Modeling and observer design for recombinant Escherichia coli strain.

A mathematical model for recombinant bacteria which includes foreign protein production is developed. The experimental system consists of an Escherichia Coli strain and plasmid pIT34 containing genes for bioluminescence and production of a protein, beta-galactosidase. This recombinant strain is constructed to facilitate on-line estimation and control in a complex bioprocess. Several batch experiments are designed and performed to validate the developed model. The design of a model structure, the identification of the model parameters and the estimation problem are three parts of a joint design problem. A nonlinear observer is designed and an experimental evaluation is performed on a batch fermentation process to estimate the substrate consumption.

Monitoring of recombinant protein production using bioluminescence in a semiautomated fermentation process.

On-line optimization of fermentation processes can be greatly aided by the availability of information on the physiological state of the cell. The goal of our "BioLux" research project was to design a recombinant cell capable of intracellular monitoring of product synthesis and to use it as part of an automated fermentation system. A recombinant plasmid was constructed containing an inducible promoter that controls the gene coding for a model protein and the genes necessary for bioluminescence. The cells were cultured in microfermenters equipped with an on-line turbidity sensor and a specially designed on-line light sensor capable of continuous measurement of bioluminescence. Initial studies were done under simple culture conditions, and a linear correlation between luminescence and protein production was obtained. Such specially designed recombinant bioluminescent cells can potentially be applied for model-based inference of intracellular product formation, as well as for optimization and control of recombinant fermentation processes.

Project, design, and use of a pilot plant for nanocapsule production.

The aim of this study was to find the scale-up parameters necessary for the preparation of nanocapsules (NCs) for pharmaceutical purposes. Starting from the laboratory scale (0.06 L), we designed and assembled a pilot plant (2 L) to produce NCs with the so-called emulsification-diffusion technique. We wanted to check if classical tools adequate for the pharmaceutical industry and for industrial scale-up purposes according to well-known chemical engineering technique could be used to perform the NC preparation. Experiments were carried out by varying some operative parameters, such as the impeller speed, the agitation duration for the emulsion preparation, and the reagent concentrations. As expected, good accordance between the NC produced at the laboratory scale and at the pilot plant scale was obtained. We conclude that the pilot plant can be used to perform a scale-up study of the industrial production of NC.

[Methods of obtaining and formation mechanisms of polymer nanoparticles]. / Méthodes d'obtention et mécanismes de formation de nanoparticules polymériques.

Severals processes exist today for manufacturing colloidal systems of nanospheres or nanocapsules. These nanoparticles have applications in various industrial fields such as cosmetic, pharmacy, food industry, agrochemicals.... The formation of nanoparticles allows the protection of an active molecule by a polymeric coating and the release of this product following a perfectly defined profile, which depends on the nature of the polymer, the type of particle and the field of use. The purpose of this article is to expose the different methods of preparation of nanoparticular systems. These methods are classified in two mains categories. The first gathers most of the methods which are based on polymerization reactions, the second presents the use of preformed polymers (of natural or synthetic origin). A thorough study is devoted to the mechanisms of formation, in order to find the advantages and the disadvantages of each technique to support the development of manufactoring processes.