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Dehydration-induced DNA conformational changes have been probed for the first time with the use of second harmonic microscopy. Unlike conventional approaches, second harmonic microscopy provides a label-free and real-time approach to detect DNA conformational changes. Upon dehydration, cellular DNA undergoes a transition from B- to A-form, whereas cellular nuclei change from invisible to visible under second harmonic microscopy. These results showed that DNA is a second order nonlinear optical material. We further confirmed this by characterizing the nonlinear optical properties of extracted DNA from human cells. Our findings open a new path for SHG imaging. DNA can change its conformations under many circumstances. For example: normal cells turning into cancerous cells and drug molecules binding with DNA. Therefore, the detection of DNA conformational changes with second harmonic microscopy will be a useful tool in cancer therapy and new drug discovery.

Label-free and real-time imaging of dehydration-induced DNA conformational changes in cellular nucleus using second harmonic microscopy