Abstract

High-Throughput Microfluidic Cytometry

Andrew J deMello, Principal Investigator, ETH Zurich

Flow cytometry is a ubiquitous analytical technique for enumerating and sorting cellular populations. Because of its quantitative and multi-parametric nature and the fact that cells may be probed at high throughputs, flow cytometry is considered to be the gold standard method for measuring the physical and chemical properties of a large cellular populations. Although modern-day flow cytometers are adept at processing thousands of cells per second, almost all require unacceptably large sample/reagent volumes and do not allow the acquisition of spatially resolved information. To address these issues, imaging flow cytometry (IFC) marries the advantages of optical microscopy and flow cytometry to allow the for high-throughput imaging of cells within flowing environments. I will describe how we have leveraged the capabilities of microfluidic systems to form novel IFC platforms able to manipulate, process and assay cells in a controlled and high-throughput manner. Examples will include chip-based imaging flow cytometers that leverage either inertial or viscoelastic focusing. Such systems operate at throughputs exceeding 400,000 cells/s, extract fluorescence, brightfield, and darkfield images and are capable of multi-parametric quantification and sub-cellular localization of structures down to 500 nm. Finally, I will describe recent activities focused on the development of a viscoelastic-based microfluidic platform able to measure the mechanical properties of cells at rates of up to 100,000 cells per second. Here, fluid elasticity is used to focus and deform cells in an integrated manner and without the need for a sheath fluid.