Proc. Natl Acad. Sci. USA 110, 2082–2087 (2013)

Credit: © 2013 PNAS

When it comes to intracellular delivery, there are essentially two strategies: to take advantage of endocytosis — a naturally occurring engulfing process — or to stimulate the formation of transient pores in the cell's membrane. Endocytotic delivery vehicles usually have to be designed according to cargo and cell type. On the other hand, techniques that rely on temporal membrane disruption — such as electroporation or microinjection — allow any material to passively diffuse into the cell, yet they suffer from low delivery efficiency and limited throughput, and can damage the cargo or cause cell death. Now, Armon Sharei and colleagues show that poration can also be triggered mechanically. By squeezing cells through constrictions in series made in microfluidic channels, the authors were able to deliver proteins, nucleic acids, carbon nanotubes and other materials to various cell types at high throughput and with minimal effect on their viability. This strategy may be advantageous for high-throughput screening of drug libraries and in drug-delivery applications involving cell types that are difficult to transfect.