A model-driven approach towards rational microbial bioprocess optimization.

Due to sustainability concerns, bio-based production capitalizing on microbes as cell factories is in demand to synthesize valuable products. Nevertheless, the nonhomogenous variations of the extracellular environment in bioprocesses often challenge the biomass growth and the bioproduction yield. To enable a more rational bioprocess optimization, we have established a model-driven approach that systematically integrates experiments with modeling, executed from flask to bioreactor scale, and using ferulic acid to vanillin bioconversion as a case study. The impacts of mass transfer and aeration on the biomass growth and bioproduction performances were examined using minimal small-scale experiments. An integrated model coupling the cell factory kinetics with the three-dimensional computational hydrodynamics of bioreactor was developed to better capture the spatiotemporal distributions of bioproduction. Full-factorial predictions were then performed to identify the desired operating conditions. A bioconversion yield of 94% was achieved, which is one of the highest for recombinant Escherichia coli using ferulic acid as the precursor.

An in vitro investigation into the hemodynamic effects of orifice geometry and position on left ventricular vortex formation and turbulence intensity.

In a healthy human cardiac system, a large asymmetric clockwise vortex present in the left ventricle (LV) efficiently diverts the filling jet from the mitral annulus to the left ventricular outflow track. However, prior clinical studies have shown that artificial mitral valve replacement can affect the formation of physiological vortex, resulting in overall flow instability in the LV. Lately, the findings from several recent hemodynamic studies seem to suggest that the native D-shaped mitral annulus might be a crucial factor in the development of this physiological flow pattern, with its inherent flow stability and formation of coherent structures within the LV. This study aims to investigate the effect of orifice shape and its position with respect to the posterior wall of the ventricle on vortical formation and turbulence intensity in the LV, by utilizing four separate orifice configurations within an in vitro left heart simulator. Stereo particle image velocimetry experiments were then carried out to characterize the downstream flow field of each configuration. Our findings demonstrate that the generation of the physiological left ventricular vortical flow was not solely dependent upon the orifice shape but rather the subsequent jet-wall interaction. The distance of the orifice geometric center from the left ventricular posterior wall plays a significant role in this jet-wall interaction, and thus, vortical flow dynamics.

A D-Shaped Bileaflet Bioprosthesis which Replicates Physiological Left Ventricular Flow Patterns.

Prior studies have shown that in a healthy heart, there exist a large asymmetric vortex structure that aids in establishing a steady flow field in the left ventricle. However, the implantation of existing artificial heart valves at the mitral position is found to have a negative effect on this physiological flow pattern. In light of this, a novel D-shaped bileaflet porcine bioprosthesis (GD valve) has been designed based on the native geometry mitral valve, with the hypothesis that biomimicry in valve design can restore physiological left ventricle flow patterns after valve implantation. An in-vitro experiment using two dimensional particle velocimetry imaging was carried out to determine the hemodynamic performance of the new bileaflet design and then compared to that of the well-established St. Jude Epic valve which functioned as a control in the experiment. Although both valves were found to have similar Reynolds shear stress and Turbulent Kinetic Energy levels, the novel D-shape valve was found to have lower turbulence intensity and greater mean kinetic energy conservation.