Integrated downstream processing

Tichy, S., Vasic-Racki, D., and Wandrey, C. 1990. Electrodialysis as an integrated downstream process in amino acid production. Chemical and Biochemical Engineering Quarterly 7L127-145. 

Luyben KCAM, van der Wielen 1AM (1993) ESF program on Process Integration in Biochemical Engineering. Reports on the Workshop on Integrated Downstream Processes, Delft, 11-14 February 1993... 

The first consideration in any design and optimization problem is to decide the boundaries of the system. A reactor can rarely be optimized without considering the upstream and downstream processes connected to it. Chapter 6 attempts to integrate the reactor design concepts of Chapters 1-5 with process economics. The goal is an optimized process design that includes the costs of product recovery, in-process recycling, and by-product disposition. The reactions are... 

Grandics, R, Szathmary, S., Szathmary, Z., and O Neill, T., Integration of cell culture with continuous, on-line sterile downstream processing, Ann. N. Y. Acad. Sci., 646, 322, 1991. 

Before the details of a particular reactor are specified, the biochemical engineer must develop a process strategy that suits the biokinetic requirements of the particular organisms in use and that integrates the bioreactor into the entire process. Reactor costs, raw material costs, downstream processing requirements, and the need for auxiliary equipment will all influence the final process design. A complete discussion of this topic is beyond the scope of this chapter, but a few comments on reactor choice for particular bioprocesses is appropriate. 

In the development of cell or enzyme-based processes, many process configurations exist, including batch, fed batch and continuous operation. In general, the conversion and the separation processes (downstream processing) are regarded as separate units, and most industrial processes are based on this approach. In the last decades, however, more attention is paid to the integration of conversion and separation, leading to the development of membrane bioreactors [49, 50], and some of these concepts have reached an industrial scale. The membranes used for this type of reactors are almost exclusively polymeric, as temperatures seldomly exceed 100 °C for obvious reasons. 

One of the major expenses incurred in the application of enzymes for bioconversion processes is the cost of enzyme production (1). The total cost of production includes the cost of fermentative production as well as downstream processing requirements. Both of these factors must be optimized and integrated for maximum cost-effectiveness. 

Cruz and co-workers have used MOI s of 2 to 5 for the production of HIV-VLPs and HIV-CLPs [69]. They found that, for their system, the peak volumetric particle titre did not coincide with maximum particle quality, due to the increase of proteolytic activity in the supernatant, which is coincident with cell lysis. Nevertheless, that issue was surpassed by correct integration with downstream processing, where low weight particles were removed by gel filtration chromatography [32]. 

By reducing the solvent-power of a dense gas in several stages, fractionation of the product and unreacted reactants is possible. Fractionation is also possible by extracting the mixture, usually with the same dense gas as used in reaction, but under different process conditions. In all downstream processing schemes, various particle-formation techniques [31] or chromatographic techniques can be integrated. 

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