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Biomedical subjects

I D Bogle

Publications and source records attributed to I D Bogle.

4 recordsLinked to original sources

Synthesis of bioprocesses using physical properties data.

The aim of this article is to illustrate and evaluate a synthesis procedure which has been extended to tackle bioprocesses. Physical property information is used to screen candidate units thereby reducing the size of the synthesis problem. In this way, only units which exploit large property differences between components in a stream are selected. This is important for bioprocesses because of the large number of components and wide range of unit operations which are available. The screening technique and bioprocess-unit-design methodologies have been incorporated within an implicit enumeration algorithm which was developed for chemical process synthesis and is implemented in Java programming language. An important advantage is the ability of the bioprocess synthesis software to generate a ranked list of flowsheets which may subsequently be analyzed in more detail. Two case studies are used to evaluate the bioprocess-synthesis technique. The first system involves a product which is secreted from the host organism. The second has significantly different characteristics in that the product is intracellular and forms inclusion bodies. The latter case study, in particular, is a large synthesis problem with 12 unit operations and 20 contaminant compounds. The results show that the synthesis methodology identifies a set of economically optimal flowsheets in a reasonable computational time which demonstrates its ability to deal with large synthesis problems. Using the synthesis methodology we can generate bioprocesses which are optimal in a system-wide, rather than unit-by-unit, sense.

Algorithms↗

Performance modeling and simulation of biochemical process sequences with interacting unit operations.

Many biochemical processes consist of a sequence of operations for which optimal operating conditions (setpoints) have to be determined. If such optimization is performed for each operation separately with respect to objectives defined for each operation individually, overall process performance is likely to be suboptimal. Interactions between unit operations have to be considered, and a unique objective has to be defined for the whole process. This paper shows how a suitable optimization problem can be formulated and solved to obtain the best overall set of operating conditions for a process. A typical enzyme production process has been chosen as an example. In order to arrive at a demonstrative model for the entire sequence of unit operations, it is shown how interaction effects may be accommodated in the models. Optimal operating conditions are then determined subject to a global process objective and are shown to be different from those resulting from optimization of each separate operation. As this strategy may result in an economic benefit, it merits further research into interaction modeling and performance optimization.

Alcohol Dehydrogenase↗

Protein solubility modeling.

A thermodynamic framework (UNIQUAC model with temperature dependent parameters) is applied to model the salt-induced protein crystallization equilibrium, i.e., protein solubility. The framework introduces a term for the solubility product describing protein transfer between the liquid and solid phase and a term for the solution behavior describing deviation from ideal solution. Protein solubility is modeled as a function of salt concentration and temperature for a four-component system consisting of a protein, pseudo solvent (water and buffer), cation, and anion (salt). Two different systems, lysozyme with sodium chloride and concanavalin A with ammonium sulfate, are investigated. Comparison of the modeled and experimental protein solubility data results in an average root mean square deviation of 5.8%, demonstrating that the model closely follows the experimental behavior. Model calculations and model parameters are reviewed to examine the model and protein crystallization process.

Ammonium Sulfate↗

Sizing biological samples by photosedimentation techniques.

The performance of the Joyce-Loebl disk centrifuge in the sizing of Escherichia coli cells, protein inclusion bodies, and cell debris is evaluated. The need for a density gradient that extends throughout the entire spin fluid is highlighted, and a set of standard conditions that fulfill this requirement is defined. E. coli cells experience a reduction in their Stokes diameter when exposed to ethanol, indicating that a spin-buffer fluid combination such as glycerol-water is to be preferred for the sizing of bacteria. The instrument baseline is influenced by the presence of particles, and a method of estimating the baseline is described. The sizing of small particles is further complicated by baseline drift due to temperature sensitivity of the optical yoke. An analysis of diffusion in the spin fluid is conducted, and an expression for the sedimentation:diffusive flux ratio is derived. For the current samples, it is shown that diffusion within the spin fluid does not lead to significant errors for 0.15-microns particles, whereas the phenomenon may be significant at the manufacturer's size limit of 0.01 micron.

Centrifugation, Density Gradient↗