Siwakoti Umisha, Jones Steven A, Kumbhare Deepak, Cui Xinyan Tracy, Castagnola Elisa
Department of Biomedical Engineering, Louisiana Tech University, Ruston, LA 71272, USA.
Department of Neurosurgery, Louisiana State University Health Sciences, Shreveport, LA 71103, USA.
Biosensors (Basel). 2025 Feb 10;15(2):100. doi: 10.3390/bios15020100.
Understanding brain function requires advanced neural probes to monitor electrical and chemical signaling across multiple timescales and brain regions. Microelectrode arrays (MEAs) are widely used to record neurophysiological activity across various depths and brain regions, providing single-unit resolution for extended periods. Recent advancements in flexible MEAs, built on micrometer-thick polymer substrates, have improved integration with brain tissue by mimicking the brain's soft nature, reducing mechanical trauma and inflammation. These flexible, subcellular-scale MEAs can record stable neural signals for months, making them ideal for long-term studies. In addition to electrical recording, MEAs have been functionalized for electrochemical neurotransmitter detection. Electroactive neurotransmitters, such as dopamine, serotonin, and adenosine, can be directly measured via electrochemical methods, particularly on carbon-based surfaces. For non-electroactive neurotransmitters like acetylcholine, glutamate, and γ-aminobutyric acid, alternative strategies, such as enzyme immobilization and aptamer-based recognition, are employed to generate electrochemical signals. This review highlights recent developments in flexible MEA fabrication and functionalization to achieve both electrochemical and electrophysiological recordings, minimizing sensor fowling and brain damage when implanted long-term. It covers multi-time scale neurotransmitter detection, development of conducting polymer and nanomaterial composite coatings to enhance sensitivity, incorporation of enzyme and aptamer-based recognition methods, and the integration of carbon electrodes on flexible MEAs. Finally, it summarizes strategies to acquire electrochemical and electrophysiological measurements from the same device.
理解脑功能需要先进的神经探针来监测多个时间尺度和脑区的电信号和化学信号。微电极阵列（MEA）被广泛用于记录不同深度和脑区的神经生理活动，能够长时间提供单单元分辨率。基于微米厚聚合物基板构建的柔性MEA的最新进展，通过模仿大脑的柔软特性，改善了与脑组织的整合，减少了机械创伤和炎症。这些柔性的亚细胞尺度MEA能够记录数月的稳定神经信号，使其成为长期研究的理想选择。除了电记录外，MEA还被功能化用于电化学神经递质检测。电活性神经递质，如多巴胺、血清素和腺苷，可以通过电化学方法直接测量，特别是在碳基表面。对于乙酰胆碱、谷氨酸和γ-氨基丁酸等非电活性神经递质，则采用酶固定和基于适配体的识别等替代策略来产生电化学信号。本综述重点介绍了柔性MEA制造和功能化的最新进展，以实现电化学和电生理记录，在长期植入时将传感器污染和脑损伤降至最低。它涵盖了多时间尺度神经递质检测、用于提高灵敏度的导电聚合物和纳米材料复合涂层的开发、基于酶和适配体的识别方法的纳入，以及碳电极在柔性MEA上的整合。最后，它总结了从同一设备获取电化学和电生理测量的策略。
