Agutter, Paula Anne; (1998) Computational Fluid Dynamics as a Tool for Quantitative Biosafety Studies. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Advances being made in the use of recombinant DNA technology for the industrial scale production of health care products means that it is becoming increasingly important that bioprocesses are adequately contained. There is a need for a quantitative approach to the measurement of release from a bioprocess, both incidentally during normal operation and accidentally due to mechanical failure or operator error. Techniques exist which enable the number of organisms captured in a sampling device to be counted. However, it is necessary to relate what is captured in the sampling device to what is actually released from a unit operation. This thesis describes the use of Computational Fluid Dynamics (CFD) as a tool to assess the release of micro-organisms from bioprocesses, as part of any biosafety study. The effect of different mathematical models has been investigated and guidelines developed concerning the most appropriate protocol to use to simulate air flow patterns and the movement of micro-organisms. The consequence of the size, shape and density of the released organism upon its subsequent trajectory has been studied. It has been shown that the size and shape of the organisms must be accurately defined if the correct tracks are to be predicted since these parameters affect the degree to which organisms are dispersed by turbulent eddies. CFD predictions have been compared to experimental work within containment cabinets and processing areas. These experiments involved releasing a known number of particles into an area and counting the number that were collected by an Aerojet-General glass cyclone. These comparisons provided proof that CFD can predict correctly particle tracks and supplied information regarding the amount of adhesion exhibited between micro-organisms and walls. It was found that organisms showed only a small tendency to bounce off walls. The number of released airborne micro-organisms detected from a selection of representative bioprocess unit operations has been related to the total discharge. The percentage of organisms released from a unit operation which would be captured by a sampling device placed at a particular location has been evaluated. The largest detected release was 11 μl, which occurred whilst operating a tubular bowl centrifuge. Often sampling devices were placed in an inappropriate position to detect microbial release. The application of CFD in this field has been evaluated and there is evidence that it has the potential to be a vital adjunct in bioprocess monitoring and safety. Basic ground rules have been established to ensure the accuracy and cost-effectiveness of CFD simulations for this application.

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