Homeostasis in an organism is maintained by activities within and between cells. Therefore, one is required to analyze both the cellular activities within cells, such as metabolisms or signal transduction, and cellular interactions, such as ligand-receptor recognition. We have developed a cellular analyzing system including a "real-time cellular imaging system" and a "comprehensive analysis system for cellular responses" as shown in Fig. 1. The system has been established using newly developed chemical probes and nano-devices. As chemical probes, we have developed 1) molecular imaging probes, and 2) mass probes.As nano-devices, we built 1) nano electrochemical and optical probes, 2) a sputtered nano-film electrode, 3) nano-dot SPR, 4) a nano-dot target plate for MS, and 5) microfluidic devices. We will review each of these probes and devices, and finally introduce a "real-time cellular imaging system" with an application model using PC12 cells and a "comprehensive analysis system for cellular responses", which measured IL-1β (interleukin-1β) as an example.
Chemical Probes
2·1 Molecular imaging probesFluorescent imaging based on fluorescent probes offers a highly sensitive, high-speed spatial and temporal analysis of cells, and is widely used in the fields of biology and physiology. A cellular analyzing system including a "real-time cellular imaging system" and a "comprehensive analyzing system for cellular responses" was developed. A "real-time cellular imaging system" is a system used to measure real-time imaging of multiple phenomena of a single cell with high special and temporal resolutions for the purpose to understand the pathology and physiology in a single cell and realize to single cell level diagnosis. A "real-time cellular imaging system" includes multi-probe imaging with AFM (atomic force microscopy), optical and SECM (scanning electrochemical microscopy) modes, which provides us with topological information and biochemical reactions at the local area of the interior and exterior of a cell. Scanning electrochemical/optical microscopy was applied to image PC12 cells. On the other hand, cells respond to their specific substances via their ligands. Therefore, the comprehensive analysis of protein-protein interaction is the important issue to determine the functions of cells. For this purpose, a "comprehensive analysis system for cellular responses" was developed. This system is based on SPR (surface plasmon resonance) and MS (mass spectrometry) using a nano-fabricated substrate. The interaction between IL-1β and anti-IL-1β antibodies was detected.