Streamline-Based Microfluidic Devices for Erythrocytes and Leukocytes Separation

Abstract

In this paper, we report two devices for the continuous size-based separation of particles, such as blood cells, which is an important step for on-chip blood preparation. Unlike previously demonstrated passive fluidic devices for particle separation, the local geometry of the bifurcated side channels was used as a design parameter. The design of the devices was based on 2-D fluidic simulation of a T-shaped model. This novel approach was proved to be effective in predicting device performance. The critical particle size for separation was clearly defined in the bifurcated region by simulation under the established theoretical framework. We validated the operation principle of the devices by separating 5-and 10-µm polystyrene beads. Human leukocytes were also successfully separated from erythrocytes with 97% efficiency. The separation region of the device had a small footprint for the separation of particles in micrometer range, which makes this device a good candidate to be integrated into a lab-on-a-chip system. The particles were collected in different exit channels after they were separated, which facilitated further sensing and processing. Similar to cross-flow filters, particles were separated perpendicular to the flow direction. The filtering effect was achieved with the collection zones established by the fluidic field. Clogging was minimized by designing the minimal channel width of the devices larger than the largest particle diameter. Solvent exchange could be accomplished for particles.

Deformability based Cell Sorting using Microfluidic Ratchets Enabling Phenotypic Separation of Leukocytes Directly from Whole Blood

“…Based on this prototype design, the microfluidic ratchets are able to process whole blood at a rate of 5 µl per hour. While this throughput is low compared to other biophysical cell separation methods 10–12, 14, 15 , the throughput of this device could ultimately be improved by increasing the filtration area, as well as by paralleling the mechanism.…”

Scaling deterministic lateral displacement arrays for high throughput and dilution-free enrichment of leukocytes

“…Passive separation methods that require antibody labels include magnetic assisted cell separation (MACS) and adhesion-based systems [1], such systems have higher costs and demanding storage requirements to preserve the antibodies. Passive separation methods that do not use labels include margination [2,3], inertial focusing [4], passive magnetic separations [5], dielectrophoresis [6], lab-on-a-CD [7], standing acoustic waves [8] and others that use microfabricated obstacles to affect the path of cells based on their size [9][10][11][12]. Most of the label-free passive separation methods do not have the size resolution required to differentiate red blood cells from leukocytes with high efficiency, and the separation efficiency of these methods typically decreases with increasing haematocrit [9][10][11][12].…”

“…Passive separation methods that do not use labels include margination [2,3], inertial focusing [4], passive magnetic separations [5], dielectrophoresis [6], lab-on-a-CD [7], standing acoustic waves [8] and others that use microfabricated obstacles to affect the path of cells based on their size [9][10][11][12]. Most of the label-free passive separation methods do not have the size resolution required to differentiate red blood cells from leukocytes with high efficiency, and the separation efficiency of these methods typically decreases with increasing haematocrit [9][10][11][12]. Recent work on acoustic particle and blood cell separation is very encouraging, although processing large volumes requires a high power transducer [13].…”

Experimental study on capillary flow through polymer microchannel bends for microfluidic applications

“…The design parameters are set in such a way that the device can be used as a blood filter in future. RBCs (red blood cells) have an average diameter range from 7 to 9 μm, and WBCs (white blood cells) have an average diameter range from 6 to 20 μm [18,21,25]. For future application of this modified design in blood filtration, the channel widths and interpillar distances should be significantly higher than RBC or WBC size to avoid channel clogging [22,23].…”

“…Recent studies show that microchannel bends are very useful for blood cell separation applications because of the centrifugal force produced on particles accelerated by the microchannel bend [17]. Also, several separation techniques for microparticles have been proposed by many researchers [18][19][20][21][22][23][24][25]. These methods may be applicable in lab-on-a-chip devices in other biological applications.…”