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Although several lysis methods are available, biomedical applications are pushing the demand for miniaturised systems and thus for new ways to lyse cells in small volumes. In this work, we demonstrate in-droplet cell lysis of AC16 human cardiomyocyte cells in 20 μL droplets using high frequency surface acoustic waves. The acoustic streaming leads to high shear flow creating porous or breaking the cell membrane and releasing intracellular material. Contrary to previous work where the lysis efficiency is measured by a cell-permeant dye that can be used to determine cell viability, here we propose to quantify the DNA extracted from the cells as a measure of the lysis efficiency. This reagent-free method provides a valuable cell lysis alternative for many biological and biomedical applications, particularly for the development of point-of-care platforms.