Development of highly sensitive, flexible dual L-glutamate and GABA microsensors for in vivo brain sensing
Development of highly sensitive, flexible dual L-glutamate and GABA microsensors for in vivo brain sensing
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DOI：
10.1016/j.bios.2022.114941
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发表时间：
2022-11-28
影响因子：
12.6
通讯作者：
Cao, Hung
中科院分区：
文献类型：
--
作者：
Chu, Sung Sik;Nguyen, Hung Anh;Cao, Hung
由于当前方法的时空分辨率较低，实时跟踪体内神经递质水平在技术上一直具有挑战性。由于皮质兴奋/抑制(E：I)比值的失衡与多种神经系统疾病有关，准确监测兴奋性和抑制性神经递质水平对于研究这些疾病的潜在神经机制至关重要。具体地说，兴奋性神经递质L-谷氨酸和抑制性神经递质GABA的水平被认为在E：I平衡中起关键作用。因此，本工作研制了一种柔性电化学微传感器，用于L-谷氨酸和γ-氨基丁酸的实时同时检测。柔性聚酰亚胺基板用于在植入和测量过程中更容易操作，同时减少对大脑的损伤。此外，通过在传感器表面电化学沉积铂黑纳米结构，提高了传感器的活性表面积以获得更高的灵敏度。这种双神经递质传感器探针在不同的环境下进行了性能验证，包括体外实验、谷氨酸能神经元的体外实验和麻醉大鼠的体内实验。此外，从寿命和生物兼容性方面对传感器的性能进行了进一步的研究。总体而言，我们的L-谷氨酸：氨基丁酸双传感器微探头具有其独特的功能，可以对体内的E：I平衡进行准确、实时和长期的监测。因此，这一新的工具应该有助于研究正常脑功能和各种神经疾病的神经机制。
Real-time tracking of neurotransmitter levels in vivo has been technically challenging due to the low spatio-temporal resolution of current methods. Since the imbalance of cortical excitation/inhibition (E:I) ratios are associated with a variety of neurological disorders, accurate monitoring of excitatory and inhibitory neuro-transmitter levels is crucial for investigating the underlying neural mechanisms of these conditions. Specifically, levels of the excitatory neurotransmitter L-glutamate, and the inhibitory neurotransmitter GABA, are assumed to play critical roles in the E:I balance. Therefore, in this work, a flexible electrochemical microsensor is developed for real-time simultaneous detection of L-glutamate and GABA. The flexible polyimide substrate was used for easier handling during implantation and measurement, along with less brain damage. Further, by electro-chemically depositing Pt-black nanostructures on the sensor's surface, the active surface area was enhanced for higher sensitivity. This dual neurotransmitter sensor probe was validated under various settings for its perfor-mance, including in vitro, ex vivo tests with glutamatergic neuronal cells and in vivo test with anesthetized rats. Additionally, the sensor's performance has been further investigated in terms of longevity and biocompatibility. Overall, our dual L-glutamate:GABA sensor microprobe has its unique features to enable accurate, real-time, and long-term monitoring of the E:I balance in vivo. Thus, this new tool should aid investigations of neural mecha-nisms of normal brain function and various neurological disorders.