In this review, the basic principles and research trends of biosensors are briefly described and a nano-sensing system applying QCM (quartz crystal micro-balance), nano-diagnosis methods by AFM (atomic force microscopy) and SNOAM (scanning near-field/atomic force microscopy) is discussed intensively. The principle, construction, and applications of piezoelectric crystal sensors as a universal sensor are reviewed. This review is focused mainly on liquid phase applications, such as immune-sensors, gelation detecting sensors, and cultured cell monitoring sensors. The principle of nano-diagnosis based on the AFM or SNOAM techniques is described in detail. Finally, the binding affinity of peptide probes to proteins using AFM and the visualizing of a hybridized PNA probe on a DNA molecule using SNOAM are evaluated and discussed.