Numerical Optimization of a Microfluidic System for Hydrodynamic Trapping of Tumor Cells

Liquid biopsy is a highly effective microfluidic technique for isolating circulating tumor cells and cell-free DNA from the blood of cancer patients. Physical trapping is a label-free isolation approach that relies on cell size as a selective phenotype to improve cell isolation in liquid biopsy or to retain target cells on-chip for follow-on analysis and imaging. In silico models have been extensively used to optimize the design of the hydrodynamic trapping microfluidic device and to investigate cancer cell transmigration through narrow constrictions. While most studies focus on computational fluid dynamics (CFD) analysis of flow over particle and (or) pillar, a quantitative analysis of mechanical interaction between particle and trapping unit is missing and the literature which provides similar analysis centers on longitudinally extended geometries (e.g., micro-vessels) usually for the purpose of understanding a biological phenomenon, rather than designing a trapping apparatus. This work defines an experimentally informed description of critical pressure as a function of cell morphology and trapping unit geometry. Our findings show that a hyper-elastic definition accurately captures the stress-related softening behavior observed in cancer cells passing through microconstrictions. These findings were used to develop a model capable of predicting and extrapolating critical pressure values. The validity of the model was assessed with both regression analysis and experimental data. Coupled with CFD analysis, one can use this formulation to design efficient microfluidic devices for cell trapping and potentially perform downstream analysis of trapped cells.