Education and Publications


In-vivo pH Imaging System for Hydrogen Ion Dynamics Observation in the Brain of a Freely-Moving Mouse

16 November 2022


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 μm 2 pixel size, which is improved from the previous sensor device (128 × 32-array of 23.55 × 23.55 μm 2 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.

CMOS-based bio-image sensor spatially resolves neural activity-dependent proton dynamics in the living brain

05 February 2020


Recent studies have shown that protons can function as neurotransmitters in cultured neurons. To further investigate regional and neural activity-dependent proton dynamics in the brain, the development of a device with both wide-area detectability and high spatial-ltemporal resolution is necessary. Therefore, we develop an image sensor with a high spatial-temporal resolution specifically designed for measuring protons in vivo. Here, we demonstrate that spatially deferent neural stimulation by visual stimulation induced distinct patterns of proton changes in the visual cortex. This result indicates that our biosensor can detect micrometer and millisecond scale changes of protons across a wide area. Our study demonstrates that a CMOS-based proton image sensor with high spatial and temporal precision can be used to detect pH changes associated with biological events. We believe that our sensor may have broad applicability in future biological studies.