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Abstract The interaction between cell surface receptors and extracellular ligands is highly related to many physiological processes in living systems. Many techniques have been developed to measure the ligand-receptor binding kinetics at the single-cell level. However, few techniques can measure the physiologically relevant shear binding affinity over a single cell in the clinical environment. Here, we develop a new optical technique, termed single-cell rotational adhesion frequency assay (scRAFA), that mimics in vivo cell adhesion to achieve label-free determination of both homogeneous and heterogeneous binding kinetics of targeted cells at the subcellular level. Moreover, the scRAFA is also applicable to analyze the binding affinities on a single cell in native human biofluids. With its superior performance and general applicability, scRAFA is expected to find applications in study of the spatial organization of cell surface receptors and diagnosis of infectious diseases. 

Optical tweezers offer revolutionary opportunities for both fundamental and applied research in materials science, biology, and medical engineering. However, the requirement of a strongly focused and high-intensity laser beam results in potential photon-induced and thermal damages to target objects, including nanoparticles, cells, and biomolecules. Here, we report a new type of light-based tweezers, termed opto-refrigerative tweezers, which exploit solid-state optical refrigeration and thermophoresis to trap particles and molecules at the laser-generated cold region. While laser refrigeration can avoid photothermal heating, the use of a weakly focused laser beam can further reduce the photodamages to the target object. This novel and noninvasive optical tweezing technique will bring new possibilities in the optical control of nanomaterials and biomolecules for essential applications in nanotechnology, photonics, and life science.