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二维微化学观察通过 128×128 阵列式电荷耦合器件离子图像传感器监测肥大细胞生物胺释放。

Two-dimensional microchemical observation of mast cell biogenic amine release as monitored by a 128 × 128 array-type charge-coupled device ion image sensor.

机构信息

Department of Electrical and Electronic Information Engineering, ‡Department of Environmental and Life Sciences, §Electronics-Inspired Interdisciplinary Research Institute, and ∥Cooperative Research Facility Center, Toyohashi University of Technology , Toyohashi 441-8580, Japan.

出版信息

Anal Chem. 2014 May 6;86(9):4196-201. doi: 10.1021/ac403657w. Epub 2014 Apr 23.

Abstract

Available array-type, chemical-sensing image sensors generally only provide on/off responses to the sensed chemical and produce qualitative information. Therefore, there is a need for an array sensor design that can detect chemical concentration changes to produce quantitative, event-sensitive information. In this study, a 128 × 128 array-type image sensor was modified and applied to imaging of biogenic amines released from stimulated rat mast cells, providing recordable responses of the time course of their release and diffusion. The imaging tool was manufactured by an integrated circuit process, including complementary metal oxide semiconductor and charge-coupled device technology. It was fitted with an amine-sensitive membrane prepared from plasticized poly(vinyl chloride) including a hydrophobic anion, which allowed the sensor to detect amines, such as histamine and serotonin, in Tyrode's solution. As mast cells were larger in diameter than the pixel hollows, some pixels monitored amines released from single cells. The image from the array responses yielded sequential snapshots at a practical frame speed that followed amine concentration changes over time, after mast cell amine release was synchronized by chemical stimulation. This sensor was shown to be sensitive to amine release at very low stimulus concentrations and was able to detect localized spots of high amine release. The entire time course of the amine release was recorded, including maximum concentration at 4-6 s and signal disappearance at 30 s after stimulation. With further development, this sensor will increase opportunities to study a variety of biological systems, including neuronal chemical processes.

摘要

现有的阵列型化学感应图像传感器通常只能对感应到的化学物质提供开/关响应,并产生定性信息。因此,需要设计一种阵列传感器,能够检测化学浓度变化,从而产生定量、事件敏感的信息。在本研究中,我们对 128×128 阵列型图像传感器进行了修改,并将其应用于刺激大鼠肥大细胞释放的生物胺的成像,提供了它们释放和扩散的时间过程的可记录响应。该成像工具由集成电路工艺制造,包括互补金属氧化物半导体和电荷耦合器件技术。它配备了由包含疏阴离子的增塑聚氯乙烯制成的胺敏膜,使传感器能够在 Tyrode 溶液中检测到组胺和血清素等胺类物质。由于肥大细胞的直径大于像素凹坑,因此一些像素可以监测单个细胞释放的胺类物质。在化学刺激使肥大细胞胺类物质释放同步后,阵列响应的图像以实用的帧速生成序列快照,跟踪胺类物质浓度随时间的变化。该传感器在非常低的刺激浓度下对胺类物质的释放很敏感,并且能够检测到高胺类物质释放的局部点。记录了胺类物质释放的整个时间过程,包括刺激后 4-6 秒达到最大浓度和 30 秒信号消失。随着进一步的发展,这种传感器将增加研究各种生物系统的机会,包括神经元的化学过程。

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