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Physical (non-viral, non-chemical) approaches to delivery include direct insertion and field-mediated disruption of the cell membrane (electrical, mechanical/acoustic, shear, optical or thermal).

Here we discuss the mechanism of this combined mode operation in detail, including in-depth characterization of capabilities for delivery of plasmid DNA.

Direct delivery of nucleic acids as described in this work offers a compelling alternative that avoids the inherent shortcomings of viral vectors.

The shear mechanoporation method first reported by Zarnitsyn et al.

An array of micromachined nozzles focuses ultrasonic pressure waves, creating a high-shear environment that promotes transient pore formation in membranes of transmitted cells.

Acoustic Shear Poration (ASP) allows passive cytoplasmic delivery of small to large nongene macromolecules into established and primary cells at greater than 75% efficiency.

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