In-vivo pH Imaging System for Hydrogen Ion Dynamics Observation in the Brain of a Freely-Moving Mouse
In-vivo pH Imaging System for Hydrogen Ion Dynamics Observation in the Brain of a Freely-Moving Mouse
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DOI：
10.1109/biocas54905.2022.9948690
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发表时间：
2022-10
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通讯作者：
Mai Madokoro;Hiroshi Horiuchi;Tomoko Kobayashi;T. Horio;Yasuyuki Kimura;H. Doi;Yong-joon Choi;Kazuhiro Takahashi;T. Noda;J. Nabekura;K. Sawada
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作者：
Mai Madokoro;Hiroshi Horiuchi;Tomoko Kobayashi;T. Horio;Yasuyuki Kimura;H. Doi;Yong-joon Choi;Kazuhiro Takahashi;T. Noda;J. Nabekura;K. Sawada
为了研究正常和疾病状态下自由活动动物的活体大脑中细胞外离子的变化，有必要开发一种基于高空间吸收图像传感器装置的体内成像系统。在这里，我们报告了用于监测自由移动小鼠大脑中氢离子 (H+) 分布的体内 pH 成像系统。所开发的CMOS离子图像传感器具有5.65×4.39μm2像素尺寸的256×32阵列，比之前的传感器器件（23.55×23.55μm2像素尺寸的128×32阵列）进行了改进，并实现了0.016pH的pH分辨率和62fps的时间分辨率。还制造了适合自由移动体内实验的不带内部溶液的参比电极。传感器和参考电极都很轻，各重 1 克，可以植入实验动物体内。我们首次在清醒且不受限制的自由活动实验中成功获得了实时成像，使我们能够可视化活体大脑中的 H+ 动态。
To study changes in extracellular ions in the living brain of freely moving animals in both normal and disease states, developing an in-vivo imaging system based on a high spatially-resorbed image sensor device is necessary. Here, we report the in-vivo pH imaging system for monitoring hydrogen ion (H+) distribution in the brain of a freely-moving mouse. The developed CMOS ion image sensor has a 256 × 32 array of 5.65 × 4.39 μm2 pixel size, which is improved from the previous sensor device (128 × 32-array of 23.55 × 23.55 μm2 pixel size) and achieves a pH resolution of 0.016 pH with a temporal resolution of 62 fps. A reference electrode without an internal solution adaptable for freely-moving in-vivo experiments was also fabricated. Both the sensor and reference electrode were sufficiently lightweight at 1 g each to be implanted into the experimental animal. We have, for the first time, successfully obtained real-time imaging in awake and unrestrained freely-moving experiments, allowing us to visualize H+ dynamics in the living brain.