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An ion image sensor is an important tool to chemically and dynamically observe the two-dimensional information of a living body. However, its spatial resolution is limited because it does not have any element that prevents the diffusion of target ion like a focusing lens used in optical image sensors. This paper proposes a novel approach to enhance spatial resolution of the ion image sensor for the first time. We introduce a barrel array to suppress the lateral diffusion of target ion on the surface of ion image sensor. This micro barrel array with high aspect ratio was fabricated on the ion image sensor using SU-8. By measuring the hippocampal slice for 10 min, H+ diffusion was suppressed as compared to the ion image sensor without diffusion suppressor. The ion image sensor has lately become popular in the microscopic analysis of biological tissue in high resolution owing to the proposed diffusion suppressor.

Medically important real-time imaging of extracellular lactate and its spatiotemporal analysis has not yet been achieved. If it could be successfully realized, it would help clarify the function of physiological neurotransmission and drug discovery based on glial cell neuron lactate transport. To this end, we fabricated a 40 μm pitch, 128 × 128 pixel redox-type label-free lactate image sensor based on a potentiometric hydrogen peroxide (H 2 O 2 ) sensor array and successfully obtained a diffusion image of lactate. Further, the fabricated sensor was applied to extracellular imaging of tissue from a mouse hippocampus. A 300-μm-thick slice of the hippocampus was placed on a lactate image sensor, and when stimulated by glutamate, the output image of the sensor changed dynamically. The output voltage change (ΔV Out ) of the sensor was approximately 140 mV. Conversely, verification by a comparative experiment using an enzyme-free sensor confirmed a significant difference in the value of ΔV Out . It can thus be concluded that the observation of lactate in solution was demonstrated successfully by label-free real-time imaging of lactate from mouse hippocampus tissue with glutamate stimulation on a 40 μm-pitch sensor array.

We have developed a novel ion image sensor with a fine pixel pitch, which is shorter than one-tenth of the 23.55 μm in the previous design. In this report, we highlight the imaging potential of a 2-μm-pitch ion image sensor in the measurement of the neural activity of mouse hippocampus. This pitch is sufficiently small to observe the action of a single cell. The results of brain-slice imaging indicated that the diffusion of H+ ions was different in each region containing CA1, CA2, and DG in the hippocampus. In addition, the sensor clearly captured the distribution of neural cell responses.