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The Conformal, High-Density SpineWrap microelectrode array for Focal Stimulation and Selective Muscle Recruitment

ADVANCED FUNCTIONAL MATERIALS 2025年第16期35卷

作者： Russman, Samantha M. Montgomery-Walsh, Rhea Vatsyayan, Ritwik Sang, U. Hoi Diaz-Aguilar, Luis D. Chang, Eric Y. Tang, Qingbo Lee, Keundong Yaksh, Tony L. Ben-Haim, Sharona Ciacci, Joseph Dayeh, Shadi A. Univ Calif San Diego Dept Elect & Comp Engn Integrated Elect & Biointerfaces Lab La Jolla CA 92093 USA Univ Calif San Diego Shu Chien Gene Lay Dept Bioengn La Jolla CA 92093 USA Univ Calif San Diego Dept Neurol Surg La Jolla CA 92093 USA VA San Diego Healthcare Syst Radiol Serv La Jolla CA 92161 USA Univ Calif San Diego Dept Radiol La Jolla CA 92093 USA Univ Calif San Diego Dept Anesthesiol La Jolla CA 92093 USA

Epidural electrical stimulation (EES) of the spinal cord is widely applied for pain management and as a possible route to functional restoration after spinal cord injury. Currently, EES employs bulky, nonconformal paddle arrays with low channel counts. This limits stimulation effectiveness by requiring high stimulation currents, reduces selectivity of muscle recruitment, and requires subject-specific designs to accommodate varied neuroanatomy across the patient population. Here, on a thin-film, high-channel count microelectrode array, termed SpineWrap is reported, which wraps around the dorsolateral aspect of the rat spinal cord. SpineWrap delivers focal stimulation to selectively activate muscles due to its thin substrate, high conformability, high channel count, on-device ground, and the material properties of its platinum nanorod contacts. Through computational and in vivo studies, the SpineWrap can selectively recruit muscles in the rat lower limb and identify stimulation hotspots at a submillimeter resolution, maximizing muscle recruitment selectivity. The effect of channel count and density on muscle recruitment selectivity is also investigated and show that rat spinal cord arrays require submillimeter pitches to achieve maximal selectivity. SpineWrap represents an advancement in EES technology and, when adapted to be used chronically, has the potential to improve SCI treatment by providing more refined stimulation.

关键词： epidural electrical stimulation microelectrode array platinum nanorod spinal cord stimulation thin film

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Cellular level cryo-neuromodulation using rapid and localized cooling device combined with microelectrode array

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BIOSENSORS & BIOELECTRONICS 2025年 277卷 117257页

作者： Kim, Jaehyun Lee, Jong Seung Noh, Soyeon Seo, Eunseok Lee, Jungchul Kim, Taesung Cho, Seung-Woo Kim, Gunho Kim, Sung Soo Park, Jungyul Sogang Univ Dept Mech Engn 35 Baekbeom Ro Seoul 04107 South Korea Yonsei Univ Dept Biotechnol 50 Yonsei Ro Seoul 03722 South Korea Inst Basic Sci IBS Ctr Nanomed 50 Yonsei Ro Seoul 03722 South Korea Ulsan Natl Inst Sci & Technol UNIST Dept Mech Engn 50 UNIST gilEonyang eup Ulsan 44919 South Korea Korea Adv Inst Sci & Technol Dept Mech Engn 291 Daehak Ro Daejeon 34141 South Korea Univ Calif Santa Barbara Mol Cellular & Dev Biol Santa Barbara CA 93106 USA

Cryotherapy, a rapid and effective medical treatment utilizing low temperatures, has not been widely adopted in clinical practice due to a limited understanding of its mechanisms and efficacy. This challenge stems from the absence of methods for fast, precise, and localized spatiotemporal temperature control, as well as the lack of reliable real-time quantitative techniques for measuring and analyzing the effects of cooling. To address these limitations, this study introduces a cryo-neuromodulation platform that integrates a high-speed precision cooling device with a microelectrode array (MEA) system. This platform enables the investigation of cellular-level cryomodulation of neuronal activity and its effects on surrounding cells, providing a novel framework for advancing research in cryotherapy and neuromodulation. Experiments show that neurons recovered fully within 1 min of cooling with a fast-cooling rate (-20 degrees C/s at cooling) and that silenced neurons can influence distant cells via a well-organized network. Extended cooling durations (e.g., 10 min) resulted in altered neuronal dynamics, including delayed recovery and reduced burst activity, highlighting the importance of precise control over cooling parameters. This device offers reversible neural control, with potential applications in both research and clinical settings, such as anesthesia, pain management and treatment of neurological disorders like neocortical seizures.

