Numerical study on droplet passing through a micro-confinement for circulating tumor cell detection

Zhifeng Zhang

Various lab on a chip devices have been developed recently to detect and separate circulating tumor cells (CTCs) for early cancer detection. Because CTCs are extremely rare in the blood, next generation CTC microfilters aim at significant improvement in both efficiency and throughput. CTC microfilters based on cell deformability seem to be a promising direction. In present research, we study CTC passing through a micro filtering channel with various 3D geometries. The pressure signatures for different types of cells passing through different channels are characterized numerically. Specifically, five kinds of cross-sections, circular, square, triangular and two kinds of rectangular with aspect ratio of 2 and 5 are studied in this work. The total pressures for cell passing through the channels are calculated and reveal different behavior from what is predicted by the static surface tension model. Besides, regarding whether CTC fully blocks the channel inlet, we observe two flow regimes: CTC squeezing and shearing regime. By further studying the relation of CTC deformation at the exact critical pressure point for increasing inlet velocity, three different types of cell deformation are observed: 1) hemispherical front, 2) parabolic front, and 3) elongated CTC co-flowing with carrier media. Focusing on the circular channel, we observe a first increasing and then decreasing critical pressure change with increasing flow rate. By pressure analysis, the concept of optimum velocity is proposed to explain the behavior of CTC filtration and design optimization of CTC filter. Similar behavior is also observed in channels with symmetrical cross sections like square and triangular, but not in rectangular channels which only results in decreasing critical pressure. Finally, the CTC cytoplasm and nucleus are taken into consideration to for a compound CTC model. The interactions between the compound CTC, bloodstream, as well as the channel wall are studied numerically. The pressure signature and deformation are obtained and compared with simple droplet model. In the end, the drawback of our method is also provided with advice for improvement. Our findings will provide valuable information for the design of next generation CTC microfilters.

Numerical study on droplet passing through a micro-confinement for circulating tumor cell detection

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