Inertial focusing is the migration of particles in fluid toward equilibrium, where current theory predicts that shear-induced and wall-induced lift forces are balanced. First reported in 1961, this Segre-Silberberg effect is particularly useful for microfluidic isolation of cells and particles. Interestingly, recent work demonstrated particle focusing at high Reynolds numbers that cannot be explained by current theory. We showed that non-monotonous velocity profiles, such as those developed in curved channels, create local velocity minima around which opposing shear-induced forces dominate over wall effects. Similarly, entry effects amplified in high Reynolds flow produce an equivalent trapping mechanism in short, straight channels. This new focusing mechanism in the developing flow regime enables a 10-fold miniaturization of inertial focusing devices, while our model corrects long-standing misconceptions about the nature of mechanical forces governing inertial focusing in curved channels.

We applied the new focusing mechanism for the design and fabrication of age dependent sorting system for yeast. The budding yeast is an essential model for the molecular study of cellular aging. Many aging determinants have been studied in yeast, using single cell analysis. Current methods cannot efficiently isolate sufficient quantities of aging yeast, for bulk analysis of aging-related molecular mechanisms. We superimposed high Reynolds inertial focusing on Dean vortices trapping small particles at the channel center, to rapidly isolate large quantities of young and aging yeast from mixed populations. Together with a new algorithm to rapidly quantify bud scars in isolated populations, we showed, for the first time, that protein quality control undergoes dramatic changes early in the aging process. These results suggest that protein quality control decreases more rapidly than previously thought, thus offering important insights into the mechanistic causes of aging.