关键词： Cryo-neuromodulation Cryotherapy microelectrode array Nerve transmission Cooling

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An Efficient MEMS microelectrode array with Reliable Interelectrode Insulation Processes for In Vivo Neural Recording

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SMALL 2025年第10期21卷 e2407950页

作者： Xu, Qingda Wang, Longchun Xi, Ye Ruan, Tao Cao, Jiawei Xu, Mengfei Zheng, Kunyu Du, Zhiyuan Wei, Ning Wang, Xiaolin Yang, Bin Liu, Jingquan Shanghai Jiao Tong Univ Natl Key Lab Adv Micro & Nano Manufacture Technol Shanghai 200240 Peoples R China Shanghai Jiao Tong Univ Collaborat Innovat Ctr IFSA Dept Micro Nano Elect DCI Joint Team Shanghai 200240 Peoples R China

microelectrode arrays, particularly Utah arrays, offer irreplaceable advantages in clinical applications and play a crucial role in advancing brain-computer interactions. However, the glass-fused monolithic structure of Utah arrays limits functional expansion, and the glass insulation process is complex, costly, and time-intensive. This paper presents a microelectrode array with a simple and time-saving fabrication process, utilizing low-resistance silicon and borosilicate glass wafers as electrodes and insulation substrates, respectively. The utilization of the anodic bonding process improves production efficiency and enhances process compatibility. A one-step static wet etching process is used to form microneedle morphology to further simplify the fabrication process. Sputtered iridium oxide, as the electrode interface material, significantly reduces electrochemical impedance, and cellular experiments have confirmed its non-cytotoxicity. Moreover, the implantation into the primary visual cortex of mice has demonstrated the ability of the electrode to record in vivo electrical signals within 15 days. Movement trajectory experiments demonstrate that the mice exhibit good behavior activities following electrode implantation. The bonded microelectrode array (BMEA) presented in this work provides a universal and effective tool for neural recording, with prospective applications in multi-physiological monitoring and microelectromechanical system integration.

关键词： brain-computer interface iridium oxide MEMS microelectrode array neural recording

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Real-time monitoring of single-cell extracellular pH based on stretchable microelectrode array

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TALANTA 2025年 286卷 127453页

作者： Liu, Xiaobo Yin, Bing Yang, Chao Wang, Jiashi Yang, Rongli Wu, Shuo Dalian Univ Technol Sch Chem Dalian 116024 Peoples R China Dalian Univ Technol Sch Phys Dalian 116024 Peoples R China Dalian Univ Technol Fac Med Dalian 116024 Peoples R China Dalian Univ Technol Dept Crit Care Med Cent Hosp Dalian 116033 Peoples R China

The study of cell mechanics was significant for understanding cellular physiological functions, the mechanisms of disease occurrence, and the development of novel therapeutic approaches. However, research on the mechanism of mechanical strain action at the single-cell level was relatively lacking. Herein, we developed a serpentine stretchable sensor array capable of exerting precise mechanical strain on cells and monitoring extracellular pH (pHe) changes at single cell level. The PANI sensor array based on the serpentine structure exhibited good electrochemical stability against mechanical deformation enabling accurate measurement of pHe in single-cell during stretching. The results showed that mechanical stimulation induced cells to undergo deformation, thereby promoting increased cell acid excretion. Both stretching and compressive deformation were able to promote the increase of cell acid excretion. This sensor served as a powerful tool for researching the effect of cellular mechanics on cell metabolism at the single-cell level.

关键词： microelectrode array Stretchable sensor Single-cell detection Mechanical strain Extracellular pH

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Application of a high-density microelectrode array assay using a 3D human iPSC-derived brain microphysiological system model for in vitro neurotoxicity screening of environmental compounds

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Archives of Toxicology 2025年 1-19页

作者： Carstens, Kelly E. Gronskaya, Elena Jäckel, David Bertoli, Jessica Cuevas, Kelvin Ramirez Dorier, Julien Wang, Shan Lopez-Rodriguez, David Shafer, Timothy J. Zurich, Marie-Gabrielle Pamies, David Center for Computational Toxicology and Exposure USA Environmental Protection Agency Research Triangle Park 27707 NC United States MaxWell Biosystems AG Zurich Switzerland Department of Biomedical Sciences University of Lausanne Lausanne Switzerland Bioinformatics Competence Center University of Lausanne Lausanne CH- 1015 Switzerland Bioinformatics Competence Center Ecole Polytechnique Fédérale de Lausanne Lausanne CH- 1015 Switzerland Swiss Centre for Applied Human Toxicology (SCAHT) Basel Switzerland Institute of Earth Surface Dynamics University of Lausanne Canton de Vaud Lausanne Switzerland Stem Cells and Organoid Facility University of Lausanne Rue du Bugnon 9 Lausanne CH-1005 Switzerland

