Skip to main content

Modelling and Optimization of Microfluidic Devices for Biomedical Applications

Final Report Summary - BIOMEDMICROFLUIDICS (Modelling and Optimization of Microfluidic Devices for Biomedical Applications)

Within this project we developed a computational model of biological cells flow. The model comprises important phenomena, such as fluid dynamics, fluid-structure interaction, individual cell movements, their mutual collisions. During the model development, we ensured that it is flexible enough to capture different elastic properties arising from the
biology of cells (red blood cells, cancer cells) and extensible in order to include other biological or mechanical aspects.

Besides the mechanical properties of the cell membrane, we developed a spring-based model of cell adhesion. In this model, the adhesion is mediated by receptor-ligand bonds that are modeled with spring-like forces. In this model, the strength of the cell adhesion can be controlled by the stiffness of the bonds. Further, the stochastic nature of bond formation is modeled by association and dissociation parameters of the model. The adhesion model mimic real behavior of cells when under the same conditions, the real cells may, or may not adhere to the surface. The accuracy of the model can be assessed by the mean and the variance of number of captured cells, when performing biological experiments with different cell lines expressing different densities of ligands.

The developed model has been used for the analysis of several types of microfluidic devices. We investigated periodic obstacle arrays used for capture of rare cancer cells. We studied the influence of increased hematocrit on the trajectories of rare cells and we concluded that the probability of cell adhesion is significantly compromised when considering dense suspensions. Further we quantified how the increased hematocrit influences cell’s collision frequency in periodic obstacle arrays. We explicitly evaluated at which values of hematocrit the so called colliding mode of cell trajectories disappears. This is crucial observation because it changes optimal geometry of a periodic obstacle array when aiming at the highest probability of rare cell capture.

Another types of the devices are those for gentle cell manipulation. To avoid the decrease in cell lividity and the cell damage, it is crucial to control the cell deformations during the design of microfluidic channels. We analyzed different channels and we quantified the cell damage by controlling the shape deformations. To assess the computed damage with real hemolysis, a laboratory experiment was designed for real time measurement of intracellular calcium concentration, which will be used as marker of cell activation.

The computational model was implemented in an open-source scientific package ESPResSo. This step is unique, since it enables other biologists with strong background in modelling to use the model for their own purposes. Several research groups across Europe have been using this package for modelling of cell flow.

This project has enabled the applicant to obtain a permanent position at the host institution. He has been successfully included in the organizational structure of the faculty as well as in the teaching process. He became an associate professor and he founded his own research group.