Development of terahertz chemical microscope for detecting small molecules

Screening of the biomolecular reactions of small molecules is important in the field of such as drug discovery. While various methods which can measure the biomolecular reactions of small molecules have been developed, only few methods realized to detect biomolecular reactions of small molecules without any labels. Conventionally, surface plasmon resonance (SPR) is used for detecting biomolecular reactions without any labels. However, it is difficult for the method of SPR to measure the biomolecular reactions of small molecules because the sensitivity of SPR depends on the molecular weights. Our group has been developed a terahertz chemical microscope (TCM) to measure biomolecular reactions of small molecules without any labels. The most important component of TCM is a sensing plate which consists of Si, SiO
2
and Sapphire substrates. Terahertz (THz) pulses are emitted from sensing plate by irradiating femtosecond laser. The TCM can measure electric or chemical potential of the sensing plate surface in order to detect various kinds of biomolecular reactions. The emitted THz pulses depend on the electric or chemical potential of the sensing plate surface. Therefore, TCM can measure the biomolecular reactions of small molecules regardless of their molecular weights. In this study, reactions between concanavalin A (Con A) and mannose were measured using TCM. The Con A was immobilized on the sensing plate surface to detect the mannose. The molecular weights of mannose is 180.16 Da, and this is relatively smaller than other biomolecules. The molecular weights of this level can't be detected by SPR. Furthermore, we succeeded in the real-time measurement of the reactions by using flow cell. The results suggests the possibility of kinetics evaluation using TCM.