Unraveling the associations between human exposure to environmental chemicals and potential neurotoxicity presents significant challenges. Evaluation of neurotoxicity potential using animal testing is resource-intensive (financial, labor, and animal use) and faces uncertainties regarding biological relevance to human health outcomes. Therefore, there is a need to develop efficient and human-relevant in vitro new approach methodologies (NAMs) to screen and evaluate chemicals for neurotoxicity potential. Recording of neural network activity using microelectrode array (MEA) technology has been identified as a reliable and reproducible method for evaluating neurotoxicity. Much of this research has been performed in 2D rodent-derived cell models. The ‘BrainSpheres MEA assay’ described in this study offers a promising functional human induced pluripotent stem cell (iPSC)-derived 3D brain model comprising neurons, astrocytes, and oligodendrocytes. We demonstrate consistent spontaneous neuronal firing and network bursting parameters from 7-week-old BrainSpheres using a high-density MEA technology. The performance of this model as a human-relevant NAM was evaluated by conducting a multi-concentration, 13 day exposure study with a set of ten chemicals. Neural activity metrics were assessed and compared to results from a 2D-MEA assay using rodent cells. Loperamide and domoic acid (two assay positive controls) demonstrated similar bioactivity profiles in the BrainSphere MEA assay to the 2D-MEA assay, while acetaminophen (assay negative control) was inactive in both assays. The 2D-MEA model demonstrated more potent bioactivity for 4/7 chemicals that were active in both assays. In the future, reducing replicate variability and testing a larger set of chemicals will likely improve the accuracy and reliability of the assay. These preliminary findings suggest that the BrainSphere assay could be used alongside the rat network formation assay (rNFA) as part of a tiered strategy, where

关键词： 3D cultures BrainSphere High-density electrode array iPSC MEA microelectrode array MPS Neuronal electrical activity Neurotoxicology

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microelectrode array-evaluation of Neurotoxic Effects of Magnesium as an Implantable Biomaterial

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Journal of Materials Science & Technology 2016年第1期32卷 89-96页

作者： Ting Huang ZhonghaiWang Lina Wei Mark Kindy Yufeng Zheng Tingfei Xi Bruce Z. Gao Center for Biomedical Materials and Tissue Engineering Academy for Advanced Interdisciplinary Studies Peking University Beijing 100871 China Department of Bioengineering Clemson University Clemson SC29634 USA Departments of Neurosciences and Regenerative Medicine and Cell Biology Medical University of South Carolina Charleston SC29466 USA Ralph H. Johnson VA Medical Center Charleston SC29403 USA Department of Materials Science and Engineering College of Engineering Peking University Beijing 100871 China Shenzhen Key Laboratory of Human Tissue Regeneration and Repair Shenzhen Institute Peking University Shenzhen 518057 China

Magnesium （Mg）-based biomaterials have shown great potential in clinical applications. However, the cytotoxic effects of excessive Mg2. and the corrosion products from Mg-based biomaterials, particularly their effects on neurons, have been little studied. Although viability tests are most commonly used, a functional evaluation is critically needed. Here, both methyl thiazolyl tetrazolium （MTT） and lactate de- hydrogenase （LDH） assays were used to test the effect of Mg2. and Mg-extract solution on neuronal viability. microelectrode arrays （MEAs）, which provide long-term, real-time recording of extracellular electro- physiological signals of in vitro neuronal networks, were used to test for toxic effects. The minimum effective concentrations （ECmin） of Mg2. from the MTr and LDH assays were 3 mmol/L and 100 mmol/L respec- tively, while the ECmin obtained from the MEA assay was 0.1 mmol/L MEA data revealed significant loss of neuronal network activity when the culture was exposed to 25% Mg-extract solution, a concentra- tion that did not affect neuronal viability. For evaluating the biocompatibility of Mg-based biomaterials with neurons, MEA electrophysiological testing is a more precise method than basic cell-viability testing.

关键词： Magnesium microelectrode array Neuroelectrophysiology Neuron viability Neuronal network

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microelectrode array biosensor for studying carbohydrate-mediated interactions

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BIOSENSORS & BIOELECTRONICS 2012年第1期34卷 253-260页

作者： Chamberlain, Jeffrey W. Maurer, Karl Cooper, John Lyon, Wanda J. Danley, David L. Ratner, Daniel M. Univ Washington Dept Bioengn Seattle WA 98195 USA CombiMatrix Irvine CA 92618 USA USAF Wright Patterson AF Base Wright Patterson AFB OH 45433 USA

Carbohydrate-mediated host-pathogen interactions are essential to bacterial and viral pathogenesis, and represent an attractive target for the development of antiadhesives to prevent infection. We present a versatile microelectrode array-based platform to investigate carbohydrate-mediated protein and bacterial binding, with the objective of developing a generalizable method for screening inhibitors of host-microbe interactions. microelectrode arrays are well suited for interrogating biological binding events, including proteins and whole-cells, and are amenable to electrochemical derivitization, facilitating rapid deposition of biomolecules. In this study, we achieve microelectrode functionalization with carbohydrates via controlled polymerization of pyrrole to individual microelectrodes, followed by physisorption of neoglycoconjugates to the polypyrrole-coated electrodes. Bioactivity of the immobilized carbohydrates was confirmed with carbohydrate-binding proteins (lectins) detected by both fluorescent and electrochemical means. The platform's ability to analyze whole-cell binding was demonstrated using strains of Escherichia coli and Salmonella enterica, and the dose-dependent inhibition of S. enterica by a soluble carbohydrate antiadhesive. (c) 2012 Elsevier B.V. All rights reserved.

