“Seeing is believing.” To understand what is happening around us, we rely on tools that allow us to see the invisible. Throughout history, humans have continuously developed technologies to extend the limits of our vision. Glasses correct blurred eyesight, while microscopes reveal tiny structures such as cells and viruses that are otherwise impossible to observe. In a similar spirit, biosensors have been developed to “visualize” chemical information in biological systems. Traditionally, biosensors were designed as devices that convert the recognition of a specific chemical compound into a measurable physical signal. A classic example is the enzyme-based electrochemical biosensor, in which an enzyme such as glucose oxidase is coupled to an electrode to monitor metabolites like glucose as an electrical signal. These biosensors have been widely used and are highly quantitative, but they often require invasive insertion of electrodes into tissues, which limits their applicability for monitoring metabolism under physiological conditions. In recent years, purely protein-based fluorescent biosensors have emerged as powerful and less invasive alternatives. These biosensors can be expressed directly in living cells, tissues, and model organisms, enabling real-time and spatially resolved visualization of metabolic dynamics. Here, I briefly summarize the historical development of metabolite biosensors and highlight recent advances and applications in monitoring metabolism in living systems.
Yusuke Nasu (Thu,) studied this question.