Cell refractive index for cell biology and disease diagnosis: past, present and future

Cell refractive index is a key biophysical parameter, which has been extensively studied. It is correlated withother cell biophysical properties including mechanical,electrical and optical properties, and not only repre-sents the intracellular mass and concentration of a cell,but also provides important insight for various biolog-ical models. Measurement techniques developed earlieronly measure the effective refractive index of a cellor a cell suspension, providing only limited information on cell refractive index and hence hindering its in-depth analysis and correlation. Recently, the emergenceof microfluidic, photonic and imaging technologieshas enabled the manipulation of a single cell and the 3D refractive index of a single cell down to sub-micronresolution, providing powerfultoolstostudycellsbasedonrefractiveindex.Inthisreview,weprovideanoverview of cell refractive index models and measurement techniques includingmicrofluidic chip-basedtechniques for the last 50 years, present the applications and significance of cell refractive index in cell biol-ogy, hematology, and pathology, and discuss future research trends in the field, including 3D imagingmethods, integration with microfluidics and potential applications in new and breakthrough research areas.

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