关键词： Biosensor microelectrode array Carbohydrate Polypyrrole Customarray

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microelectrode array fabrication by electrical discharge machining and chemical etching

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IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING 2004年第6期51卷 890-895页

作者： Fofonoff, TA Martel, SM Hatsopoulos, NG Donoghue, JP Hunter, IW MIT Bioinstrumentat Lab Dept Mech Engn Cambridge MA 02139 USA Univ Chicago Dept Organismal Biol & Anat Chicago IL 60637 USA Brown Univ Dept Neurosci Providence RI 02912 USA

Wire electrical discharge machining (EDM), with a complementary chemical etching process, is explored and assessed as a method for developing microelectrode array assemblies for intracortically recording brain activity. Assembly processes based on these methods are highlighted, and results showing neural activity successfully recorded from the brain of a mouse using an EDM-based device are presented. Several structures relevant to the fabrication of microelectrode arrays are also offered in order to demonstrate the capabilities of EDM.

关键词： brain-machine interface electrical discharge machining (EDM) intracortical recording microelectrode array neural implant

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microelectrode array fabricated in low temperature cofired ceramic (LTCC) technology

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JOURNAL OF SOLID STATE ELECTROCHEMISTRY 2009年第1期13卷 129-135页

作者： Ciosek, Patrycja Zawadzki, Konrad Stadnik, Dorota Bembnowicz, Pawel Golonka, Leszek Wroblewski, Wojciech Warsaw Univ Technol Dept Analyt Chem PL-00664 Warsaw Poland Inst Biotechnol & Antibiot Dept Chem Anal PL-02516 Warsaw Poland Wroclaw Univ Technol Fac Microsyst Elect & Photon PL-50370 Wroclaw Poland

This work presents the development of a novel construction of an integrated microelectrode array. The device was fabricated on a ceramic support, with the use of low temperature cofired ceramics technology. Model potassium-selective membranes were applied on the surface of PdAg/AgCl electrodes formed on the ceramic substrate. The obtained microsensors exhibited very good repeatability, reproducibility, and sensitivity. The array of microelectrodes covered with polymeric layers of various selectivities was applied as an electronic tongue to differentiate between various diet supplements.

关键词： Electronic tongue microelectrode array LTCC technology

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microelectrode array-based system for neuropharmacological applications with cortical neurons cultured in vitro

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BIOSENSORS & BIOELECTRONICS 2007年第11期22卷 2478-2484页

作者： Xiang, Guangxin Pan, Liangbin Huang, Lihua Yu, Zhongyao Song, Xindong Cheng, Jing Xing, Wanli Zhou, Yuxiang Tsinghua Univ Med Syst Biol Res Ctr Beijing 100084 Peoples R China Tsinghua Univ Dept Biol Sci & Biotechnol Beijing 100084 Peoples R China Natl Engn Res Ctr Beijing Biochip Technol Beijing 102206 Peoples R China Tsinghua Univ State Key Lab Biomembrane & Membrane Biotechnol Beijing 100084 Peoples R China CapitalBio Corp Beijing 102206 Peoples R China

microelectrode arrays (MEAs) provide a means to investigate the electrophysiological behavior of neuronal systems through the measurements from neuronal culture preparations. Changes in activity patterns of neuronal networks are usually detected by applying neural chemicals. Because of the difficulties of fabricating the arrays, and the delicate and less reliable properties of cortical neurons, MEA-based systems with cortical neuronal networks for neuropharmacological applications are technically difficult, therefore restricting their utility. Here, we report a new approach to the development of such MEA-based system with sensitive and durable MEAs conveniently fabricated and the culture conditions optimized. Upon growth differentiation, cortical neurons, cultured directly on MEAs, reach a developmentally stable and reliable activity state. With this system, we monitored the global spontaneous activities of neuronal networks and demonstrated the fine discrimination for specific substances and unique property of cortical neurons, which validated both the applicability and necessity of such system in pharmacological bioassay. (c) 2006 Elsevier B.V. All rights reserved.

关键词： microelectrode array neuropharmacology cortical neurons microfabrication electrophysiology spontaneous activity

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