Inertial microfluidics has been attracting considerable interest in recent years due to immensely promising applications in cell biology. Despite the intense attention, the primary focus has been on development of inertial microfluidic devices with less emphasis paid to elucidation of the inertial focusing mechanics. The incomplete understanding, and sometimes confusing experimental results that indicate a different number of focusing positions in square or rectangular microchannels under similar flow conditions, have led to poor guidelines and difficulties in design of inertial microfluidic systems. In this work, we describe and experimentally validate a two-stage model inertial focusing in microchannels. Our analysis and experimental results show that not only the well-accepted shear-induced and wall-induced lift forces act on particles within flow causing equilibration near microchannel sidewalls, but the rotation-induced lift force influences the position of these equilibria. In addition, for the first time, we experimentally measure lift coefficients, which previously could only be obtained from numerical simulations. More importantly, insights offered by our two-stage model of inertial focusing are broadly applicable to cross-sectional geometries beyond rectangular. With elucidation of the equilibration mechanism, we envision better guidelines for the inertial microfluidics community, ultimately leading to improved performance and broader acceptance of the inertial microfluidic devices in a wide range of applications, from filtration to cell separations.

The manipulation of cells and particles suspended in viscoelastic fluids in microchannels has drawn increasing attention, in part due to the ability for single-stream three-dimensional focusing in simple channel geometries. Improvement in the understanding of non-Newtonian effects on particle dynamics has led to expanding exploration of focusing and sorting particles and cells using viscoelastic microfluidics. Multiple factors, such as the driving forces arising from fluid elasticity and inertia, the effect of fluid rheology, the physical properties of particles and cells, and channel geometry, actively interact and compete together to govern the intricate migration behavior of particles and cells in microchannels. Here, we review the viscoelastic fluid physics and the hydrodynamic forces in such flows and identify three pairs of competing forces/effects that collectively govern viscoelastic migration. We discuss migration dynamics, focusing positions, numerical simulations, and recent progress in viscoelastic microfluidic applications as well as the remaining challenges. Finally, we hope that an improved understanding of viscoelastic flows in microfluidics can lead to increased sophistication of microfluidic platforms in clinical diagnostics and biomedical research.

Circulating tumor cells (CTCs) carry a wealth of information on primary and metastatic tumors critical for precise cancer detection, monitoring, and treatment. Numerous microfluidic platforms have been developed in the past few years to capture these rare cells in patient bloodstream for deciphering the critical information needed. However, the practical need for a high-quality method of CTC isolation remains to be met. Herein, we demonstrate a novel multi-flow microfluidic device that is able to sensitively provide high purity (>87%) of separation outcome without labeling. Our device is constructed and configured based on the phenomenal effect of size-dependent inertial migration. The recovery rate of >93% has been achieved using spiked cancer cells at clinically relevant concentrations (10 cells per 5 mL and above). We have also successfully detected CTCs from 6 out of 8 non-small-cell-lung-cancer (NSCLC) patients, while none for 5 healthy control subjects. With these results, we envision our approach is a promising alternative for reliable CTC capture, and thus for facilitating the progress of extracting information from CTCs to personalize treatment strategies for solid tumor patients.

Inertial microfluidics has been attracting considerable interest in recent years due to immensely promising applications in cell separations and sorting. Despite the intense attention, the moderate efficiencies and low purity of the reported devices have hindered their widespread acceptance. In this work, we report on a simple inertial microfluidic system with high efficiency (>99%) and purity (>90%). Our system builds on the concept of two-stage inertial migration which permits precise prediction of particle or cell position within the microchannel. Our design manipulates the inertial equilibrium positions by modulating channel aspect ratio to achieve a complete separation. Here, we successfully demonstrate a complete separation of particles and isolation of rare cells in blood spiked with human prostate epithelial tumor (HPET) cells. Based on the planar structure, large separation spacing and predictable focusing, we envision promising applications and easy integration of our system with existing lab-on-a-chip systems for cell separations.

Massive growth of the microfluidics field has triggered numerous advances in focusing, separating, ordering, concentrating, and mixing of microparticles. Microfluidic systems capable of performing these functions are rapidly finding applications in industrial, environmental, and biomedical fields. Passive and label-free methods are one of the major categories of such systems that have received enormous attention owing to device operational simplicity and low costs. With new platforms continuously being proposed, our aim here is to provide an updated overview of the state of the art for passive label-free microparticle separation, with emphasis on performance and operational conditions. In addition to the now common separation approaches using Newtonian flows, such as deterministic lateral displacement, pinched flow fractionation, cross-flow filtration, hydrodynamic filtration, and inertial microfluidics, we also discuss separation approaches using non-Newtonian, viscoelastic flow. We then highlight the newly emerging approach based on shear-induced diffusion, which enables direct processing of complex samples such as untreated whole blood. Finally, we hope that an improved understanding of label-free passive sorting approaches can lead to sophisticated and useful platforms toward automation in industrial, environmental, and biomedical fields.