“Magnetic fields pass through tissue undiminished and without producing harmful effects, motivating their use as a wireless, minimally invasive means to control neural activity. here, we review mechanisms and techniques coupling magnetic fields to changes in electrochemical potentials across neuronal membranes. biological magnetoreception, although incompletely understood, is discussed as a potential source of inspiration. the emergence of magnetic properties in materials is reviewed to clarify the distinction between biomolecules containing transition metals and ferrite nanoparticles that exhibit significant net moments. we describe recent developments in the use of magnetic nanomaterials as transducers converting magnetic stimuli to forms readily perceived by neurons and discuss opportunities for multiplexed and bidirectional control as well as the challenges posed by delivery to the brain. the variety of magnetic field conditions and mechanisms by which they can be coupled to neuronal signaling cascades highlights the desirability of continued interchange between magnetism physics and neurobiology.”
Wheeler, M. A., Smith, C. J., Ottolini, M., Barker, B. S., Purohit, A. M., Grippo, R. M., … Güler, A. D.. (2016). Genetically targeted magnetic control of the nervous system. Nature Neuroscience
“Optogenetic and chemogenetic actuators are critical for deconstructing the neural correlates of behavior. however, these tools have several limitations, including invasive modes of stimulation or slow on/off kinetics. we have overcome these disadvantages by synthesizing a single-component, magnetically sensitive actuator,magneto,comprising the cation channel trpv4 fused to the paramagnetic protein ferritin. we validated noninvasive magnetic control over neuronal activity by demonstrating remote stimulation of cells using in vitro calcium imaging assays, electrophysiological recordings in brain slices, in vivo electrophysiological recordings in the brains of freely moving mice, and behavioral outputs in zebrafish and mice. as proof of concept, we used magneto to delineate a causal role of striatal dopamine receptor 1 neurons in mediating reward behavior in mice. together our results present magneto as an actuator capable of remotely controlling circuits associated with complex animal behaviors.”
Adamczyk, A. K., & Zawadzki, P.. (2020). The Memory-Modifying Potential of Optogenetics and the Need for Neuroethics. NanoEthics
“Optogenetics is an invasive neuromodulation technology involving the use of light to control the activity of individual neurons. even though optogenetics is a relatively new neuromodulation tool whose various implications have not yet been scrutinized, it has already been approved for its first clinical trials in humans. as optogenetics is being intensively investigated in animal models with the aim of developing novel brain stimulation treatments for various neurological and psychiatric disorders, it appears crucial to consider both the opportunities and dangers such therapies may offer. in this review, we focus on the memory-modifying potential of optogenetics, investigating what it is capable of and how it differs from other memory modification technologies (mmts). we then outline the safety challenges that need to be addressed before optogenetics can be used in humans. finally, we re-examine crucial neuroethical concerns expressed in regard to other mmts in the light of optogenetics and address those that appear to be unique to the memory-modifying potential of optogenetic technology.”
Kole, K., Zhang, Y., Jansen, E. J. R., Brouns, T., Bijlsma, A., Calcini, N., … Celikel, T.. (2020). Assessing the utility of Magneto to control neuronal excitability in the somatosensory cortex. Nature Neuroscience
Keifer, O., Kambara, K., Lau, A., Makinson, S., & Bertrand, D.. (2020). Chemogenetics a robust approach to pharmacology and gene therapy. Biochemical Pharmacology
“Modern developments in organic chemistry, molecular biology, virology, and genetics have opened new, exciting possibilities to better understand physiology and to create innovative, robust therapeutics. one such possibility is the burgeoning field of chemogenetics, a sub-field of chemical genetics that encompasses engineering macromolecules (particularly proteins) to modify how they interact with endogenous and exogenous ligands (particularly small molecules). early efforts in chemogenetics were focused on parsing the function of a specific enzyme within a closely-related family by creating orthogonal enzyme-ligand pairs (e.g. kinases paired with antagonists). this powerful concept quickly expanded into engineered g-protein-coupled receptors (e.g. dreadds/rassl), and more recently into engineered ligand-gated ion channels (elgic). the modifications to the receptor focused on eliminating their activation by endogenous ligands, while preserving or enhancing their interaction with pharmacological agents (e.g. small molecule agonist). creation of such an engineered receptor and delivering it selectively to specific cell types opens new possibilities of accurately and precisely controlling cellular activity. control of this activity then increases our understanding of the cells function in normal physiology, while also creating the possibility of using it as a therapeutic to address pathophysiology. the dreadds/rassl and elgic approaches have been particularly impactful in neurosciences but have applications in multiple fields. in this work we introduce the history of the chemogenetic approach, review the seminal work with dreadds/rassls and elgic, highlight the breadth of applications, and discuss the strengths and weaknesses associated with this technology, especially in the context of its development into a therapeutic.”
Magnus, C. J., Lee, P. H., Bonaventura, J., Zemla, R., Gomez, J. L., Ramirez, M. H., … Sternson, S. M.. (2019). Ultrapotent chemogenetics for research and potential clinical applications. Science
“Chemogenetics enables noninvasive chemical control over cell populations in behaving animals. however, existing small-molecule agonists show insufficient potency or selectivity. there is also a need for chemogenetic systems compatible with both research and human therapeutic applications. we developed a new ion channel–based platform for cell activation and silencing that is controlled by low doses of the smoking cessation drug varenicline. we then synthesized subnanomolar-potency agonists, called upsems, with high selectivity for the chemogenetic receptors. upsems and their receptors were characterized in brains of mice and a rhesus monkey by in vivo electrophysiology, calcium imaging, positron emission tomography, behavioral efficacy testing, and receptor counterscreening. this platform of receptors and selective ultrapotent agonists enables potential research and clinical applications of chemogenetics.”
Poth, K. M., Texakalidis, P., & Boulis, N. M.. (2021). Chemogenetics: Beyond Lesions and Electrodes. Neurosurgery
“The field of chemogenetics has rapidly expanded over the last decade, and engineered receptors are currently utilized in the lab to better understand molecular interactions in the nervous system. we propose that chemogenetic receptors can be used for far more than investigational purposes. the potential benefit of adding chemogenetic neuromodulation to the current neurosurgical toolkit is substantial. there are several conditions currently treated surgically, electrically, and pharmacologically in clinic, and this review highlights how chemogenetic neuromodulation could improve patient outcomes over current neurosurgical techniques. we aim to emphasize the need to take these techniques from bench to bedside.”
Vlasov, K., Van Dort, C. J., & Solt, K.. (2018). Optogenetics and Chemogenetics. In Methods in Enzymology
“Optogenetics and chemogenetics provide the ability to modulate neurons in a type- and region-specific manner. these powerful techniques are useful to test hypotheses regarding the neural circuit mechanisms of general anesthetic end points such as hypnosis and analgesia. with both techniques, a genetic strategy is used to target expression of light-sensitive ion channels (opsins) or designer receptors exclusively activated by designer drugs in specific neurons. optogenetics provides precise temporal control of neuronal firing with light pulses, whereas chemogenetics provides the ability to modulate neuronal firing for several hours with the single administration of a designer drug. this chapter provides an overview of neuronal targeting and experimental strategies and highlights the important advantages and disadvantages of each technique.”
Everybody’s Happy Now
No more Mammy, no more Pappy:
Ain’t we lucky, ain’t we happy?
Everybody’s oh so happy,
Everybody’s happy now!
Sex galore, but no more marriages;
No more pushing baby carriages;
No one has to change a nappy
Ain’t we lucky, ain’t we happy:
Everybody’s happy now.
Dope for tea and dope for dinner,
Fun all night, and love and laughter;
No remorse, no morning after.
Where’s the sin, and who’s the sinner?
Everybody’s happy now!
Girls pneumatic, girls exotic,
Girls ecstatic, girls erotic
Hug me, Baby; make it snappy.
Everybody’s oh so happy,
Everybody’s happy now!
Lots to eat and hours for drinking
Soma cocktails–no more thinking.
NO MORE THINKING, NO MORE THINKING!
~ Aldous Huxley
Aldous Huxley – a Fabian socialist advocating mind-control (a wolf in sheep’s clothing)
ec.europa.eu/commission/presscorner/detail/en/IP_13_54 “Graphene” will investigate and exploit the unique properties of a revolutionary carbon-based material. Graphene is an extraordinary combination of physical and chemical properties: it is the thinnest material, it conducts electricity much better than copper, it is 100-300 times stronger than steel and it has unique optical properties. The use of graphene was made possible by European scientists in 2004, and the substance is set to become the wonder material of the 21st century, as plastics were to the 20th century, including by replacing silicon in ICT products. Graphene_and_Human_Brain_Project_win_largest_research_excellence_award_in_history__as_battle_for_sustained_science_funding_continues
Further References
Lin, H. Y., Nurunnabi, M., Chen, W. H., & Huang, C. H.. (2019). Graphene in neuroscience. In Biomedical Applications of Graphene and 2D Nanomaterials
“Graphene and graphene-derived materials have been widely applied in various biomedical fields. in neuroscience, graphene and its derivatives can be applied as nanocarriers for drug delivery, as compelling biocompatible substrates for tissue engineering, as conductive electrodes for obtaining the stimulation response in studying neural networks, as low photobleaching nanocomposite tags in bioimaging, as enhancers for guiding neural growth and differentiation as regenerative medicine, and so forth. among these applications, the material composition, functionalization, and dimension of graphene are considerably important. in this chapter, we provide a brief review to address the accomplishments and further perspective of graphene and its related materials applied in neuroscience.”
Perini, G., Palmieri, V., Ciasca, G., De Spirito, M., & Papi, M.. (2020). Unravelling the potential of graphene quantum dots in biomedicine and neuroscience. International Journal of Molecular Sciences
“Quantum dots (qds) are semiconducting nanoparticles that have been gaining ground in various applications, including the biomedical field, thanks to their unique optical properties. recently, graphene quantum dots (gqds) have earned attention in biomedicine and nanomedicine, thanks to their higher biocompatibility and low cytotoxicity compared to other qds. gqds share the optical properties of qd and have proven ability to cross the blood-brain barrier (bbb). for this reason, gqds are now being employed to deepen our knowledge in neuroscience diagnostics and therapeutics. their size and surface chemistry that ease the loading of chemotherapeutic drugs, makes them ideal drug delivery systems through the bloodstream, across the bbb, up to the brain. gqds-based neuroimaging techniques and theranostic applications, such as photothermal and photodynamic therapy alone or in combination with chemotherapy, have been designed. in this review, optical properties and biocompatibility of gqds will be described. then, the ability of gqds to overtake the bbb and reach the brain will be discussed. at last, applications of gqds in bioimaging, photophysical therapies and drug delivery to the central nervous system will be considered, unraveling their potential in the neuroscientific field.”
Orecchioni, M., Bordoni, V., Fuoco, C., Reina, G., Lin, H., Zoccheddu, M., … Delogu, L. G.. (2020). Toward High-Dimensional Single-Cell Analysis of Graphene Oxide Biological Impact: Tracking on Immune Cells by Single-Cell Mass Cytometry. Small
“Considering the potential exposure to graphene, the most investigated nanomaterial, the assessment of the impact on human health has become an urgent need. the deep understanding of nanomaterial safety is today possible by high-throughput single-cell technologies. single-cell mass cytometry (cytometry by time-of flight, cytof) shows an unparalleled ability to phenotypically and functionally profile complex cellular systems, in particular related to the immune system, as recently also proved for graphene impact. the next challenge is to track the graphene distribution at the single-cell level. therefore, graphene oxide (go) is functionalized with agins2 nanocrystals (go–in), allowing to trace go immune–cell interactions via the indium (115in) channel. indium is specifically chosen to avoid overlaps with the commercial panels (>30 immune markers). as a proof of concept, the go–in cytof tracking is performed at the single-cell level on blood immune subpopulations, showing the go interaction with monocytes and b cells, therefore guiding future immune studies. the proposed approach can be applied not only to the immune safety assessment of the multitude of graphene physical and chemical parameters, but also for graphene applications in neuroscience. moreover, this approach can be translated to other 2d emerging materials and will likely advance the understanding of their toxicology.”
Song, Q., Jiang, Z., Li, N., Liu, P., Liu, L., Tang, M., & Cheng, G.. (2014). Anti-inflammatory effects of three-dimensional graphene foams cultured with microglial cells. Biomaterials
Kitko, K. E., & Zhang, Q.. (2019). Graphene-based nanomaterials: From production to integration with modern tools in neuroscience. Frontiers in Systems 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.”
Garcia-Cortadella, R., Schwesig, G., Jeschke, C., Illa, X., Gray, A. L., Savage, S., … Garrido, J. A.. (2021). Graphene active sensor arrays for long-term and wireless mapping of wide frequency band epicortical brain activity. Nature Communications
“Graphene active sensors have demonstrated promising capabilities for the detection of electrophysiological signals in the brain. their functional properties, together with their flexibility as well as their expected stability and biocompatibility have raised them as a promising building block for large-scale sensing neural interfaces. however, in order to provide reliable tools for neuroscience and biomedical engineering applications, the maturity of this technology must be thoroughly studied. here, we evaluate the performance of 64-channel graphene sensor arrays in terms of homogeneity, sensitivity and stability using a wireless, quasi-commercial headstage and demonstrate the biocompatibility of epicortical graphene chronic implants. furthermore, to illustrate the potential of the technology to detect cortical signals from infra-slow to high-gamma frequency bands, we perform proof-of-concept long-term wireless recording in a freely behaving rodent. our work demonstrates the maturity of the graphene-based technology, which represents a promising candidate for chronic, wide frequency band neural sensing interfaces.”
