Grant to Rice Fast Tracks Cell-Sorting Advance

Mike Williams Nov 14, 2014

A Rice University professor shooting cells down a track for analysis sees a need for speed, and the government agrees. Jacob Robinson, an assistant professor of electrical and computer engineering, has won a prestigious Young Faculty Award from the Defense Advanced Research Projects Agency (DARPA) to pursue technology that will greatly speed the process of cell sorting, an essential task for synthetic biologists.

The multiyear awards fund research by untenured faculty members and are designed to develop the next generation of academic scientists, engineers and mathematicians “who will focus a significant portion of their career” on defense and national security issues, according to DARPA.

Through his research, Robinson expects to help researchers gain new understanding of how the activities of specific neurons and circuits in the brain influence human behavior, which would enhance the military’s efforts to improve soldier training and performance and to help recovery from traumatic brain injuries and post-traumatic stress disorder.

An important part of the process is the ability to evaluate the electrical properties of neural cells, and the more, the better. The goal is to improve voltage-sensitive fluorescent proteins for imaging neural activity.

The traditional sorting technique, fluorescence-activated cell sorting (FACS), is effective for selecting cells based on protein expression, but it cannot measure how these proteins behave when they experience electrical activity similar to what occurs inside the brain, Robinson said. Instead, researchers must perform the painstaking process of evaluating electrical properties of individual cells using patch-clamp electrophysiology. This process represents the major bottleneck for developing new voltage-sensitive fluorescent proteins, he said, because one researcher can process only 10 to 20 cells a day. Robinson’s technique would seamlessly combine the two techniques. “We want to find a way to quickly sort cells based on their electrical activity, so we call this electrophysiology-assisted cell sorting – E-phACS – as an homage to FACS.”

Robinson and his colleagues are off to a flying start; they have fabricated an assortment of microfluidic and nanowire technologies to quickly evaluate and sort cells. The DARPA grant will enable them to streamline the process with the immediate goal of evaluating and sorting up to 100 cells, and eventually thousands, per day.

The E-phACS devices to be developed at Rice will use microfluidics to move a single cell into a miniature recording chamber, where it will be pierced by a nanowire that measures transmembrane voltages. The fluid then pops the live cell off the wire and sorts it into one of several batches, making room for the next cell in the chute. All this happens within seconds, Robinson said, and because the devices are so small, many can operate in parallel.

Purified batches of mutant variants can then be studied. “We want to be able to grab mutant cells, find the ones that are exceptional and ask, ‘What makes you so special?’ We can then isolate these cells and look at their gene sequences and gene expression profiles,” he said.

“Our theme is to take the big and bulky tools neuroscientists have been using since the 1980s and integrate them into a chip-scaled platform. That will to allow us to do things more efficiently, faster, a lot cheaper,” he said. “We look at this as a platform that will accelerate both synthetic neurobiology as well as basic neuroscience.”

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