Mechanical membrane permeabilization by direct contact. (A) Scrape
loading, where a rubber spatula or similar scraping object can be used to
simultaneously dislodge cells and permeabilize them. (B) Bead loading, wherein
micron-scale beads can be rolled across a cell monolayer for controlled cell
injury via collisions. (C) Filtroporation, where a solution of cells is passed
through holes in filter membranes, such as a track-etched polycarbonate filter.
(D) Microfluidic cell squeezing, where cells membranes are disrupted by rapid
deformation that occurs with passage through microfabricated constrictions. (E)
Permeabilization with nanoneedle arrays. (i) The array is first centrifuged or
otherwise pressed against cells adhered to a rigid substrate. (ii) The array is
then removed to enable cargo influx through membrane disruptions in the target
cells.