Cherian, R. S., Sandeman, S., Ray, S., Savina, I. N., Ashtami, J., & Mohanan, P. V.. (2019). Green synthesis of Pluronic stabilized reduced graphene oxide: Chemical and biological characterization. Colloids and Surfaces B: Biointerfaces
“The wonder material graphene has numerous potential applications in nanoelectronics, biomedicine, storage devices, etc. synthesis of graphene is highly challenging due to the toxic chemicals used and its low yield. in the present study, a facile green route for synthesis of reduced graphene oxide (rgo) was carried out using ascorbic acid as reducing agent. rgo was stabilized using pluronic p123 polymer to give pluronic stabilized reduced graphene oxide (rgo-p) and gave superior yield (15 mg graphene oxide yielded ˜13 mg rgo-p). despite the potential neuroscience applications of graphene, the impending toxicological outcome upon interaction with neurons is not well understood. here, differentiated pc-12 neuron-like cells exposed to rgo-p showed a dose-dependent cytotoxicity. membrane disruption and cytoskeletal integrity remained uncompromised after 24 h exposure. oxidative stress in pc-12 was evident due to an increase in ros generation in dose and time-dependent manner. in vivo acute toxicity was assessed in mice administered with 10 mg/kg body weight of rgo-p. there were no evident changes in behaviour, motor function or other morphological changes. in conclusion, rgo-p was successfully synthesized and provided superior yield. even though in vitro toxicity testing showed dose-dependent toxicity, in vivo toxic effect was not apparent.”
Bramini, M., Alberini, G., Colombo, E., Chiacchiaretta, M., DiFrancesco, M. L., Maya-Vetencourt, J. F., … Cesca, F.. (2018). Interfacing graphene-based materials with neural cells. Frontiers in Systems Neuroscience
“The scientific community has witnessed an exponential increase in the applications of graphene and graphene-based materials in a wide range of fields, from engineering to electronics to biotechnologies and biomedical applications. for what concerns neuroscience, the interest raised by these materials is two-fold. on one side, nanosheets made of graphene or graphene derivatives (graphene oxide, or its reduced form) can be used as carriers for drug delivery. here, an important aspect is to evaluate their toxicity, which strongly depends on flake composition, chemical functionalization and dimensions. on the other side, graphene can be exploited as a substrate for tissue engineering. in this case, conductivity is probably the most relevant amongst the various properties of the different graphene materials, as it may allow to instruct and interrogate neural networks, as well as to drive neural growth and differentiation, which holds a great potential in regenerative medicine. in this review, we try to give a comprehensive view of the accomplishments and new challenges of the field, as well as which in our view are the most exciting directions to take in the immediate future. these include the need to engineer multifunctional nanoparticles (nps) able to cross the blood-brain-barrier to reach neural cells, and to achieve on-demand delivery of specific drugs. we describe the state-of-the-art in the use of graphene materials to engineer three-dimensional scaffolds to drive neuronal growth and regeneration in vivo, and the possibility of using graphene as a component of hybrid composites/multi-layer organic electronics devices. last but not least, we address the need of an accurate theoretical modeling of the interface between graphene and biological material, by modeling the interaction of graphene with proteins and cell membranes at the nanoscale, and describing the physical mechanism(s) of charge transfer by which the various graphene materials can influence the excitability and physiology of neural cells.”
Capasso, A., Rodrigues, J., Moschetta, M., Buonocore, F., Faggio, G., Messina, G., … Lisi, N.. (2021). Interactions between Primary Neurons and Graphene Films with Different Structure and Electrical Conductivity. Advanced Functional Materials
“Graphene-based materials represent a useful tool for the realization of novel neural interfaces. several studies have demonstrated the biocompatibility of graphene-based supports, but the biological interactions between graphene and neurons still pose open questions. in this work, the influence of graphene films with different characteristics on the growth and maturation of primary cortical neurons is investigated. graphene films are grown by chemical vapor deposition progressively lowering the temperature range from 1070 to 650 °c to change the lattice structure and corresponding electrical conductivity. two graphene-based films with different electrical properties are selected and used as substrate for growing primary cortical neurons: i) highly crystalline and conductive (grown at 1070 °c) and ii) highly disordered and 140-times less conductive (grown at 790 °c). electron and fluorescence microscopy imaging reveal an excellent neuronal viability and the development of a mature, structured, and excitable network onto both substrates, regardless of their microstructure and electrical conductivity. the results underline that high electrical conductivity by itself is not fundamental for graphene-based neuronal interfaces, while other physico–chemical characteristics, including the atomic structure, should be also considered in the design of functional, bio-friendly templates. this finding widens the spectrum of carbon-based materials suitable for neuroscience applications.”
Rauti, R., Secomandi, N., Martín, C., Bosi, S., Severino, F. P. U., Scaini, D., … Ballerini, L.. (2020). Tuning Neuronal Circuit Formation in 3D Polymeric Scaffolds by Introducing Graphene at the Bio/Material Interface. Advanced Biosystems
“2D cultures are useful platforms allowing studies of the fundamental mechanisms governing neuron and synapse functions. yet, such models are limited when exploring changes in network dynamics due to 3d-space topologies. 3d platforms fill this gap and favor investigating topologies closer to the real brain organization. graphene, an atom-thick layer of carbon, possesses remarkable properties and since its discovery is considered a highly promising material in neuroscience developments. here, elastomeric 3d platforms endowed with graphene cues are exploited to modulate neuronal circuits when interfaced to graphene in 3d topology. ex vivo neuronal networks are successfully reconstructed within 3d scaffolds, with and without graphene, characterized by comparable size and morphology. by confocal microscopy and live imaging, the 3d architecture of synaptic networks is documented to sustain a high rate of bursting in 3d scaffolds, an activity further increased by graphene interfacing. changes are reported in the excitation/inhibition ratio, potentially following 3d-graphene interfacing. a hypothesis is thus proposed, where the combination of synapse formation under 3d architecture and graphene interfaces affects the maturation of gabaergic inhibition. this will tune the balance between hyperpolarizing and depolarizing responses, potentially contributing to network synchronization in the absence of changes in gabaergic phenotype expression.”
Thunemann, M., Lu, Y., Liu, X., Klllç, K., Desjardins, M., Vandenberghe, M., … Kuzum, D.. (2018). Deep 2-photon imaging and artifact-free optogenetics through transparent graphene microelectrode arrays. Nature Communications
“Recent advances in optical technologies such as multi-photon microscopy and optogenetics have revolutionized our ability to record and manipulate neuronal activity. combining optical techniques with electrical recordings is of critical importance to connect the large body of neuroscience knowledge obtained from animal models to human studies mainly relying on electrophysiological recordings of brain-scale activity. however, integration of optical modalities with electrical recordings is challenging due to generation of light-induced artifacts. here we report a transparent graphene microelectrode technology that eliminates light-induced artifacts to enable crosstalk-free integration of 2-photon microscopy, optogenetic stimulation, and cortical recordings in the same in vivo experiment. we achieve fabrication of crack- and residue-free graphene electrode surfaces yielding high optical transmittance for 2-photon imaging down to ~ 1 mm below the cortical surface. transparent graphene microelectrode technology offers a practical pathway to investigate neuronal activity over multiple spatial scales extending from single neurons to large neuronal populations.”
Garcia-Cortadella, R., Schäfer, N., Cisneros-Fernandez, J., Ré, L., Illa, X., Schwesig, G., … Guimerà-Brunet, A.. (2020). Switchless multiplexing of graphene active sensor arrays for brain mapping. Nano Letters
“Sensor arrays used to detect electrophysiological signals from the brain are paramount in neuroscience. however, the number of sensors that can be interfaced with macroscopic data acquisition systems currently limits their bandwidth. this bottleneck originates in the fact that, typically, sensors are addressed individually, requiring a connection for each of them. herein, we present the concept of frequency-division multiplexing (fdm) of neural signals by graphene sensors. we demonstrate the high performance of graphene transistors as mixers to perform amplitude modulation (am) of neural signals in situ, which is used to transmit multiple signals through a shared metal line. this technology eliminates the need for switches, remarkably simplifying the technical complexity of state-of-the-art multiplexed neural probes. besides, the scalability of fdm graphene neural probes has been thoroughly evaluated and their sensitivity demonstrated in vivo. using this technology, we envision a new generation of high-count conformal neural probes for high bandwidth brain machine interfaces.”
Liu, X., Lu, Y., Iseri, E., Shi, Y., & Kuzum, D.. (2018). A compact closed-loop optogenetics system based on artifact-free transparent graphene electrodes. Frontiers in Neuroscience
“Electrophysiology is a decades-old technique widely used for monitoring activity of individual neurons and local field potentials. optogenetics has revolutionized neuroscience studies by offering selective and fast control of targeted neurons and neuron populations. the combination of these two techniques is crucial for causal investigation of neural circuits and understanding their functional connectivity. however, electrical artifacts generated by light stimulation interfere with neural recordings and hinder the development of compact closed-loop systems for precise control of neural activity. here, we demonstrate that transparent graphene micro-electrodes fabricated on a clear polyethylene terephthalate film eliminate the light-induced artifact problem and allow development of a compact battery-powered closed-loop optogenetics system. we extensively investigate light-induced artifacts for graphene electrodes in comparison to metal control electrodes. we then design optical stimulation module using micro-led chips coupled to optical fibers to deliver light to intended depth for optogenetic stimulation. for artifact-free integration of graphene micro-electrode recordings with optogenetic stimulation, we design and develop a compact closed-loop system and validate it for different frequencies of interest for neural recordings. this compact closed-loop optogenetics system can be used for various applications involving optogenetic stimulation and electrophysiological recordings.”
Lu, Y., Lyu, H., Richardson, A. G., Lucas, T. H., & Kuzum, D.. (2016). Flexible Neural Electrode Array Based-on Porous Graphene for Cortical Microstimulation and Sensing. Scientific Reports
“Neural sensing and stimulation have been the backbone of neuroscience research, brain-machine interfaces and clinical neuromodulation therapies for decades. to-date, most of the neural stimulation systems have relied on sharp metal microelectrodes with poor electrochemical properties that induce extensive damage to the tissue and significantly degrade the long-term stability of implantable systems. here, we demonstrate a flexible cortical microelectrode array based on porous graphene, which is capable of efficient electrophysiological sensing and stimulation from the brain surface, without penetrating into the tissue. porous graphene electrodes show superior impedance and charge injection characteristics making them ideal for high efficiency cortical sensing and stimulation. they exhibit no physical delamination or degradation even after 1 million biphasic stimulation cycles, confirming high endurance. in in vivo experiments with rodents, same array is used to sense brain activity patterns with high spatio-temporal resolution and to control leg muscles with high-precision electrical stimulation from the cortical surface. flexible porous graphene array offers a minimally invasive but high efficiency neuromodulation scheme with potential applications in cortical mapping, brain-computer interfaces, treatment of neurological disorders, where high resolution and simultaneous recording and stimulation of neural activity are crucial.”
Chen, J., Yu, Q., Fu, W., Chen, X., Zhang, Q., Dong, S., … Zhang, S.. (2020). A highly sensitive amperometric glutamate oxidase microbiosensor based on a reduced graphene oxide/prussian blue nanocube/gold nanoparticle composite film-modified pt electrode. Sensors (Switzerland)
“A simple method that relies only on an electrochemical workstation has been investigated to fabricate a highly sensitive glutamate microbiosensor for potential neuroscience applications. in this study, in order to develop the highly sensitive glutamate electrode, a 100 µm platinum wire was modified by the electrochemical deposition of gold nanoparticles, prussian blue nanocubes, and reduced graphene oxide sheets, which increased the electroactive surface area; and the chitosan layer, which provided a suitable environment to bond the glutamate oxidase. the optimization of the fabrication procedure and analytical conditions is described. the modified electrode was characterized using field emission scanning electron microscopy, impedance spectroscopy, and cyclic voltammetry. the results exhibited its excellent sensitivity for glutamate detection (lod = 41.33 nm), adequate linearity (50 nm–40 µm), ascendant reproducibility (rsd = 4.44%), and prolonged stability (more than 30 repetitive potential sweeps, two-week lifespan). because of the important role of glutamate in neurotransmission and brain function, this small-dimension, high-sensitivity glutamate electrode is a promising tool in neuroscience research.”
Park, D. W., Ness, J. P., Brodnick, S. K., Esquibel, C., Novello, J., Atry, F., … Ma, Z.. (2018). Electrical Neural Stimulation and Simultaneous in Vivo Monitoring with Transparent Graphene Electrode Arrays Implanted in GCaMP6f Mice. ACS Nano
“Electrical stimulation using implantable electrodes is widely used to treat various neuronal disorders such as parkinson’s disease and epilepsy and is a widely used research tool in neuroscience studies. however, to date, devices that help better understand the mechanisms of electrical stimulation in neural tissues have been limited to opaque neural electrodes. imaging spatiotemporal neural responses to electrical stimulation with minimal artifact could allow for various studies that are impossible with existing opaque electrodes. here, we demonstrate electrical brain stimulation and simultaneous optical monitoring of the underlying neural tissues using carbon-based, fully transparent graphene electrodes implanted in gcamp6f mice. fluorescence imaging of neural activity for varying electrical stimulation parameters was conducted with minimal image artifact through transparent graphene electrodes. in addition, full-field imaging of electrical stimulation verified more efficient neural activation with cathode leading stimulation compared to anode leading stimulation. we have characterized the charge density limitation of capacitive four-layer graphene electrodes as 116.07-174.10 μc/cm2 based on electrochemical impedance spectroscopy, cyclic voltammetry, failure bench testing, and in vivo testing. this study demonstrates the transparent ability of graphene neural electrodes and provides a method to further increase understanding and potentially improve therapeutic electrical stimulation in the central and peripheral nervous systems.”
