A team of bioengineers from the University of Tokyo and UCLA have developed a method for expediting the time it takes for sorting large liquid droplets that potentially contain individual live cells that can be sorted intact and in bulk.

According to the researchers, the technique could potentially mean faster screening times, by as much as 20 times faster, than currently available droplet microfluidic technologies in medical and biotechnical applications for antibodies, biofuels and other products manufactured by cells.

Such microfluidic devices contain microscopic lanes where millions of fluid drops are routed and behave as miniature test tubes, growing cells and fostering chemical reactions. In some instances, drops containing growth or reactions can be sorted to isolate cells of interest from the remaining cells.

Droplets roughly a third of the thickness of a human hair in diameter have been used to grow or react to cells. Yet, the smaller mass of droplets makes them easier to sort at higher rates by instruments.

However, the droplets are not large enough to encourage the growth and long-term survival of most cells. As such, increasing the diameter of a droplet slightly more than two-fold results in 10 times as much volume, enough to completely encase a cell, producing a liquid cushion that keeps cells alive longer, enabling them to grow and divide within the droplet.

Yet, the larger droplets tended to break apart during processing in previous systems, mostly as a result of their higher inertia as they were moved around.

"Up until now, the slower speeds required to move these larger droplets diminishes many of the advantages of using microfluidics, so we set out to change that," said Dino Di Carlo, a professor of engineering and medicine at UCLA and a senior author of the study. "The key in this research is: instead of applying a very strong electric field all at once to move and sort a droplet, which usually rips the droplets apart, we apply a much smaller electric field around each droplet many times in a sequential manner, to slowly divert it from its path. Imagine deflecting a balloon with many small fans all aligned and synchronized to blow only when the balloon passes versus using one large wildly turbulent fan."

The team demonstrated the technique using large droplets with a variety of cells, including cancer cells, stem cells, microalgae and yeast, discovering that it could keep cells alive, growing and secreting biological products longer in the larger droplets and enabled the team to sort the cells at significantly higher speeds. The advance brings automated sorting and analytical processing speeds of large droplets in line with that of smaller droplets.

"This opens up some new avenues in biologic and cell therapy manufacturing, precision medicine, regenerative medicine and green biotechnology," Di Carlo said. "For example, we can now incubate and grow all kinds of cells and then use microfluidic processing to search for cells with particular important growth or production traits. This could include finding the most promising T cells to fight cancers, or cells that secrete antibodies for infectious diseases such as COVID-19."

Di Carlo said the technique could be applied to agriculture-based biotechnologies because the system could sort algae needed for biofuels or vitamin production at faster rates.

The research appears in Science Advances.