene oxide , 2012, Inorganic Materials.

[40]  Ruhong Zhou,et al.  Reduced Cytotoxicity of Graphene Nanosheets Mediated by Blood-Protein Coating. , 2015, ACS nano.

[41]  Qin Song,et al.  The promotion of neurite sprouting and outgrowth of mouse hippocampal cells in culture by graphene substrates. , 2011, Biomaterials.

[42]  Zhenqiang Ma,et al.  Electrical Neural Stimulation and Simultaneous in Vivo Monitoring with Transparent Graphene Electrode Arrays Implanted in GCaMP6f Mice. , 2018, ACS nano.

[43]  Haiping Fang,et al.  Destructive extraction of phospholipids from Escherichia coli membranes by graphene nanosheets. , 2013, Nature nanotechnology.

[44]  P. Romero,et al.  Cell survival and differentiation with nanocrystalline glass-like carbon using substantia nigra dopaminergic cells derived from transgenic mouse embryos , 2017, PloS one.

[45]  J. Coleman,et al.  High-yield production of graphene by liquid-phase exfoliation of graphite. , 2008, Nature nanotechnology.

[46]  Shouwu Guo,et al.  Morphology change and detachment of lipid bilayers from the mica substrate driven by graphene oxide sheets. , 2014, Langmuir : the ACS journal of surfaces and colloids.

[47]  Dong Liu,et al.  The structural development of primary cultured hippocampal neurons on a graphene substrate. , 2016, Colloids and surfaces. B, Biointerfaces.

[48]  X. Duan,et al.  Graphene nanomesh , 2010, Nature nanotechnology.

[49]  A. Ferrari,et al.  Production and processing of graphene and 2d crystals , 2012 .

[50]  R. Haag,et al.  Functionalized graphene sheets for intracellular controlled release of therapeutic agents. , 2017, Nanoscale.

[51]  Chunhai Fan,et al.  Distribution and biocompatibility studies of graphene oxide in mice after intravenous administration , 2011 .

[52]  Yuehe Lin,et al.  Aptamer/graphene oxide nanocomplex for in situ molecular probing in living cells. , 2010, Journal of the American Chemical Society.

[53]  G. Eda,et al.  Large-area ultrathin films of reduced graphene oxide as a transparent and flexible electronic material. , 2008, Nature nanotechnology.

[54]  John A Rogers,et al.  In‐Plane Deformation Mechanics for Highly Stretchable Electronics , 2017, Advanced materials.

[55]  David C. Martin,et al.  Polymerization of the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) around living neural cells. , 2007, Biomaterials.

[56]  Haifeng Liu,et al.  Graphene‐Based Materials in Regenerative Medicine , 2015, Advanced healthcare materials.

[57]  Rodrigo Ramos Catharino,et al.  Reduced graphene oxide induces transient blood–brain barrier opening: an in vivo study , 2015, Journal of Nanobiotechnology.

[58]  A. Terzic,et al.  Functionalized Carbon Nanotube and Graphene Oxide Embedded Electrically Conductive Hydrogel Synergistically Stimulates Nerve Cell Differentiation. , 2017, ACS applied materials & interfaces.

[59]  Nelson Durán,et al.  Nanotoxicity of graphene and graphene oxide. , 2014, Chemical research in toxicology.

[60]  X. Cui,et al.  Electrically Controlled Drug Delivery from Graphene Oxide Nanocomposite Films , 2014, ACS nano.

[61]  Z. Marković,et al.  In vitro comparison of the photothermal anticancer activity of graphene nanoparticles and carbon nanotubes. , 2011, Biomaterials.

[62]  R. Stoltenberg,et al.  Evaluation of solution-processed reduced graphene oxide films as transparent conductors. , 2008, ACS nano.

[63]  Fuping Qian,et al.  Accelerating bioelectric functional development of neural stem cells by graphene coupling: Implications for neural interfacing with conductive materials. , 2016, Biomaterials.

[64]  J. Rogers,et al.  Inorganic semiconducting materials for flexible and stretchable electronics , 2017, npj Flexible Electronics.

[65]  Peng Chen,et al.  Interfacing live cells with nanocarbon substrates. , 2010, Langmuir : the ACS journal of surfaces and colloids.

[66]  Petr Král,et al.  Sandwiched graphene--membrane superstructures. , 2010, ACS nano.

[67]  Oscar N. Ruiz,et al.  Graphene oxide: a nonspecific enhancer of cellular growth. , 2011, ACS nano.