John, A. A., Subramanian, A. P., Vellayappan, M. V., Balaji, A., Mohandas, H., & Jaganathan, S. K.. (2015). Carbon nanotubes and graphene as emerging candidates in neuroregeneration and neurodrug delivery. International Journal of Nanomedicine
“Neuroregeneration is the regrowth or repair of nervous tissues, cells, or cell products involved in neurodegeneration and inflammatory diseases of the nervous system like alzheimer’s disease and parkinson’s disease. nowadays, application of nanotechnology is commonly used in developing nanomedicines to advance pharmacokinetics and drug delivery exclusively for central nervous system pathologies. in addition, nanomedical advances are leading to therapies that disrupt disarranged protein aggregation in the central nervous system, deliver functional neuroprotective growth factors, and change the oxidative stress and excitotoxicity of affected neural tissues to regenerate the damaged neurons. carbon nanotubes and graphene are allotropes of carbon that have been exploited by researchers because of their excellent physical properties and their ability to interface with neurons and neuronal circuits. this review describes the role of carbon nanotubes and graphene in neuroregeneration. in the future, it is hoped that the benefits of nanotechnologies will outweigh their risks, and that the next decade will present huge scope for developing and delivering technologies in the field of neuroscience.”
Rauti, R., Musto, M., Bosi, S., Prato, M., & Ballerini, L.. (2019). Properties and behavior of carbon nanomaterials when interfacing neuronal cells: How far have we come?. Carbon
“In the last two decades, an increasing amount of studies have investigated the use of components based on carbon-(nano)materials in the engineering of neural interfaces, to improve the performance of current state of the art devices. carbon is an extremely versatile element, characterized by a variety of allotropes and structures with different properties due to their sp, sp2 or sp3 hybridization. among the diverse carbon nanomaterials, carbon nanotubes and graphene are naturally excellent electrical conductors, thus representing ideal candidates for interfacing electrical-excitable tissues. in addition, their dimensional range holds the potential to enhance the material interactions with bio-systems. successful interfacing of the nervous system with devices that record or modulate neuronal electrical activity requires their stable electrical coupling with neurons. the efficiency of this coupling can be improved significantly by the use of conductive, ad hoc designed, nanomaterials. here we review different carbon-based nanomaterials currently under investigation in basic and applied neuroscience, and the recent developments in this research field, with a special focus on in vitro studies.”
Zheng, Z., Huang, L., Yan, L., Yuan, F., Wang, L., Wang, K., … Liu, Y.. (2019). Polyaniline functionalized graphene nanoelectrodes for the regeneration of PC12 cells via electrical stimulation. International Journal of Molecular Sciences
“The regeneration of neurons is an important goal of neuroscience and clinical medicine. the electrical stimulation of cells is a promising technique to meet this goal. however, its efficiency highly depends on the electrochemical properties of the stimulation electrodes used. this work reports on the preparation and use of a highly electroactive and biocompatible nanoelectrode made from a novel polyaniline functionalized graphene composite. this nanocomposite was prepared using a facile and efficient polymerization-enhanced ball-milling method. it was used to stimulate the growth of pc12 cells under various electrical fields. the enhanced growth of axons and improved wound regeneration of pc12 cells were observed after this treatment, suggesting a promising strategy for neuro traumatology.”
Guan, S., Wang, J., & Fang, Y.. (2019). Transparent graphene bioelectronics as a new tool for multimodal neural interfaces. Nano Today
“A central challenge of neuroscience is to monitor the coordinated activity of neural circuits underlying information processing and behavior. combining the advantages of electrical and optical modalities can provide unprecedented access to the spatiotemporal dynamics of neural activity. transparent graphene bioelectronics has emerged as a suitable tool for the seamless integration of electrophysiological recording with optical imaging and optogenetic stimulation, opening up a variety of new opportunities in both neuroscience research and clinical applications.”
Lu, Y., Liu, X., & Kuzum, D.. (2018). Graphene-based neurotechnologies for advanced neural interfaces. Current Opinion in Biomedical Engineering
“Understanding how neuron populations transform activities of individual neurons into complex behaviors is one of the biggest challenges of neuroscience research. however, current neural monitoring and controlling technologies provide insufficient spatiotemporal resolution to unravel neural circuit functions. to this end, multifunctional neurotechnologies combining electrical, optical and chemical sensing and stimulation modalities have been proposed to overcome resolution limits. research in multifunctional probes has fueled the demand for new materials to build minimally invasive chronic interfaces to the brain. graphene has recently emerged as a neural interface material offering several outstanding properties, such as optical transparency, flexibility, high conductivity, functionalization and biocompatibility. the unique combination of these properties in a single material system makes graphene an attractive choice for multi-modal probing of neural activity. in this review, we discuss recent advances in graphene-based neurotechnologies, highlight different approaches and consider emerging directions inspired by unique characteristics of graphene.”
Fischer, R. A., Zhang, Y., Risner, M. L., Li, D., Xu, Y., & Sappington, R. M.. (2018). Impact of Graphene on the Efficacy of Neuron Culture Substrates. Advanced Healthcare Materials
“How graphene influences the behavior of living cells or tissues remains a critical issue for its application in biomedical studies, despite the general acceptance that graphene is biocompatible. while direct contact between cells and graphene is not a requirement for all biomedical applications, it is often mandatory for biosensing. therefore, it is important to clarify whether graphene impedes the ability of cells to interact with biological elements in their environment. here, a systematic study is reported to determine whether applying graphene on top of matrix substrates masks interactions between these substrates and retinal ganglion cells (rgcs). six different platforms are tested for primary rgc cultures with three platforms comprised of matrix substrates compatible with these neurons, and another three having a layer of graphene placed on top of the matrix substrates. the results demonstrate that graphene does not impede interactions between rgcs and underlying substrate matrix, such that their positive or negative effects on neuron viability and vitality are retained. however, direct contact between rgcs and graphene reduces the number, but increases basal activity, of functional cation channels. the data indicate that, when proper baselines are established, graphene is a promising biosensing material for in vitro applications in neuroscience.”
Wang, R., Shi, M., Brewer, B., Yang, L., Zhang, Y., Webb, D. J., … Xu, Y. Q.. (2018). Ultrasensitive Graphene Optoelectronic Probes for Recording Electrical Activities of Individual Synapses. Nano Letters
“The complex neuronal circuitry connected by submicron synapses in our brain calls for technologies that can map neural networks with ultrahigh spatiotemporal resolution to decipher the underlying mechanisms for multiple aspects of neuroscience. here we show that, through combining graphene transistor arrays with scanning photocurrent microscopy, we can detect the electrical activities of individual synapses of primary hippocampal neurons. through measuring the local conductance change of graphene optoelectronic probes directly underneath neuronal processes, we are able to estimate millivolt extracellular potential variations of individual synapses during depolarization. the ultrafast nature of graphene photocurrent response allows for decoding of activity patterns of individual synapses with a sub-millisecond temporal resolution. this new neurotechnology provides promising potentials for recording of electrophysiological outcomes of individual synapses in neural networks.”
Moschetta, M., Lee, J. Y., Rodrigues, J., Podestà, A., Varvicchio, O., Son, J., … Capasso, A.. (2021). Hydrogenated Graphene Improves Neuronal Network Maturation and Excitatory Transmission. Advanced Biology
“Graphene is regarded as a viable bio-interface for neuroscience due to its biocompatibility and electrical conductivity, which would contribute to efficient neuronal network signaling. here, monolayer graphene grown via chemical vapor deposition is treated with remote hydrogen plasma to demonstrate that hydrogenated graphene (hgr) fosters improved cell-to-cell communication with respect to pristine graphene in primary cortical neurons. when transferred to polyethylene terephthalate, hgr exhibits higher wettability than graphene (water contact angle of 83.7° vs 40.7°), while preserving electrical conductivity (≈3 kω □-1). a rich and mature network is observed to develop onto hgr. the intrinsic excitability and firing properties of neurons plated onto hgr appears unaltered, while the basic passive and active membrane properties are fully preserved. the formation of excitatory synaptic connections increases in hgr with respect to pristine graphene, leading to a doubled miniature excitatory postsynaptic current frequency. this study supports the use of hydrogenation for tailoring graphene into an improved neuronal interface, indicating that wettability, more than electrical conductivity, is the key parameter to be controlled. the use of hgr can bring about a deeper understanding of neuronal behavior on artificial bio-interfaces and provide new insight for graphene-based biomedical applications.”
Bourrier, A., Shkorbatova, P., Bonizzato, M., Rey, E., Barraud, Q., Courtine, G., … Delacour, C.. (2019). Monolayer Graphene Coating of Intracortical Probes for Long-Lasting Neural Activity Monitoring. Advanced Healthcare Materials
“The invasiveness of intracortical interfaces currently used today is responsible for the formation of an intense immunoresponse and inflammatory reaction from neural cells and tissues. this leads to a high concentration of reactive glial cells around the implant site, creating a physical barrier between the neurons and the recording channels. such a rejection of foreign analog interfaces causes neural signals to fade from recordings which become flooded by background noise after a few weeks. despite their invasiveness, those devices are required to track single neuron activity and decode fine sensory or motor commands. in particular, such quantitative and long-lasting recordings of individual neurons are crucial during a long time period (several months) to restore essential functions of the cortex, disrupted after injuries, stroke, or neurodegenerative diseases. to overcome this limitation, graphene and related materials have attracted numerous interests, as they gather in the same material many suitable properties for interfacing living matter, such as an exceptionally high neural affinity, diffusion barrier, and high physical robustness. in this work, the neural affinity of a graphene monolayer with numerous materials commonly used in neuroprostheses is compared, and its impact on the performance and durability of intracortical probes is investigated. for that purpose, an innovative coating method to wrap 3d intracortical probes with a continuous monolayer graphene is developed. experimental evidence demonstrate the positive impact of graphene on the bioacceptance of conventional intracortical probes, in terms of detection efficiency and tissues responses, allowing real-time samplings of motor neuron activity during 5 weeks. since continuous graphene coatings can easily be implemented on a wide range of 3d surfaces, this study further motivates the use of graphene and related materials as it could significantly contribute to reduce the current rejection of neural probes currently used in many research areas, from fundamental neurosciences to medicine and neuroprostheses.”
Liu, X., Lu, Y., & Kuzum, D.. (2018). High-Density Porous Graphene Arrays Enable Detection and Analysis of Propagating Cortical Waves and Spirals. Scientific Reports
“Cortical propagating waves have recently attracted significant attention by the neuroscience community. these travelling waves have been suggested to coordinate different brain areas and play roles in assisting neural plasticity and learning. however, it is extremely challenging to record them with very fine spatial scales over large areas to investigate their effect on neural dynamics or network connectivity changes. in this work, we employ high-density porous graphene microelectrode arrays fabricated using laser pyrolysis on flexible substrates to study the functional network connectivity during cortical propagating waves. the low-impedance porous graphene arrays are used to record cortical potentials during theta oscillations and drug-induced seizures in vivo. spatiotemporal analysis on the neural recordings reveal that theta oscillations and epileptiform activities have distinct characteristics in terms of both synchronization and resulting propagating wave patterns. to investigate the network connectivity during the propagating waves, we perform network analysis. the results show that the propagating waves are consistent with the functional connectivity changes in the neural circuits, suggesting that the underlying network states are reflected by the cortical potential propagation patterns.”
Ye, S., Yang, P., Cheng, K., Zhou, T., Wang, Y., Hou, Z., … Ren, L.. (2016). Drp1-Dependent Mitochondrial Fission Mediates Toxicity of Positively Charged Graphene in Microglia. ACS Biomaterials Science and Engineering
“The unique physicochemical properties of graphene and its derivatives enable their application in the diagnostics and therapy of central nervous system (cns) diseases. however, the potential impacts of surface properties of functionalized graphene on microglia remain poorly understood. herein, we used graphene oxides (go), polyethylene glycol (peg)- and polyethylenimine (pei)-functionalized go, which possess different surface charges, to investigate their effects on microglia by focusing on mitochondrial dynamics. the positively charged go-pei was found to promote mitochondrial fission as observed in bv-2 cells with mitochondria labeled by dsred2-mito, indicating that alterations in mitochondrial dynamics depend on the surface properties of graphene. concurrent to mitochondrial fragmentation, treatment with positively charged go-pei induced an increase in mitochondrial recruitment of dynamin-related protein (drp1). additionally, go-pei treatment also led to apoptotic and autophagic cell death. however, drp1 silencing by small interfering rna (sirna) could effectively attenuate go-pei-induced apoptotic and autophagic cell death, indicating that mitochondrial fragmentation occurs upstream of go-pei-mediated toxicity in microglia. overall, our study indicated that positively charged go-pei might cause deleterious influence on the central immune homeostasis by drp1-dependent mitochondrial fragmentation, and provide the strategies for the rational design of graphene-based materials in neuroscience.”
Balch, H. B., McGuire, A. F., Horng, J., Tsai, H. Z., Qi, K. K., Duh, Y. S., … Wang, F.. (2021). Graphene Electric Field Sensor Enables Single Shot Label-Free Imaging of Bioelectric Potentials. Nano Letters
“The measurement of electrical activity across systems of excitable cells underlies current progress in neuroscience, cardiac pharmacology, and neurotechnology. however, bioelectricity spans orders of magnitude in intensity, space, and time, posing substantial technological challenges. the development of methods permitting network-scale recordings with high spatial resolution remains key to studies of electrogenic cells, emergent networks, and bioelectric computation. here, we demonstrate single-shot and label-free imaging of extracellular potentials with high resolution across a wide field-of-view. the critically coupled waveguide-amplified graphene electric field (cage) sensor leverages the field-sensitive optical transitions in graphene to convert electric potentials into the optical regime. as a proof-of-concept, we use the cage sensor to detect native electrical activity from cardiac action potentials with tens-of-microns resolution, simultaneously map the propagation of these potentials at tissue-scale, and monitor their modification by pharmacological agents. this platform is robust, scalable, and compatible with existing microscopy techniques for multimodal correlative imaging.”
