TFT sensor array for real-time cellular characterization, stimulation, impedance measurement and optical imaging of in-vitro neural cells
TFT sensor array for real-time cellular characterization, stimulation, impedance measurement and optical imaging of in-vitro neural cells
复制标题
DOI：
10.1016/j.bios.2020.112546
复制
发表时间：
2020-12-01
影响因子：
12.6
通讯作者：
Toshiyoshi, Hiroshi
中科院分区：
文献类型：
--
作者：
Shaik, Faruk Azam;Ihida, Satoshi;Toshiyoshi, Hiroshi
神经元细胞群的实时体外多模态表征涉及高度复杂的相互依赖的现象和过程。尽管已经报道了各种微电极阵列（MEA），但诊断技术在传感面积、光学透明度、分辨率和模式数量方面受到限制。本文提出了一种用于神经元整体研究的光学透明薄膜晶体管（TFT）阵列生物传感器芯片，其中TFT电极用于六种模式，包括动作电位（AP）和局部场电位（LFP）的细胞外电压记录、电流或电压刺激、化学刺激、电阻抗测量和光学成像。该传感器采用大传感区域 (15.6 mm x 15.6 mm) 和 200 x 150 的氧化铟锡 (ITO) 电极阵列，像素间距为 50 μm 或 100 μm，时间分辨率为 10 ms；这些性能可与最先进的 MEA 设备相媲美。 TFT电极阵列是基于开关矩阵架构设计的。通过测量 TFT 的电气特性来检查 TFT 的可靠性和稳定性。阻抗谱功能通过在电极上绘制神经元位置和状态（细胞存活或死亡、污染）来验证，这促进了电领域的生化研究，为通过光学显微镜对细胞的视觉观察增加了定量视图。使用电生理学、电化学和光学表征来研究体外神经元培养。详细的信号分析证明了生物测定的能力。
Real-time in-vitro multi-modality characterization of neuronal cell ensemble involves highly complex interdependent phenomena and processes. Although a variety of microelectrode arrays (MEAs) have been reported, diagnosis techniques are limited in term of sensing area, optical transparency, resolution and number of modalities. This paper presents an optically transparent thin-film-transistor (TFT) array biosensor chip for neuronal ensemble investigation, in which TFT electrodes are used for six modalities including extracellular voltage recording of both action potential (AP) and local field potential (LFP), current or voltage stimulation, chemical stimulation, electrical impedance measurement, and optical imaging. The sensor incorporates a large sensing area (15.6 mm x 15.6 mm) with a 200 x 150 array of indium-tin-oxide (ITO) electrodes placed at a 50 mu m or 100 mu m pixel pitch and with 10 ms temporal resolution; these performances are comparable to the state-of-theart MEA devices. The TFT electrode array is designed based on the switch matrix architecture. The reliability and stability of TFTs are examined by measuring their electrical characteristics. Impedance spectroscopy function is verified by mapping the neuron position and the status (cells alive or dead, contamination) on the electrodes, which facilitates the biochemical studies in electrical domain that adds quantitative views to visual observation of cells through the optical microscopy. An in-vitro neuron culture is studied using electrophysiological, electrochemical, and optical characterization. Detailed signal analysis is demonstrated to prove the capability of bioassay.