Microscale bioreactor

Index Entries Microscale bioreactor polydimethylsiloxane microreactor immobilized enzymes urease enzyme silicon wafer. 

Recently, there has been success in generating cocultures that more faithfully reproduce in vivo metastatic microenvironments. An ex vivo microscale liver perfusion bioreactor was used to assess metastatic seeding, mimicking the salient features of fluid dynamics and functionality of hepatic parenchyma. Invasion and subsequent growth of breast and prostate carcinoma cells were detected by two-photon microscopy of fluorescently labeled cells. Tumors... 

Fig. 1. Comparison of typical solid-state fermentation (SSF) and submerged liquid fermentation (SLF) systems. A stirred-bed SSF bioreactor of the design of Durand and Chereau [2] is compared with a typical stirred SLF bioreactor. For each bioreactor an expanded view of the microscale is also shown, in order to highlight differences between the micro-structure of the two systems. The relative scales make it clear that mixing is possible on much smaller scales in SLF than in SSF, since in SSF mixing cannot take place at scales smaller than the particle size. Note that particle sizes in SSF are commonly larger than 1 mm...

Both microscale and macroscale phenomena have the potential to control bioreactor performance. These are illustrated in Fig. 3 for an aerobic process. These processes occur within a spatially heterogeneous physical system, as was demonstrated in Fig. 1, a substrate bed consisting of moist solid particles between which are gas-filled voids. During the fermentation the bulk of the growth occurs at the particle surfaces. 

The microscale processes demonstrated in Fig. 3 are intrinsic to SSF due to the particulate nature of the substrate. They occur in all bioreactors and relatively little can be done to influence them in the way the bioreactor is designed and operated since they occur at the surface and inside the individual substrate particles. The most that can be achieved through bioreactor design and operational strategies is to promote exchange between the particle and air phases and to ensure that the transport processes within the air phase are not limiting. 

Despite our very hmited ability to influence these processes in the way we operate the bioreactor, it is still essential to understand their influence on the system. Understanding how and when microscale processes control process performance can prevent unfruitful attempts to improve performance by manipulating the operational variables of the bioreactor. Such understanding might point to more useful strategies. For example, for a process controlled by intraparticle mass transfer, it might be possible to disrupt barriers to diffusion within the substrate particle, such as plant cell walls. Independently of these reasons, characterization of at least some of the microscale phenomena is necessary for the construction of appropriate expressions to include in macroscale material and energy balances. 

Many mass transfer models exist, but most of them depend on three assumptions and are simplified versions of actual mass transfer mechanisms, many of which occur simultaneously. The first assumption is that the different phases and the phase interface offer resistance to mass transfer in series, in a similar manner to heat transfer resistances. The second assumption maintains that mass transfer is controlled by the phase equilibrium near the interface, which changes more quickly than the bulk phase equilibrium (Azbel, 1981). In other words, mass transfer occurs at the microscale level (van Elk et ak, 2007). Finally, gases are assumed to be single component. Multiple component problems are more complicated because each individual gas component making up the mixture has to be considered for the limiting gas-liquid mass transfer step. The complexity grows further once the relationships between each gas component and, for example, the bacteria in a bioreactor are considered. 

Here the exponent p is dependent on the ratio of the particle size to the microscale of the eddies. In the case of tower bioreactors, the energy dissipation rate per unit mass can simply be calculated from... 

One additional area that is on the horizon is the potential to optimize biologically based processes with microscale equipment. An approach developed by BioProces-sors is a Simcell platform, which is an automated miniaturized system for cell culture development. This platform is capable of running and monitoring hundreds of complex bio-reactions. This automated platform has been used to conduct high-throughput cell culture experiments for process development purposes. The system performs bioreactor operations such as cell inoculation and culture monitoring and control. 

Stem Cell Isolation and Initial Characterization Bioprocess Development and Optimization Based on Microscale High-Throughput Profiling Monitoring and Control of Bioreactor... 

Microscale devices may serve as a tool for optimization of culture conditions while also providing the precise control over the cell microenvironment. Arrays of micro-bioreactors have been developed to study growth and differentiation of hESCs in a perfusion system (Cimetta et al., 2009 FigaUo et al., 2007), as well as a micro-bioreactor with a periodic flow-stop perfusion system for coculture of hESCs with human feeder cells (Korin et al., 2009). 

Introduction Overview of the Field Principles of Bioreactor Design Microscale Technologies Cardiac Tissue Engineering Bioreactors Vascular... 

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