Shokoueinejad, M., Park, D. W., Jung, Y. H., Brodnick, S. K., Novello, J., Dingle, A., … Williams, J.. (2019). Progress in the field of micro-electrocorticography. Micromachines
“Since the 1940s electrocorticography (ecog) devices and, more recently, in the last decade, micro-electrocorticography (μecog) cortical electrode arrays were used for a wide set of experimental and clinical applications, such as epilepsy localization and brain-computer interface (bci) technologies. miniaturized implantable μecog devices have the advantage of providing greater-density neural signal acquisition and stimulation capabilities in a minimally invasive fashion. an increased spatial resolution of the μecog array will be useful for greater specificity diagnosis and treatment of neuronal diseases and the advancement of basic neuroscience and bci research. in this review, recent achievements of ecog and μecog are discussed. the electrode configurations and varying material choices used to design μecog arrays are discussed, including advantages and disadvantages of μecog technology compared to electroencephalography (eeg), ecog, and intracortical electrode arrays. electrode materials that are the primary focus include platinum, iridium oxide, poly(3,4-ethylenedioxythiophene) (pedot), indium tin oxide (ito), and graphene. we discuss the biological immune response to μecog devices compared to other electrode array types, the role of μecog in clinical pathology, and brain-computer interface technology. the information presented in this review will be helpful to understand the current status, organize available knowledge, and guide future clinical and research applications of μecog technologies.”
Monaco, A. M., & Giugliano, M.. (2014). Carbon-based smart nanomaterials in biomedicine and neuroengineering. Beilstein Journal of Nanotechnology
“The search for advanced biomimetic materials that are capable of offering a scaffold for biological tissues during regeneration or of electrically connecting artificial devices with cellular structures to restore damaged brain functions is at the forefront of interdisciplinary research in materials science. bioactive nanoparticles for drug delivery, substrates for nerve regeneration and active guidance, as well as supramolecular architectures mimicking the extracellular environment to reduce inflammatory responses in brain implants, are within reach thanks to the advancements in nanotechnology. in particular, carbon-based nanostructured materials, such as graphene, carbon nanotubes (cnts) and nanodiamonds (nds), have demonstrated to be highly promising materials for designing and fabricating nanoelectrodes and substrates for cell growth, by virtue of their peerless optical, electrical, thermal, and mechanical properties. in this review we discuss the state-of-the-art in the applications of nanomaterials in biological and biomedical fields, with a particular emphasis on neuroengineering.”
“Magnetic resonance imaging (mri) compatible neural electrodes are important for combining high-resolution electrophysiological measurements with more global mri mapping of brain activity, which is critical for fundamental neuroscience studies, as well as clinical evaluation and monitoring. copper is a favorable material to use in mri because it has magnetic susceptibility close to water and tissues. however, the cytotoxicity of copper precludes its direct implantation for neural recording. here, we overcome this limitation by developing a graphene encapsulated copper (g-cu) microelectrode. the toxicity of copper is largely eliminated, as evidenced by the in vitro cell tests and in vivo histology studies. local field potentials and single-unit spikes were recorded from rodent brains with the g-cu microelectrodes. notably, the g-cu microelectrodes show no image artifacts in a 7.0 t mri scanner, indicating minimal magnetic field distortion in their vicinity. this high mri compatibility of our g-cu probes would open up new opportunities for fundamental brain activity studies and clinical applications requiring continuous mri and electrophysiological recordings.”
“As a powerful tool for monitoring and modulating neural activities, implantable neural electrodes constitute the basis for a wide range of applications, including fundamental studies of brain circuits and functions, treatment of various neurological diseases, and realization of brain-machine interfaces. however, conventional neural electrodes have the issue of mechanical mismatch with soft neural tissues, which can result in tissue inflammation and gliosis, thus causing degradation of function over chronic implantation. furthermore, implantable neural electrodes, especially depth electrodes, can only carry out limited data sampling within predefined anatomical regions, making it challenging to perform large-area brain mapping. with excellent electrical, mechanical, and chemical properties, carbonbased nanomaterials, including graphene and carbon nanotubes (cnts), have been used as materials of implantable neural electrodes in recent years. electrodes made from graphene and cnt fibers exhibit low electrochemical impedance, benefiting from the porous microstructure of the fibers. this enables a much smaller size of neural electrode. together with the low young’s modulus of the fibers, this small size results in very soft electrodes. soft neural electrodes made from graphene and cnt fibers show a much-reduced inflammatory response and enable stable chronic in vivo action potential recording for 4-5 months. combining different modalities of neural interfacing, including electrophysiological measurement, optical imaging/stimulation, and magnetic resonance imaging (mri), could leverage the spatial and temporal resolution advantages of different techniques, thus providing new insights into how neural circuits process information. transparent neural electrode arrays made from graphene or cnts enable simultaneous calcium imaging through the transparent electrodes, from which concurrent electrical recording is taken, thus providing complementary cellular information in addition to high-temporal-resolution electrical recording. transparent neural electrodes from carbon-based nanomaterials can record well-defined neuronal response signals with negligible light-induced artifacts from cortical surfaces under optogenetic stimulation. graphene and cnt-based materials were used to fabricate mri-compatible neural electrodes with negligible artifacts under high field mri. simultaneous deep brain stimulation (dbs) and functional magnetic resonance imaging (fmri) with graph…”
Li, G., Yang, J., Yang, W., Wang, F., Wang, Y., Wang, W., & Liu, L.. (2018). Label-free multidimensional information acquisition from optogenetically engineered cells using a graphene transistor. Nanoscale
“The optogenetic technique, which allows the manipulation of cellular activity patterns in space and time by light, has transformed the field of neuroscience. however, acquiring multidimensional optogenetic information remains challenging despite the fact that several cellular information detection methods have been proposed. herein, we present a new method to acquire label-free multidimensional information from optogenetically engineered cells using a graphene transistor. using a graphene film to form a strong densely packed layer with cells, the cellular action potentials were characterized as light-activated transistor conductance signals, which quantified the multidimensional optogenetic information. based on this approach, some important cellular optogenetic information, including electrophysiological state, cell concentration, expression levels of opsin and response to variable light intensity, were also precisely detected. furthermore, the graphene transistor was also used to distinguish cells expressing different channelrhodopsin-2 variants. our study offers a general detection method of multidimensional optogenetic information for extending the applications of the optogenetic technique and provides a novel sensor for the development of future biological prosthetic devices.”
Liu, S., Zhao, Y., Hao, W., Zhang, X. D., & Ming, D.. (2020). Micro- and nanotechnology for neural electrode-tissue interfaces. Biosensors and Bioelectronics
“Implantable neural electrodes can record and regulate neural activities with high spatial resolution of single-neuron and high time resolution of sub-millisecond, which are the most extensive window in neuroscience research. however, the mechanical mismatch between conventional stiff electrodes and soft neural tissue can lead to inflammatory responses and degradation of signals in chronic recordings. although remarkable breakthroughs have been made in sensing and regulation of neural signals, the long-term stability and chronic inflammatory response of the neural electrode-tissue interfaces still needs further development. in this review, we focus on the latest developments for the optimization of neural electrode-tissue interfaces, including electrode materials (graphene fiber-based and cnt fiber-based), electrode structures (flexible electrodes), nano-coatings and hydrogel-based neural interfaces. the parameters of impedance, charge injection limit, signal-to-noise ratio and neuron lost zone are used to evaluate the electrochemical performance of the devices, the recording performance of biosignals and the stability of the neural interfaces, respectively. these optimization methods can effectively improve the long-term stability and the chronic inflammatory response of neural interfaces during the recording and modulation of biosignals.”
Wu, T., Li, Y., Liang, X., Liu, X., & Tang, M.. (2021). Identification of potential circRNA-miRNA-mRNA regulatory networks in response to graphene quantum dots in microglia by microarray analysis. Ecotoxicology and Environmental Safety
“Along with the increasing application of graphene quantum dots (gqds) in the fields of biomedicine and neuroscience, it is important to assess the probably adverse effects of gqds in the central nervous system (cns) but their underlying toxic mechanisms is still unclear. in this study, we evaluate the molecular mechanisms associated with circular rnas (circrnas) of nitrogen-doped gqds (n-gqds) and amino-functionalized gqds (a-gqds) damaging the cell viability and cellular structure in microglia by an integrative analysis of rna microarray. the differentially expressed circrna (decircrnas)-mirna- differentially expressed mrna (demrnas) regulatory networks were conducted in bv2 microglial cells treated with 25 µg/ml n-gqds, 100 µg/ml n-gqds and 100 µg/ml a-gqds. based on that, the protein-coding genes in each cerna network were collected to do bio-functional analysis to evaluate signaling pathways that were indirectly mediated by circrnas. some pathways that could play indispensable roles in the neurotoxicity of n-gqds or both two kinds of gqds were found. low-dosed n-gqds exposure mainly induced inflammatory action in microglia, while high-dosed n-gqds and a-gqds exposure both affect olfactory transduction and gabaergic synapse. meanwhile, several classical signaling pathways, including mtor, erbb and mapk, could make diverse contributions to the neurotoxicity of both two kinds of gqds. these circrnas could be toxic biomarkers or protective targets in neurotoxicity of gqds. more importantly, they emphasized the necessity of comprehensive analysis of latent molecular mechanisms through epigenetics approaches in biosafety assessment of graphene-based nanomaterials.”
Liu, & Speranza. (2019). Functionalization of Carbon Nanomaterials for Biomedical Applications. C — Journal of Carbon Research
“Over the past decade, carbon nanostructures (cnss) have been widely used in a variety of biomedical applications. examples are the use of cnss for drug and protein delivery or in tools to locally dispense nucleic acids to fight tumor affections. cnss were successfully utilized in diagnostics and in noninvasive and highly sensitive imaging devices thanks to their optical properties in the near infrared region. however, biomedical applications require a complete biocompatibility to avoid adverse reactions of the immune system and cnss potentials for biodegradability. water is one of the main constituents of the living matter. unfortunately, one of the disadvantages of cnss is their poor solubility. surface functionalization of cnss is commonly utilized as an efficient solution to both tune the surface wettability of cnss and impart biocompatible properties. grafting functional groups onto the cnss surface consists in bonding the desired chemical species on the carbon nanoparticles via wet or dry processes leading to the formation of a stable interaction. this latter may be of different nature as the van der waals, the electrostatic or the covalent, the π-π interaction, the hydrogen bond etc. depending on the process and on the functional molecule at play. grafting is utilized for multiple purposes including bonding mimetic agents such as polyethylene glycol, drug/protein adsorption, attaching nanostructures to increase the cnss opacity to selected wavelengths or provide magnetic properties. this makes the cnss a very versatile tool for a broad selection of applications as medicinal biochips, new high-performance platforms for magnetic resonance (mr), photothermal therapy, molecular imaging, tissue engineering, and neuroscience. the scope of this work is to highlight up-to-date using of the functionalized carbon materials such as graphene, carbon fibers, carbon nanotubes, fullerene and nanodiamonds in biomedical applications.”
Guo, C. X., Ng, S. R., Khoo, S. Y., Zheng, X., Chen, P., & Li, C. M.. (2012). RGD-peptide functionalized graphene biomimetic live-cell sensor for real-time detection of nitric oxide molecules. ACS Nano
Crowe, M., Lai, Y., Wang, Y., Lu, J., Zhao, M., Tian, Z., … Diao, J.. (2017). A Proteoliposome Method for Assessing Nanotoxicity on Synaptic Fusion and Membrane Integrity. Small Methods
“Nanoparticles have received significant research interest for potential biomedical applications. before nanomaterials are administered to patients, their biocompatibility should be thoroughly evaluated through in vitro experiments and other preclinical procedures. many studies have sought to assess the toxicity of nanomaterials on synaptic transmission for neuroscience applications. however, it may be hard to perform such experiments because of the difficulty associated with delivering synthesized nanomaterials across cell membranes. here, an in vitro method is demonstrated that mimics neuronal exocytosis, which features protein-reconstituted liposomes for nanotoxicity testing; the effects of graphene oxide and pristine graphene on fusogenic activity and membrane integrity are examined. these results demonstrate the potential of this system as a novel in vitro platform for assessing the biocompatibility of nanomaterials, drug molecules, and other substances.”
Bramini, M., Rocchi, A., Benfenati, F., & Cesca, F.. (2019). Neuronal Cultures and Nanomaterials. In Advances in Neurobiology
“In recent years, the scientific community has witnessed an exponential increase in the use of nanomaterials for biomedical applications. in particular, the interest of graphene and graphene-based materials has rapidly risen in the neuroscience field due to the properties of this material, such as high conductivity, transparency and flexibility. as for any new material that aims to play a role in the biomedical area, a fundamental aspect is the evaluation of its toxicity, which strongly depends on material composition, chemical functionalization and dimensions. furthermore, a wide variety of three-dimensional scaffolds have also started to be exploited as a substrate for tissue engineering. in this application, the topography is probably the most relevant amongst the various properties of the different materials, as it may allow to instruct and interrogate neural networks, as well as to drive neural growth and differentiation. this chapter discusses the in vitro approaches, ranging from microscopy analysis to physiology measurements, to investigate the interaction of graphene with the central nervous system. moreover, the in vitro use of three-dimensional scaffolds is described and commented.”
