Showing papers on "Bioprocess published in 1997"

A study of the use of computer simulations for the design of integrated downstream processes

Abstract: Simulation may be used as a powerful tool for accelerating bioprocess design. This paper demonstrates the use of simulations in exploring the nature and impact of the interactions that exist in a typical bioprocess for the recovery of an intracellular protein. The study shows that an integrated approach to design must be adopted in order to achieve acceptable process designs. Data from a fedbatch fermentation, with verified models for cell harvesting, cell disruption and cell debris removal have been integrated to demonstrate the consequence of process design and operating decisions on the resulting process performance. The trade-offs between product recovery and the extent of cell debris removal for a range of operating conditions have been represented through a series of windows of operation which show how process conditions must be altered in order for given process performance levels to be realised. The capacity to account for process performance including the impact of interactions is seen as a pre-requisite for rigorous bioprocess sequence design and optimisation.

Measurement of bioprocess containment by quantitative polymerase chain reaction

Abstract: This thesis describes the development and application of a method for the measurement of the release of genetically modified micro-organisms from large scale bioprocesses. Polymerase chain reaction (PCR) assays for two E. coli K-12 strains have been shown to be specific for the target strain and have sufficiently low limits of detection (less than 50 cells per PCR) for monitoring of bioprocess release. A quantitative PCR assay, using a competitive internal standard, for one E. coli strain allows measurement of the concentration of the bacteria over a range of up to 6 orders of magnitude with a measurement error of ±0.11 logs. This method has been applied to samples taken from an Aerojet General Cyclone air sampling device allowing the determination of the number of whole cells of the target organism in a sampled aerosol. Using this method, good correlation has been observed between the number of cells released by atomisation into a fixed, contained volume and the number of cells captured and enumerated. Aspects of large scale fermentation, homogenisation and centrifugation unit operations have been studied to determine the effectiveness of their containment. Airborne release of process micro-organisms has been detected in some instances, but the scale of the release was generally found to be small considering the total biomass involved in the bioprocess. Implications of the methodology and the findings from model and case studies on current engineering practice and bioprocess risk assessment are discussed. Areas for further improvement of the method and applications outside of bioprocess containment validation are identified.

Data reconciliation in bioprocess development

Abstract: Thesis (Sc. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1997.