Microfluidic devices for stiffness dependent enrichment of red blood cell subpopulations

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Ahmed, Faisal
Aidun, Cyrus K.
Barabino, Gilda A.
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Microfluidic devices were designed, fabricated and tested for enriching red blood cell subpopulations based on their stiffness. First, stiffness dependent margination of red blood cells in high aspect ratio straight microchannels was studied with simulation tools. Stiff red blood cells marginate to channel walls whereas normal ones migrate to the central core of the channel regardless whether cell-cell interactions are present or not. Cells of different stiffness reach their equilibrium locations faster in channels with smaller cross sections. Increasing flow Reynolds number and hence the shear rate and, cell volume fraction or hematocrit results in stronger segregation between normal and stiff red blood cells. Based on the results of the simulations, two types of cell enrichment devices were designed and fabricated, simple straight channel device and multistep device. The simple straight channel device was tested for a wide range of Reynolds number and hematocrit values. Cell enrichment gets better with increasing flow Reynolds number and hematocrit up to certain threshold for each of them, and after that threshold no significant improvement of performance is observed. Statistical analysis on experimental data found the effect of individual parameters, flow Reynolds number and hematocrit, to be strong. Significant interaction between these two factors implies that the extent of the effect of one factor (e.g. flow Reynolds number) changes when the value of the other factor (e.g. volume fraction) varies and for best performance of the devices the combination of flow Reynolds number and hematocrit needs to be optimized. The multistep device performs more than three times better than the single step device. This research work revealed new information about stiffness dependent cell enrichment with straight channel microfluidic devices and improved their performance through optimizing flow parameters and new design.
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