Model-based optimization of a preparative ion-exchange step for antibody purification

A method using a model-based approach to design and optimize an ion-exchange step in a protein purification process is proposed for the separation of IgG from a mixture containing IgG, BSA and myoglobin. The method consists of three steps. In the first step, the model is calibrated against carefully designed experiments. The chromatographic model describes the convective and dispersive flow in the column, the diffusion in the adsorbent particles, and the protein adsorption using Langmuir kinetics with mobile phase modulators (MPM). In the second step, the model is validated against a validation experiment and analyzed. In the third and final step, the operating conditions are optimized. In the optimization step, the loading volume and the elution gradient are optimized with regard to the most important costs: the fixed costs and the feed cost. The optimization is achieved by maximizing the objective functions productivity (i.e. the production rate for a given amount of stationary phase) and product yield (i.e. the fraction of IgG recovered in the product stream). All optimization is conducted under the constraint of 99% purity of the IgG. The model calibration and the analysis show that this purification step is determined mainly by the kinetics, although as large a protein as IgG is used in the study. The two different optima resulting from this study are a productivity of 2.7 g IgG/(s m3) stationary phase and a yield of 90%. This model-based approach also gives information of the robustness of the chosen operating conditions. It is shown that the bead diameter could only be increased from 15 microm to 35 microm with maximum productivity and a 99% purity constraint due to increased diffusion hindrance in larger beads.     

The Geometry of Binary Collisions and Generalized Radon Transforms

Elastic collisions are characterized by the conservation of momentum and energy. We consider some geometrical aspects of such collisions, when the energy of one particle can be expressed in terms of the moments as . The geometry of elastic collisions is essential for the regularizing property of the gain term in the Boltzmann equation, which was proved by P.-L. Lions. We show how such results can be deduced from a regularity theorem for generalized Radon transforms by Sogge & Stein. This is possible for and for ; we also show that the same technique cannot be used with other choices of . (Accepted May 20, 1996)     

Magnetron Plasma Sputter Deposited W-Layers Permeability Influence on the Cycling Stability of thin Film Electrochromic Modules

Physics of Atomic Nuclei - The processes of thin film electrochromic modules degradation during their cycling through the formation of blisters within the PVD sputtered tungsten oxide electrode...     

Trifluoromethyl phosphaalkenes of the type F3CPC(OR)NR2: Synthesis,spectroscopic investigations,and ligand properties [1]

The one-pot reaction of the alcohol adducts F₃CP(H)CF₂OR of perfluoro-2-phosphapropene with secondary amines in a 1:3 molar ratio affords the stable phosphaalkenes F₃CPC(OR)NR₂ (R = Me, Et) 1–4 in yields of 58%. NMR and He(I) PE spectroscopic investigations show that the lone pair electrons on nitrogen and oxygen participate in n/π conjugation. In contrast to typical low-coordinated double bonds the new derivatives do not react with alcohols, amines, and 1,3-dienes. The derivatives are more closely related to the phosphaalkenes F₃C(F)NR₂ than to perfluoro-2-phosphapropene. The reaction of F₃C(OEt)NMe₂ ( 3 ) with Cr(CO)₅THF yields the η¹(P) complex Cr(CO)₅[F₃CPC(OEt)NMe₂] ( 7 ) with an unusually long sp² PC bond (1.809 Å).