Abstract
Transmitted light microscopy has enabled researchers to visualize subcellular dynamics at negligible phototoxicity, leading to important discoveries such as chromosomes and cell division. With the development of phase contrast microscopy in the 1940s and 50s, which dramatically improved the imaging contrast of unstained samples, and the more recent advances of quantitative phase contrast (QPC) techniques [ 1], it is now possible to precisely measure the optical path difference (OPD) that light experiences when traveling through a biological sample at diffraction-limited (∼250 nm) resolution [ 2]. The OPD is directly proportional to the ‘dry mass’, i.e. the quantity of cellular content such as proteins, lipids and nucleic acids, in the observed volume, and thereby provides valuable quantitative insights into global cellular composition and metabolism. This information is not only important in basic biological research but has potential as a tool for diagnosis of diseases such as cancer, sickle cell disease, diabetes, malaria, viral infection, and SARS-CoV-2.

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