Cross-stream transport of asymmetric particles driven by oscillating shear

We study the dynamics of asymmetric, deformable particles in oscillatory, linear shear flow. By simulating the motion of a dumbbell, a ring polymer, and a capsule we show that cross-stream migration occurs for asymmetric elastic particles even in linear shear flow if the shear rate varies in time. The migration is generic as it does not depend on the particle dimension. Importantly, the migration velocity and migration direction are robust to variations of the initial particle orientation, making our proposed scheme suitable for sorting particles with asymmetric material properties.Comment: 5 pages, 4 figure

Inertio-elastic focusing of bioparticles in microchannels at high throughput

Controlled manipulation of particles from very large volumes of fluid at high throughput is critical for many biomedical, environmental and industrial applications. One promising approach is to use microfluidic technologies that rely on fluid inertia or elasticity to drive lateral migration of particles to stable equilibrium positions in a microchannel. Here, we report on a hydrodynamic approach that enables deterministic focusing of beads, mammalian cells and anisotropic hydrogel particles in a microchannel at extremely high flow rates. We show that on addition of micromolar concentrations of hyaluronic acid, the resulting fluid viscoelasticity can be used to control the focal position of particles at Reynolds numbers up to Re≈10,000 with corresponding flow rates and particle velocities up to 50 ml min[superscript −1] and 130 m s[superscript −1]. This study explores a previously unattained regime of inertio-elastic fluid flow and demonstrates bioparticle focusing at flow rates that are the highest yet achieved.National Institute for Biomedical Imaging and Bioengineering (U.S.) (P41 BioMicroElectroMechanical Systems Resource Center)National Institute for Biomedical Imaging and Bioengineering (U.S.) (P41 EB002503)National Science Foundation (U.S.). Graduate Research FellowshipUnited States. Army Research Office (Institute for Collaborative Biotechnologies Grant W911NF-09-0001

Tumor-on-a-chip platforms to study cancer-immune system crosstalk in the era of immunotherapy

Immunotherapy is a powerful therapeutic approach able to re-educate the immune system to fight cancer. A key player in this process is the tumor microenvironment (TME), which is a dynamic entity characterized by a complex array of tumor and stromal cells as well as immune cell populations trafficking to the tumor site through the endothelial barrier. Recapitulating these multifaceted dynamics is critical for studying the intimate interactions between cancer and the immune system and to assess the efficacy of emerging immunotherapies, such as immune checkpoint inhibitors (ICIs) and adoptive cell-based products. Microfluidic devices offer a unique technological approach to build tumor-on-a-chip reproducing the multiple layers of complexity of cancer-immune system crosstalk. Here, we seek to review the most important biological and engineering developments of microfluidic platforms for studying cancer-immune system interactions, in both solid and hematological tumors, highlighting the role of the vascular component in immune trafficking. Emphasis is given to image processing and related algorithms for real-time monitoring and quantitative evaluation of the cellular response to microenvironmental dynamic changes. The described approaches represent a valuable tool for preclinical evaluation of immunotherapeutic strategies

Shape-Based Separation of Micro-/Nanoparticles in Liquid Phases

The production of particles with shape-specific properties is reliant upon the separation of micro-/nanoparticles of particular shapes from particle mixtures of similar volumes. However, compared to a large number of size-based particle separation methods, shape-based separation methods have not been adequately explored. We review various up-to-date approaches to shape-based separation of rigid micro-/nanoparticles in liquid phases including size exclusion chromatography, field flow fractionation, deterministic lateral displacement, inertial focusing, electrophoresis, magnetophoresis, self-assembly precipitation, and centrifugation. We discuss separation mechanisms by classifying them as either changes in surface interactions or extensions of size-based separation. The latter includes geometric restrictions and shape-dependent transport properties

A high-throughput microfluidic approach for 1000-fold leukocyte reduction of platelet-rich plasma

Leukocyte reduction of donated blood products substantially reduces the risk of a number of transfusion-related complications. Current ‘leukoreduction’ filters operate by trapping leukocytes within specialized filtration material, while allowing desired blood components to pass through. However, the continuous release of inflammatory cytokines from the retained leukocytes, as well as the potential for platelet activation and clogging, are significant drawbacks of conventional ‘dead end’ filtration. To address these limitations, here we demonstrate our newly-developed ‘controlled incremental filtration’ (CIF) approach to perform high-throughput microfluidic removal of leukocytes from platelet-rich plasma (PRP) in a continuous flow regime. Leukocytes are separated from platelets within the PRP by progressively syphoning clarified PRP away from the concentrated leukocyte flowstream. Filtrate PRP collected from an optimally-designed CIF device typically showed a ~1000-fold (i.e. 99.9%) reduction in leukocyte concentration, while recovering >80% of the original platelets, at volumetric throughputs of ~1?mL/min. These results suggest that the CIF approach will enable users in many fields to now apply the advantages of microfluidic devices to particle separation, even for applications requiring macroscale flowrates

