Bioreactor arrays

The two patents described above were particularly important in the initiation of the developments of biodesulfurization catalysts. The bioreactor arrays required for operation and growth method constituted key elements in the following developments of the area, which would condition viability and successful path to industrialization. A sulfur bioavailability assay was incorporated into the screen for monitoring the sulfur uptake by the microorganisms, and the concept formed a claim in the patents [67,91], The objective... 

Cimetta, E., E. FigaUo et al. 2009. Micro-bioreactor arrays for controlling cellular environments Design principles for human embryonic stem cell applications. Methods 47 81-89. 

Figallo, E., C. Cannizzaro et al. 2007. Micro-bioreactor array for controlling cellular microenvironments. 

Luni C, Feldman HC, Pozzobon M, De Coppi P, Meinhart CD, Elvassore N. 2010. Microhter-bioreactor array with buoyancy-driven stirring for human hematopoietic stem cell culture. Biomicrofluidics 4(3). 

Several protein assemblies have successfully been fabricated on the solid surfaces sifter the bioinformation transduction. These include the following molecular systems molecularly interfaced redox enzymes on the electrode surfaces, calmodulin / protein hybrides, and ordered antibody array on protein A. These protein assemblies find a wider application in various fields such as biosensors, bioreactors, and intelligent materials. 

Electronic noses provide new possibilities for monitor the state of a cultivation non-in-vasively in real-time. The electronic nose uses an array of chemical gas sensors that monitors the off-gas from the bioreactor. By taking advantage of the off-gas components different affinities towards the sensors in the array it is possible with the help of pattern recognition methods to extract valuable information from the culture in a way similar to the human nose. For example, with artificial neural networks, metabolite and biomass concentration can be predicted, the fermentability of a medium before starting the fermentation estimated, and the growth and production stages of the culture visualized. In this review these and other recent results with electronic noses from monitoring microbial and cell cultures in bioreactors are described. 

The sensors of the electronic nose are assembled in an array. The array is normally a small electronic unit that integrates the different sensors into a practical circuit card or another appropriate system that is easy to insert into the electronic nose instrument. If the array is to be used in a flow injection setup the unit also comprises a flow cell compartment with minimal volume. The system depicted in Fig. 2 shows how MOS and MOSFET arrays are integrated in a flow injection system [11]. Larger arrays can be integrated into silicon chips, as described for CP sensors where, for example an ASIC chip with 32 sensors has been fabricated with BiCMOS technology and having an area of 7 x 7 mm [18]. If the array is be inserted in the headspace volume of a bioreactor, the technical solution is a remote array probe that can be placed in a gas sample container [19]. 

A typical sensor array system interfaced to a bioreactor representative of the studies described in this paper is shown in Fig. 3. The bioreactor off-gas is conducted to a container by its overpressure. At sample injection the gas in the container is withdrawn by a suction pump placed in the electronic nose instrument. The sample gas passes the sensor array, which is distributed over three serially coupled units. In the example in Fig. 3 the first unit contains ten MOSFET sensors, the second six MOS sensors and the third unit an infrared sensor. After injection, a valve is switched to a reference carrier gas, taken from the ambient air or from a gas flask with a controlled composition. 

In a number of different bioreactor cultivations with bacteria, yeasts, molds and mammalian cells, it was shown how the electronic nose can serve to visualize the course of the processes. The pattern recognition method that best manages to mirror the complex sensor array responses during extended cultivations is two- or three-dimensional PCA. Examples from such electronic nose applications are given below. 

Powers MJ, Domansky K, Kaazempur-Mofrad MR, Kalezi A, Capitano A, Upad-hyaya A, et al. A microfabricated array bioreactor for perfused 3D liver culture. Biotechnol Bioeng 2002 78 257-69. 

Plum, A. and Rehorek, A. (2005) Strategies for continuous on-line high performance liquid chromatography coupled with diode array detection and electrospray tandem mass spectrometry for process monitoring of sulfonated azo dyes and their intermediates in anaerobic-aerobic bioreactors. J Chrom A, 1084 (1-2), 119-133. 

A major study should be attempted to compare the different bioreactor performance characteristics. Comparisons between BCs and airlift reactors are available, but a wider array is lacking, but needed. Research towards this end, such as Bouaifi et al. (2001) who compared stirred-tank reactors and BCs, is sparse. Different bioreactor designs have quite unique scaling abilities and associated costs, and the economic benefits and decisions would be better understood if such studies would be more common. 

To study CAVD in a controlled system, animal models of valvular dysfunction are utilized in the laboratory setting. The same principles used to diagnose AS in humans may be applied in the study of the progression of this disease in a wide array of animal models. Valvular cells extracted from bovine sources have been widely used due to the ease of extraction and because the structure of the bovine aortic valve is similar to the human aortic valve [65-67]. Porcine models have been utilized to a large extent for studies of the aortic valve, since the heart and cardiovascular system are nearer in size to the human equivalents [68-70]. A relevant porcine model for aortic valve calcification has been developed by Balachandran et al [71] in which the effects of cyclic stretch were studied using porcine aortic valve leaflets in a unidirectional stretch bioreactor. Calcification was significantly... 

Bioreactors are thus expected to operate in a large array of environments. Bioreactors currently in use in industrial environment can be roughly classified on the basis of aeration and stirring characteristics (Figure 7.1). 

---