Acetone-butanol fermentation revisited.

http://utsc.utoronto.ca/%7Ebritto/publications/amtox.pdf

NH4+ toxicity in higher plants: a critical review

High cell-density culture of Escherichia coli

The inhibition of the Anammox process: A review

Animal cell culture technology has advanced significantly over the last few decades and is now generally considered a reliable, robust and relatively mature technology. A range of biotherapeutics are currently synthesized using cell culture methods in large scale manufacturing facilities that produce products for both commercial use and clinical studies. The robust implementation of this technology requires optimization of a number of variables, including 1) cell lines capable of synthesizing the required molecules at high productivities that ensure low operating cost; 2) culture media and bioreactor culture conditions that achieve both the requisite productivity and meet product quality specifications; 3) appropriate on-line and off-line sensors capable of providing information that enhances process knowledge; and 4) good understanding of culture performance at different scales to ensure smooth scale-up. Successful implementation also requires appropriate strategies for process development, scale-up and process characterization and validation that enable robust operation that is compliant with current regulations. This review provides an overview of the state-of-the art technology in key aspects of cell culture, e.g., engineering of highly productive cell lines and optimization of cell culture process conditions. We also summarize the current thinking on appropriate process development strategies and process advances that might affect process development.

Cell culture processes for monoclonal antibody production.

A Large bioreactor is an inhomogenous system with concentration gradients which depend on the fluid dynamics and the mass transfer of the reactor, the feeding strategy, the saturation constant, and the cell density. The responses of Escherichia coli cells to short-term oscillations of the carbon/energy substrate in glucose limited fed-batch cultivations were studied in a two-compartment reactor system consisting of a stirred tank reactor (STR) and an aerated plug flow reactor (PFR) as a recycle loop. Short-term glucose excess or starvation in the PFR was simulated by feeding of glucose to the PFR or to the STR alternatively. The cellular response to repeated short-term glucose excess was a transient increase of glucose consumption and acetate formation. But, there was no accumulation of acetate in the culture, because it was consumed in the STR part where the glucose concentration was growth limiting. However, acetate accumulated during the cultivation if the oxygen supply in the PFR was insufficient, causing higher acetate formation. The biomass yield was then negatively influenced, which was also the case if the PFR was used to simulate a glucose starvation zone. The results suggest that short-term heterogeneities influence the cellular physiology and growth, and can be of major importance for the process performance. (c) 1995 John Wiley & Sons, Inc.

Influence of substrate oscillations on acetate formation and growth yield in Escherichia coli glucose limited fed-batch cultivations.

Mechanisms of ammonia and ammonium ion toxicity in animal cells: transport across cell membranes.

Physiology of cultured animal cells

Immobilized vegetative cells ofC. acetobutylicum has a similar product formation pattern when incubated in a simple glucose-salts solution as ordinary growing cells. If vegetative cells of the organism are immobilized in the solvent production phase, solvents are continuously produced on extended incubation.

Calcium alginate immobilized cells of clostridium acetobutylicum for solvent production

A technique for maintaining constant activity during continuous production with immobilized, non-growing cells has been developed A single stage continuous system with alginate immobilized Clostridium acetobutylicum, was mainly fed with a glucose medium that supported fermentation of acetone-butanol but did not permit microbial growth The inactivation that occured during these conditions was prevented by pulse-wise addition of nutrients to the reactor

Lena Häggström

Papers

Influence of substrate oscillations on acetate formation and growth yield in Escherichia coli glucose limited fed-batch cultivations.

Mechanisms of ammonia and ammonium ion toxicity in animal cells: transport across cell membranes.

Physiology of cultured animal cells

Calcium alginate immobilized cells of clostridium acetobutylicum for solvent production

Control of immobilized, non-growing cells for continuous production of metabolites