Asymmetry of blood flow and cancer cell adhesion in a microchannel with symmetric bifurcation and confluence

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Bifurcations and confluences are very common geometries in biomedical microdevices. Blood flow at microchannel bifurcations has different characteristics from that at confluences because of the multiphase properties of blood. Using a confocal micro-PIV system, we investigated the behaviour of red blood cells (RBCs) and cancer cells in microchannels with geometrically symmetric bifurcations and confluences. The behaviour of RBCs and cancer cells was strongly asymmetric at bifurcations and confluences whilst the trajectories of tracer particles in pure water were almost symmetric. The cell-free layer disappeared on the inner wall of the bifurcation but increased in size on the inner wall of the confluence. Cancer cells frequently adhered to the inner wall of the bifurcation but rarely to other locations. Because the wall surface coating and the wall shear stress were almost symmetric for the bifurcation and the confluence, the result indicates that not only chemical mediation and wall shear stress but also microscale haemodynamics play important roles in the adhesion of cancer cells to the microchannel walls. These results provide the fundamental basis for a better understanding of blood flow and cell adhesion in biomedical microdevices.

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The authors are grateful for helpful discussions with Dr. R. Lima in Braganca Polytechnic Institute, and Prof. C. T. Lim in National University of Singapore. This study was supported by Grant-in-Aid for Scientific Research (S) from the Japan Society for the Promotion of Science (JSPS; No. 19100008) and by a Grant-in-Aid for Young Scientists (A) from the JSPS (No. 19686016). We also acknowledge the support from the 2007 Global COE Program “Global Nano-Biomedical Engineering Education and Research Network Centre”.

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Correspondence to Takuji Ishikawa.

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Distribution of RBCs and cell-free layers around the bifurcation. The movie is taken by a standard halogen light, and hematocrit is about 10%. (MOV 1345 kb)

Distribution of RBCs and cell-free layers around the confluence. The movie is taken by a standard halogen light, and hematocrit is about 10%. (MOV 1355 kb)

Movie 1

Distribution of RBCs and cell-free layers around the bifurcation. The movie is taken by a standard halogen light, and hematocrit is about 10%. (MOV 1345 kb)

Movie 2

Distribution of RBCs and cell-free layers around the confluence. The movie is taken by a standard halogen light, and hematocrit is about 10%. (MOV 1355 kb)

Appendix A: Confocal micro-PIV system

Appendix A: Confocal micro-PIV system

The confocal micro-PIV system used in this study shown in Fig. 1 consisted of an inverted microscope (IX71; Olympus, Tokyo, Japan), a confocal scanning system (CSU22; Yokogawa, Tokyo, Japan), a high-speed camera (Phantom v7.1; Vision Research, Wayne, NJ, USA), a diode-pumped solid-state (DPSS) laser (Laser Quantum, Cheshire, UK), a syringe pump (KD Scientific, Holliston, MA, USA) to achieve constant flow, a thermo plate (Tokai Hit, Shizuoka, Japan) to control the temperature and an objective lens (magnification, 20×; N.A., 0.75; W.D., 0.17 mm; Olympus). The estimated thickness of the measurement plane (optical slice thickness) was 4.97 μm. By exposing the labelled cells to the laser, the system enabled us to track individual cells inside a blood flow of up to 20% Hct with high resolution and low optical thickness. The recorded images were evaluated in Image J (NIH, Bethesda, MD, USA) using the manual tracking MtrackJ plug-in.

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Ishikawa, T., Fujiwara, H., Matsuki, N. et al. Asymmetry of blood flow and cancer cell adhesion in a microchannel with symmetric bifurcation and confluence. Biomed Microdevices 13, 159–167 (2011).

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  • Microchannel
  • Blood flow
  • Red blood cells
  • Cancer cells
  • Bifurcation
  • Confluence