High efficiency vortex trapping of circulating tumor cells

Abstract

Circulating tumor cells (CTCs) are important biomarkers for monitoring tumor dynamics and efficacy of cancer therapy. Several technologies have been demonstrated to isolate CTCs with high efficiency but achieve a low purity from a large background of blood cells. We have previously shown the ability to enrich CTCs with high purity from large volumes of blood through selective capture in microvortices using the Vortex Chip. The device consists of a narrow channel followed by a series of expansion regions called reservoirs. Fast flow in the narrow entry channel gives rise to inertial forces, which direct larger cells into trapping vortices in the reservoirs where they remain circulating in orbits. By studying the entry and stability of particles following entry into reservoirs, we discover that channel cross sectional area plays an important role in controlling the size of trapped particles, not just the orbital trajectories. Using these design modifications, we demonstrate a new device that is able to capture a wider size range of CTCs from clinical samples, uncovering further heterogeneity. This simple biophysical method opens doors for a range of downstream interventions, including genetic analysis, cell culture, and ultimately personalized cancer therapy.

Functional profiling of circulating tumor cells with an integrated vortex capture and single-cell protease activity assay

“…Larger cells, such as CTCs, are stably trapped within the microvortices that form in the reservoirs, while smaller red and white blood cells enter but do not form stable limit cycles or orbits (19). The performance of this vortex system has been described extensively in other reports (6,20). We then exchange solutions while under continuous flow to wash out plasma proteins and leave pure cells within a continuously exchanging Fig.…”

Design of a Single-Layer Microchannel for Continuous Sheathless Single-Stream Particle Inertial Focusing

“…Notably, as the flow rate further increases, the two previously unstable equilibrium positions along the short-channel faces reappear again as F WL becomes less dominant than F SG , leading to recovery to the four equilibrium positions. 36,38,[53][54][55][56] As for curved channels, the particle migration trajectory and equilibrium positions are determined by the relative magnitude of the inertial lift and Dean drag force. 57 According to the quasi-quantitative formula derived by Di Carlo et al…”

On‐Chip Generation of Vortical Flows for Microfluidic Centrifugation

“…The inline expansion chamber design shown in Figure b can be considered a dual‐cavity variant to the single cavity design although we note that in this case, the entire channel flow expands into the chamber to generate a pair of vortices; the vortex pair is expected to remain symmetric as long as the flow does not become unstable beyond a critical Reynolds number; breaking the symmetry of the microchambers and hence the vortices that are generated within, on the other hand, was shown to be useful, for example, in facilitating control over the chirality in the assembly process of supramolecular systems . Extensions in the microchamber designs to increase the throughput and efficiency of separation, for example, for sequential cell enrichment or tumour cell isolation, was also demonstrated through multiplexing wherein a large number of inline chambers arrays, both in series and in parallel were employed (Figure d).…”