Govindhan, M., Liu, Z., & Chen, A.. (2016). Design and electrochemical study of platinum-based nanomaterials for sensitive detection of nitric oxide in biomedical applications. Nanomaterials
“The extensive physiological and regulatory roles of nitric oxide (no) have spurred the development of no sensors, which are of critical importance in neuroscience and various medical applications. the development of electrochemical no sensors is of significant importance, and has garnered a tremendous amount of attention due to their high sensitivity and selectivity, rapid response, low cost, miniaturization, and the possibility of real-time monitoring. nanostructured platinum (pt)-based materials have attracted considerable interest regarding their use in the design of electrochemical sensors for the detection of no, due to their unique properties and the potential for new and innovative applications. this review focuses primarily on advances and insights into the utilization of nanostructured pt-based electrode materials, such as nanoporous pt, pt and ptau nanoparticles, ptau nanoparticle/reduced graphene oxide (rgo), and ptw nanoparticle/rgo-ionic liquid (il) nanocomposites, for the detection of no. the design, fabrication, characterization, and integration of electrochemical no sensing performance, selectivity, and durability are addressed. the attractive electrochemical properties of pt-based nanomaterials have great potential for increasing the competitiveness of these new sensors and open up new opportunities in the creation of novel no-sensing technologies for biological and medical applications.”
Kostarelos, K., Vincent, M., Hebert, C., & Garrido, J. A.. (2017). Graphene in the Design and Engineering of Next-Generation Neural Interfaces. Advanced Materials
“Neural interfaces are becoming a powerful toolkit for clinical interventions requiring stimulation and/or recording of the electrical activity of the nervous system. active implantable devices offer a promising approach for the treatment of various diseases affecting the central or peripheral nervous systems by electrically stimulating different neuronal structures. all currently used neural interface devices are designed to perform a single function: either record activity or electrically stimulate tissue. because of their electrical and electrochemical performance and their suitability for integration into flexible devices, graphene-based materials constitute a versatile platform that could help address many of the current challenges in neural interface design. here, how graphene and other 2d materials possess an array of properties that can enable enhanced functional capabilities for neural interfaces is illustrated. it is emphasized that the technological challenges are similar for all alternative types of materials used in the engineering of neural interface devices, each offering a unique set of advantages and limitations. graphene and 2d materials can indeed play a commanding role in the efforts toward wider clinical adoption of bioelectronics and electroceuticals.”
Castagnola, E., Garg, R., Rastogi, S. K., Cohen-Karni, T., & Cui, X. T.. (2020). 3D Fuzzy Graphene Microelectrode Array for Neurotransmitter Sensing at Sub-cellular Spatial Resolution. ChemRxiv
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“Dopamine (da) is a monoamine neurotransmitter involved in the modulation of various physiological brain functions, including learning, motivation, reward, and motor functions. the development of a high sensitivity real-time sensor for multi-site detection of da with high spatial resolution has critical implications for both neuroscience and clinical communities to improve understanding and treatments of neurological and neuropsychiatric disorders. here, we present high-surface area out-of-plane grown three-dimensional (3d) fuzzy graphene (3dfg) microelectrode arrays (meas) for highly selective, sensitive, and stable da electrochemical sensing. 3dfg microelectrodes present a remarkable sensitivity to da (2.87 ± 0.25 na/nm, with lod of 990±15 pm), the highest reported for nanocarbon meas using fast scan cyclic voltammetry (fscv). the high surface area of 3dfg allows for miniaturization of electrode down to 2 x 2 µm2, without compromising the electrochemical performance. moreover, 3dfg meas are electrochemically stable under 7.2 million scans of continuous fscv cycling, present exceptional selectivity over the most common interferents in vitro with minimum fouling by electrochemical byproducts, and can discriminate da and serotonin (5-ht) in response to the injection of their 50:50 mixture. these results highlight the potential of 3dfg meas as a promising platform for fscv based multi-site detection of da with high sensitivity, selectivity, and spatial resolution.”
Pampaloni, N. P., Giugliano, M., Scaini, D., Ballerini, L., & Rauti, R.. (2019). Advances in nano neuroscience: From nanomaterials to nanotools. Frontiers in Neuroscience
“During the last decades, neuroscientists have increasingly exploited a variety of artificial, de-novo synthesized materials with controlled nano-sized features. for instance, a renewed interest in the development of prostheses or neural interfaces was driven by the availability of novel nanomaterials that enabled the fabrication of implantable bioelectronics interfaces with reduced side effects and increased integration with the target biological tissue. the peculiar physical-chemical properties of nanomaterials have also contributed to the engineering of novel imaging devices toward sophisticated experimental settings, to smart fabricated scaffolds and microelectrodes, or other tools ultimately aimed at a better understanding of neural tissue functions. in this review, we focus on nanomaterials and specifically on carbon-based nanomaterials, such as carbon nanotubes (cnts) and graphene. while these materials raise potential safety concerns, they represent a tremendous technological opportunity for the restoration of neuronal functions. we then describe nanotools such as nanowires and nano-modified mea for high-performance electrophysiological recording and stimulation of neuronal electrical activity. we finally focus on the fabrication of three-dimensional synthetic nanostructures, used as substrates to interface biological cells and tissues in vitro and in vivo.”
Liu, X., Ren, C., Lu, Y., Hattori, R., Shi, Y., Zhao, R., … Kuzum, D.. (2019). Decoding ECoG High Gamma Power from Cellular Calcium Response using Transparent Graphene Microelectrodes. In International IEEE/EMBS Conference on Neural Engineering, NER
“The ecog has been widely used in human brain research, while 2-photon microscopy has been broadly applied to basic neuroscience studies using animal models. bridging the gap between the 2-photon microscopy and the ecog is critical for transferring the vast amount of neuroscience knowledge obtained from animal models to human brain studies. here we develop an lstm recurrent neural network model to decode the ecog high gamma power from the cellular calcium activities obtained by multimodal ecog recordings and 2-photon calcium imaging enabled by transparent graphene microelectrode arrays. in both awake and anesthetized states, our model can successfully decode the stimulus-induced ecog high gamma power increases and its spontaneous fluctuations in the absence of stimulus.”
Lee, J. H., Shin, Y. C., Jin, O. S., Han, D. W., Kang, S. H., Hong, S. W., & Kim, J. M.. (2012). Enhanced neurite outgrowth of PC-12 cells on graphene-monolayer-coated substrates as biomimetic cues. Journal of the Korean Physical Society
Gutruf, P., Good, C. H., & Rogers, J. A.. (2018). Perspective: Implantable optical systems for neuroscience research in behaving animal models—Current approaches and future directions. APL Photonics
“Perspective: biomedical sensing and imaging with optical fibers-innovation through convergence of science disciplines apl photonics 3, 100902 (2018); doi.org/10.1063/1.5040861 invited article: enhanced four-wave mixing in waveguides integrated with graphene oxide apl photonics 3, 120803 (2018); doi.org/10.1063/1.5045509 single crystal diamond micro-disk resonators by focused ion beam milling apl photonics 3, 126101 (2018); doi.”
Geracitano, L. A., Fagan, S. B., & Monserrat, J. M.. (2021). Analysis of global and Latin-American trends in nanotoxicology with a focus on carbon nanomaterials: a scientometric approach. Journal of Chemical Technology and Biotechnology
“BACKGROUND: the scientific trends and developments in the field of nanotoxicology were analyzed through a scientometric approach. this study aimed to describe and unravel the main topics on nanomaterials concerning their potential toxicity. it was generated four databases: two for global nanotoxicological papers (ds1 and ds2) and two with a latin-american focus (la1 and la2). ds2 and la2 databases were constructed with studies dealing with the toxic effects of carbon nanomaterials. scientometric analyses were performed using citespace software. the following items were evaluated: frequencies, burst, centrality for co-citations of web of science categories, keywords, references, authors, and countries. results: global analysis resulted in a total of 29 798 papers for ds1 and 3835 for ds2. latin-american papers resulted in 1397 articles for la1 and 148 for la2. scientometric analyses indicated a specialization of the topics covered over time, ranging from general categories (such as chemistry) to more specialized ones (such as genetics or neurosciences). nano-silver prevailed in the nanotoxicological studies and graphene dominated in the field of carbon nanomaterials. in the last 5 years, a prominent growth has been observed in the number of studies that focus on the potential impact of nanomaterials on the environment. conclusion: the research efforts in nanotoxicology have been mainly concentrated on assays that use nano-silver; meanwhile, in carbon nanomaterials, the focus has been concentrated on toxicological tests with graphene. overall, we stress the importance of nanotoxicology as a strategy to obtain scientific information that can aid in the environmental sustainability of nanotechnologies.”
Abbasi, R.. (2018). Interpretable Machine Learning with Applications in Neuroscience. UC Berkeley Electronic Theses and Dissertations
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“This thesis is divided into two parts. in part i, we examine the properties of thin sheets of carbon and boron nitride. we begin with an introduction to the theory of elastic sheets, where the stretching and bending modes are considered in detail. the coupling between stretching and bending modes is thought to play a crucial role in the thermodynamic stability of atomically-thin 2d sheets such as graphene.”
Wang, L., Jiang, T., Song, Y., Shi, W., & Cai, X.. (2014). Dopamine detection using a patch-clamp system on a planar microeletrode array electrodeposited by polypyrrole/graphene nanocomposites. Science China Technological Sciences
Golparvar, A. J., & Yapici, M. K.. (2018). Graphene-coated wearable textiles for EOG-based human-computer interaction. In 2018 IEEE 15th International Conference on Wearable and Implantable Body Sensor Networks, BSN 2018
“Electrooculography (eog) is a well-known approach to analyze eye movement features. applications of eog can be found in various areas including medical diagnosis, neurosciences, control systems, sensors and interfaces for human-computer interaction (hci). however, standard gel-based electrodes limit wearability and portability which hinder the development of long-term eog monitoring applications. to overcome these limitations, we have employed graphene-coated fabric electrodes as suitable alternatives for the currently used silver/silver chloride (ag/agcl) ‘wet’ electrodes. proof of the concept is provided by side by side comparison of conventional electrodes and fabric electrodes in automatic blink detection with sequential multi-step thresholding algorithm. additionally, the eog biopotentials are converted into real-time digital signals which could be used as clock signals to facilitate the development of hci applications.”
Govindhan, M., & Chen, A.. (2016). Enhanced electrochemical sensing of nitric oxide using a nanocomposite consisting of platinum-tungsten nanoparticles, reduced graphene oxide and an ionic liquid. Microchimica Acta
“We describe a high-performance nitric oxide (no) sensor by using a nanocomposite consisting of platinum-tungsten alloy nanoparticles, sheets of reduced graphene oxide and an ionic liquid (ptw/rgo-il) that was deposited onto the surface of a glassy carbon (gc) electrode. the modified gc electrode exhibits excellent electrocatalytic activity toward the oxidation of no with a strong peak at 0.78 v vs. ag/agcl due to the synergistic effects of bimetallic ptw nanoparticles, reduced graphene oxide nanosheets and an ionic liquid. the sensor possesses a detection limit as low as 0.13 nm, high sensitivity (3.01 μa μm−1 cm2), and good selectivity over electroactive interferents that may exist in biological systems. the sensor was tested to selectively distinguish no in actual human serum and urine samples, confirming potential practical applications. in our perception, the approach described here may be extended to the fabrication of various kind of composites made from metal nanostructures, graphene and ionic liquids for medical and environmental analysis. [figure not available: see fulltext.]”
Monaco, A. M., & Giugliano, M.. (2015). Correction to Carbon-based smart nanomaterials in biomedicine and neuroengineering [Beilstein J. Nanotechnol. 5, (2014) 1849-1863] doi:10.3762/bjnano.5.196. Beilstein Journal of Nanotechnology
Vázquez-Guardado, A., Yang, Y., Bandodkar, A. J., & Rogers, J. A.. (2021). Author Correction: Recent advances in neurotechnologies with broad potential for neuroscience research (Nature Neuroscience, (2020), 23, 12, (1522-1536), 10.1038/s41593-020-00739-8). Nature Neuroscience
“In the version of this article initially published, errors occurred in the text and fig. 2 legend. in the paragraph beginning ‘advances in materials science are essential attempts…’ the platinum–silicone composites should have been described as ‘300 µm electrode diameter, 35 nm thickness, 1.4 ocm2 impedance, 57 µc/cm2 cics.’ in the paragraph beginning ‘microand nanofabrication techniques …’ the array of 360 recording sites for fast addressing should have been described as having sampling rates of ~277 hz. in the paragraph beginning ‘another area of progress …’ single- or few-layer sheets of graphene should have been described as having impedances of 1.6 ocm2 and 91 ocm2, respectively, while structures defined by colloidal sphere lithography and traditional photolithography should have been described as having impedances of 1.63 ocm2 and 0.14 oµm2, respectively. in the paragraph beginning ‘incorporating lenses and imaging …’ the phrase ‘at high sampling rates (16 hz) and fine resolution (~15 µm)’ should have cited ref. 74. in the fig. 2 legend, panel f should read ‘flexible array of 360 gold electrodes (300 × 300 µm2, spaced by 500 µm) supported by a backplane of active matrix electronics on a thin (25 µm) polyimide substrate for micro-electrocorticography (10 × 9 mm2) from the auditory cortex at a density of 400 electrodes cm–2.’ the references for panels g and h were swapped; they should read ‘g, ref. 34, springer nature; h, ref. 29, aaas.’ the errors have been corrected in the pdf and html versions of this article.”
Nasri, B., Wu, T., Alharbi, A., Gupta, M., Ranjitkumar, R., Sebastian, S., … Shahrjerdi, D.. (2017). Heterogeneous integrated CMOS-graphene sensor array for dopamine detection. In Digest of Technical Papers – IEEE International Solid-State Circuits Conference
“Understanding dopamine (da) signaling in the brain is essential for advancing our knowledge of pathological disorders such as drug addiction, parkinson’s disease, and schizophrenia. currently, fast-scan cyclic voltammetry (fscv) with carbon microfiber (cmf) electrodes is the method of choice in neuroscience labs for monitoring the concentration of phasic (transient) da release. this method offers sub-second temporal resolution and high specificity because the signal of interest occurs at a known potential. however, existing cmf electrodes are bulky, limiting the spatial resolution to single-site measurements. further, they are produced through manual processes (e.g. cutting cmfs under optical microscope), thus introducing significant device variability [1]. lastly, when long probes (3-to-5cm) are used to monitor da release in deep brain structures of large animals, environmental noise severely diminishes the detection limit [1]. to address these problems, we combine advances in nanofabrication with silicon chip manufacturing to create a heterogeneous integrated cmos-graphene sensor for accurate measurement of da with high spatiotemporal resolution (fig. 15.7.1).”