[68]  Edward S Boyden,et al.  Engineering genetic circuit interactions within and between synthetic minimal cells , 2016, Nature chemistry.

[69]  Francesca Tatini,et al.  Graphene as a photothermal switch for controlled drug release. , 2014, Nanoscale.

[70]  J. Kysar,et al.  Measurement of the Elastic Properties and Intrinsic Strength of Monolayer Graphene , 2008, Science.

[71]  O. Akhavan.  Graphene nanomesh by ZnO nanorod photocatalysts. , 2010, ACS nano.

[72]  R. Verdejo,et al.  In Vitro Evaluation of Biocompatibility of Uncoated Thermally Reduced Graphene and Carbon Nanotube-Loaded PVDF Membranes with Adult Neural Stem Cell-Derived Neurons and Glia , 2016, Front. Bioeng. Biotechnol..

[73]  Omid Akhavan,et al.  Graphene nanomesh promises extremely efficient in vivo photothermal therapy. , 2013, Small.

[74]  H. Jeong,et al.  High-quality graphene via microwave reduction of solution-exfoliated graphene oxide , 2016, Science.

[75]  Rong Huang,et al.  Enhancement of electrical signaling in neural networks on graphene films. , 2013, Biomaterials.

[76]  Yuhan Shi,et al.  A Compact Closed-Loop Optogenetics System Based on Artifact-Free Transparent Graphene Electrodes , 2018, Front. Neurosci..

[77]  Mei Jin,et al.  In vitro and in vivo brain-targeting chemo-photothermal therapy using graphene oxide conjugated with transferrin for Gliomas , 2016, Lasers in Medical Science.

[78]  Kian Ping Loh,et al.  High mobility, printable, and solution-processed graphene electronics. , 2010, Nano letters.

[79]  L. Cohen,et al.  Brain–machine interface in chronic stroke rehabilitation: A controlled study , 2013, Annals of neurology.

[80]  Yan Wang,et al.  Stealth Immune Properties of Graphene Oxide Enabled by Surface-Bound Complement Factor H. , 2016, ACS nano.

[81]  S. Hosseinzadeh,et al.  In vitro osteogenic differentiation potential of the human induced pluripotent stem cells augments when grown on Graphene oxide-modified nanofibers. , 2019, Gene.

[82]  Moon Gyu Sung,et al.  Enhanced Differentiation of Human Neural Stem Cells into Neurons on Graphene , 2011, Advanced materials.

[83]  T. Xia,et al.  Understanding biophysicochemical interactions at the nano-bio interface. , 2009, Nature materials.

[84]  Andre K. Geim,et al.  Electric Field Effect in Atomically Thin Carbon Films , 2004, Science.

[85]  Xiaoming Yang,et al.  Well-dispersed chitosan/graphene oxide nanocomposites. , 2010, ACS applied materials & interfaces.

[86]  R. Ruoff,et al.  Chemical methods for the production of graphenes. , 2009, Nature nanotechnology.

[87]  Jianzhu Chen,et al.  Graphene multilayers as gates for multi-week sequential release of proteins from surfaces. , 2011, ACS nano.

[88]  P. Tresco,et al.  Response of brain tissue to chronically implanted neural electrodes , 2005, Journal of Neuroscience Methods.

[89]  Sabine Szunerits,et al.  Reduction and functionalization of graphene oxide sheets using biomimetic dopamine derivatives in one step. , 2012, ACS applied materials & interfaces.

[90]  Giuseppe Iannaccone,et al.  Electronics based on two-dimensional materials. , 2014, Nature nanotechnology.

[91]  Tae-Jin Lee,et al.  Efficient mRNA delivery with graphene oxide-polyethylenimine for generation of footprint-free human induced pluripotent stem cells. , 2016, Journal of controlled release : official journal of the Controlled Release Society.

[92]  Sihong Wang,et al.  Ultratransparent and stretchable graphene electrodes , 2017, Science Advances.

[93]  Huang-Hao Yang,et al.  Using graphene to protect DNA from cleavage during cellular delivery. , 2010, Chemical communications.

[94]  R. Wightman,et al.  Detecting subsecond dopamine release with fast-scan cyclic voltammetry in vivo. , 2003, Clinical chemistry.

[95]  R. Ewing,et al.  A versatile multicomponent assembly via β-cyclodextrin host-guest chemistry on graphene for biomedical applications. , 2013, Small.

[96]  R. Ruoff,et al.  Reduced graphene oxide by chemical graphitization. , 2010, Nature communications.

