High throughput multi-modal microfluidic system for isolation of blood cells
MetadataShow full item record
In this study, we have developed a novel, multimodal microfluidic platform for cell sorting which utilizes size and adhesion as label-free biomarkers. The size biomarker is chosen as it is a distinguishing characteristic of subpopulation of blood cells and is easily tied to hydrodynamic and inertial separation forces and fractionation methods. The adhesion biomarker is chosen to be a more specific sorting parameter since cell molecular interactions govern important physiological processes such as stem cell homing, inflammation, immune modulation, and cancer metastasis. The separation device consists of a microchannel with periodically arranged diagonal ridges. In the first part of the study, we have studied the impact of hydrodynamics caused by the diagonal ridges on microparticle flow and how it can be optimized for size based sorting. We find that the diagonal ridges create helical flow fields that impact similar particles of different z-positions differently. We have successfully demonstrated that by incorporating z-axis focusing of the sample inlet so as to position all particles to a uniform z-position, we can make consistent the particle exposure to transverse flow fields resulting in more accurate size-dependent sorting. With this key insight we have substantially improved the efficiency and accuracy of size based sorting. In the second part of this work, we have studied the impact of specific molecular attachment to the diagonal ridges on cell trajectories for use in adhesion based sorting. The unique aspect of this sorting design is the impact of the gap size on cell trajectories and cell kinetics, in which a sufficiently small gap size can lightly squeeze the cells while flowing under the ridged part of the channel to increase the surface area for interaction between the ligand on cell surface and coated receptor molecule but large enough so that biomechanical markers, stiffness and viscoelasticity, do not dominate the cell separation mechanism. This way we can flow the cells at high flow rate to achieve high throughput, while maintaining sensitivity to adhesiveness. We are able to successfully sort HL60 and Jurkat cells based on their PSGL-1 expression. We believe this simple and cost effective multimodal blood cell sorting device can be used to fulfill the unmet requirements of a point of care diagnostic tool with high throughput and purity.