The brain is essentially made up of around 100 billion neurons, accompanied by ten times as manynon-neuronal cells (Glial cells). Action potentials generated by these neurons are transmitted between cells as electrical signals. On the other hand, it is known that chemical substances or ions called neurotransmitters move between the tiny voids at the cell-cell junctions and play an important role both in controlling brain functions as chemical signals, as well as in the pathophysiology of the brain. In other words, in order to investigate detailed brain functions and pathologies based on the elucidation of chemical signal transduction mechanisms, it is necessary to develop technology to visualise and measure the dynamics of chemical substances distributed in the extracellular space from a few micrometres (cellular level) to several hundred µm (cell population level). However, most conventional devices for chemical signal detection tend to rely on passing an electric current through a single tiny electrode with a diameter of several tens of microns, or electrodes arranged at intervals of several 100 microns.These barriers to miniaturization and downsizinghave, up to now, prevented the realization of sensors capable of measuring the distribution of chemical information at the micron level.

Professor Sawada's laboratory however, has developed a semiconductor image sensor that captures ion movement like a camera. It achieves this by using semiconductor technology to miniaturise and integrate potential detection elements that are sensitive to hydrogen ions, which has promoted the development of highly functional sensors. The researchers fabricated an imaging device for multisensing in which metal electrodes are formed in a lattice shape at intervals of 6 µm on the developed sensor array, and realized the real-time simultaneous measurement of lactate and hydrogen ions involved in memory formation by applying a recognition element (enzyme) that selectively detects biomolecules. In addition, recognition elements corresponding to biomolecules can be also patterned on the electrode array, enabling the simultaneous multichemical measurement of two or more types of neurotransmitters.

In the past, one type of biomolecule was measured with a single-point electrode, or one to three types of biomolecules were measured with an electrode array sensor with low spatial resolution. The newly developed feature of “capturing, visualizing, and measuring” two types of chemicals on a surface with high spatial resolution enables the detection of chemical signals in microscopic regions, such as between cells, along with spatiotemporal analysis. This advancement offers insights into chemical phenomena that were previously inaccessible using point-based sensors. In a collaborative experiment with researchers from the Faculty of Medicine, University of Yamanashi, experts in brain science and pharmacology, the response of hippocampal cells (responsible for memory) to drug stimulation was observed. The researchers simultaneously measured lactate release and extracellular pH. This breakthrough enables direct placement and measurement of cells and tissues without any labeling, allowing observation of spatiotemporal changes in ions and neurotransmitters in biological samples. Building on this world-first ion image sensor technology, the team aims to advance its development for social implementation and medical applications.

We plan to proceed with the further enhancement of the functionality and performance of sensors to expand the range of substances to be measured. Furthermore, using sections of diseased tissue, such as brain tissue and tissue forming solid tumours, we plan to undertake applied measurements to elucidate the physiological significance of how molecular dynamics in the environment outside the cell changes in time and space. We also plan to apply this technology to analyzing interactions among chemical substances in the complex extracellular microenvironment and to verify their pharmacological effects.