| Circulating tumor cells(CTCs)are cancerous cells in the peripheral blood shed from primary tumors.They are carried around in the circulation of a cancer patient prior to the emergence of clinical symptoms,which means that CTCs can be a harbinger of cancer formation and metastasis.Therefore,to illuminate the role that CTCs play in the development of cancer,effective strategies for separating extremely low concentrations of tumor cells must be put forward.The filtration strategy based on the fact that CTCs are typically stiffer and larger than normal blood cells is prevailing for its ease of operation,structural simplicity,high throughput,and low cost.In this paper,volume of fluid(VOF)multiphase flow models are adopted for determining the cells’ filtering processes,which can provide insights into the design of CTC microfilters.Moreover,the cellular injuries should be as low as possible for the benefit of the subsequent research.Although some simulation results for CTC microfilters have been reported before,most of them focused on the influence of filtering channel geometries on the pressure drop and entrance time.To the best of our knowledge,the impact of the filtering process on cellular injuries is not well elucidated and the cellular damage characterized by membrane area strain remains elusive.In general,the main cellular damage in the physical process is caused by the excessive tensile stress of the cell membrane.As reported in the previous literature,the 5%-6%cell area strain will lead to lysis of the lipid bilayer under a dynamic situation with low strain rates,which denotes that the area strain can be an indicator of cellular injury.Thus,the average lysis limit of 5.5%is taken as a critical area strain in our model.The cells are considered damaged if the area strain is larger than the critical value.Under the guidance of this criterion,we explored the effect of different parameters,such as filter geometric pattern,filtering film thickness,and flow rate,on cell membrane strain in dynamic processes.A better design pattern that is suitable for the microfilters is determined as the slit-shaped one and the optimized thickness and flow rate are obtained as well.That is,with these optimal parameter settings,minimal damage is done to the filtered cells.These findings will direct the fabrication of next generation microfilters that meet the higher throughput,lower cellular injury requirements. |
