Construction Of Implantable PEDOT:PSS Conducting Polymer Neural Electrode Interface For Neural Signal Recording

Research in neurobioelectronics is crucial for understanding the fundamental mechanisms of the human mind and treating neurological disorders.With advancements in microelectronic implantation technology,the integration of AI technology with neurobioelectronics holds great promise in developing braincompatible "Electropharmacy" for the treatment of neurodegenerative and neurological disorders.Implantable neural microelectrodes act as a link between brain tissue and electronic devices,enabling the implementation of functional microdevices for neuronal stimulation or recording to address and assess abnormal brain activity.Most existing neural microelectrodes are made of rigid materials such as silicon or metals(e.g.,platinum,iridium,tungsten,nickel-chromium)that directly contact brain tissue.However,these materials possess inferior electrochemical properties,mismatched mechanical properties,poor biocompatibility,and cannot provide long-term stable neural stimulation and recording.To overcome these scientific challenges,there is a need to develop high-performance,tailored,and non-invasive neural microinterfaces that can establish optimal connections between neural electrodes and neural tissues.In the last few decades,conducting polymer-based interfaces have garnered significant attention as buffer barrier materials between neural microelectrodes and brain tissue.Specifically,poly(3,4-dioxoethylenethiophene):poly(styrenesulfonate)(PEDOT:PSS)has emerged as a material of interest in various research and applications within neurobioelectronic interfaces,including implantable electrode recording and stimulation,neuroregeneration,and therapeutic drug delivery.Neural microelectrodes modified with PEDOT:PSS-based conducting polymer interfaces exhibit high signalto-noise ratio(SNR)recording conductivity,charge injection capability for safe and efficient stimulation,and mechanical properties resembling that of tissue.However,despite these advantages,the current conductive polymer-based interfaces still face performance limitations when exposed to the brain tissue environment.These limitations include a high Young’s modulus,weak interfacial adhesion,poor long-term stability,and tissue mismatch.These factors significantly impede commercialization and practical applications of the device.Therefore,the rational design of high-performance microelectrode interfaces,the comprehensive evaluation of performance metrics,and the construction of microelectrode devices are key factors determining the practical application of conductive polymer neural microelectrodes.In this dissertation,PEDOT:PSS-based conducting polymers have been utilized as interfacial conductive layers to enhance capacitance and ion-electron transport.Multiple interfaces have been designed and prepared,including the strongly adhesive and high-capacitance PEDOTMe OH:PSS/PDA microelectrode interface,the soft and robust PU-PEDOT:PSS hydrogel interface constructed through a facile one-step electrolysis technique.Additionally,a high-performance conducting polymer hydrogel modified at the miniaturized and multi-channel microelectrode interface has been achieved for the first time,successfully implanted into the brain for long-term stable recording.The interfacial adhesion mechanism and the structural relationship of the conducting polymer hydrogel phase network have been investigated.The mechanical,electrochemical,and in vivo neural signal recording capabilities of conducting polymer interfaces have been systematically examined,and a new evaluation method for the long-term stability of neural electrode interfaces has been proposed.Finally,microelectrode devices modified with conducting polymer hydrogel interfaces have been successfully implanted into the mouse cerebral cortex,enabling high-resolution chronic neurophysiological recordings.These findings provide technical support and theoretical guidance for the microdevice’s commercialization and practical application of PEDOT:PSS-based conducting polymer interfaces.The research details and results are as follows:1.An adhesive interfacial anchoring strategy is proposed to fabricate interpenetrating conducting polymer networks through a two-step electropolymerization process,aiming to create a strongly adhesive PEDOTMe OH:PSS/PDA interface.This strategy addresses the issues of weak adhesion and low capacitance commonly observed in existing conducting polymer interfaces used in the field of neurobioelectronics.Conducting polymers have shown great potential as neural interfaces due to their superior biocompatibility,electrical properties,and mechanical characteristics,making them suitable for diverse applications such as deep brain stimulation.However,current conducting polymer-based neural interfaces face several challenges and limitations including complex fabrication procedures,weak interfacial adhesion,poor long-term stability and fidelity,and expensive microfabrication,which greatly hinder their widespread practical applications and commercialization.In this study,we have developed an adhesive and long-term stable conducting polymer neural interface using a simple twostep electropolymerization method.The methodology involves pre-polymerization of polydopamine(PDA)as an adhesive thin layer,followed by electropolymerization of hydroxymethylated 3,4-ethylenedioxythiophene(EDOT-Me OH)with polystyrene sulfonate(PSS)to form stable interpenetrating PEDOT-Me OH:PSS/PDA networks.The resulting PEDOT-Me OH:PSS/PDA interface exhibits significantly improved interfacial adhesion to metallic electrodes,demonstrating 93% area retention even under vigorous sonication for 20 minutes.This represents one of the most robust conducting polymer interfaces reported to date.Utilizing this simple methodology,we can easily fabricate the PEDOT-Me OH:PSS/PDA interface on ultrasmall Pt-Ir wire microelectrodes(diameter: 10 