Adaptive Imaging Cytometry to Estimate Parameters of Gene Networks Models in Systems and Synthetic Biology

The use of microfluidics in live cell imaging allows the acquisition of dense time-series from individual cells that can be perturbed through computer-controlled changes of growth medium. Systems and synthetic biologists frequently perform gene expression studies that require changes in growth conditions to characterize the stability of switches, the transfer function of a genetic device, or the oscillations of gene networks. It is rarely possible to know a priori at what times the various changes should be made, and the success of the experiment is unknown until all of the image processing is completed well after the completion of the experiment. This results in wasted time and resources, due to the need to repeat the experiment to fine-tune the imaging parameters. To overcome this limitation, we have developed an adaptive imaging platform called GenoSIGHT that processes images as they are recorded, and uses the resulting data to make real-time adjustments to experimental conditions. We have validated this closed-loop control of the experiment using galactose-inducible expression of the yellow fluorescent protein Venus in Saccharomyces cerevisiae. We show that adaptive imaging improves the reproducibility of gene expression data resulting in more accurate estimates of gene network parameters while increasing productivity ten-fold.