UBC researchers have used new fabrication techniques to develop a microfluidic platform able to monitor how individual cells respond to varying biochemical environments on an unprecedented scale.
Applying techniques used to manufacture integrated electronic circuits, assistant professor Carl Hansen and colleagues have developed a programmable micro-scale cell trap and imaging platform capable of analyzing over 256 simultaneous time-lapsed living cell experiments.
"The combination of throughput—the number of individual cells we can isolate—and programmable, precision control over the environment around the cell, allows for unique studies of how cells process changing stimuli to make decisions," says Hansen, with the UBC Center for High-Throughput Biology and Department of Physics and Astronomy.
Over 12 hours, the system was is able to monitor the reaction of thousands of individual cells to 32 unique environmental conditions, resulting in raw data consisting of 50,000 images. The results were published this week in the Proceedings of the National Academy of Sciences.
"The ability to generate large-scale data sets on single cells will allow the development and testing of quantitative models of cellular decision-making, with implications to understanding basic biology and ultimately disease."
Each cell within an organism carries the same genetic information that governs growth, development and differentiation. However, cells adapt to their environment by selecting the correct subset of genes to express in response to environmental cues in a complex process called signalling. The large number of environmental cues and genetic differences that need to be isolated and measured to study cell signalling has proven very difficult to recreate and capture in the lab.
A particular challenge in such studies is the ever present heterogeneity that exists between seemingly identical cells, a feature that is lost in ensemble measurements that average over thousands to millions of cells. Single cell techniques are thus crucial to understanding the biology. Working with colleagues at Seattle's Institute for Systems Biology, Hansen developed a device that exploits lithographic techniques used to make integrated electronic circuits and new methods in micro-fabrication. They used the 'high-throughput' imaging platform to analyze the response of eight strains of yeast to 32 dynamically changing simulation conditions. This new type of analysis revealed new effects of cellular network memory that had been undetected by conventional methods.
In the long run, microscale methods for the miniaturization and parallelization of biological measurements have potential to enable a wide range of cost effective measurements with applications ranging from fundamental biology to medical diagnostics and drug discovery.
