How to Hijack A Cell

If we could somehow make our own cells do our bidding, they might manufacture insulin, attack tumors and do other helpful things. But hijacking a cell is not easy. Current methods entail penetrating the cell walls with a virus, which tends to inflict permanent damage.

In 2009 researchers at the Massachusetts Institute of Technology solved this problem, by accident. The researchers were playing around with a method of implanting cells with large molecules and nanomaterials using a microscopic water gun. Mainly, they were trying to get things inside a cell—the sorts of things that might alter a cell's behavior while keeping it alive. Chemical engineer Armon Sharei noticed that some of the water-shot cells became momentarily misshapen, and while they were, the material was getting inside them. “It turns out if you deform a cell fast enough, you can temporarily break down its membrane,” Sharei says. The water gun was too crude a tool, however. They needed a gentler way to squeeze cells.

Sharei, working under Klavs F. Jensen, a founder of the field of microfluidics, and biotech pioneer Robert S. Langer, developed a silicon-and-glass microchip that is etched with channels through which cells flow. The channels narrow gradually, until the gap tapers into a space slimmer than the cells themselves. The squeezed cells are supple, and they force their way through. In the process, temporary holes form in the cell membrane. The holes are tiny but wide enough to let in a variety of behavior-altering agents, including proteins, nucleic acids and carbon nanotubes. The technique works even on stem and immune cells, which were too sensitive to be manipulated using previous methods. “We were taken aback by how many cells this approach could apply to,” Sharei says.

Since the initial discovery, the group has developed 16 different chips with channel arrays designed to squeeze different cells. More chips are coming, and the device, which can already process 500,000 cells a second, continues to get faster and more efficient. The group has started a company to commercialize the technology—called SQZ Biotech—and scientists in France, Germany, the Netherlands and the U.K. will soon be using its products.