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      A flexible neural implant with ultrathin substrate for low-invasive brain–computer interface applications

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          Abstract

          Implantable brain–computer interface (BCI) devices are an effective tool to decipher fundamental brain mechanisms and treat neural diseases. However, traditional neural implants with rigid or bulky cross-sections cause trauma and decrease the quality of the neuronal signal. Here, we propose a MEMS-fabricated flexible interface device for BCI applications. The microdevice with a thin film substrate can be readily reduced to submicron scale for low-invasive implantation. An elaborate silicon shuttle with an improved structure is designed to reliably implant the flexible device into brain tissue. The flexible substrate is temporarily bonded to the silicon shuttle by polyethylene glycol. On the flexible substrate, eight electrodes with different diameters are distributed evenly for local field potential and neural spike recording, both of which are modified by Pt-black to enhance the charge storage capacity and reduce the impedance. The mechanical and electrochemical characteristics of this interface were investigated in vitro. In vivo, the small cross-section of the device promises reduced trauma, and the neuronal signals can still be recorded one month after implantation, demonstrating the promise of this kind of flexible BCI device as a low-invasive tool for brain–computer communication.

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          Response of brain tissue to chronically implanted neural electrodes.

          Chronically implanted recording electrode arrays linked to prosthetics have the potential to make positive impacts on patients suffering from full or partial paralysis. Such arrays are implanted into the patient's cortical tissue and record extracellular potentials from nearby neurons, allowing the information encoded by the neuronal discharges to control external devices. While such systems perform well during acute recordings, they often fail to function reliably in clinically relevant chronic settings. Available evidence suggests that a major failure mode of electrode arrays is the brain tissue reaction against these implants, making the biocompatibility of implanted electrodes a primary concern in device design. This review presents the biological components and time course of the acute and chronic tissue reaction in brain tissue, analyses the brain tissue response of current electrode systems, and comments on the various material science and bioactive strategies undertaken by electrode designers to enhance electrode performance.
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            Neuronal ensemble control of prosthetic devices by a human with tetraplegia.

            Neuromotor prostheses (NMPs) aim to replace or restore lost motor functions in paralysed humans by routeing movement-related signals from the brain, around damaged parts of the nervous system, to external effectors. To translate preclinical results from intact animals to a clinically useful NMP, movement signals must persist in cortex after spinal cord injury and be engaged by movement intent when sensory inputs and limb movement are long absent. Furthermore, NMPs would require that intention-driven neuronal activity be converted into a control signal that enables useful tasks. Here we show initial results for a tetraplegic human (MN) using a pilot NMP. Neuronal ensemble activity recorded through a 96-microelectrode array implanted in primary motor cortex demonstrated that intended hand motion modulates cortical spiking patterns three years after spinal cord injury. Decoders were created, providing a 'neural cursor' with which MN opened simulated e-mail and operated devices such as a television, even while conversing. Furthermore, MN used neural control to open and close a prosthetic hand, and perform rudimentary actions with a multi-jointed robotic arm. These early results suggest that NMPs based upon intracortical neuronal ensemble spiking activity could provide a valuable new neurotechnology to restore independence for humans with paralysis.
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              Neuronal cell loss accompanies the brain tissue response to chronically implanted silicon microelectrode arrays.

              Implantable silicon microelectrode array technology is a useful technique for obtaining high-density, high-spatial resolution sampling of neuronal activity within the brain and holds promise for a wide range of neuroprosthetic applications. One of the limitations of the current technology is inconsistent performance in long-term applications. Although the brain tissue response is believed to be a major cause of performance degradation, the precise mechanisms that lead to failure of recordings are unknown. We observed persistent ED1 immunoreactivity around implanted silicon microelectrode arrays implanted in adult rat cortex that was accompanied by a significant reduction in nerve fiber density and nerve cell bodies in the tissue immediately surrounding the implanted silicon microelectrode arrays. Persistent ED1 up-regulation and neuronal loss was not observed in microelectrode stab controls indicating that the phenotype did not result from the initial mechanical trauma of electrode implantation, but was associated with the foreign body response. In addition, we found that explanted electrodes were covered with ED1/MAC-1 immunoreactive cells and that the cells released MCP-1 and TNF-alpha under serum-free conditions in vitro. Our findings suggest a potential new mechanism for chronic recording failure that involves neuronal cell loss, which we speculate is caused by chronic inflammation at the microelectrode brain tissue interface.
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                Author and article information

                Contributors
                linzude@sjtu.edu.cn
                jqliu@sjtu.edu.cn
                Journal
                Microsyst Nanoeng
                Microsyst Nanoeng
                Microsystems & Nanoengineering
                Nature Publishing Group UK (London )
                2096-1030
                2055-7434
                25 December 2022
                25 December 2022
                2022
                : 8
                : 133
                Affiliations
                [1 ]GRID grid.16821.3c, ISNI 0000 0004 0368 8293, National Key Laboratory of Science and Technology on Micro/Nano Fabrication, , Shanghai Jiao Tong University, ; 200240 Shanghai, China
                [2 ]GRID grid.16821.3c, ISNI 0000 0004 0368 8293, Department of Micro/Nano Electronics, , Shanghai Jiao Tong University, ; 200240 Shanghai, China
                [3 ]GRID grid.16821.3c, ISNI 0000 0004 0368 8293, Department of Neurosurgery, Center for Functional Neurosurgery, Ruijin Hospital, , Shanghai Jiao Tong University School of Medicine, ; 200025 Shanghai, China
                Author information
                http://orcid.org/0000-0003-4140-1516
                Article
                464
                10.1038/s41378-022-00464-1
                9789992
                36575664
                7dc51c36-c177-4252-af3b-2070ace5bf57
                © The Author(s) 2022

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 26 April 2022
                : 3 June 2022
                : 30 June 2022
                Funding
                Funded by: National Key R&D Program of China under grant 2020YFB1313502; Strategic Priority Research Program of Chinese Academy of Sciences (Grant No. XDA25040100, ;XDA25040200 and XDA25040300); National Natural Science Foundation of China (No. 42127807-03); Shanghai Municipal Science and Technology Major Project (2021SHZDZX); SJTU Trans-med Award(No.2019015, 21X010301627); Oceanic Interdisciplinary Program of Shanghai Jiao Tong University (No.SL2020ZD205, SL2020MS017, SL2103); Scientific Research Fund of Second Institute of Oceanography, MNR (No.SL2020ZD205);
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                © The Author(s) 2022

                sensors,nanobiotechnology
                sensors, nanobiotechnology

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