CPM Seminar

Microfluidic Biosensors for Single Cell Growth Studies

Michel Godin

Department of Physics
University of Ottawa

Microfluidic devices offer the ability to readily manipulate nanolitre to picolitre volumes of biological material. These devices can integrate various biosensors providing a platform capable of manipulating, processing and analyzing biological samples often with single cell or single molecule sensitivity. In this talk, I will describe a microfluidics-based mass sensor capable of accurately quantifying buoyant mass, density and size of nanoparticles and of individual cells.

Mass measurement provides a powerful universal analytical detection method since it does not depend on other physical or chemical properties of the target. Mass is measured by monitoring the change in the resonance frequency of a mechanical resonator resulting from added sample mass. Resolving small mass changes requires the resonator to be light and to ring at a very pure tone-that is, with a high quality factor. While extraordinary sensitivity has been achieved in vacuum, resolution is severely degraded in solution, thus preventing many applications in nanotechnology and the life sciences where fluid is required. We have overcome this limitation by placing the fluid inside a hollow resonating microcantilever surrounded by an external vacuum. The combination of the low resonator mass (100 ng) and high quality factor (15,000) enables an improvement in mass resolution of six orders of magnitude over a high-end commercial quartz crystal microbalance. Our suspended microchannel resonators have a mass resolution of 300 attograms allowing us to measure the mass, size and density of single bacteria and nanoparticles with high-throughput, as well as sub-monolayers of proteins adsorbed from solution. Central to these results is our observation that viscous loss due to the fluid is negligible compared to the intrinsic damping of our silicon crystal resonator. This gives access to intriguing applications, such as mass-based flow cytometry, the direct detection of pathogens, or the non-optical sizing and mass density measurement of colloidal particles. We have studied the growth kinetics of single bacterial, yeast and mammalian cells by trapping single cells within the suspended microchannel, gaining insight into the growth kinetics of cells.