Presence and frequency of rare circulating tumor cells (CTCs) in bloodstreams of cancer patients are pivotal to early cancer detection and treatment monitoring. Here, we use a spiral microchannel with inherent centrifugal forces for continuous, size-based separation of CTCs from blood (Dean Flow Fractionation (DFF)) which facilitates easy coupling with conventional downstream biological assays. Device performance was optimized using cancer cell lines (> 85% recovery), followed by clinical validation with positive CTCs enumeration in all samples from patients with metastatic lung cancer (n = 20; 5–88 CTCs per mL). The presence of CD133+ cells, a phenotypic marker characteristic of stem-like behavior in lung cancer cells was also identified in the isolated subpopulation of CTCs. The spiral biochip identifies and addresses key challenges of the next generation CTCs isolation assay including antibody independent isolation, high sensitivity and throughput (3 mL/hr); and single-step retrieval of viable CTCs.
The paper reports a new method for three-dimensional observation of the location of focused particle streams along both the depth and width of the channel cross-section in spiral inertial microfluidic systems. The results confirm that particles are focused near the top and bottom walls of the microchannel cross-section, revealing clear insights on the focusing and separation mechanism. Based on this detailed understanding of the force balance, we introduce a novel spiral microchannel with a trapezoidal cross-section that generates stronger Dean vortices at the outer half of the channel. Experiments show that particles focusing in such device are sensitive to particle size and flow rate, and exhibits a sharp transition from the inner half to the outer half equilibrium positions at a size-dependent critical flow rate. As particle equilibration positions are well segregated based on different focusing mechanisms, a higher separation resolution is achieved over conventional spiral microchannels with rectangular cross-section.
We present a systematic, multiscale, fully detailed numerical modeling for dynamics of fluid flow and ion transport covering Ohmic, limiting, and overlimiting current regimes in conductance of ion-selective membrane. By numerically solving the Poisson-Nernst-Planck-Navier-Stokes equations, it is demonstrated that the electroconvective instability, arising from the electric field acting upon the extended space charge layer, and the induced strong vortical fluid flow are the dominant factors of the overlimiting current in the planar membrane system. More importantly, at the transition between the limiting and the overlimiting current regimes, hysteresis of electric current is identified. The hysteresis demonstrates the important role of the electroconvective flow in enhancing of current in electrolyte systems with ion-selective membrane.
Elucidating the mechanism of electrokinetic molecular concentration in terms of theoretical limits for the concentration factor and their scaling laws.