CellSqueeze

CellSqueeze is a method for deforming a cell as it passes through a small opening, disrupting the cell membrane and allowing material to be inserted into the cell.

When used for the delivery of transcription factors, the device produced a marked improvement in colony formation compared with other methods like electroporation and cell-penetrating peptides. The method is a high-throughput, vector-free microfluidic platform for intracellular delivery of a wide range of materials, including carbon nanotubes, proteins and siRNA. The technique has been used for over 20 cell types, including embryonic stem cells and naïve immune cells. Cells can be sqeezed 'at a rate of about one million per second, which makes this method quite fast and easy compared to other methods like electroporation and cell-penetrating peptide use. An added benefit is that when the cells undergo the squeezing procedure, they show no changes in the genes they express and no other long-term effects. On the other hand, when a jolt of electricity (through electroporation) is applied to the cells to make them more permeable to deliver DNA and RNA, more than 7,000 genes are affected. This less invasive approach makes CellSqueeze preferable in some studies that require the gene expression and genes to be controlled at all times.

The microfluidics platform is a device made up of channels etched into a wafer through which cells initially flow freely. As they move through the device, the channel width gradually narrows. The cell's flexible membrane allows it to change shape and become thinner and longer, allowing it to squeeze through. As the cell becomes more and more narrow, it shrinks in width by about 30 to 80 times its original size and it is at this time that the forced rapid change in cell shape temporarily creates holes in the membrane, without damaging or killing the cell.

While the cell membrane is disrupted, target molecules that pass by can enter the cell through the holes in the membrane. As the cell returns to its normal shape, the holes in the membrane close. Virtually any type of molecule can be delivered into any type of cell.

Applications have focused on immune cells, delivering:

The process was originally developed by Armon Sharei, in the lab of Langer and Jensen at Massachusetts Institute of Technology. In 2014 Sharei founded SQZ Biotech to demonstrate the technology. That year, SQZ Biotech won the $100,000 grand prize in the annual startup competition sponsored by Boston-based accelerator MassChallenge.

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