PT - JOURNAL ARTICLE AU - Yiwen Li AU - Weston B. Struwe AU - Philipp Kukura TI - Single molecule mass photometry of nucleic acids AID - 10.1101/2020.01.14.904755 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.01.14.904755 4099 - http://biorxiv.org/content/early/2020/01/14/2020.01.14.904755.short 4100 - http://biorxiv.org/content/early/2020/01/14/2020.01.14.904755.full AB - Mass photometry is a recently developed methodology capable of detection, imaging and mass measurement of individual proteins under solution conditions. Here, we show that this approach is equally applicable to nucleic acids, enabling their facile, rapid and accurate detection and quantification using sub-picomoles of sample. The ability to count individual molecules directly measures relative concentrations in complex mixtures without need for separation. Using a dsDNA ladder, we find a linear relationship between the number of bases per molecule and the associated imaging contrast for up to 1200 bp, enabling us to quantify dsDNA length with 4 bp accuracy. These results introduce mass photometry as an accurate and rapid single molecule method complementary to existing DNA characterisation techniques.