Tasnim, N.. (2018). An Integrated Study Towards Curing Neurodegenerative Disorders Using Materials Science and Stem Cell-based Tissue Engineering Approaches. ProQuest Dissertations and Theses
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“Neurodegenerative diseases affect around one billion people globally that are characterized by irreversible degeneration of brain tissues. these diseases cause serious effects on patients degrading their brain functions and causing enormous physical and mental health issues. parkinson’s disease (pd) is one of the most common neurodegenerative disorder affecting millions of people worldwide which results from loss of dopaminergic (da) neurons in the mid-brain. unfortunately, no medical treatment is effective to date for these significant brain disorders, except some symptomatic therapies only focusing on improving the quality of patient’s life. two current approaches hold great promise in targeting pd as well as other neurodegenerative diseases, by surgically implanting electrodes for deep brain stimulation (dbs) and transplanting healthy neuronal cells at the site of tissue loss, due to disease in the brain. however, cells for transplantation need to be delivered via a scaffold. nerve regeneration in a scaffold of appropriate biomaterial is of great importance while being implanted inside the animal body for further clinical applications. in this dissertation, both approaches for treating pd were incorporated by in vitro studies using surface-engineering and tissue-engineering techniques. for the first approach, graphene oxide (go) coatings on commercially available 316l stainless steel (ss) surfaces was done to reduce the neurotoxicity of ss and modified surfaces showed hydrophilicity, biocompatibility, cell proliferation, and decreased reactive oxygen species (ros) expression with shsy-5y neuroblastoma cell lines. transplantation of stem cells in vivo is another approach for reducing the progression of pd by reversing the loss of affected da neurons. so, our second approach included differentiation of mesenchymal stem cells into da neurons using sonic hedgehog, fibroblast growth factor, basic fibroblast growth factor and brain-derived neurotrophic factor, while they were cultured within collagen coated three-dimensional (3d) graphene foams. 3d multilayer graphene scaffold could mimic the actual brain tissue environment and more closely exhibit morphologies, functions and other necessary characteristics compared to 2d culture on tissue culture plastic. the graphene-based scaffolds were not cytotoxic as cells seemed to retain viability and proliferated substantially during in vitro culture. these results suggest the utility of graphene-based mater…”
Rastogi, S. K., & Cohen-Karni, T.. (2019). Nanoelectronics for neuroscience. In Encyclopedia of Biomedical Engineering
“Characterizing the electrical activity between neuronal cells is crucial in understanding the complex processes in the brain, both in healthy and diseased tissue. neural interface technology that enables recording of the neuronal electrical activity as well as stimulation of the neurons has attracted great attention for both experimental and clinical applications. in this article, we discuss the fundamentals of the bioelectrical signals recording, and the advancements in the field of nano-bioelectronics, that is, the different kinds of materials and designs used to improve the cellular-device interface to enable recording and stimulation of the neuronal cells. furthermore, we discuss the development of synthetic biomaterials that enable fusion of electronics and bioactive scaffolds which are essential to regenerative engineering. we also discuss the technical and scientific challenges associated with these technologies, and the future prospects and opportunities.”
Salazar, P., Martín, M., Ford, R., O’Neill, R. D., & González-Mora, J. L.. (2018). Neurotransmitter microsensors for neuroscience. In Encyclopedia of Interfacial Chemistry: Surface Science and Electrochemistry
“Brain communication is mediated by exocytosis release of neurotransmitters into the synaptic cleft. over the last four decades researchers have explored diverse electrochemical techniques for sensing different oxidizable catecholamines such as dopamine, serotonin, and norepinephrine and their metabolites in individual cells, culture cells, and in in vivo applications. nowadays, carbon fiber microelectrodes are still the gold standard in neurochemical and neurophysiological studies although new materials, such as carbon nanotubes, polymers, graphene, and nanoparticles, have been introduced to improve their sensitivity, selectivity, and long-term stability. this article reviews the main issues involved in the design and application of such electrochemical microsensors for in vivo monitoring of key electroactive neurotransmitters.”
“This chapter provides an overview of the features and application of emerging nanomaterials and miniaturized electronic circuits for in vitro neuroscience research. innovative detection methods and sensors based on nanomaterials offer unprecedented spatial and temporal resolution to elucidate patterns of neuronal firings less invasively and with better signal-to-noise ratio. the chapter begins with a brief discussion of nanoparticles and quantum dots{,} and their application in sensor technology. incorporation of one-dimensional nanostructures in cell cultures can be used to induce superior and directed neuronal adhesion and growth. possibilities for the use of nanowires as probes{,} nanoelectrodes{,} optical enhancers and electrical detectors are explored and the use of the amazing two-dimensional nanostructure graphene in the field of neuroscience is examined{,} including some of the challenges with incorporating graphene in sensing field effect transistors for detection of neural cells activity. example applications of nanotechnologies in neuroscience{,} ranging from sensing of structural deformation of cells to stimulation of neuroregeneration{,} are described. the chapter concludes with a perspective on the challenges and developments anticipated with the application of nanotechnologies in neuroscience.”
Liu, X., Lu, Y., & Kuzum, D.. (2018). Investigation of Propagating Cortical Waves and Spirals Recorded by High Density Porous Graphene Arrays. In Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBS
“Propagating waves along the cortical surface have recently attracted significant attention by the neuroscience community. however, whether these propagating waves imply network connectivity changes for the neural circuits is not known. in this work, we employ a high density porous graphene microelectrode array and perform in vivo experiments with rodents to investigate network connectivity during cortical propagating waves. the spatial-temporal analysis of the cortical recordings reveals various types of propagating waves across the recording area. network analysis results show that these propagating waves are consistent with the functional connectivity changes in the neural circuits, suggesting that the underlying network states are reflected by the cortical potential propagation patterns.”
Du, L., Hu, L., & Wu, C.. (2016). Micro/nano neuronal network cell biosensors. In Micro/Nano Cell and Molecular Sensors
“Neuronal network cell biosensors were developed by coupling the neuronal network with multisite detection devices. in this chapter, we will mainly focus on three major issues, including the patterned growth of neuronal networks, principles of various detection devices, and the application of neuronal network-based biosensors in the field of neuroscience and biomedicine. in the culture of neuronal networks, several neuronal patterning techniques will be discussed in detail, such as photolithography, micro-contact printing, microfluidics, etc. the transfection methods were employed in the bioengineering of neuronal networks in order to modify the function of neuronal network. in the field of neuronal network-based biosensor, there are two kinds of multisite detection devices: microelectrode array (mea) and field-effect transistor (fet). the basic working principle of fet and its advantages will be presented. based on this knowledge, two other emerging fetsutilized nanomaterials (graphene fet and nanowire fet) will also be introduced. at the end, some examples of neuronal network-based biosensors will be presented by discussing their application in the neuroscience research and drug detection.”
“Tubular microactuators (tmas) fabricated by photodeformable liquid crystal polymers (lcps) pave a significant way for smart microfluidic applications with contactless, spatial, and precise manipulation of liquids. to realize liquid transportation in these tmas, lcps should have excellent photodeformation property and suitable mechanical properties. herein, linear liquid crystal polymers (llcps) with different mesogen orientations are used to prepare tmas to study their liquid transportation behaviors. the mesogen orientation in each llcp is formed spontaneously and varies with the spacer length, leading to different deformations of llcp films. it is found that only llcps with mesogens oriented out-of-plane realize self-support of the tmas, whereas the tmas with mesogens oriented in-plane are so weak that they collapse in the radial direction, indicating the importance of mesogen orientation in fabricating three-dimensional structures. upon attenuated 470?nm light irradiation, the tmas deform to an asymmetric conical structure, leading to the motion of liquid slug toward the narrow side. the liquid motion is accelerated in the tma with longer spacer, showing the control of liquid speed by the mesogen orientation. these photocontrolled tmas are expected to be applied in biological applications, such as whole blood analysis and flow cytometry, for precise liquid manipulation.”
Tian, K., Yang, S., Niu, J., & Wang, H.. (2021). Enhanced Thermal Conductivity and Mechanical Toughness of the Epoxy Resin by Incorporation of Mesogens without Nanofillers. IEEE Access
“Epoxy resin is widely used due to its electrical insulation performances, but low elongation defects at the break, low thermal conductivity, and high brittleness limit its application scenarios. in this paper, the mesogen is utilized to improve the thermal conductivity and mechanical toughness of the traditional epoxy resin. both the mechanical performances, including the impact strength, tensile strength, the bending strength, and the thermal behaviors, including the thermal conductivity, are investigated. results show that with the biphenyl liquid crystal epoxy resin(blcer) content of 10%, the impacting strength, tensile strength, and bending strength are increased by 71%, 21%, and 11%, respectively. the thermal conductivity of the composites increases to 2.26 times that of pure epoxy resin. both the enhanced mechanical and thermal performance of the epoxy resin by the mesogen incorporation are further investigated. it is indicated that the mesogen in the biphenyl liquid crystal epoxy resin significantly improve both the mechanical toughness and thermal conductivity of the epoxy resin by the formation of the micro-crack behavior and the thermal conductive networks, respectively. with the aids of the mesogen, the improved variety of properties in epoxy resin without reducing its original performance is attractive in the industry application with great demand in the balance of the comprehensive performances.”
Wang, L., Zhang, Y., Zhan, C., You, Y., Zhang, H., Ma, J., … Wei, R.. (2019). Synthesis and photoinduced anisotropy of polymers containing nunchaku-like unit with an azobenzene and a mesogen. Polymers
“A series of polymers containing nunchaku-like unit with an azo chromophore and a mesogen group was successfully prepared and photoinduced anisotropy of the obtained polymers was minutely investigated. firstly, monomers containing nunchaku-like unit with an azo chromophore and a mesogen group linked by flexible group were synthesized. the structure of the monomers was confirmed via nmr cosy spectra. subsequently, the obtained monomers were polymerized into corresponding polymers through raft polymerization. the prepared polymer samples were characterized through nmr, ftir, gel permeation chromatography (gpc), and uv-vis testing while the thermal properties of the samples were investigated through differential scanning calorimeter (dsc) and thermogravimetric analysis (tga) measurements. the photoinduced isomerization of the polymers, which was researched in situ via measuring uv-vis spectra of the polymer solutions and spin-coated films under irradiation with 450 nm light or putting in darkness, demonstrated the rapid trans-cis-trans isomerization of the polymers. when irradiated with a linearly polarized light, significant photoinduced birefringence and dichroism were observed, suggesting photoinduced isomerization of azobenzene can drive orientation of mesogen in the system. this study blazes a way to design the optical materials with light-controllable birefringence and dichroism.”
Liu, C., Ding, W., Liu, Y., Zhao, H., & Cheng, X.. (2020). Self-assembled star-shaped aza-BODIPY mesogen affords white-light emission. New Journal of Chemistry
“A novel multifunctional star-shaped aza-bodipy mesogen was synthesized by a click reaction. this star-shaped aza-bodipy mesogen undergoes self-assembly into a hexagonal columnar phase in its bulk state and spherical gels in organic solvents. based on the investigation of the absorption and emission spectra and surface morphologies, j-aggregates are observed in their liquid crystalline (lc), gel and solid states, while h-aggregates are observed in n-hexane solution. additionally, this star-shaped aza-bodipy mesogen acts as a chemosensor toward cn- ions via a nucleophilic addition reaction, and the corresponding addition product can yield white light emission (wle) upon doping with blue dye. this star-shaped aza-bodipy mesogen is represented as the first example of an aza-bodipy derivative with lc, organogel and white light emission properties.”
Kawano, S. I., Kato, M., Soumiya, S., Nakaya, M., Onoe, J., & Tanaka, K.. (2018). Columnar Liquid Crystals from a Giant Macrocycle Mesogen. Angewandte Chemie – International Edition
“Columnar liquid crystals composed of a giant macrocyclic mesogen were prepared. the giant macrocyclic mesogen has a square hollow with a 2.5 nm diagonal, which was bounded by diindolo[3,2-b:2′,3′-h]carbazole (diindolocarbazole) moieties as the edges and bis(salicylidene)-o-phenylenediamine (salphen) moieties as the corners. the shape and size of the macrocycle were directly observed by scanning tunneling microscopy (stm). each side of the bright square in the stm image corresponds to a diindolocarbazole moiety, and the length of the sides was consistent with the result of the single crystal analysis of diindolocarbazole. finally, we successfully obtained a giant macrocycle with long and branched side chains, which exhibited a rectangular columnar lc phase over a wide temperature range. to the best of our knowledge, it contained the largest discrete inner space of any thermotropic columnar liquid crystal composed of macrocyclic mesogens.”
He, R., Wen, P., Ye, Y., Oh, E., Kang, S. W., Lee, S. H., & Lee, M. H.. (2020). Bulk-mediated in-situ homogeneous photoalignment induced by reactive mesogen containing diphenylacetylene moiety. Liquid Crystals
“We designed and synthesised a reactive mesogen containing diphenylacetylene moiety in the mesogenic core and two polymerisable acrylate groups at both ends. by irradiating linearly polarised uv light on the conventional host lc mixture containing a small amount of the synthesised reactive mesogen in a sandwiched cell without an alignment layer, we demonstrated an in-situ photo-induced homogeneous alignment of liquid crystals without a pre-treated alignment layer, which was achieved by an irreversible polarisation-selective [2 + 2] photodimerization of diphenylacetylene moiety with linearly polarised uv irradiation at above the isotropic temperature of lc mixture. the resulting homogeneous alignment showed a superior initial dark state, negligible pretilt angle and excellent stabilities. furthermore, the in-plane switching (ips) lc cell prepared by this method exhibited a better dark state and electro-optic performance compared to that with conventional-rubbed polyimide alignment layer. the single photoirradiation process automatically resulted in a perfect alignment matching of optical axes between the top and bottom substrates in the lc cell, giving rise to an excellent dark state overcoming an intrinsic misalignment issue and complex fabrication process. the proposed in-situ alignment method is a promising candidate for cost-effective, green-manufacturing, and high-quality alignment technique in the manufacturing of high-resolution liquid crystal displays.”
