Interrogating dynamic phenotypes using a high-throughput single cell microfluidic platform

R. James Taylor
The Institute for Systems Biology, The University of British Columbia

Elucidating complex biological networks is of central interest for understanding cellular function and 
the mechanisms of disease.  Genetics and chemical biology have emerged as powerful techniques for 
dissecting cellular circuits through the controlled perturbations of protein function, and traditional 
studies have been successful in elucidating the roles of core pathway components.  However, current 
experimental techniques generally lack the ability for precise modulation of environmental stimuli and 
are limited to averaged measurements of large populations of cells.  This lack of precise temporal 
control of the chemical environment limits the ability to interrogate kinetic information processing 
circuits or cellular response to temporal stimuli, while the ensemble averaging conceals the 
ever-present heterogeneity in the cellular response.  

We have developed microfluidic technology for the dynamic analysis of single cells over time using 
well defined and highly controlled chemical environments.  Our technology allows for the temporal 
control of the microenvironment, enabling the study of complex biomolecular circuits under time 
varying stimuli.  Such control is necessary for the analysis of signalling dynamics and the uncovering 
of kinetic phenotypes.  Our system is high throughput with 256 different experiments able to be run 
simultaneously.  Each experiment contains on average the analysis 100 live single cells with a 
sampling rate of 15min, allowing for over a million data points per experiment. We are currently using 
our platform to interrogate the dynamics of MAPK signaling pathways in yeast.