Cell culture in microfluidic systems has primarily been conducted in devices comprised of polydimethylsiloxane (PDMS) or other elastomers. As polystyrene (PS) is the most characterized and commonly used substrate material for cell culture, microfluidic cell culture would ideally be conducted in PS-based microsystems that also enable tight control of perfusion and hydrodynamic conditions, which are especially important for culture of vascular cell types. Here, we report a simple method to prototype perfusable PS microfluidics for endothelial cell culture under flow that can be fabricated using standard lithography and wet laboratory equipment to enable stable perfusion at shear stresses up to 300 dyn/cm(2) and pumping pressures up to 26 kPa for at least 100 h. This technique can also be extended to fabricate perfusable hybrid PS-PDMS microfluidics of which one application is for increased efficiency of viral transduction in non-adherent suspension cells by leveraging the high surface area to volume ratio of microfluidics and adhesion molecules that are optimized for PS substrates. These biologically compatible microfluidic devices can be made more accessible to biological-based laboratories through the outsourcing of lithography to various available microfluidic foundries.
To delineate the influence of hemodynamic force on cell adhesion processes, model in vitro fluidic assays that mimic physiological conditions are commonly employed. Herein, we offer a framework for solution of the three-dimensional Navier- Stokes equations using computational fluid dynamics (CFD) to estimate the forces resulting from fluid flow near a plane acting on a sphere that is either stationary or in free flow, and we compare these results to a widely used theoretical model that assumes Stokes flow with a constant shear rate. We find that while the full three-dimensional solutions using a parabolic velocity profile in CFD simulations yield similar translational velocities to those predicted by the theoretical method, the CFD approach results in approximately 50% larger rotational velocities over the wall shear stress range of 0.1-5.0 dynes cm-2. This leads to an approximately 25% difference in force and torque calculations between the two methods. When compared with experimental measurements of translational and rotational velocities of microspheres or cells perfused in microfluidic channels, the CFD simulations yield significantly less error. We propose that CFD modelling can provide better estimations of hemodynamic force levels acting on perfused microspheres and cells in flow fields through microfluidic devices used for cell adhesion dynamics analysis.
Total cavopulmonary connection is the result of a series of palliative surgical repairs performed on patients with single ventricle heart defects. The resulting anatomy has complex and unsteady hemodynamics characterized by flow mixing and flow separation. Although varying degrees of flow pulsatility have been observed in vivo, non-pulsatile (time-averaged) boundary conditions have traditionally been assumed in hemodynamic modeling, and only recently have pulsatile conditions been incorporated without completely characterizing their effect or importance. In this study, 3D numerical simulations with both pulsatile and non-pulsatile boundary conditions were performed for 24 patients with different anatomies and flow boundary conditions from Georgia Tech database. Flow structures, energy dissipation rates and pressure drops were compared under rest and simulated exercise conditions. It was found that flow pulsatility is the primary factor in determining the appropriate choice of boundary conditions, whereas the anatomic configuration and cardiac output had secondary effects. Results show that the hemodynamics can be strongly influenced by the presence of pulsatile flow. However, there was a minimum pulsatility threshold, identified by defining a weighted pulsatility index (wPI), above which the influence was significant. It was shown that when wPI < 30%, the relative error in hemodynamic predictions using time-averaged boundary conditions was less than 10% compared to pulsatile simulations. In addition, when wPI < 50, the relative error was less than 20%. A correlation was introduced to relate wPI to the relative error in predicting the flow metrics with non-pulsatile flow conditions.