Dissipative particle dynamics simulation of cell entry into a micro-channel

High-Throughput Characterization of Cell Adhesion Strength Using Long-Channel Constriction-Based Microfluidics

“…As can be seen from Figure d, cell velocity drops sharply close to zero at the beginning of contact with the microchannel . Then, the cell is squeezed into the microchannel at a very slow and constant velocity until cell deformation is finished .…”

“…Therefore, a single cell built as the viscoelasticity model is more reasonable in the transit stage. , The viscous part was ignored for the convenience of calculation. The elastic part was usually characterized by three energy potential terms, i.e., in-plane energy term, bending energy term, and volume restraint term. , Those three terms are all highly correlated with the degree of cell deformation; therefore, we proposed a simplified spring model to describe the linear elasticity of a single cell in constriction (see Figure b). According to Hooke’s law, the friction force F f is given by where μ denotes the coefficient of sliding friction, k is the elasticity coefficient determined by cell deformability or stiffness, r is the spherical cell radius, and w is the width of the microchannel.…”

“…The adhesion strength of a cancer cell is a meaningful biomarker of its metastatic potential, tightly associated with various metastatic processes; for example, cancer cells escape from a primary tumor, and circulating tumor cells (CTCs) are anchored to the vessel wall. − Constriction-based microfluidics, − which can enable single-cell mechanophenotyping at high throughputs, have already realized cell deformability measurement. − ,,, However, due to the influence of cell size heterogeneity, , accurately evaluating cell adhesion strength based on constricted microchannel remains difficult.…”

“…Generally, the size of constricted microchannel should be smaller than that of cancer cells; therefore, single cells are driven by a pressure difference to pass through constriction. , In addition, the constricted microchannel generally consists of two kinds, i.e., short-channel constriction (<150 μm) ,,,, and long-channel constriction (>200 μm). ,,,− The short-channel constriction can only realize the characterization of cell deformability, whereas the long-channel constriction can realize the assessment of both cell deformability and adhesion strength . Because cell passage through a long-channel constriction commonly consists of two processes, i.e., cell entry and cell transit. ,, The flow pressure difference drives a cell to deform to enter the constriction; therefore, cell deformation dominates the whole process of cell entry. While the process of cell transit through the constriction is mainly determined by the flow pressure difference and surface friction between the cell membrane and microchannel wall; , thus, the cell transit process can be used to evaluate cell adhesion strength.…”

“…While the process of cell transit through the constriction is mainly determined by the flow pressure difference and surface friction between the cell membrane and microchannel wall; , thus, the cell transit process can be used to evaluate cell adhesion strength. Besides, cell transit also consists of two stages, i.e., the acceleration stage and the constant velocity stage . In the acceleration stage, forces such as pressure difference and surface friction exerted on a single cell are unbalanced, and the duration is short (∼100 ms); therefore, it seems meaningless to utilize the acceleration stage for mechanical phenotype quantification, whereas cell transit velocity remains constant when the maximum is reached in the constant velocity stage .…”