Integrated microfluidic device for single-cell high throughput screening in dynamic gene expression analysis

Over the past decade, interest in microfluidics has surged as applications have trended towards novel biological assays. Specifically, the ability of microfluidics to parallelize cellular studies through array-based chip designs has attracted researchers interested in investigating cellular function under a wide variety of environmental conditions. The capability of microfluidic devices to control microenvironment conditions and induce dynamic perturbation to cellular systems makes microfluidics (or "lab-on-a-chip") an attractive platform to study gene expression dynamics. In this project, the functionality of microfluidic technology is exploited to design and construct a device for isolation and observation of cells in high throughput. The integration of a concentration gradient with homogenous medium within each chamber was designed specifically to investigate gene regulation in Saccharomyces cerevisiae under various concentrations of chemical inducers. These devices were designed to sustain cells for extended periods of time with high temporal resolution to study dynamic gene expression in single cells. The device builds on previous studies by probing up to eight distinct cell cultures in parallel. The microfluidic platform was then used to study yeast cells at various levels of inducer perturbations. Further experimentation revealed the utility of a parallel gradient by producing an induction curve of the yeast response. Such high-throughput designs will prove essential to yeast systems biology research as it strives to understand the complex regulatory interactions that dictate cell function by probing vast regions of parameter spac