[97]  Jianwen Zhao,et al.  Electrical and Spectroscopic Characterizations of Ultra-Large Reduced Graphene Oxide Monolayers , 2009 .

[98]  Nicholas K. Geitner,et al.  Competitive Binding of Natural Amphiphiles with Graphene Derivatives , 2013, Scientific Reports.

[99]  Wei Wu,et al.  Shape Effects of Cylindrical versus Spherical Unimolecular Polymer Nanomaterials on in Vitro and in Vivo Behaviors , 2019, Research.

[100]  Youngsin Park,et al.  Cell reprogramming into the pluripotent state using graphene based substrates. , 2014, Biomaterials.

[101]  Anna Devor,et al.  Deep 2-photon imaging and artifact-free optogenetics through transparent graphene microelectrode arrays , 2018, Nature Communications.

[102]  Klaus Kern,et al.  Electronic transport properties of individual chemically reduced graphene oxide sheets. , 2007, Nano letters.

[103]  R. Karnik,et al.  Fundamental transport mechanisms, fabrication and potential applications of nanoporous atomically thin membranes. , 2017, Nature nanotechnology.

[104]  M. S. Sarto,et al.  Graphite nanoplatelets and Caenorhabditis elegans: insights from an in vivo model. , 2012, Nano letters.

[105]  Edmund J. Crampin,et al.  Minimum information reporting in bio–nano experimental literature , 2018, Nature Nanotechnology.

[106]  M. Abidian,et al.  A Review of Organic and Inorganic Biomaterials for Neural Interfaces , 2014, Advanced materials.

[107]  S. Banerjee,et al.  Large-Area Synthesis of High-Quality and Uniform Graphene Films on Copper Foils , 2009, Science.

[108]  Soon-Bok Lee,et al.  Double-layer CVD graphene as stretchable transparent electrodes. , 2014, Nanoscale.

[109]  Kai Yang,et al.  Carbon materials for drug delivery & cancer therapy , 2011 .

[110]  Hyunmin Yi,et al.  Biofabrication with chitosan. , 2005, Biomacromolecules.

[111]  Jon A. Mukand,et al.  Neuronal ensemble control of prosthetic devices by a human with tetraplegia , 2006, Nature.

[112]  The effect of intrinsic crumpling on the mechanics of free-standing graphene , 2015, Nature communications.

[113]  Shuk Han Cheng,et al.  Effect of carbon nanotubes on developing zebrafish (Danio Rerio) embryos , 2007, Environmental toxicology and chemistry.

[114]  Defu He,et al.  Chronic exposure to graphene‐based nanomaterials induces behavioral deficits and neural damage in Caenorhabditis elegans , 2017, Journal of applied toxicology : JAT.

[115]  Ge Yang,et al.  Effect of Graphene on Nonneuronal and Neuronal Cell Viability and Stress. , 2017, Nano letters.

[116]  B. Luan,et al.  Detecting Interactions between Nanomaterials and Cell Membranes by Synthetic Nanopores. , 2017, ACS nano.

[117]  Yanwu Zhu,et al.  Reduction Kinetics of Graphene Oxide Determined by Electrical Transport Measurements and Temperature Programmed Desorption , 2009 .

[118]  Xiliang Luo,et al.  Highly stable carbon nanotube doped poly(3,4-ethylenedioxythiophene) for chronic neural stimulation. , 2011, Biomaterials.

[119]  C. Coletti,et al.  Peripheral Neuron Survival and Outgrowth on Graphene , 2017, Front. Neurosci..

[120]  Edward S. Boyden,et al.  Expansion microscopy , 2015, Science.

[121]  Rossana Rauti,et al.  Graphene Oxide Nanosheets Reshape Synaptic Function in Cultured Brain Networks. , 2016, ACS nano.

[122]  K. Boheler,et al.  Graphene Sheet-Induced Global Maturation of Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells. , 2017, ACS applied materials & interfaces.

[123]  Á. Alegría,et al.  Kinetic Study of the Graphite Oxide Reduction: Combined Structural and Gravimetric Experiments under Isothermal and Nonisothermal Conditions , 2010 .

[124]  Michael J. Black,et al.  Assistive technology and robotic control using motor cortex ensemble‐based neural interface systems in humans with tetraplegia , 2007, The Journal of physiology.

[125]  A. Reina,et al.  Large area, few-layer graphene films on arbitrary substrates by chemical vapor deposition. , 2009, Nano letters.

