Intracortical neural microelectrodes,which can directly interface with local neural microcircuits with high spatial and temporal resolution,are critical for neuroscience research,emerging clinical applications,and bra...Intracortical neural microelectrodes,which can directly interface with local neural microcircuits with high spatial and temporal resolution,are critical for neuroscience research,emerging clinical applications,and brain computer interfaces(BCI).However,clinical applications of these devices remain limited mostly by their inability to mitigate inflammatory reactions and support dense neuronal survival at their interfaces.Herein we report the development of microelectrodes primarily composed of extracellular matrix(ECM)proteins,which act as a bio-compatible and an electrochemical interface between the microelectrodes and physiological solution.These ECM-microelectrodes are batch fabricated using a novel combination of micro-transfer-molding and excimer laser micromachining to exhibit final dimensions comparable to those of commercial silicon-based microelectrodes.These are further integrated with a removable insertion stent which aids in intracortical implantation.Results from electrochemical models and in vivo recordings from the rat’s cortex indicate that ECM encapsulations have no significant effect on the electrochemical impedance characteristics of ECM-microelectrodes at neurologically relevant frequencies.ECM-microelectrodes are found to support a dense layer of neuronal somata and neurites on the electrode surface with high neuronal viability and exhibited markedly diminished neuroinflammation and glial scarring in early chronic experiments in rats.展开更多
Extracellular matrix(ECM)-based implantable neural electrodes(NEs)were achieved using a microfabrication strategy on naturalsubstrate-based organic materials.The ECM-based design minimized the introduction of non-natu...Extracellular matrix(ECM)-based implantable neural electrodes(NEs)were achieved using a microfabrication strategy on naturalsubstrate-based organic materials.The ECM-based design minimized the introduction of non-natural products into the brain.Further,it rendered the implants sufficiently rigid for penetration into the target brain region and allowed them subsequently to soften to match the elastic modulus of brain tissue upon exposure to physiological conditions,thereby reducing inflammatory strain fields in the tissue.Preliminary studies suggested that ECM-NEs produce a reduced inflammatory response compared with inorganic rigid and flexible approaches.In vivo intracortical recordings from the rat motor cortex illustrate one mode of use for these ECM-NEs.展开更多
基金This work was primarily funded by the National Institutes of Health(NIHR21-EB022209(Allen))+2 种基金with additional support from the NIH(U01-NS094340(Cullen))the Dept.of Veterans Affairs(Merit Review Award#B1097-I(Cullen))Microfabrication was carried out in the Singh Center for Nanotechnology,supported in part by the US National Science Foundation National Nanotechnology Coordinated Infrastructure Program under Grant 15-42153.
文摘Intracortical neural microelectrodes,which can directly interface with local neural microcircuits with high spatial and temporal resolution,are critical for neuroscience research,emerging clinical applications,and brain computer interfaces(BCI).However,clinical applications of these devices remain limited mostly by their inability to mitigate inflammatory reactions and support dense neuronal survival at their interfaces.Herein we report the development of microelectrodes primarily composed of extracellular matrix(ECM)proteins,which act as a bio-compatible and an electrochemical interface between the microelectrodes and physiological solution.These ECM-microelectrodes are batch fabricated using a novel combination of micro-transfer-molding and excimer laser micromachining to exhibit final dimensions comparable to those of commercial silicon-based microelectrodes.These are further integrated with a removable insertion stent which aids in intracortical implantation.Results from electrochemical models and in vivo recordings from the rat’s cortex indicate that ECM encapsulations have no significant effect on the electrochemical impedance characteristics of ECM-microelectrodes at neurologically relevant frequencies.ECM-microelectrodes are found to support a dense layer of neuronal somata and neurites on the electrode surface with high neuronal viability and exhibited markedly diminished neuroinflammation and glial scarring in early chronic experiments in rats.
基金This work was funded by the Defense Advanced Research Projects Agency(DARPA)MTO under the auspices of Dr.Jack Judy through the Space and Naval Warfare Systems Center,Pacific Grant/Contract No.N66001-11-1-4014.
文摘Extracellular matrix(ECM)-based implantable neural electrodes(NEs)were achieved using a microfabrication strategy on naturalsubstrate-based organic materials.The ECM-based design minimized the introduction of non-natural products into the brain.Further,it rendered the implants sufficiently rigid for penetration into the target brain region and allowed them subsequently to soften to match the elastic modulus of brain tissue upon exposure to physiological conditions,thereby reducing inflammatory strain fields in the tissue.Preliminary studies suggested that ECM-NEs produce a reduced inflammatory response compared with inorganic rigid and flexible approaches.In vivo intracortical recordings from the rat motor cortex illustrate one mode of use for these ECM-NEs.