Circulating tumor cells (CTCs) are highly correlated with the invasive behavior of cancer, so their isolations and quantifications are important for biomedical applications such as cancer prognosis and measuring the responses to drug treatments. In this paper, we present the development of a microfluidic device for the separation of CTCs from blood cells based on the physical properties of cells. For use as a CTC model, we successfully separated human breast cancer cells (MCF-7) from a spiked blood cell sample by combining multi-orifice flow fractionation (MOFF) and dielectrophoretic (DEP) cell separation technique. Hydrodynamic separation takes advantage of the massive and high-throughput filtration of blood cells as it can accommodate a very high flow rate. DEP separation plays a role in precise post-processing to enhance the efficiency of the separation. The serial combination of these two different sorting techniques enabled high-speed continuous flow-through separation without labeling. We observed up to a 162-fold increase in MCF-7 cells at a 126 µL min⁻¹ flow rate. Red and white blood cells were efficiently removed with separation efficiencies of 99.24% and 94.23% respectively. Therefore, we suggest that our system could be used for separation and detection of CTCs from blood cells for biomedical applications.

Epithelial-to-mesenchymal transition leads to loss of EpCAM and different physical properties in circulating tumor cells from metastatic breast cancer

We developed a new microfluidic method for focusing microparticles through the combined use of inertial lift forces and turbulent secondary flows generated in a topographically patterned microchannel. The mechanism of particle focusing is based on the hydrodynamic inertial forces exerted on particles migrating along a non-circular microchannel, i.e.tubular pinch effect and wall effect, which induce particle movement away from walls and along a specific lateral position in the microchannel. With the extraordinary geometry of multi-orifice microchannel, an ordered and focused particle distribution was achieved at central or side regions according to a particle Reynolds number (Re_p) range. The focusing of particles was controlled by the particle Reynolds number, microchannel length, and volume fraction of particles in suspension. This method will be beneficial in particle focusing processes in a microfluidic device since it offers continuous, high-throughput performance and simple operation.

Significance: Skin-interfaced, wireless devices for clinical-grade monitoring of physiological parameters are of growing interest for uses that range from healthcare to sports performance. This paper introduces a multifunctional skin-mounted microfluidic platform for capture and biomarker analysis of microliter volumes of sweat, a biofluid that can be collected noninvasively, with potential relevance in biophysical sensing. The focus is on colorimetric and digital assessments of a collection of parameters related to stress, including concentrations of vitamin C, cortisol, and glucose, along with quantitative measurements of sweat rate and galvanic skin response. The results represent important additions to a portfolio of emerging capabilities in skin-interfaced technologies for physiological monitoring, with particular relevance to conditions that follow from unhealthy levels of physical and mental stress.

Over the past two decades, circulating tumor cells (CTCs) have been widely recognized for their importance in clinical trials. While most enrichment methods for these cells have been conducted through the batch process due to their rarity in blood and the need for large sample volumes, the batch process leads to unavoidable cell loss. Given the heterogenetic features of CTCs, this cell loss may limit the validity of research that relies on the isolation of CTCs; such research includes cancer prognosis, diagnosis of minimal residual diseases, assessment of tumor sensitivity to anticancer drugs, and the personalization of anticancer therapies. Recent advances in microfluidic approaches have made it possible to enrich CTCs with a small degree of cell loss. In this review, we highlight several microfluidic-based positive and negative enrichment methods that are the subject of considerable research interest (e.g. EpCAM-dependent assay and EpCAM-independent assay) and suggest a microfluidic-based single cell analysis platform for the down-stream analysis of CTCs. We also discuss critical concerns and future directions for research.