[126]  Huajian Gao,et al.  Graphene microsheets enter cells through spontaneous membrane penetration at edge asperities and corner sites , 2013, Proceedings of the National Academy of Sciences.

[127]  M. Prato,et al.  Selective organic functionalization of graphene bulk or graphene edges. , 2011, Chemical communications.

[128]  Hua Bai,et al.  Three-dimensional self-assembly of graphene oxide and DNA into multifunctional hydrogels. , 2010, ACS nano.

[129]  Lin Zhao,et al.  Protein corona mitigates the cytotoxicity of graphene oxide by reducing its physical interaction with cell membrane. , 2015, Nanoscale.

[130]  H. Dai,et al.  Ultrasmall reduced graphene oxide with high near-infrared absorbance for photothermal therapy. , 2011, Journal of the American Chemical Society.

[131]  Sailing He,et al.  Observation of multiphoton-induced fluorescence from graphene oxide nanoparticles and applications in in vivo functional bioimaging. , 2012, Angewandte Chemie.

[132]  J. Coleman,et al.  Liquid phase production of graphene by exfoliation of graphite in surfactant/water solutions , 2008, 0809.2690.

[133]  Qing Hua Wang,et al.  Bi- and trilayer graphene solutions. , 2011, Nature nanotechnology.

[134]  Xinyan Tracy Cui,et al.  Enhanced dopamine detection sensitivity by PEDOT/graphene oxide coating on in vivo carbon fiber electrodes. , 2017, Biosensors & bioelectronics.

[135]  G. Wallace,et al.  Processable aqueous dispersions of graphene nanosheets. , 2008, Nature nanotechnology.

[136]  Anton J. Enright,et al.  The zebrafish reference genome sequence and its relationship to the human genome , 2013, Nature.

[137]  Qin Tu,et al.  Effects of surface charges of graphene oxide on neuronal outgrowth and branching. , 2014, The Analyst.

[138]  J. Coleman,et al.  Biological recognition of graphene nanoflakes , 2018, Nature Communications.

[139]  Xiaogang Qu,et al.  Using Graphene Oxide High Near‐Infrared Absorbance for Photothermal Treatment of Alzheimer's Disease , 2012, Advanced materials.

[140]  A. Diaspro,et al.  Developmental refinement of synaptic transmission on micropatterned single layer graphene. , 2018, Acta biomaterialia.

[141]  Won Jong Kim,et al.  Photothermally triggered cytosolic drug delivery via endosome disruption using a functionalized reduced graphene oxide. , 2013, ACS nano.

[142]  Li-Tang Yan,et al.  Computer simulation of cell entry of graphene nanosheet. , 2013, Biomaterials.

[143]  Li Cao,et al.  Photoluminescence properties of graphene versus other carbon nanomaterials. , 2013, Accounts of chemical research.

[144]  Serge Picaud,et al.  Purified Neurons can Survive on Peptide‐Free Graphene Layers , 2013, Advanced healthcare materials.

[145]  Abraham K. Badu-Tawiah,et al.  Mass spectrometry imaging reveals the sub-organ distribution of carbon nanomaterials. , 2015, Nature nanotechnology.

[146]  H. Ye,et al.  Evidences of the Effect of GO and rGO in PCL Membranes on the Differentiation and Maturation of Human Neural Progenitor Cells. , 2018, Macromolecular bioscience.

[147]  A. Vaziri,et al.  High-speed volumetric imaging of neuronal activity in freely moving rodents , 2018, Nature Methods.

[148]  Wentao Xu,et al.  Versatile p-Type Chemical Doping to Achieve Ideal Flexible Graphene Electrodes. , 2016, Angewandte Chemie.

[149]  Kevin J. Otto,et al.  Poly(3,4-ethylenedioxythiophene) as a Micro-Neural Interface Material for Electrostimulation , 2009, Front. Neuroeng..

[150]  J. Chang,et al.  Expansion microscopy , 2018, Journal of microscopy.

[151]  V. Bouchiat,et al.  Impact of crystalline quality on neuronal affinity of pristine graphene. , 2016, Biomaterials.

[152]  Jared P. Ness,et al.  Graphene-based carbon-layered electrode array technology for neural imaging and optogenetic applications , 2014, Nature Communications.

[153]  Zhuang Liu,et al.  Graphene based gene transfection. , 2011, Nanoscale.

[154]  Jian Wang,et al.  Application of Graphene Based Nanotechnology in Stem Cells Research. , 2015, Journal of nanoscience and nanotechnology.

