(162g) Mechanical Response of Cancer Cells in a Microfluidic Capillary

Circulating tumor cells (CTCs) are considered the primary cause of cancer metastasis. CTCs are disseminated from the primary tumor and transported to distant organs by blood flow, where new tumors are instigated. Despite the significance of CTC transport in microcirculation for cancer metastasis, quantitative understanding is lacking. In vivo studies directly examining CTCs in micro-capillaries lack adequate control of flow conditions and conduit geometry. Moreover, tracking individual cells at high spatial and temporal resolution becomes difficult due to limitations in deep tissue imaging and the out-of-plane motion of CTCs in microcirculatory networks.

To understand the hydrodynamic transport of CTCs through microcirculation, we have developed a minimal microfluidic capillary model that consists of a narrow channel to confine flowing brain and prostate cancer tumor cells. The driving pressures are controlled to subject the cells to hemodynamic range of shear stresses. By integrating an on-chip manometer and high-speed imaging, the device allows for the simultaneous characterization of five different parameters including the cell size, blockage pressure, velocity, elongation and entry time into the constriction. Our results show that the dependence of blockage pressure and entry times on cell confinement are the best metrics to identify the metastatic variations between cell lines, suggesting that these two parameters suffice to characterize CTC transport in capillaries.

By characterizing our device with simple model systems including viscous drops and soft elastic particles, we find that the blockage pressure and entry times show no apparent dependence on elastic modulus or drop interfacial tension, but depend significantly on drop internal viscosity. Thus, our results suggest that in the hemodynamic range of shear stresses, the metastatic potential of circulating cells can be characterized by an internal viscosity. We test this hypothesis with a variety of tumor cell lines (leukemia, prostate, brain cancer) and find strikingly that the blockage pressure (and entry times) for all the cancer cell types lies between two universal bounds determined by the viscous drop and elastic particle limit respectively. From a device perspective, our study opens new opportunities for single-cell microfluidic viscometry that has been difficult to realize experimentally.