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.

Fan (2011) Targeting autophagy enhances sorafenib lethality for hepatocellular carcinoma via ER stressrelated apoptosis,

Introduction: Human gut microbiota is believed to be directly or indirectly involved in cardiovascular diseases and hypertension. However, the identification and functional status of the hypertension-related gut microbe(s) have not yet been surveyed in a comprehensive manner.Methods: Here we characterized the gut microbiome in hypertension status by comparing fecal samples of 60 patients with primary hypertension and 60 gender-, age-, and body weight-matched healthy controls based on whole-metagenome shotgun sequencing.Results: Hypertension implicated a remarkable gut dysbiosis with significant reduction in within-sample diversity and shift in microbial composition. Metagenome-wide association study (MGWAS) revealed 53,953 microbial genes that differ in distribution between the patients and healthy controls (false discovery rate, 0.05) and can be grouped into 68 clusters representing bacterial species. Opportunistic pathogenic taxa, such as, Klebsiella spp., Streptococcus spp., and Parabacteroides merdae were frequently distributed in hypertensive gut microbiome, whereas the short-chain fatty acid producer, such as, Roseburia spp. and Faecalibacterium prausnitzii, were higher in controls. The number of hypertension-associated species also showed stronger correlation to the severity of disease. Functionally, the hypertensive gut microbiome exhibited higher membrane transport, lipopolysaccharide biosynthesis and steroid degradation, while in controls the metabolism of amino acid, cofactors and vitamins was found to be higher. We further provided the microbial markers for disease discrimination and achieved an area under the receiver operator characteristic curve (AUC) of 0.78, demonstrating the potential of gut microbiota in prediction of hypertension.Conclusion: These findings represent specific alterations in microbial diversity, genes, species and functions of the hypertensive gut microbiome. Further studies on the causality relationship between hypertension and gut microbiota will offer new prospects for treating and preventing the hypertension and its associated diseases.

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.

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 for size-based separation of particles and cells. The inertial forces can be manipulated by expanding the microchannel geometry, leading to formation of microvortices which selectively isolate and trap particles or cells from a mixture. In this work, we aim to enhance our understanding of particle trapping in such microvortices by developing a model of selective particle trapping. Design and operational parameters including flow conditions, size of the trapping region, and target particle concentration are explored to elucidate their influence on trapping behavior. Our results show that the size dependence of trapping is characterized by a threshold Reynolds number, which governs the selective entry of particles into microvortices from the main flow. We show that concentration enhancement on the order of 100,000× and isolation of targets at concentrations in the 1/mL is possible. Ultimately, the insights gained from our systematic investigation suggest optimization solutions that enhance device performance (efficiency, size selectivity, and yield) and are applicable to selective isolation and trapping of large rare cells as well as other applications.

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.

In this paper, we report an inertial microfluidic device with simple geometry for continuous extraction of large particles with high size-selectivity (<2 lm), high efficiency ($90%), and high purity (>90%). The design takes advantage of a high-aspect-ratio microchannel to inertially equilibrate cells and symmetric chambers for microvortex-aided cell extraction. A side outlet in each chamber continuously siphons larger particles, while the smaller particles or cells exit through the main outlet. The design has several advantages, including simple design, small footprint, ease of paralleling and cascading, one-step operation, and continuous separation with ultra-selectivity, high efficiency and purity. The described approach is applied to manipulating cells and particles for ultraselective separation, quickly and effectively extracting larger sizes from the main flow, with broad applications in cell separations. V C 2013 AIP Publishing LLC.