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

Abstract

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.

Going beyond 20 μm-sized channels for studying red blood cell phase separation in microfluidic bifurcations

“…This is a large range by comparison with most previous in vitro studies, where a unique value of the feed hematocrit has been used, ranging from 10% in Ref. 15 to 40% in Ref. 10.…”

“…2,8,10,15,37,[45][46][47] On one hand, despite the development of microfluidics in the last decade, in vitro experiments have not yet permitted to explore phase separation in bifurcations with branches of characteristic size smaller than 20 lm nor in asymmetric channels with at least one branch smaller (both in depth and width) than the other ones. In addition, "room-sized" experimental models, designed according to the principles of kinematic and dynamic similarity, cannot reproduce the complex rheological properties of RBCs.…”

“…This should ultimately allow a better understanding of the physics at play and a parametrical characterization of the phase-separation effect in steady state, potentially improving the phenomenological description of Pries et al 33,37 The aim of the present paper is to present the experimental methodologies and measurement techniques developed for that purpose, especially in the case of channels of capillary size or slightly larger (typically below 20 lm), including asymmetric bifurcations, in the full physiological hematocrit range. The main originalities of the experiment are the following: first, we design polydimethylsiloxane (PDMS) micro-bifurcations made of square channels with different sizes, while most of the recent previous studies used bifurcations made of rectangular channels with unique depth, 15,45,47 which are easier to fabricate; 48 second, we are interested in regimes which are seldom studied (moderately to highly concentrated RBC suspension flows in small micro-channels), while in most previous studies, channels with sizes superior or equal to 20 lm have been used; 2,8,10,15,[45][46][47] and third, we simultaneously aim at a rigorous control of the experimental conditions, including the possibility of varying independently the inlet hematocrit and the flow rate ratio between both daughter branches, and at an in situ quantitative measurement of the flow parameters. This is extremely challenging in the considered flow regimes and necessitates a combination of various metrologies, including the comparison with reference measurements, in order to validate the results.…”

A microfluidic device for partial cell separation and deformability assessment

“…Recently, Ishikawa et al [10] and Leble et al [11] have shown the existence of thin CFL in the centre of the microchannel, just downstream of a confluence. This phenomenon is due to the existence of a CFL in both inner walls and a consequent formation of a triangular CFL in the region of the confluence apex [10,11].…”

“…This phenomenon is due to the existence of a CFL in both inner walls and a consequent formation of a triangular CFL in the region of the confluence apex [10,11]. Faivre et al [12] and Sollier et al [13] have demonstrated that the CFL could be enhanced by using a microchannel containing a constriction followed by sudden expansion to separate plasma from the whole in vitro blood.…”