Circulating tumor cells (CTCs) and circulating clusters of cancer and stromal cells have been identified in the blood of patients with malignant cancer and can be used as a diagnostic for disease severity, assess the efficacy of different treatment strategies and possibly determine the eventual location of metastatic invasions for possible treatment. There is thus a critical need to isolate, propagate and characterize viable CTCs and clusters of cancer cells with their associated stroma cells. Here, we present a microfluidic device for mL/min flow rate, continuous-flow capture of viable CTCs from blood using deterministic lateral displacement (DLD) arrays. We show here that a DLD array device can isolate CTCs from blood with capture efficiency greater than 85% CTCs at volumetric flow rates of up to 10 mL/min with no effect on cell viability
Deterministic lateral displacement arrays have shown great promise for size-based particle analysis and purification in medicine and biology. Here, we demonstrate that the use of an array of triangular rather than circular posts significantly enhances the performance of these devices by reducing clogging, lowering hydrostatic pressure requirements, and increasing the range of displacement characteristics. Experimental data and theoretical models are presented to create a compelling argument that future designs of deterministic lateral displacement arrays should employ triangular posts. The effect of practical considerations, such as vertex rounding, post size, and shape, is also discussed.
We present a deterministic, nonthermal ratchet where the trajectory of particles in a certain size range is not reversible when the sign of the pressure gradient is reversed at a low Reynolds number. This effect is produced by employing triangular rather than the conventional circular posts in an array that selectively displaces particles transported through the array. The ratchet irreversibly moves particles of a certain size range in a direction orthogonal to an oscillating flow, with no net displacement of the fluid itself. The underlying mechanism of this ratchet is shown to be connected to irreversible particle-post interactions and the asymmetric fluid velocity distribution through the gap between the triangular posts. Diffusion plays no role in this ratchet, and hence the device parameters presented here can be scaled up to high rates of flow, of clear importance in separation technologies.
We present a versatile method for continuous-flow, on-chip biological processing of cells, large bio-particles, and functional beads. Using an asymmetric post array in pressure-driven microfluidic flow, we can move particles of interest across multiple, independent chemical streams, enabling sequential chemical operations. With this method, we demonstrate on-chip cell treatments such as labeling and washing, and bacterial lysis and chromosomal extraction. The washing capabilities of this method are particularly valuable because they allow many analytical or treatment procedures to be cascaded on a single device while still effectively isolating their reagents from cross-contamination.
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