Introduction
Circulating tumor cells (CTCs) in microcirculation undergo significant deformation and frictional interactions within microcapillaries. To understand the physical parameters governing ...their flow-induced transport, we studied the pressure-driven flow of cancer cells in a microfluidic model of a capillary network.
Methods
Our microfluidic device contains an array of parallel constrictions separated by regions where cells can repetitively deform and relax. To characterize the transport behavior, we measured the entry time, transit time, and shape deformation of tumor cells as they squeeze through the network.
Results
We found that entry and transit times of cells are much lower after repetitive deformation as their elongated shape enables easy transport in subsequent constrictions. Furthermore, upon repetitive deformation, the cells were able to relieve only 25% of their 40% imposed compressional strain, suggesting that tumor cells might have undergone plastic deformation or fatigue. To investigate the influence of surface friction, we characterized the transport behavior in the absence and presence of bovine serum albumin (BSA) coating on the constriction walls. We observed that BSA coating reduces the entry and transit time significantly. Finally, using two breast tumor cell lines, we investigated the effect of metastatic potential on transport properties. We found that the cell lines could be distinguished only upon surface treatment with BSA, thus surface-induced friction is an indicator of metastatic potential.
Conclusions
Our results suggest that pre-deformation can enhance the transport of CTCs in microcirculation and that frictional interactions with capillary walls can play an important role in influencing the transport of metastatic CTCs.
Primary cancers disseminate both single circulating tumor cells (CTCs) and CTC “clusters,” the latter of which have been shown to demonstrate greater metastatic propensity and adverse impact on ...prognosis. Many devices developed to isolate single CTCs also capture CTC clusters, but there is translational potential for a platform specifically designed to isolate CTC clusters. Herein, we introduce our microfluidic device for isolating CTC clusters (“Microfluidic Isolation of CTC Clusters” or MICC), which is equipped with ∼10 000 trap chambers that isolate tumor cell clusters based on their large sizes and dynamic force balance against a pillar obstacle in the trap chamber. Whole blood is injected, followed by a wash step to remove blood cells and a final backflush to release intact clusters for downstream analysis. Using clusters from tumor cell-line and confocal microscopy, we verified the ability of the MICC platform to specifically capture tumor cell clusters in the trap chambers. Our flow rate optimization experiments identified 25 μl/min for blood injection, 100 μl/min as wash flow rate, and 300 μl/min as the release flow rate – indicating that 1 ml of whole blood can be processed in less than an hour. Under these optimal flow conditions, we assessed the MICC platform’s capture and release performance using blood samples spiked with different concentrations of clusters, revealing a capture efficiency of 66%–87% and release efficiency of 76%–90%. The results from our study suggest that the MICC platform has the potential to isolate CTC clusters from cancer patient blood, enabling it for clinical applications in cancer management.
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