In-Situ Sensing Internal Structure of Single Cell by Robotic Ausculation

Cytoskeletal architecture, transmembrane proteins, and signaling pathways cooperate together into one large system that can communicate with the extracellular microenvironment and inner organelles to regulate various cell behaviors, such as morphological changes, proliferation, and migration. The viscoelastic properties are important label-free biomarkers for revealing the cellular mechanical architecture. Atomic force microscopy (AFM) is one of the pioneering research tools used to investigate multiparametric mechanical mapping at the single-cell level without compromising the living condition of the cell. Conventional AFM mechanical measurements depend on the movements of a piezoelectric actuator attached to the probe for motion control. Various types of measurements can be performed, such as indentation, force relaxation, creep, and microrheology. However, due to the contact mechanism between the sample and probe, the measurements are dominated by the near-membrane structure of the cell. Based on active microrheology, the auscultation nanorobot has been developed with an external high-speed actuator and sensor system. The external mechanical excitation travels from the focal adhesion complex to the cellular membrane while the probe maintains motion similar to stress relaxation. With the decoupling of signals acquired by active microrheology and auscultation, the internal structure of a single cell can be revealed.