Nonlinearity in finite-Reynolds-number flow results in particle migration transverse to fluid streamlines, producing the well-known “tubular pinch effect” in cylindrical pipes. Here we investigate these nonlinear effects in highly confined systems where the particle size approaches the channel dimensions. Experimental and numerical results reveal distinctive dynamics, including complex scaling of lift forces with channel and particle geometry. The unique behavior described in this Letter has broad implications for confined particulate flows.

Encapsulation of cells within picoliter-size monodisperse drops provides new means to perform quantitative biological studies on a single-cell basis for large cell populations. Variability in the number of cells per drop due to stochastic cell loading is a major barrier to these techniques. We overcome this limitation by evenly spacing cells as they travel within a high aspect-ratio microchannel; cells enter the drop generator with the frequency of drop formation.While drop-based microfluidics 1,2 promises breakthrough applications in biotechnology such as directed evolution, 3 tissue printing 4 and bead-based PCR in emulsions, 5 it also facilitates many quantitative studies of biology at the most fundamental level, that of single cells. Because each cell can be made to reside within its own picoliter-volume drop, chemically isolated from all other drops, cell-secreted molecules rapidly achieve detectable concentrations in the confined fluid surrounding the encapsulated cell. Similarly, uptake of trace chemicals specific to individual cells can be probed due to their depletion within the confined extracellular fluid. Moreover, highly monodisperse drops of water in an inert and immiscible carrier fluid can be formed at rates of several kHz using microfluidic techniques, 6 and these drops can be pairwise combined, 7 split in two, 8 and selected based on the contents of individual drops. 9,10 Despite their great potential, studies of single cells in drops suffer from an intrinsic limitation; because the process of loading cells into drops is purely random, the distribution is dictated by Poisson statistics. Thus, the probability of a drop containing k cells is λ k exp(−λ) / k!, where λ is the average number of cells per drop, so the ratio of drops containing one cell to those containing two is 2/λ. This means that to minimize the number of drops that contain more than a single cell requires very low average loading densities, meaning that most drops actually contain no cells whatsoever. This constraint significantly reduces the number of usable drops; for example, only 15.6 % of all drops will contain one cell if no more than one in ten of the occupied drops can be allowed to hold two or more cells.Recent work describes a method to passively sort drops containing single cells from smaller empty drops after each cell triggers its own encapsulation upon entering a narrow aqueous jet formed in a flow-focusing device. 11 This clever mechanism can also be used to sort cells based on their size since, for this system, drops are always slightly larger than the cell they contain; however, to overcome the inherent limitations of stochastic encapsulation of cells within controlled-size (monodisperse) drops, one (and only one) cell should be present whenever a drop is generated. This can be achieved manually for each drop, 12 or passively, and with a much higher throughput, by organizing cells in the direction of flow so that they enter the microfluidic nozzle with the same frequency at which drops form. * These autho...

Rapid separation and filtration of particles in solution has a wide range of applications including blood cell separation, ultrasound contrast agent preparation, and purification of fermentation products. However, current techniques that provide quick processing rates are high in complexity. We present a rapid microfluidic filtration technology capable of separating particles based on size, with purities from 90 to 100% and high-volume throughputs of 1 mL/min. Data for separation of rigid particles, deformable emulsions, and platelets from whole blood are presented. The system is based upon differential inertial focusing of particles of varying sizes and allows continuous separation based only on intrinsic hydrodynamic forces developed in a flow through an asymmetrically curved channel. A theoretical description of the underlying forces is developed, and in combination with data determining a size cutoff for separation, a semiempirical relationship describing how channel geometry is related to this cutoff is shown. Cascading separations in series is shown to be useful for increasing purity and yield. This type of microfluidic system can filter deformable particles, is largely independent of particle density, and can provide throughputs typical of macroscale filtration in a compact format, enabling applications in blood filtration and particle concentration.