Advanced Filter for Circulating Tumor Cells

Virtual performance assessment of an advanced filter for circulating tumor cells

Cancer cells can be found in the bloodstream either as single tumor cells or as clusters. CTC enrichment and isolation techniques are necessary in diagnostics but current approaches . In [1] Sarioglu et al proposed a microchip technology to capture CTC clusters independently of tumor-specific markers from unprocessed blood. CTC clusters are isolated through specialized bifurcating traps under low–shear stress conditions that preserve their integrity, and the authors claim that even two-cell clusters that are deformable enough to squeeze through the filter gaps are captured efficiently. The principle is based on the bifurcation of the flow at the top edge of a triangular obstacle and the characteristics of the flow field in the funnel just before the bifurcation that creates a tendency of CTC clusters to orient such that each of their two cells would choose a different path. Addtionally, if one of the cells in the cluster would partly clog one of the openings, the flow would be slightly diverted to the other opening dragging the second cell towards that opening.

We have carried out a simulation study of (diluted) full blood flowing through the proposed chip geometry containing a number of two-cell clusters. While we indeed observe that some of the clusters rotate such that they get stuck at the top of the bifurcation edge, many of the CTC clusters do not align as intended but orient parallel to the flow and therefor squeeze through the filter gaps. Whether this is an effect of other cells disturbing the flow field suffiently to annihilate the orienting effect will be assessed in further simulations with varying cell density.

References

  • A F. Sarioglu, N. Aceto, N. Kojic, M.C. Donaldson, M. Zeinali, B. Hamza, A. Engstrom, H. Zhu, T.K. Sundaresan, D.T. Miyamoto, X. Luo, A. Bardia, B.S. Wittner, S. Ramaswamy, T. Shioda, D.T. Ting, S.L. Stott, R. Kapur, S. Maheswaran, D.A. Haber, M. Toner, A microfluidic device for label-free, physical capture of circulating tumor cell clusters, Nature Methods 12(7), pp 685, 2015.