Dynamics and Control of Oscillatory Bioreactors

Bioreactors are widely used in many industries to generate a range of products using various host cells e.g., yeast, insect, and mammalian cells. Depending on the process, product, and host cell, some bioreactors exhibit sustained periodic behavior in key process variables such as metabolite concentrations, biomass, and product titer. Such dynamical behavior can arise from different mechanisms, including predator-prey dynamics, substrate inhibition, and cell sub-population synchrony. Oscillatory dynamical behavior is undesirable as it can impact downstream processes, especially in a continuous operation, and can make process operations and product quality control more challenging. This article provides an overview of oscillatory dynamics. The mechanisms that give rise to the oscillations and process control strategies for suppressing the oscillations are discussed, while providing insights that go beyond past studies. Alternative process configurations are proposed for bypassing the mechanisms that generate oscillations.Comment: Submitted to Biotechnology Progress, ICB V Special Issue (invited). Pavan Inguva and Krystian Ganko contributed equally to this work. Corresponding author: Richard D. Braat

Electrical coupling of neuro-ommatidial photoreceptor cells in the blowfly

A new method of microstimulation of the blowfly eye using corneal neutralization was applied to the 6 peripheral photoreceptor cells (R1-R6) connected to one neuro-ommatidium (and thus looking into the same direction), whilst the receptor potential of a dark-adapted photoreceptor cell was recorded by means of an intracellular microelectrode. Stimulation of the photoreceptor cells not impaled elicited responses in the recorded cell of about 20% of the response elicited when stimulating the recorded cell. This is probably caused by gap junctions recently found between the axon terminals of these cells. Stimulation of all 6 cells together yielded responses that were larger and longer than those obtained with stimulation of just the recorded cell, and intensity-response curves that deviated more strongly from linearity. Evidence is presented that the resistance of the axon terminal of the photoreceptor cells quickly drops in response to a light flash, depending on the light intensity. Incorporating the cable properties of the cell body and the axon, the resistance of the gap junctions, and the (adapting) terminal resistance, a theoretical model is presented that explains the measurements well. Finally, it is argued that the gap junctions between the photoreceptor cells may effectively uncouple the synaptic responses of the cells by counteracting the influence of field potentials.

Quantum and Semiclassical Calculations of Cold Atom Collisions in Light Fields

We derive and apply an optical Bloch equation (OBE) model for describing collisions of ground and excited laser cooled alkali atoms in the presence of near-resonant light. Typically these collisions lead to loss of atoms from traps. We compare the results obtained with a quantum mechanical complex potential treatment, semiclassical Landau-Zener models with decay, and a quantum time-dependent Monte-Carlo wave packet (MCWP) calculation. We formulate the OBE method in both adiabatic and diabatic representations. We calculate the laser intensity dependence of collision probabilities and find that the adiabatic OBE results agree quantitatively with those of the MCWP calculation, and qualitatively with the semiclassical Landau-Zener model with delayed decay, but that the complex potential method or the traditional Landau-Zener model fail in the saturation limit.Comment: 21 pages, RevTex, 7 eps figures embedded using psfig, see also http://www.physics.helsinki.fi/~kasuomin

Biomanufacturing and testbed development for the continuous production of monoclonal antibodies

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