Towards the understanding of the behaviour of deformable cells in in vitro microfluidic environments for the development of ex vivo diagnostics and treatments

Fluid dynamics influence cells in suspension in a multitude of settings. Red blood cells and white blood cells are advected through biological microchannels in both the cardiovascular and lymphatic systems and, as a result, are subject to a wide variety of complex fluidic forces as they pass through. In vivo, it is hypothesised that microfluidic forces influence different biological processes such as the spread ing of infection, cancer metastasis and cell viability, highlighting the importance of fluid dynamics in the blood and lymphatic vessels. This suggests that in vitro devices carrying cell suspensions, such as lab-on-a-chip, flow cytometry and some steps of cell therapies, also influence the viability and functionality of cells. Indeed, retaining cell viability is important in the emerging field of cell therapy as cells need to be returned to patients’ bodies. However, several studies have pointed to high shear regimes as a contributing factor to cell death. It is, therefore, unclear how laminar flow affects cell viability, how inertial forces affect cells’ passage and how the latter influences the former. This thesis begins by reviewing the current studies which have investigated how these fluidic forces affect the reactions of suspended cells. The influence that varying Reynolds number, and the corresponding wall shear stress (1.5-10 Pa) has on the viability of different circulating cell lines in two different systems is then investigated. Next, the inertial positions of two represen tative breast cancer cell lines were found. Finally, the influence that varying elastic modulus has on the inertial positions of circulating cells in laminar pipe flow was investigated by altering the elastic moduli of two representative cancer cell lines by 18% and 35%. It was found that increasing shear stress in a cone and plate above 3 Pa caused cell death of up to 91.8% to occur in breast cancer cells, however, wall shear stress as high as 10 Pa in circulation has little to no effect on cell viability of breast cancer cells or T-cells. Certain cell types including neuroblastoma cells and fibroblasts are affected and viability was as low as 28.4% and 25.3% respectively at similar shear levels. Inertial lift forces that move cells towards the centre of the channel protect them from experiencing detrimental levels of wall shear stress, indicating that wall shear stress in Poiseuille flow is not a good predictor of cell viability during advection. Finally, it was found that benign, stiffer cancer cells had a larger distribution across the channel width than metastatic, deformable cancer cells, however, a decrease in the deformability of the benign cells resulted in migration towards the channel centre.