Single Live Cell Assays with Label-free Optical Biosensor for the Development of Diagnostic Methods

The collection of single-cell level information has become essential in the development of drug molecules, diagnostics, and therapeutics, as cellular responses measured at the population level often lack the resolution necessary to fully understand the underlying biological phenomena-whether in response to drugs, mechanical stimuli, or activation signals. Label-free optical biosensors offer an excellent platform for investigating such processes. This study presents a label-free resonant waveguide grating (RWG) method, developed using a fluidic system that includes a rotating fluid layer covering a sensor array and integrated microfluidic channels. We analyzed adhesion phenomena at the small-population level and the cellular responses to mechanically induced shear stress generated by fluid rotation. Our findings demonstrate that optically measured wavelength shift kinetics can accurately predict both the mechanical detachment dynamics of cells and the characteristics of the rotational flow field. Additionally, cellular responses to enzymatic digestion were clearly detectable and manifested as a significant reduction in near-surface cell mass.