Kwok, M. H., Bohannon, C. A., Crooks, J. L., Li, R., Zhao, B., & Zhu, L.. (2020). Grafting density-induced smectic A to hexagonal columnar transition in mesogen-free isotactic liquid crystalline polyethers with n-dodecylsulfonyl side groups. Giant
“Highly dipolar mesogen-free liquid crystalline polymers are excellent candidates for achieving large spontaneous polarization under relatively low electric fields for advanced electrical and optical applications. in this report, the effect of grafting density of n-dodecylsulfonyl side chains on the mesogen-free liquid crystalline self-assembly of comb-like isotactic poly(oxypropylene) was studied. when the grafting density was 80–100%, a stable 21 helical chain conformation was induced by the strong dipole-dipole interactions among the sulfonyl groups in the side chains. consequently, a smectic a self-assembly was induced. when the grafting density decreased to 60–80%, a poor and possibly imbalanced 21 helical chain conformation was formed due to the frequent absence of the n-dodecylsulfonyl side chains along the main chain. as a result, a hexagonal columnar self-assembly was realized. this study demonstrated that a delicate interplay between the molecular defects and dipole-dipole interactions can lead to different self-assembly structures.”
Pan, H., Xiao, A., Zhang, W., Luo, L., Shen, Z., & Fan, X.. (2019). Hierarchical nanostructures of a liquid crystalline block copolymer with a hydrogen-bonded calamitic mesogen. Polymer
“With a pyridine derivative containing a calamitic mesogen 4-((6-((4’-((4-hexylphenyl)ethynyl)-[1,1′-biphenyl]-4-yl)oxy)hexyl)oxy)pyridine (hebc6) used as the hydrogen-bonding acceptor and polydimethylsiloxane-b-poly(2,5-bis(4-carboxy phenyl)styrene) (pdms-b-pm3h) as the hydrogen-bonding donor, a series of supramolecular liquid crystalline block copolymers (slcbcps) were prepared through hydrogen bonding. in the supramolecular block, the calamitic mesogen was decoupled from the motion of pm3h chains by using a flexible spacer. different microphase-separated nanostructures and liquid crystalline (lc) structures were obtained by varying the degree of polymerization of the pm3h block and the molar ratio of hebc6 to pdms-b-pm3h. the slcbcps can self-assemble into hexagonally packed cylinders (hex), lamellae (lam), and inverted hex. smectic a phase and parallel packing of the calamitic mesogens were also observed on a smaller length scale, and these two ordered structures are synergistic and promotional. therefore, hierarchically ordered structures can be obtained from these slcbcps.”
Wang, M., Bao, W. W., Chang, W. Y., Chen, X. M., Lin, B. P., Yang, H., & Chen, E. Q.. (2019). Poly[(side-on mesogen)-Alt-(end-on mesogen)]: A compromised molecular arrangement. Macromolecules
Keerthiga, R., Kaliyappan, T., & Kannan, P.. (2019). Studies on twist bent core zinc (II) methacrylate supramolecular columnar hexagonal phase mesogen derived from azobenzene moiety and its photo luminescent behaviours. Inorganic Chemistry Communications
“A class of zn(ii) polymethacrylate mesogen was tailored with photoluminescent property as well as high thermal stability by wrapping the zn(ii) metal in polymethacrylate mesogenic core. the versatile thermal stability of the mesophase was accounted by long chain terminal alkoxy groups and jacketed zn(ii) metal core. the extended stable mesophase with rise in temperature was achieved by excellent coordination between the supramolecular ligand with that of metal core. the schiff base was prepared by treating (1-bromo (4-dodecyloxy azobenzene)) with octadecyl amine in ethanolic medium. the schiff base obtained was polymerised with methacrylic acid (ma) in presence of aibn as free radical initiator. the supramolecular mesogenic ligand (pma-l) was further complexed with zn(ii) acetate in 1:1 m ratio. the zn(ii) supramolecular mesogen was extensively characterized by 1h nmr, 13c nmr and ft-ir. the mesomorphic behaviour was studied by xrd diffractogram, dsc, pom. the zn(ii) supramolecular exhibits columnar phase transition due the molecular stacking in disc shape. the disc shape mesophase of the zn(ii) supramolecular mesogen was achieved by sandwich pattern of metal core between two organic ligands arrangement. the photo physical character of the zn(ii)polymeric mesogen was studied by absorption and fluorescence spectral method.”
He, R., Oh, E., Ye, Y., Wen, P., Jeong, K. U., Lee, S. H., … Lee, M. H.. (2019). Fabrication of highly efficient coatable polarizer from tolane-based smectic reactive mesogen. Polymer
“This work is aimed to fabricate ultra-thin coatable polarizers on a single substrate based on ‘host-guest’ effect between highly ordered smectic reactive mesogen (rm) and dichroic dye. we designed and synthesized a new tolane-based rm with a highly ordered smectic a phase at room temperature. polymerizable ‘host-guest’ mixture was formulated from the host rm, dichroic dye and additives, then spin-coated on a single substrate having an alignment layer. subsequent in-situ photopolymerization by uv irradiation successfully resulted in a coatable polarizer with good polarizing properties. the fabricated coatable polarizer showed a dichroic ratio (dr) of 16.4 and a degree of polarization (dop) of 99.3% with the thickness of 4 μm. the resulting coatable polarizer possessed a considerable solvent resistance, good thermal stability and robust mechanical properties. moreover, we prepared a tn-mode lc cell by using the prepared coatable polarizers inside the cell (in-cell), in which the coatable polarizers acted as a polarizer and an alignment layer, simultaneously. the resulting tn cell with in-cell polarizers exhibited a decent electro-optical behavior. we believe that the coatable polarizer proposed in this study possesses practical application potential in ultra-thin lcds or flexible oleds.”
Lyu, X. L., Pan, H. B., Shen, Z. H., & Fan, X. H.. (2018). Self-assembly and Properties of Block Copolymers Containing Mesogen-Jacketed Liquid Crystalline Polymers as Rod Blocks. Chinese Journal of Polymer Science (English Edition)
“Mesogen-jacketed liquid crystalline polymer (mjlcp) has attracted great attention because of its rigid conformation, facile synthesis, and structural controllability. in this feature article, the self-assembly of mjlcp-based block copolymers (bcps) is briefly reviewed, especially the nanostructures of rod-coil diblock copolymers (dibcps), rod-rod dibcps, and triblock copolymers. in addition, the properties of the self-assembled bcps are also summarized, including their applications as liquid crystalline thermoplastic elastomers and solid polymer electrolytes. the article also discusses the major challenges and future directions in the study of mjlcp-based bcps.”
Lee, M., Bae, J. W., Kim, A., Yun, H. S., & Song, K.. (2015). Alignments of reactive mesogen using rubbed glass substrates. Polymer (Korea)
“Alignments of photo-reactive mesogen were induced using bare glass substrates without a polymer alignment layer. it was found by using polarized ftir spectroscopy, polarized microscopy, and birefringence measurement experiments that the reactive mesogen could be aligned along the rubbing direction although the glass substrate without an alignment layer was used. the induction mechanism of the rubbed bare glass is ascribed to that polymers from rubbing clothes are coated on the glass substrate along the rubbing direction and lead the alignment of liquid crystals through intermolecular interactions.”
Kamarudin, M. A., Khan, A. A., Williams, C., Rughoobur, G., Said, S. M., Nosheen, S., … Wilkinson, T. D.. (2016). Self-assembled liquid crystalline nanotemplates and their incorporation in dye-sensitised solar cells. Electrochimica Acta
“Liquid junction dye-sensitised solar cells (dsscs) suffer from solvent evaporation and leakage which limit their large-scale production. here, we have prepared dssc using a simple and cheap fabrication process with improved photovoltaic parameters and stability. a binary mixture of smectic a (sma) and nematic liquid crystal (nlc) was used to provide a self-assembled template for a polymerisable reactive mesogen lc. the layered structure of sma combined with a low viscosity nlc forms a polygonal structure that provides an ordered and continuous template for reactive mesogens. once the reactive mesogen is polymerised under uv light, the sma:nlc mixture is washed away, resulting in a polymer network template containing nanochannels. we demonstrate the incorporation of these templates into dsscs and find that dsscs containing these nanochannels show improved open-circuit voltage (voc) (0.705 v) and short-circuit current (jsc) (13.25 ma cm−2) compared to that of the liquid electrolyte (voc = 0.694 v and jsc = 10.46 ma cm−2). the highest obtained power conversion efficiency with sm-pe was 5.94% which is higher than that of the reference solar cell (5.51%). these can be attributed to the improved ionic conductivity and ionic diffusion of sm-pe where the presence of the nanochannels aided the ionic conduction in the polymer electrolyte. in addition, it is hypothesized that the light scattering effect of the polymerised reactive mesogen also contributed to the improved performance of the photovoltaic devices. this finding is important because it is known fact that when a polymer is added to liquid electrolyte, the ionic conductivity will decrease although the stability is improved.”
Yeom, Y. S., Cho, K. Y., Seo, H. Y., Lee, J. S., Im, D. H., Nam, C. Y., & Yoon, H. G.. (2020). Unprecedentedly high thermal conductivity of carbon/epoxy composites derived from parameter optimization studies. Composites Science and Technology
“Efficient removal of heat accumulation from electronic devices has been considered an important issue because it is prone to induce reduced lifetime, heat shock, ignition, and malfunction during their operation. to that end, optimized epoxy composites, which are fabricated by dispersing a mesogen-containing polymer compatibilizer (bpib)-applied multi-layered graphene nanoplate (mgnp) filler into a mesogen-containing epoxy (dgebp) matrix (bpib-mgnp/epoxy), are designed toward high thermal conductivity at the low filler loading content. various effects on its thermal conductivity, including size, thickness, and dispersion of fillers along with the crystalline property of epoxy, are systematically investigated by comparing with their intermediate counterpart materials. the extended micromechanics model, which was modified using a power law from its initial one, was employed to address the filler size effects on its thermal conductivity as well as an exponential increase of thermal conductivity with increasing filler loading content. thickness effects of carbon fillers are examined by comparing gnp/epoxy composites with single-layered graphene filler-based epoxy composites. the effects of dispersion properties of the fillers in the epoxy composites are also investigated using the theory prediction plot based on the extended micromechanics model. the comparison between experimental and theoretical prediction led us to study crystalline properties of the bpib-mgnp/epoxy composites because it was unexpected and beyond the theoretical traces. an ashby plot is prepared to evaluate the state of our results by comparing them with the reported state-of-the-art composite performances.”
Palani, T., Saravanan, C., & Kannan, P.. (2011). Pendant triazole ring assisted mesogen containing side chain liquid crystalline polymethacrylates: Synthesis and characterization. Journal of Chemical Sciences
Lugger, J. A. M., Mulder, D. J., Bhattacharjee, S., & Sijbesma, R. P.. (2018). Homeotropic Self-Alignment of Discotic Liquid Crystals for Nanoporous Polymer Films. ACS Nano
“Nanostructured polymer films with continuous, membrane-spanning pores from polymerizable hexagonal columnar discotic liquid crystals (lcs) were fabricated. a robust alignment method was developed to obtain homeotropic alignment of columns between glass surfaces by adding a small amount of a tri(ethylene glycol) modified analogue of the mesogen as a dopant that preferentially wets glass. the homeotropic lc alignment was fixated via a photoinitiated free radical copolymerization of a high-temperature tolerant trisallyl mesogen with a divinyl ester. removal of the hydrogen-bonded template from the aligned columns afforded a nanoporous network with pores of nearly 1 nm in diameter perpendicular to the surface, and without noticeable collapse of the nanopores. the effect of pore orientation was demonstrated by an adsorption experiment in which homeotropic film showed a threefold increase in the initial uptake rate of methylene blue compared to planarly aligned films.”
Baliyan, V. K., Lee, B., & Song, J. K.. (2020). Quantum Dot Arrays Fabricated Using in Situ Photopolymerization of a Reactive Mesogen and Dielectrophoresis. ACS Applied Materials and Interfaces
“Dielectrophoresis (dep) is an excellent tool for manipulating small particles within a liquid or gas medium. however, when the size of the particles is too small, such as with quantum dots (qds), it is difficult to manipulate the particles using dep because the dielectrophoretic force (fdep) depends on the volume of the particles and is therefore too weak to achieve particle migration. herein, we demonstrate a novel method for controlling nanoscale qd particles using dep by introducing photopolymerized reactive mesogen (rm) bead vehicles. the size of an rm bead is well-controlled by the rm concentration in the medium, and when the size is approximately 0.2 μm or larger, the rm beads can be arbitrarily manipulated using dep under moderate electric fields. interestingly, during photopolymerization, qd particles are easily absorbed by polymerized rm beads and most of the qds are embedded within the rm beads. hence, we can fabricate periodic qd arrays by manipulating the rm beads containing such dots. in addition, we can fabricate multicolor qd arrays by repeating the processes using different qd particles. the shape of a dep-assisted qd-rm network pattern can be precisely predicted by calculating the gradient of the square of the electric field (σe2) and the corresponding fdep. this new technology may be useful for the fabrication of optical devices, displays, photonic crystal devices, and bioapplications.”
