Theory of activated-rate processes under shear with application to shear-induced aggregation of colloids

Using a novel approximation scheme within the convective diffusion (two body Smoluchowski) equation framework, we unveil the shear-driven aggregation mechanism at the origin of structure-formation in sheared colloidal systems. The theory, verified against numerics and experiments, explains the induction time followed by explosive (irreversible) rise of viscosity observed in charge-stabilized colloidal and protein systems under steady shear. The Arrhenius-type equation with shear derived here, extending Kramers theory in the presence of shear, is the first analytical result clearly showing the important role of shear-drive in activated-rate processes as they are encountered in soft condensed matter

Effects of temperature and concentration on mechanism and kinetics of thermally induced deposition from coffee extracts

Production of soluble (instant) coffee powders typically involves extraction of roasted coffee by water followed by evaporation in order to concentrate extracts before spray or freeze drying to produce dry coffee powder. In the course of evaporation, deposition of dissolved material from coffee extracts is a major cause of fouling at the heat exchange surfaces of evaporators. Therefore, in order to improve the design and optimization of evaporation processes of coffee extracts, better understanding of the deposition mechanism and kinetics is needed. In this study, optical waveguide lightmode spectroscopy (OWLS) was used to monitor the initial formation of nanometer scale deposits on surfaces exposed to coffee extracts. OWLS measurements were complemented by light scattering from extract solutions, gravimetry of macroscopic deposits, and scanning electron microscopy imaging of deposited layers. Primary molecular-scale layers of about 1 mg m^−2 were rapidly formed in the first stage of deposition, even at ambient temperature, followed by the secondary deposition with kinetics strongly dependent on temperature. Secondary deposition rates were low and largely independent of the extract concentration at ambient temperature, but became strongly dependent on the extract concentration at elevated temperatures. In particular, activation energies for the deposition between 25◦C and 70◦C were much higher for the original extract (13.3 mass %, solids) than for diluted extracts (up to 1.3 mass %, solids). Furthermore, heating of the original extracts above 60◦C resulted in rapid aggregation of suspended macromolecules into large clusters, while only gradual aggregation was observed in diluted extracts

Modelling the breakup of solid aggregates in turbulent flows

The breakup of solid aggregates suspended in a turbulent flow is considered. The aggregates are assumed to be small with respect to the Kolmogorov length scale and the flow is assumed to be homogeneous. Further, it is assumed that breakup is caused by hydrodynamic stresses acting on the aggregates, and breakup is therefore assumed to follow a first-order kinetic where KB(x) is the breakup rate function and x is the aggregate mass. To model KB(x), it is assumed that an aggregate breaks instantaneously when the surrounding flow is violent enough to create a hydrodynamic stress that exceeds a critical value required to break the aggregate. For aggregates smaller than the Kolmogorov length scale the hydrodynamic stress is determined by the viscosity and local energy dissipation rate whose fluctuations are highly intermittent. Hence, the first-order breakup kinetics are governed by the frequency with which the local energy dissipation rate exceeds a critical value (that corresponds to the critical stress). A multifractal model is adopted to describe the statistical properties of the local energy dissipation rate, and a power-law relation is used to relate the critical energy dissipation rate above which breakup occurs to the aggregate mass. The model leads to an expression for KB(x) that is zero below a limiting aggregate mass, and diverges for x → ∞. When simulating the breakup process, the former leads to an asymptotic mean aggregate size whose scaling with the mean energy dissipation rate differs by one third from the scaling expected in a non-fluctuating flo

Continuous chromatographic processes with a small number of columns: Comparison of simulated moving bed with Varicol, PowerFeed, and ModiCon

The Simulated Moving Bed process and its recent extensions called Varicol, PowerFeed and ModiCon are studied, in the case where a small number of columns are used, i.e. from three to five. A multiobjective optimization approach, using genetic algorithms and a detailed model of the multicolumn chromatographic process, is applied to optimize each process separately, and allow for comparison of the different operating modes. The non-standard SMB processes achieve better performance than SMB, due to the availability of more degrees of freedom in the operating conditions of the process, namely the way to carry out asynchronous switches for Varicol, and the different flow rates and feed concentration during the switching interval for PowerFeed and for ModiCon, respectively. We also consider the possibility of combining two non-standard operating modes in a new hybrid process, and evaluate also in this case the possible performance. Finally, a critical assessment of the results obtained and of the potential for practical implementation of the different techniques is reporte

Aggregation Mechanism of an IgG2 and two IgG1 Monoclonal Antibodies at low pH: From Oligomers to Larger Aggregates

Purpose: To identify the aggregation mechanism and the stability characteristics of three different monoclonal antibodies under acidic conditions. Methods: The aggregation kinetics is analyzed by a combination of light scattering, size exclusion chromatography and fluorescence techniques and the aggregation data are correlated to protein structure, hydrophobicity, charge and antibody subclass. Results: In the investigated conditions, the antibody aggregation follows a mechanism consisting of two-steps: reversible monomer oligomerization followed by irreversible cluster-cluster aggregation. The kinetics of the two steps is differently affected by the operating conditions: mild destabilizing conditions induce formation of oligomers which are stable within weeks, while stronger denaturing conditions promote aggregation of oligomers to larger aggregates which eventually precipitate. For different antibodies significant differences in both oligomerization and growth rates are found, even for antibodies belonging to the same subclass. For all antibodies the aggregate formation is accompanied by a structure re-organization with an increase in the ordered β-sheet structures. At low pH the aggregation propensity of the investigated antibodies does not correlate with antibody subclass, surface net charge and hydrophobicity of the non-native state. Conclusions: The aggregation mechanism of three antibodies in acidic conditions as well as differences and analogies in their stability behavior has been characterize

