Inertio-elastic focusing of bioparticles in a microchannel at ultra-high throughput

Many biological and industrial fluids are filled with micro-scale particles that can serve as "state markers" for real-world issues, such as human health and public infrastructure. In order to extract this valuable information from such fluids, the controlled manipulation of particles is often necessary. Microfluidic technologies based on viscosity-dominant flows have achieved this essential step in small-volume (5 1 ml) fluid samples, while inertial focusing in microchannels has been used to process large-volume (-0(10 ml)) fluid samples. However, inertial focusing has primarily been limited to particles suspended in Newtonian fluids. For example, the extent to which bioparticles can be focused in complex fluids (e.g., whole blood) not been explored. Using an imaging technique (particle trajectory analysis (PTA)) that generates non-blurred images of focused bioparticles with velocities up to 2 m.s', we find that PC-3 (prostate) cancer cell lines undergo a radical shift in equilibrium position when the suspending fluid is whole blood (as opposed to diluted blood). We also find that the diluted blood sample exhibits a Newtonian viscosity profile while the whole blood sample exhibits a non-Newtonian (shear-thinning) viscosity profile. Previous studies of particle focusing in microchannels have been limited to inertia-dominant or elasticity-dominant flows. Inertia and elasticity are non-linear effects that tend to destabilize a fluid flow alone, but when simultaneously important, these effects have been shown to act constructively to stabilize it (e.g., turbulent drag reduction in macroscale pipes using high-molecular weight polymer solutions). We show that in dilute (0.1% w/v hyaluronic acid (HA) in water) polymer solutions, bioparticles focus (and remain focused) to a single equilibrium position at Reynolds numbers up to Re ~ 10,000 (with Weissenberg numbers up to Wi ~ 2,000). We find that PTA (as well as pI-PIV) can be used to construct particle focusing histograms and fluid velocity profiles based on seeded particles with velocities in excess of 100 m.s'. We show that viscoelastic normal stresses are the primary drivers of particle focusing (relative to shear-thinning or secondary flow effects), and that these effects can be tuned to focus and stretch bioparticles based on fluid rheology. Given that particle focusing can occur in a previously inaccessible flow regime in which both inertia (Re >> 1) and elasticity (Wi >> 1) are present, we anticipate the development of: 1) numerical models to provide insight into the physical basis of this novel phenomenon, and 2) microfluidic technologies capable of rapidly processing very large volumes (-0(1000 ml)) of biological and industrial fluids. Thesis Supervisors: Mehmet Toner I Professor of Health Sciences and Technology I Harvard Medical School Gareth H. McKinley I Professor of Mechanical Engineering I Massachusetts Institute of Technology