Particle Focusing in Microchannels

The ability to control the motion of particles and cells in microchannels has been a center of fascination since the advent of microfluidics. Entire fields have been created in order to accomplish separation, volume reduction and overall positioning of particles and cells within microfluidic devices in the fastest and most accurate manner possible. While most of these technologies rely on low Reynolds number operation, one technique entitled inertial focusing takes advantage of the inertia of the surrounding fluid and the interaction between a particle and the channel itself which cause the lateral migration of particles across streamlines to equilibrium positions within a flow. The major advantage of inertial microfluidics in biomedical and microfluidic applications is that it is inherently high throughput being dependent on inertia whereas most microfluidic concepts are dependent on low Reynolds number operation.Engineering and Applied Science

Role of viscoelasticity and non-linear rheology in flows of complex fluids at high deformation rates

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Mechanical Engineering, 2013.Some pages printed landscape orientation. Cataloged from PDF version of thesis.Includes bibliographical references (pages 365-399).We combine pressure, velocimetry and birefringence measurements to study three phenomena for which the fluid rheology plays a dominant role: 1) shear banding in micellar fluids, 2) extension-dominated flows in microfluidic devices, and 3) flow-induced particle migration in microchannels. Firstly, worm-like micellar solutions are model non-Newtonian fluids having a single relaxation time [beta]. At shear rates larger than ... however, these systems exhibit shear banding and non-linear rheological behavior, whose importance is characterized by the Weissenberg number ... We develop a stability criterion for the onset of a purely viscoelastic instability for shear-banding fluids, to establish the limitations of conventional rheometric techniques for studying these fluids. A second challenge for conventional rheometers is inertially-driven secondary flows. The onset of these flows is governed by the Reynolds number ... where U is the velocity, D is the flow geometry length and v is the fluid kinematic viscosity. We develop microfluidic devices to impose shear and extensional deformation rates up to ...at low Re. These experiments combine pressure measurements, micro-particle image velocimetry ([mu]-PIV) and birefringence measurements. We develop a microfluidic chip that enables applied rheologists to quantitatively differentiate between fluid formulations intended for applications at high deformation rates. Finally, we study the interplay between fluid inertia and elasticity on particle migration. The inertially-dominated case is governed by the channel Reynolds number Re, and particle Reynolds number ... where a is the particle diameter. In a microfluidic device, the particle and channel size are on the same order, and hence migration occurs at ... in the so-called 'inertial focusing' regime which may have applications in clinical medicine. However, most physiological fluids are viscoelastic and therefore particle migration in these fluids occurs at high Reynolds and Weissenberg numbers, which is a mostly unstudied regime. We combine pressure measurements, streak imaging, [my]-PIV and particle trajectory analysis (PTA) to study the migration of polystyrene beads. Inertia drives particles toward the channel walls, whereas elasticity drives particles toward the channel centerline even at Re, ~ 2000.by Thomas Joseph Ober.Ph. D

Coupled Dynamics of Particles and Fluid-Fluid Interfaces

The study of the interaction between particles and fluid-fluid interfaces is essential to a variety of applications. A systematic way to understand those phenomena is to consider them in two different limits: single particle versus multiple particles. One particular example of a single particle problem is the particle’s interaction with an acoustic bubble. Many bubble-based systems use oscillating microbubbles to trap particles, which further leads to applications including live animal trapping and cell manipulation. On the other hand, when multiple particles are involved, the study of the suspension injection and drainage has drawn much attention, which has the implication in biotechnology and food processing. The objective of this research is to study and gain a fundamental understanding of the coupled dynamics between particles and fluid-fluid interfaces via experimental and theoretical approaches. First, we work on a project with a single-particle trapping via acoustic bubble. In this work, we quantify the magnitudes of secondary radiation force exerted by the oscillating bubble inside a microchannel for varying actuation frequencies and voltages. By combining well-developed theories that connect bubble oscillation yielding secondary radiation force to the acoustic actuation, we derive the expression to predict the critical input voltage that leads to particle release into the flow, which agrees with the experimental results. The next phase of the research emphasizes the dynamics of the collection of particles. We experimentally investigate the effect of particle concentration on the viscous fingering behavior when the suspension is withdrawn from a Hele-Shaw cell. In particular, we quantify the fingering growth rate with varying initial particle concentrations. Our results reveal that the fingering growth rate increases with increasing particle concentrations, while the total drainage time also appears to be increasing. This successfully proves that the drainage efficiency is enhanced due to the presence of the particles. In addition, we observe the particles entrained into the thin film on the plate after drainage, which also varies with the particle concentration and the ratio between gap thickness and particle diameter. Using a simplified model, we also find an entrainment criterion in agreement with the experimental results