Ndaya, D., Bosire, R., Vaidya, S., & Kasi, R. M.. (2020). Molecular engineering of stimuli-responsive, functional, side-chain liquid crystalline copolymers: Synthesis, properties and applications. Polymer Chemistry
“This review describes the recent progress made in designing stimuli-responsive, functional, side-chain, end-on mesogen attached liquid crystalline polymers (lcps). developments in synthetic methodologies including controlled and living techniques provide an easy access to well-defined liquid crystalline polymers. for example, the synthesis of linear liquid crystalline block copolymers (lcbcps), block copolymers with a linear, coil-coil, non-lc block and an end-on mesogen attached lc block, provides a route to polymers with morphology and properties akin to conventional block copolymers. however, synthesis of topologically branched lcbcps with a branched coil-coil non-liquid lc block and an end-on mesogen attached lc block is used to manipulate the phase behavior, morphology and alignment kinetics of the resultant polymer. furthermore, synthesis of branched liquid crystalline random copolymers wherein the branched coil-coil non lc unit and end-on mesogen lc unit are statistically distributed results in never-before-seen helical and curved interfaces with new and enhanced properties. finally, synthetic strategies to incorporate organic dye molecules into a variety of liquid crystalline polymer frameworks produce new optically active and adaptive soft materials. in the outlook section, the need for topologically diverse synthetic and naturally derived liquid crystalline polymer architectures along with processing tools and field directed assemblies to produce functional materials and their applications are discussed. this journal is”
Ishinabe, T., Isa, H., Shibata, Y., & Fujikake, H.. (2021). Flexible polymer network liquid crystals using imprinted spacers bonded by UV-curable reactive mesogen for smart window applications. Journal of Information Display
“We propose junction-type, vertically aligned polymer network liquid crystals using plastic substrates for flexible smart windows, in which the spacers are formed with the imprinting method and are bonded to the substrate surface by uv-curable reactive mesogen (rm). we clarified that the optical property can be improved by suppressing the aggregation of rms around the spacers through thinning of the coating of the rm and the simultaneous improvement of the wettability of the parallel alignment film. we achieved excellent haze properties of 3.0% with voltage off and 92.7% with voltage on, and high curvature performance with a small curvature radius of 9.0 mm.”
Yu, E. S., Kim, S. U., Suh, J. H., Kim, J., Na, J. H., & Lee, S. D.. (2016). The domain mixing effect on the electro-optical properties of liquid crystals using polyimide doped with reactive mesogen. Journal of Information Display
“This paper investigates the enhancement of the electro-optic (eo) properties of liquid crystal (lc) devices by the domain mixing effect of vertical-alignment polyimide (pi) doped with reactive mesogen (rm). the mixture of pi and rm on a glass substrate was exposed to ultraviolet light and was thermally annealed to produce circular microdomains of the lc polymer (lcp) in the pi background. due to the appearance of such lcp microdomains depending on the rm doping concentration, the eo properties such as the threshold voltage and the response times were significantly improved in a vertically aligned configuration of the lcs.”
Chen, X. F., Shen, Z., Wan, X. H., Fan, X. H., Chen, E. Q., Ma, Y., & Zhou, Q. F.. (2010). Mesogen-jacketed liquid crystalline polymers. Chemical Society Reviews
“The photoinduced surface relief formation via mass transfer upon irradiation with patterned light has long been a subject of extensive investigation. in azobenzene-containing liquid crystalline materials, uv light irradiation that generates the cis isomer leads to the liquid crystal to isotropic photochemical transition. due to this phase change, efficiency of the mass transfer to generate a surface relief grating (srg) becomes markedly greater. we have previously indicated that azobenzene-colored srg-inscribed film can be bleached by removing a hydrogen-bonded azobenzene mesogen. however, this process largely reduces the height feature of the srg corrugation. herein, we propose an extended procedure where a colorless mesogen is filled successively after the removal of the azobenzene side chain. the process involves four stages: (i) srg inscription in a hydrogen-bonded supramolecular azobenzene material; (ii) crosslinking (insolubilization) of the srg film; (iii) removal of azobenzene mesogen by rinsing with a solvent, and (iv) stuffing the hollow film with a different mesogen. although the final stuffing stage was insufficient at the present stage, this work demonstrates the possibility and validity of the strategy of mesogen replacement.”
Lehmann, M., Hecht, M., Herbst, S., Cui, K., & Würthner, F.. (2020). Unfolding multi-stranded perylene bisimide LC columns-a mesogen design for efficient nanoscale multilayer self-assembly. Chemical Communications
“A mesogen tethered, twofold bay-substituted perylene bisimide (pbi) is found to generate a columnar phase, which unfolds and gradually transforms to a completely nanosegregated multilayer columnar-lamellar liquid crystal. the structure is based on the formation of bundles of h-bonded pbi strands in the central layer. this design opens the way to new complex multifunctional materials. this journal is”
Orodepo, G. O., Bhoje Gowd, E., & Ramakrishnan, S.. (2020). Periodically spaced side-chain liquid crystalline polymers. Macromolecules
“The melt-transesterification polymerization of diethyl malonate derivatives bearing a pendant mesogen, with α,ωalkanediols of varying lengths generated a series of side-chain liquid crystalline polymers, wherein the intervening backbone alkylene spacer segment was systematically varied; the effect of the backbone spacer segment on the liquid crystalline property was examined using differential scanning calorimetry (dsc), x-ray scattering, and polarizing light microscopic investigations. two different mesogen units, based on 4,4’-dialkoxydiazobenzene or 4,4’-dialkoxybiphenyl, were examined; it was seen that most polyesters derived from the diazobenzene mesogen exhibited a stable nematic mesophase, whereas most of those based on biphenyl transformed directly to an isotropic melt. x-ray scattering studies revealed that the polymers carrying biphenyl units formed a well-ordered lamellar structure in the solid state, which was interpreted as being generated via the zigzag folding of the polymer backbone, thus permitting the pendant mesogens and the folded backbone to occupy alternate layers. based on the slope of the linear variation of the interlamellar spacing as a function of backbone segment length, it was inferred that the backbone is not in an extended all-trans conformation but is disordered; from the value of the intercept, which roughly corresponded to the length of an extended pendant mesogenic segment, it was inferred that the pendant mesogens were interdigitated. the formation of a highly ordered structure in the solid state appears to drive up the melting transition and preclude the formation of the liquid crystalline (lc) phase in the biphenyl series; however, when a flexible hydrophilic tetra(oxyethylene) spacer was incorporated, the polyester revealed a stable mesophase owing to the significant lowering of the melting transition. comparison of pairs of isomeric polyesters, one having the mesogen within the pendant segment and the other within the backbone, revealed the strong tendency for the main-chain isomer to exhibit smectic mesophases, whereas the side-chain isomer exhibited a nematic mesophase.”
Sensorische Augmentation
Die sensorische Augmentation zielt darauf ab, den sensorischen Bereich oder die Schärfe zu erweitern, indem entweder Geräte oder Wearables verwendet werden, die externe Informationen für die menschlichen Sinne “übersetzen”, oder indem die angeborenen Sinne modifiziert werden. Informationen können durch eine Kombination von Sensoren gesammelt werden, die am Körper angebracht oder implantiert sind. Die Sinne können erweitert werden, indem Frequenzen außerhalb des normalen menschlichen Bereichs in Frequenzen übersetzt werden, die gesehen, gehört oder anderweitig erkannt werden können. Dies könnte es dem Benutzer ermöglichen, durch Wände hindurch zu sehen”, Vibrationen zu spüren und in der Luft befindliche Chemikalien sowie Veränderungen in Magnetfeldern zu erkennen. Es wurden auch invasivere Optionen zur Verbesserung der vorhandenen Sinne demonstriert, z. B. die Beschichtung von Netzhautzellen mit Nanopartikeln, um das Sehen im Infrarotspektrum zu ermöglichen.
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Zukünftige Möglichkeiten. Die möglichen Anwendungen von Gehirnschnittstellen sind atemberaubend. Zu den therapeutischen Vorteilen könnten gehören: Heilung von Lähmungen, Wiederherstellung des Seh- und Hörvermögens, Management der geistigen Gesundheit und Behandlung der Alzheimer-Krankheit. Gehirnschnittstellen könnten auch als leistungsstarke Diagnosewerkzeuge eingesetzt werden und die Entwicklung anderer Technologien und Methoden zur Augmentation des Menschen beeinflussen. In Bezug auf die Augmentation könnten Gehirnschnittstellen: die Konzentration und Gedächtnisfunktion verbessern, zu neuen Formen der kollaborativen Intelligenz führen oder sogar ermöglichen, dass neue Fähigkeiten und Wissen einfach “heruntergeladen” werden. Auch die Manipulation der physischen Welt allein mit Gedanken wäre möglich; vom Türgriff bis zum Flugzeug könnte theoretisch und neuerdings auch praktisch alles von jedem Ort der Welt aus gesteuert werden.
Das Projekt ist eine bilaterale Kooperation zwischen dem Amt für Wehrplanung der Bundeswehr in Deutschland und dem Development, Concepts and Doctrine Centre in Großbritannien. Die Ergebnisse des Projekts zu den strategischen Implikationen werden für ein breites Publikum im gesamten Verteidigungs- und Sicherheitssektor relevant sein. Obwohl es sich nicht um eine wissenschaftliche Publikation handelt, stützt sie sich in hohem Maße auf Forschungsergebnisse, um einen Überblick über die wichtigsten Chancen und Gefahren zu geben. Viele Technologien, die das Potenzial haben, bis zum Jahr 2050 einen strategischen Vorteil zu bieten, existieren bereits, und weitere Fortschritte werden zweifelsohne eintreten.
Wichtige Schlussfolgerungen und Erkenntnisse (S.23)
-Menschen haben seit Anbeginn der Menschheit versucht, sich selbst zu verbessern – aber in den nächsten 30 Jahren wird sich unsere Fähigkeit, den menschlichen Körper zu manipulieren, radikal verbessern.
-Human Augmentation umfasst Wissenschaft und Technologien, die die menschliche Leistung optimieren oder verbessern.
-Es gibt viele verschiedene Definitionen von menschlicher Augmentation. Es ist wichtig, einen Konsens und einen einheitlichen Ansatz für die menschliche Augmentation zu finden, damit die verschiedenen Disziplinen effektiv zusammenarbeiten und ihre Vorteile nutzen können.
-Wir müssen einen menschenzentrierten Ansatz wählen, um die Möglichkeiten der Human Augmentation zu nutzen. Die Betrachtung des Menschen als Plattform – mit physischen, psychologischen und sozialen Aspekten – wird dabei zentral sein.
-Zunehmende Datenmenge, Komplexität und Geschwindigkeit stellen die Rolle des Menschen im Krieg in Frage, werden ihn aber nicht ersetzen: Krieg ist ein menschliches Unterfangen; Menschen haben Fähigkeiten, die von Maschinen noch nicht übertroffen werden; und kulturelle und gesellschaftliche Normen werden Zeit brauchen, um die Rolle von Maschinen zu akzeptieren.
-Die Augmentation des Menschen ist unvermeidlich, denn: Wir haben bereits Technologien entwickelt und es gibt kein Zurück mehr; es gibt Bedrohungen und Chancen, die wir angehen sollten; und es gibt eine wachsende Nachfrage seitens der Gesellschaft.
Ministry of Defence
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Sensory augmentation
Sensory augmentation aims to extend the sensory range or acuity either by using gadgets or wearables to ‘translate’ external information for the human senses or by modification of innate senses. Information can be collected through a combination of sensors mounted or implanted on the body. The senses can be extended by translating frequencies beyond the normal human range into frequencies that can been seen, heard or otherwise detected. This could allow the user to ‘see’ through walls, sense vibrations and detect airborne chemicals and changes to magnetic fields. More invasive options to enhance existing senses have also been demonstrated, for example, coating retinal cells with nanoparticles to enable vision in the infrared spectrum.
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Future opportunities. The potential applications of brain interfaces are staggering. Therapeutic benefits could include: cure of paralysis; restoration of sight and hearing; mental health management; and treatment for Alzheimer’s disease. Brain interfaces could also be used as powerful diagnostic tools and inform the development of other human augmentation technologies and methods. In terms of augmentation, brain interfaces could: enhance concentration and memory function; lead to new forms of collaborative intelligence; or even allow new skills and knowledge to be simply ‘downloaded’. Manipulating the physical world with thoughts alone would also be possible; anything from a door handle to an aircraft could, in theory and more recently in practice, be controlled from anywhere in the world.
The project is a bilateral cooperation between Bundeswehr Office for Defence Planning in Germany and the Development, Concepts and Doctrine Centre in the UK. The output from the strategic implications project will be relevant to a wide audience across the defence and security sector. Whilst this is not a scientific publication, it draws extensively on research to provide an overview of where the key opportunities and threats are. Many technologies that have the potential to deliver strategic advantage out to 2050 already exist and further advances will undoubtedly occur.
Key deductions and insights (p.23)
•People have sought to augment themselves since the dawn of humanity – but over the next 30 years our ability to manipulate the human body will radically improve.
•Human augmentation encompasses science and technologies that optimise or enhance human performance.
•There are many different definitions of human augmentation. Finding consensus and an agreed approach to human augmentation will be essential in allowing different disciplines to collaborate effectively and realise its benefits.
•We need to adopt a human-centric approach to realise the opportunities of human augmentation. Thinking of the human as a platform – with physical, psychological and social aspects – will be central to this.
•Increasing data, complexity and speed is challenging the role of people in war but will not replace them: war is a human endeavour; people have skills that are still unrivalled by machines; and cultural and societal norms will take time to accommodate the role of machines.
•Human augmentation is inevitable because: we have already developed technologies and there is no going back; there are threats and opportunities that we should address; and there is a growing demand from society.
