Growth of the microfluidics field has triggered numerous advances in focusing and separating microparticles, with such systems rapidly finding applications in biomedical, chemical, and environmental fields. The use of shear-thinning viscoelastic fluids in microfluidic channels is leading to evolution of elasto-inertial focusing. Herein, we showed that the interplay between the elastic and shear-gradient lift forces, as well as the secondary flow transversal drag force that is caused by the non-zero second normal stress difference, lead to different particle focusing patterns in the elasto-inertial regime. Experiments and 3D simulations were performed to study the effects of flowrate, particle size, and the shear-thinning extent of the fluid on the focusing patterns. The Giesekus constitutive equation was used in the simulations to capture the shear-thinning and viscoelastic behaviors of the solution used in the experiments. At low flowrate, with Weissenberg number Wi ~ O(1), both the elastic force and secondary flow effects push particles towards the channel center. However, at a high flowrate, Wi ~ O(10), the elastic force direction is reversed in the central regions. This remarkable behavior of the elastic force, combined with the enhanced shear-gradient lift at the high flowrate, pushes particles away from the channel center. Additionally, a precise prediction of the focusing position can only be made when the shear-thinning extent of the fluid is correctly estimated in the modeling. The shear-thinning also gives rise to the unique behavior of the inertial forces near the channel walls which is linked with the ‘warped’ velocity profile in such fluids.

Numerical modeling has played a pivotal role in advancing inertial microfluidics, tracing its development from inception and offering deeper insights into the microscale phenomena governing inertial focusing. These computational approaches have simultaneously supported the proliferation of on-chip technologies. Initially adopted across diverse industries for passive and high-throughput operations such as trapping, separation, and sorting of particles, the greatest potential of inertial microfluidics lies in biomedical applications, where it serves as a cornerstone for processing cells in clinical and research settings. As the range of applications continues to expand, microfluidic devices are evolving into increasingly complex systems capable of handling diverse cell types and particles within miniature chip architectures. This growing complexity necessitates the enhancement of conventional numerical techniques and the integration of innovative computational approaches to address these emerging challenges. This review aims to provide an overview of the available numerical techniques, highlighting their advantages and limitations. We explore recent strides in computational inertial microfluidics, emphasizing advancements within the last four years and the emergence of innovative methodologies such as smoothed particle hydrodynamics. Furthermore, we describe the nascent role of machine learning in inertial microfluidics, noting its limited adoption compared to conventional microfluidics and highlighting the potential to transform the field, as well as challenges that need to be overcome.

We conducted a systematic numerical investigation of spherical, prolate and oblate particles in an inertial shear flow between two parallel walls, using smoothed particle hydrodynamics (SPH). It was previously shown that above a critical Reynolds number, spherical particles experience a supercritical pitchfork bifurcation of the equilibrium position in shear flow between two parallel walls, namely that the central equilibrium position becomes unstable, leading to the emergence of two new off-centre stable positions (Fox et al., J. Fluid Mech., vol. 915, 2021). This phenomenon was unexpected given the symmetry of the system. In addition to confirming this finding, we found, surprisingly, that ellipsoidal particles can also return to the centre position from the off-centre positions when the particle Reynolds number is further increased, while spherical particles become unstable under this increased Reynolds number. By utilizing both SPH and the finite element method for flow visualization, we explained the underlining mechanism of this reverse of bifurcation by altered streamwise vorticity and symmetry breaking of pressure. Furthermore, we expanded our investigation to include asymmetric particles, a novel aspect that had not been previously modelled, and we observed similar trends in particle dynamics for both symmetric and asymmetric ellipsoidal particles. While further validation through laboratory experiments is necessary, our research paves the road for development of new focusing and separation methods for shaped particles.

Inertial focusing has been utilized to advance assisted reproductive technologies (ART) for animal breeding and in vitro fertilization (IVF) by separating sperm cells from biofluids with complex cell backgrounds. While existing studies have aimed to design and optimize sperm separation devices, the fundamental mechanism behind the unique focusing behavior of sperm in spiral channels remains largely unknown: sperm cells focus near the outer wall, whereas most other cells focus near the inner wall. This is primarily due to the lack of a direct modelling scheme for capturing the detailed inertial migration of sperm cells in the spiral channels. In this work, we developed a 3D DNS-PT modeling approach that can predict the inertial focusing of sperm cells with long tails. Unlike previous studies that considered rotating spheres, the novelty of our approach is in extracting the inertial lift force for a triaxial ellipsoid (which represents the asymmetric oval-shaped sperm head) and accounting for the tail effect through appropriate boundary conditions, thus capturing their cumulative impact on sperm focusing behavior. Furthermore, we conducted inertial microfluidics experiments with fluorescent images of spermatozoa to validate the modelling results. We discovered that the effect of the tail, rather than the sperm head shape or orientation, is the primary determinant of the unique inertial focusing position of sperm cells in microchannels. The modelling results provided significant insights into the evolution of particle distribution in the channel cross-section along the flow direction, which was previously unknown due to the limitations of imaging techniques. The predicted particle trajectories enabled detailed analysis and explanation of the distinct migration paths of sperm cells and spherical particles. This work bridges the gap in our understanding of the inertial migration of sperm and other flagellated cells, facilitating the better design and optimization of sorting and separation devices.

Premature clearance and limited organ targeting remain major barriers for nanoparticle (NP) drug delivery. Hitchhiking NPs on red blood cells (RBCs) can enhance circulation and organ‐selective accumulation, but most approaches require ex vivo RBC extraction and reinfusion, limiting clinical translation. Here, we report an in situ RBC‐hitchhiking strategy, named i‐Bind, which employs polyphenol surface functionalization to enable spontaneous NP attachment to RBCs directly in the bloodstream. Driven by strong interactions of phenolic motifs with RBC membranes, i‐Bind NPs exhibited markedly enhanced and more stable hitchhiking onto RBCs under flowing whole blood conditions. In both healthy and diseased mice, i‐Bind NPs preferentially target the lungs, resulting in an over 20‐fold increase in lung‐to‐liver deposition ratio compared to unmodified NPs. Additionally, i‐Bind NPs show preferential targeting to distinct lung immune cell subsets in a pathology‐dependent manner, including cDC2s in healthy lungs, neutrophils in acute lung injury, and cDC1s in lung metastases. In a melanoma lung metastasis model, delivery of the STING agonist diABZI via i‐Bind NPs significantly inhibited lung metastasis progression by reprogramming the lung immune microenvironment. Collectively, i‐Bind provides a simple and versatile platform for organ‐targeted drug delivery and immune reprogramming.