μm).The modified microelectrodes exhibit two orders of magnitude lower impedance compared to commercial products and demonstrate superior long-term stability,with a retention of high charge injection capacity up to99.5% after 10,000,000 biphasic input pulse cycles.These findings highlight the potential of this simple methodology and the fabricated high-performance and stable neural interface as a powerful tool for advanced neuroscience research and cutting-edge clinical applications,such as brain-controlled intelligence.2.We propose a composite copolymeric microphase semi-separated conducting polymer hydrogel strategy,which is a novel approach in the field of neuro-bioelectronics.This strategy utilizes a simple and cost-effective one-step electrical synthesis method to construct a soft and robust PU-PEDOT:PSS hydrogel interface,leading to a breakthrough in conducting polymer hydrogel research and standardizing the evaluation system of neural electrode interfaces.Our approach involves the construction of a hydrogel interface with a bicontinuous microphase semi-separated phase network structure using PEDOT:PSS and polyurethane(PU)through a molecular mechanical interlocking strategy.The PU-PEDOT:PSS hydrogel interface prepared using this method exhibits several advantageous properties.It is softer(with a Young’s modulus of approximately10 MPa)compared to the PEDOT:PSS interface,making it more compatible with brain tissue.The interface demonstrates stable adhesion to the electrode interface,as evidenced by no significant delamination occurring even after ultrasound treatment lasting more than one hour.Additionally,the interface shows excellent long-term stability in vitro,with less than a 10% change in charge injection capacity(CIC)value after 500 million cycles of bidirectional injection pulse stimulation.With its advantageous properties and the utilization of a simple and cost-effective electrochemical integration technique,the electro-polymerized PU-PEDOT:PSS hydrogel interface can be successfully integrated with commercial electrodes.This integration enhances the performance of commercial electrode products and provides theoretical guidance in the field of brain-computer interfaces.The cost-effectiveness and ease of integration offered by the PU-PEDOT:PSS hydrogel interface contribute to its widespread application and facilitate advancements in the field of neurobioelectronics.3.We have successfully achieved controllable modification of a conducting polymer hydrogel microinterface onto implantable microwire electrodes.Through in vivo experiments,we have demonstrated the long-term stability,biocompatibility,and high-resolution performance of the microelectrode interface.These findings provide a solid foundation for the large-scale development and practical application of conducting polymer hydrogel microelectrode interfaces in neuroscience research and cutting-edge clinical applications.The development and advancement of neuroscience heavily rely on implantable neural microelectrodes capable of selective,high-fidelity,and long-term stable neural signal recording using microfabrication techniques.While there has been progress in miniaturization,the challenge remains in developing microelectrode interface devices that exhibit longterm stability and biocompatibility while maintaining the ability to record neuronal signals.To address this challenge,we prepared microwire electrode devices with a diameter of 10 μm to improve spatial resolution.Using a precise and controllable electro-synthesis technique,we co-deposited the PEDOT:PSS conductive phase and PU mechanical phase onto the microwire electrode recording sites.This approach allowed us to construct a conducting polymer hydrogel microinterface with strong adhesion,high capacitance,and long-term stability.By employing this microfabrication strategy,we effectively constructed a robust conducting polymer hydrogel interface within a 16-channel microelectrode device with a 10 μm diameter.This interface enabled the recording of biopotentials from a targeted population of neurons with weak signal strength.Even after long-term implantation into mouse brains,continuous recording of individual neuronal signals was possible,ensuring long-term stable and selective neural recordings.These advancements have the potential to greatly facilitate neuroscience research and clinical neurotechnology.In conclusion,this dissertation presents groundbreaking achievements in the field of conducting polymer interfaces.It introduces the electrodeposition of a double-layer interpenetrating conducting polymer interface and a one-step electrosynthesis grafting strategy for a bicontinuous microphase semi-separated conducting polymer hydrogel interface.These strategies result in the construction of a conducting polymer interface with strong adhesion and high capacitance,as well as a soft and robust conducting polymer hydrogel interface.The research conducted in this dissertation elucidates the underlying mechanisms of conducting polymer interfaces through molecular engineering and phase engineering modifications.It also establishes a standardized evaluation system for assessing the long-term stability of these interfaces.Additionally,this work achieves the rapid integration of a conducting polymer hydrogel interface with high spatial resolution and ultra-small microelectrode recording sites,addressing the challenges of weak adhesion,poor tissue adaptability,difficult long-term stability,and complicated microprocessing preparations associated with current conducting polymer interfaces.Furthermore,the findings of this research provide crucial theoretical guidance and technical support for the development,commercialization,and clinical application of high-performance conducting polymer neuroelectrode interfaces.These advancements pave the way for improved device performance,expanded commercialization prospects,and enhanced practicality in the field of conducting polymer interfaces.