Pilot-scale verification of a computer-based simulation for the centrifugal recovery of biological particles

Clarkson, A. I.; Bulmer, M.; Titchener-Hooker, NJ

doi:10.1007/s004490050186

Cited by 7 publications

(12 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The simulation was constructed using the verified models described in the literature data [3,4,9,10,14] for both the individual unit operations and the integrated processes. The process performance was measured in terms of a total volumetric enzyme productivity, Y (unit activity/unit time) and the levels of debris removal achieved relative to the total amount of solids present in the feedstream, S (%).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

The application of a Pareto optimisation method in the design of an integrated bioprocess

Zhou

Titchener-Hooker

2003

Bioprocess and Biosystems Engineering

Self Cite

View full text Add to dashboard Cite

A rapid method for designing integrated bioprocesses, using a combination of a windows of operation and a Pareto optimisation approach, is described in this paper. Within bioprocesses, multiple objectives are common, and achieving a satisfactory trade-off amongst the design objectives is crucial. Conventional optimisation results in the identification of the best operating policy for a given desired performance but gives little insight into how the process performance changes in the vicinity of the solution. In this paper, we explore the use of a Pareto optimisation technique to locate the optimal conditions for an integrated bioprocessing sequence and the benefits of first reducing the feasible space by the development of a series of windows of operation to provide a smaller search area for the optimisation. The final results are then presented in performance trade-off graphs and look-up tables, which give the design engineer an easily manageable solution set to work with. In this way, the decision-making procedure for design is made faster and more transparent. Two case studies illustrate the results from this integrated design methodology, some of which are counter-intuitive compared with the general design experience.

show abstract

Section: Methodsmentioning

confidence: 99%

“…Increasing k from 96% to 100% gradually, the set of Pareto optimal points was achieved by solving problem (4). The results are displayed in Figs.…”

Section: Case Imentioning

confidence: 99%

The application of a Pareto optimisation method in the design of an integrated bioprocess

Zhou

Titchener-Hooker

2003

Bioprocess and Biosystems Engineering

Self Cite

View full text Add to dashboard Cite

show abstract

“…The fed-batch fermentation was modelled using the approach of Wang, Cooney and Wang [33] based on the following assumptions [32]: initial batch volume; 45 l, yield of cells on substrate; 0.49 g (DCW)/g glucose, initial cell concentration at start of batch phase; 0.16 g (DCW)/l, final cell concentration at the end of batch phase; 0.25 g (DCW)/l, final cell concentration at the end of fed-batch fermentation; 40 g (DCW)/l. Cell size and cell wall strength data as determined by the rate of both protein release and change in cell debris size distribution that accompanied high pressure disruption were obtained from previously published work [2], [5]. Siddiqi [2] showed that the point of cell harvest in a batch fermentation and the choice of growth rate in fed-batch operation alter the cell's susceptibility to breakage by homogenisation requiring this operation to be tailored to suit the fermentation conditions in an integrated fashion.…”

Section: Fermentationmentioning

confidence: 99%

“…The flowsheet shows part of a process for the production and isolation of an intracellular product alcohol dehydrogenase (ADH) from a S. cerevisiae strain and is typical of that used for the production of a soluble intracellular protein or enzyme. It is a useful generic process for the study of bioprocess modelling and has been used at UCL for initial trials to establish a set of bioprocess unit operation models, verified by comparison with pilot scale data [1][2][3][4][5][6][7][8][9].…”

Section: Theorymentioning

confidence: 99%

See 1 more Smart Citation

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

Zhou

Holwill

Titchener-Hooker

1997

Bioprocess Engineering

Self Cite

View full text Add to dashboard Cite

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. IntroductionDownstream processes for protein production and purification of biomolecules are often complex and may consist of many unit operations. The sequence for the recovery of a typical intracellular enzyme may require as many as eight steps to yield a crude enzyme [29]. Subsequent purification based on chromatography may necessitate a significant number of additional stages and hence the overall yield is often low. To increase the overall process efficiency it is desirable to operate each stage at a high yield, or to reduce the number of steps [12]. The latter approach may require substitution of new operations to enable such a truncation in the sequence without loss in performance. However in both cases a systematic approach to process design and operation is needed which takes account of any interactions existing between steps since these can severely influence subsequent performance. Previous workers have examined such process interactions. Changes in the morphology of P. chrysogenum that occur during fermentation have been shown to result in very different filtration rates being achieved in subsequent downstream processing [27] while the conditions of bead milling S. cerevisiae impact the efficiency of subsequent depth filtration [24]. Here a clear compromise between the extent of milling to achieve good product release and the consequent blockage of the filter medium by fines was apparent. These results suggest that it is necessary to analyse bioprocesses in an integrated fashion such that changes in the performance due to altered specifications in one step can be predicted. Without such a capacity the process chain cannot be operated to yield its potential since a high yield in one step may lead to lower recovery for the next step. A clear example of this is the trade-off between homogenisation conditions chosen for protein release and the issue of subsequent cell debris separation by centrifugation. Here a high yield at the homogenisa...

show abstract

UCL biochemical engineering

Shamlou¹,

Dunnill²,

Hoare³

et al. 1998

Biotechnol. Bioeng.

View full text Add to dashboard Cite

Pilot-scale verification of a computer-based simulation for the centrifugal recovery of biological particles

Cited by 7 publications

References 0 publications

The application of a Pareto optimisation method in the design of an integrated bioprocess

The application of a Pareto optimisation method in the design of an integrated bioprocess

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

UCL biochemical engineering

Contact Info

Product

Resources

About