Fundamentals and Applications of FluidFM Technology in Single-Cell Studies

This review describes the potential of FluidFM technology and its implementation in studying the interface between a single cell (prokaryote or eukaryote) and a surface or a surrounding area. A combination of microfluidics with conventional atomic force microscope (AFM) makes this platform efficient to address challenges associated with various biomolecular systems and biophysical activities down to single-cell levels. Upon regulating the pressure through a microchanneled cantilever via a pressure controller, a wide range of studies are feasible. These include isolating and displacing a single living cell to measure the cell-substrate and intercellular adhesion forces, intracellular injection of biomolecules as drug delivery systems, extraction of cellular fluid for downstream analyses, and characterization of cell structures to obtain the mechanical properties. For single-cell adhesion experiments, the irreversible chemical-based cell immobolization in conventional AFM has been replaced with the reversible pressure-controlled approach in this platform; this not only reduces the experiment time-it also helps in performing serial and rapid measurement with improved statistics. This approach also ensures the retention of cell viability after each experiment.