Genetically engineering any organism requires first getting its cells to take in foreign DNA. To do this, scientists often perform a process called electroporation, in which they expose cells to an electric field.

If that field is at just the right magnitude, it will open up pores within the cell membrane, through which DNA can flow. But it can take scientists months or even years to figure out the exact electric field conditions to reversibly unlock a membrane’s pores.

A new microfluidic device developed by MIT engineers may help scientists quickly home in on the electric field “sweet spot” — the range of electric potentials that will harmlessly and temporarily open up membrane pores to let DNA in. In principle, the simple device could be used on any microorganism or cell, significantly speeding up the first step in genetic engineering.

“We’re trying to reduce the amount of experimentation that’s needed,” says Cullen Buie, the Esther and Harold E. Edgerton Associate Professor of mechanical engineering at MIT. “Our big vision for this device and future iterations is to be able to take a process that usually takes months or years, and do it in a day or two.”

Buie and his colleagues, including postdoc Paulo Garcia, graduate student Zhifei Ge, and lecturer Jeffrey Moran, have published their results this week in the journal Scientific Reports.

“A shot in the dark”

Currently, scientists can order various electroporation systems — simple instruments that come with a set of instructions for penetrating an organism’s cell membranes. Each system may include instructions for roughly 100 different organisms, such as strains of bacteria and yeast, each of which requires a unique electric field and set of experimental conditions for permeation. However, Buie says the number of organisms for which these instructions are known is but a fraction of what actually exists in nature.

“There’s a tremendous amount of biodiversity we’re unable to access,” Buie says. “Part of the problem is, we can’t even get the DNA in, much less get it expressed by the organism. And for electroporation, the search for the conditions that might work is like a shot in the dark.”

For electroporation to work, the applied electric field must be strong enough to puncture the membrane temporarily, but not so strong as to do so permanently, which would cause a cell to die.

“It’s like surgery — this is pretty invasive,” Buie says. “There’s a sweet spot between killing them and not affecting them at all, that you need to find to be able to open them reversibly, just enough so that DNA gets in and they reseal on their own.”

Whether an electric field penetrates a membrane also depends on a cell’s surrounding conditions. Scientists have also had to experiment with parameters such as the composition of a cell’s solution and the way in which the electric field is applied.

“For a novel organism, it could take you months or years to develop new conditions so that the cell is happy and will survive the poration process, and it will uptake the DNA,” Buie says.