Intracellular delivery of macromolecules is a challenge in research and therapeutic
applications. Existing vector-based and physical methods have limitations, including their
reliance on exogenous materials or electrical fields, which can lead to toxicity or off-target
effects. We describe a microfluidic approach to delivery in which cells are mechanically
deformed as they pass through a constriction 30–80% smaller than the cell diameter. The
resulting controlled application of compression and shear forces results in the formation of …

Results Delivery Method. We hypothesize that the rapid mechanical deformation of a cell, as
it passes through a constriction with a minimum dimension smaller than the cell diameter,
results in the formation of transient membrane disruptions or holes (Fig. 1A). The size and
frequency of these holes would be a function of the shear and compressive forces
experienced by the cell during its passage through the constriction. Material from the
surrounding medium may then diffuse directly into the cell cytosol throughout