There are many fundamental bottlenecks that slow biology research down. Many of them are so basic that we rarely talk about them.

One example is DNA delivery. In other words, after a scientist synthesizes a gene, there’s no guarantee that they can then get that gene into an organism! In fact, the overwhelming majority of lifeforms on Earth have never been engineered. This is part of the reason why scientists tend to just use a handful of easy-to-work-with cells, like E. coli and yeast.

But for a recent preprint, Cultivarium - a nonprofit research org in Boston - built a custom electroporation robot that can explore many parameters to figure out which settings are best suited for transforming various types of cells. Electroporation is a technique wherein cells are literally shocked with electricity. This pulse of electricity punches holes in the cell membrane, thus allowing nearby DNA to float inside. One major benefit of electroporation is that it can be used on LOTS of different types of organisms, from bacteria to archaea and eukaryotes.

The robot that Cultivarium made can test wash buffers, plasmids, organisms, voltages, and much more to find settings that actually work for a given new, non-model microbe. And using this custom device, they "report the first electroporation protocols...for eight non-model bacteria."

There are a couple key findings in this paper. For one, "the wash buffer used to prepare cells for electroporation had a significant effect on [transformation efficiency.]" Sometimes, remarkably so; "for each strain, one buffer showed at least 100-fold higher [transformation efficiencies] over other tested buffers."

Also, the voltage applied to the cells is super important. "Voltages greater than 1 kV had a variable effect, resulting in up to 1000-fold improvement in some species."

After finding settings that are *good enough* to transform a particular microbe, these researchers integrated an active learning pipeline to "iteratively improve...conditions to drive toward optimal parameters..."

Using their robot, they tested 538 conditions over three cycles of experiments to improve the transformation protocol for a non-model microbe, called Cupriavidus necator. They were very quickly able to increase the transformation efficiency by 8.6-fold, just by tweaking wash buffers and voltages and other parameters!

We love these efforts to improve fundamental aspects of biology research. They are highly underrated, and we’ll be covering more stuff like this in the future.

Link to paper: biorxiv.org/content/10.…