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.

Microfluidic devices have been widely applied to trapping and isolation of cells and clusters for controllable intercellular environments and high-throughput analysis, triggering numerous advances in disease diagnosis and single-cell analysis. Passive hydrodynamic cell trapping is one of the simple and effective methods that has been gaining attention in recent years. Our aim here is to review the existing passive microfluidic trapping approaches, including microposts, microfiltration, microwells, and trapping chambers, with emphasis on design principles and performance. We summarize the remarkable advances that hydrodynamic trapping methods offer, as well as the existing challenges and prospects for development. Finally, we hope that an improved understanding of hydrodynamic trapping approaches can lead to sophisticated and useful platforms to advance medical and biological research.

An agarose microwell platform developed for in vitro lung carcinoma spheroid culture and drug response evaluation of targeted anti-cancer therapies.

Circulating tumor cell (CTC) clusters that are shed from the primary tumor into the bloodstream are associated with a poor prognosis, elevated metastatic potential, higher proliferation rate, and distinct molecular features compared to single CTCs. Studying CTC clusters may give us information on the differences in the genetic profiles, somatic mutations, and epigenetic changes in circulating cells compared to the primary tumor and metastatic sites. Microfluidic systems offer the means of studying CTC clusters through the ability to efficiently isolate these rare cells from the whole blood of patients in a liquid biopsy. Microfluidics can also be used to develop in vitro models of CTC clusters and make possible their characterization and analysis. Ultimately, microfluidic systems can offer the means to gather insight on the complexities of the metastatic process, the biology of cancer, and the potential for developing novel or personalized therapies. In this review, we aim to discuss the advantages and challenges of the existing microfluidic systems for working with CTC clusters. We hope that an improved understanding of the role microfluidics can play in isolation, formation, and characterization of CTC clusters, which can lead to increased sophistication of microfluidic platforms in cancer research.

Cancer is the leading cause of death globally, with 90% of deaths being caused by cancer metastasis. Circulating tumor cells (CTCs) play an important role in early diagnosis of cancer...