Fig. 1: Working principle of the proposed microscale cell shredder.

a Cells are introduced into the cross-junction of the microchannel. The stress applied on the cell is optimized to disrupt the cell membrane and release subcellular components, while maintaining the integrity of mitochondria. The overview of the microfluidics chip is shown in the inset. b The applied mean stress, modulated by controlling the volumetric flow rate for a given channel geometry, has been optimized by the maximal protein yield (an indication of quantity of the extracted subcellular contents) and the maximal mitotracker positive events (a hallmark of functional mitochondria). Results were obtained by shredding HEK293 cells (10⁶ cells/mL) by a range of shear stress and plotted as mean ± SD (n = 3 independent experiments). A finite element simulation model was established by COMSOL Multiphysics® to illustrate the fluidic flow at the cross-junction. Give a volumetric flow rate at 60 μl/min, c illustrates the velocity profile and the stagnation point at the centre (where the flow velocity is zero), and d illustrates the stress distribution and the extensional flow fields around the stagnation point, which contributes significantly to the cell deformation and disruption