[155]  V. Viasnoff,et al.  Human Rett-derived neuronal progenitor cells in 3D graphene scaffold as an in vitro platform to study the effect of electrical stimulation on neuronal differentiation , 2018, Biomedical materials.

[156]  Omid Akhavan,et al.  Toxicity of graphene and graphene oxide nanowalls against bacteria. , 2010, ACS nano.

[157]  S. Dante,et al.  Simple and effective graphene laser processing for neuron patterning application , 2013, Scientific Reports.

[158]  Andre K. Geim,et al.  Two-dimensional atomic crystals. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[159]  Jinkee Hong,et al.  Multilayered Graphene Nano-Film for Controlled Protein Delivery by Desired Electro-Stimuli , 2015, Scientific Reports.

[160]  Zhongfan Liu,et al.  Self-Terminating Confinement Approach for Large-Area Uniform Monolayer Graphene Directly over Si/SiOx by Chemical Vapor Deposition. , 2017, ACS nano.

[161]  Jared P. Ness,et al.  Fabrication and utility of a transparent graphene neural electrode array for electrophysiology, in vivo imaging, and optogenetics , 2016, Nature Protocols.

[162]  Kwang S. Kim,et al.  Roll-to-roll production of 30-inch graphene films for transparent electrodes. , 2010, Nature nanotechnology.

[163]  W. S. Hummers,et al.  Preparation of Graphitic Oxide , 1958 .

[164]  Rongqin Huang,et al.  Multifunctional mesoporous silica-coated graphene nanosheet used for chemo-photothermal synergistic targeted therapy of glioma. , 2013, Journal of the American Chemical Society.

[165]  Q. Lan,et al.  Transferrin modified graphene oxide for glioma-targeted drug delivery: in vitro and in vivo evaluations. , 2013, ACS applied materials & interfaces.

[166]  T. Lucas,et al.  Transparent and flexible low noise graphene electrodes for simultaneous electrophysiology and neuroimaging , 2014, Nature Communications.

[167]  M. Bate,et al.  The drosophila neuromuscular junction: a model system for studying synaptic development and function. , 1996, Annual review of neuroscience.

[168]  Zhuang Liu,et al.  Nano-graphene oxide for cellular imaging and drug delivery , 2008, Nano research.

[169]  F. Benfenati,et al.  Interfacing Graphene-Based Materials With Neural Cells , 2018, Front. Syst. Neurosci..

[170]  Yang Xu,et al.  Cytotoxicity effects of graphene and single-wall carbon nanotubes in neural phaeochromocytoma-derived PC12 cells. , 2010, ACS nano.

[171]  N. Birbaumer,et al.  Brain–computer interfaces for communication and rehabilitation , 2016, Nature Reviews Neurology.

[172]  Tu Hong,et al.  Membrane cholesterol mediates the cellular effects of monolayer graphene substrates , 2018, Nature Communications.

[173]  Roland G. S. Goh,et al.  Band‐like Transport in Surface‐Functionalized Highly Solution‐Processable Graphene Nanosheets , 2008 .

[174]  Lei Wu,et al.  Graphene microelectrode arrays for neural activity detection , 2015, Journal of biological physics.

[175]  D. Furgeson,et al.  Zebrafish as a correlative and predictive model for assessing biomaterial nanotoxicity. , 2009, Advanced drug delivery reviews.

[176]  Juewen Liu,et al.  Orthogonal Adsorption Onto Nano‐Graphene Oxide Using Different Intermolecular Forces for Multiplexed Delivery , 2013, Advanced materials.

[177]  A. Raichur,et al.  Graphene oxide based multilayer capsules with unique permeability properties: facile encapsulation of multiple drugs. , 2012, Chemical communications.

[178]  S. Kwon,et al.  Establishment of feeder-free culture system for human induced pluripotent stem cell on DAS nanocrystalline graphene , 2016, Scientific Reports.

[179]  B. Kasemo,et al.  Graphene oxide and lipid membranes: interactions and nanocomposite structures. , 2012, Nano letters.

[180]  E. López-Dolado,et al.  Graphene-Derived Materials Interfacing the Spinal Cord: Outstanding in Vitro and in Vivo Findings , 2017, Front. Syst. Neurosci..

[181]  Carl W. Magnuson,et al.  Transfer of CVD-grown monolayer graphene onto arbitrary substrates. , 2011, ACS nano.

[182]  M. Yoshimura,et al.  Submerged Liquid Plasma for the Synchronized Reduction and Functionalization of Graphene Oxide , 2014, Scientific Reports.