We have developed a quartz-crystal microbalance (QCM), in which fundamental frequency decreases with increasing mass on the electrode in aqueous solution. When a 27 MHz QCM is employed, a mass of 0.62 ng/cm² deposited on the electrode decreases the frequency by 1 Hz. Thus, when the host molecule is immobilized on the QCM electrode, the binding behavior of guest molecules could be observed in nanogram level in aqueous solution. In this review, we report that the biomolecular recognitions and reactions at the water-substrate interface by using the QCM technique, such as 1) protein binding to a sugar lipid monolayer at the air-water interface, and 2) oligo nucleotides biding to a nucleolipids monolayer at the air-water interface.