Analytical Modeling And Experimental Optimization Of Herringbone Microfluidic Chip For Capture Of Circulating Tumor Cells

Circulating tumor cells(CTCs)are tumor cells shed from primary and metastatic tumor sites,and generally believed to be the “liquid biopsy” of the tumors as well as the main source of cancer metastasis.However,isolating CTCs is technically challenging because of their scarcity in blood samples.Staggered herringbone micromixer disrupts streamlines and induces chaotic mixing and microvortex.Recently,the herringbone chip has been exploited for rare cell capture from a hetereogeneous suspension because of the enhanced interactions between cells and antibodyimmobilized device surfaces induced by herringbone microstructures.Yet,very limited research has been focused on the theoretical modeling and optimization of herringbone chips for enhancing the performance of rare cell capture from complex biological samples.We developed an analytical model to investigate the interactions between cells and antibody-immobilized device surface in a herringbone microfluidic chip for geometrical optimization to achieve high capture efficiency of circulating tumor cells(CTCs)from patients’ blood samples.For on-chip cell capture,the cell has to travel close to the device surface within a distance of cell radius and meanwhile,the adhesion force for cell capture has to be higher than the shear detachment force,which is defined as an effective cell-surface contact.We extensively investigated how geometrical parameters(width of herringbone groove,spacing between herringbone grooves,height of herringbone groove,and height of microchannel),flow rates and flow directions(forward flow,reverse flow)affect the cell-surface contact.All effective contacts were enumerated for selection of physical parameters with high contact events in the herringbone chips.