Monitoring coalescence behavior of soft colloidal particles in water by small-angle light scattering

The fractal dimension (D f) of the clusters formed during the aggregation of colloidal systems reflects correctly the coalescence extent among the particles (Gauer et al., Macromolecules 42:9103, 2009). In this work, we propose to use the fast small-angle light scattering (SALS) technique to determine the D f value during the aggregation. It is found that in the diffusion-limited aggregation regime, the D f value can be correctly determined from both the power law regime of the average structure factor of the clusters and the scaling of the zero angle intensity versus the average radius of gyration. The obtained D f value is equal to that estimated from the technique proposed in the above work, based on dynamic light scattering (DLS). In the reaction-limited aggregation (RLCA) regime, due to contamination of small clusters and primary particles, the power law regime of the average structure factor cannot be properly defined for the D f estimation. However, the scaling of the zero angle intensity versus the average radius of gyration is still well defined, thus allowing one to estimate the D f value, i.e., the coalescence extent. Therefore, when the DLS-based technique cannot be applied in the RLCA regime, one can apply the SALS technique to monitor the coalescence extent. Applicability and reliability of the technique have been assessed by applying it to an acrylate copolymer colloi

Closing Plenary Talk - Versatile macromolecules and their biomedical applications

Polymer reaction and colloidal engineering have reached a level of maturity allowing us to synthesize macromolecules and small particles covering very wide and often even overlapping ranges of sizes and compositions. On the other hand, the number of potential applications in various areas is very large, and the limiting step is probably mostly in our capability to imagine a “certain” structure to solve a “certain” problem. In this presentation we discuss through a number of examples, how to define the properties that a material should have to solve a certain problem, and then how to synthesize the corresponding macromolecule. In particular, we focus on a class of polymers exhibiting a comb-like structure, where the pendants have a chemical composition, length and order along the backbone that can be accurately controlled through controlled free radical polymerization techniques. Each pendant is prepared before hand through living techniques, including ring-opening polymerization, which allows preparing macromonomers with very different properties in terms of hydrophilicity, hydrophobicity, biodegradability, etcetera. The result is a very versatile macromolecule that can be adapted to provide the specific functionalities, including self-assembly and nanoparticle stabilization, needed to solve a particular problem. Specific applications will be discussed mainly in the area of drug delivery and tissue engineering. Starting from the specific problem to be solved, the desired properties of the appropriate macromolecules are discussed and the corresponding synthesis process is described. Finally, an outlook on different application areas is provided

Optimizing control of simulated moving bed separations ofmixtures subject to the generalized Langmuir isotherm

Simulated moving bed (SMB) is a cost-efficient separation technique that offers high productivity and low solvent consumption. SMB has gained importance in the pharmaceutical and fine chemical industry to perform complex separation tasks. However, an open and challenging problem is the optimal, robust operation of the SMB process. We have developed a control scheme that integrates the optimization and control of the SMB unit. A significant feature of the controller is that only minimal information of the system has to be provided, i.e. the linear adsorption behavior of the mixture to be separated and the average void fraction of the columns. Therefore, a full characterization of the adsorption behavior of the mixture and the columns is no longer required. In this ‘cycle to cycle' control scheme, the measurements, optimization and control actions are performed once in every cycle. This paper presents simulation results of the control scheme applied to the separation of binary mixtures characterized by generalized Langmuir isotherms. The results are presented and analyzed in the frame of the triangle theory that has been recently extended to encompass these types of isotherms. Besides, online optimum performance of the SMB unit is compared with off-line optimization carried out using genetic algorithm. The results show that the controller fulfills the product and process specifications while operating the SMB unit optimally, regardless of the different types of Langmuir isotherms that the systems exhibi

Aggregation Stability of a Monoclonal Antibody During Downstream Processing

ABSTRACT: Purpose: To study the effect of several operative parameters, particularly pH and salt concentration, on the stability and aggregation kinetics of IgG solutions under the conditions typically encountered in downstream processing. Methods: The time evolution of the aggregates is analyzed by a combination of dynamic light scattering, size exclusion chromatography (SEC) and field flow fractionation (FFF). Secondary structure changes are monitored by circular dichroism. Results: For the given antibody, it is found that at pH lower than 4.0 addition of salt induces a reversible aggregation to oligomers accompanied by an increase in the content of the β-sheet structure. The aggregation rate increases monotonically with the salt concentration. Both the SEC and FFF techniques are successfully applied to obtain the oligomer distributions, and their results are consistent. The modified Lumry-Eyring kinetic model can well describe the time evolutions of the oligomers. Conclusions: For the given antibody, low pH and presence of salt induce conformational changes that are responsible for the reversible aggregation, but in the investigated conditions only small soluble oligomers are formed and oligomer sizes larger than trimer are negligible. For this reason, no accompanied macroscopic changes can be observe

The Role of Digitalization in the Continuous Integrated Manufacturing of Therapeutic Proteins

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