A joint effort between researchers at the Institute for Systems Biology and the University of British Columbia has resulted in new technology promising to bring scientists that much closer to understanding cell responses to the environment and other stimuli.
The scientists recently demonstrated a proof of principle using their new, fully automated, high-throughput microfluidic single-cell experimental imaging platform. Lead investigator Tim Galitski, a researcher at ISB, says the new platform has integrated digital technology that makes it comparatively more high-throughput than currently available microfluidic tools. "It's analogous to what happened to electronic circuits when there was the transition from analog to digital," Galitski says. "With a digital circuit, you can get a lot more to happen in a coordinated way on the chip." The group based its work on the research of Galitski's colleague, Carl Hansen, an assistant professor at UBC who worked on developing microvalves during his postdoctoral days in Stephen Quake's lab at Stanford University.
"We've built on those advances and used them to make a large-scale, high-throughput device that performs robustly and enables us to carry out dynamic experiments over the period of a day with hundreds of individual experiments and completely computer-¬control the whole process," Galitski says. "The entire experiment is preprogrammed at the level of the microscope and the fluidics on the chip."
Galitski's lab led the proof of principle, which involved using the new platform to conduct 3,000 live-cell experiments to elucidate the response of a yeast pheromone to genetic and environmental changes. The idea was to learn whether the pathway exhibits memory of previous stimuli and to identify genes that may play a role in how long those memories last.
"The engineering challenges mainly involved getting hundreds and hundreds of these experiments to work in a robust way over many hours as well as almost innumerable small engineering challenges in making that happen — things like the resistance to flow in the device," he says. "So in early designs, some valves would fail because of the high pressures required. … It's a cycle of ironing out those problems at an engineer level."
Moving forward, Galitski and his team would like to further develop their platform to become even more robust and to offer more control over the experiments. "We would like to increase the throughput on it and increase the independence of the individual experiments," he says. "Ideally, we would like to be able to individually control large numbers of individual experiments or, instead of looking at strains with one mutation, look at ones with a combination of mutations to better approximate the real genetic complexities that are involved in biomedical problems and biological responses."