Papers by Kerstin Wohlgemuth
Crystal Growth & Design, Feb 16, 2017
Gassing crystallization is an induced nucleation process during batch cooling crystallization 16 ... more Gassing crystallization is an induced nucleation process during batch cooling crystallization 16 with the aim to control the nucleation step and thus product crystal properties. All previous studies have been made at lab scale and show that the metastable zone or the supersaturation at 18 which gassing is started is crucial for the success of gassing crystallization. Since the metastable 19 zone width depends on many factors, the purpose of this paper was to verify the hypothesis that 20 especially for parameter combinations which result in broad metastable zone widths the success 21 of gassing crystallization is independent of crystallizer scale and geometry. The studies were 22 made for the substance system succinic acid/water in a 1 L lab and a 30 L pilot scale crystallizer. 23 The effect of gassing on the metastable zone width and the median diameter was evaluated for 24 varying process parameters (saturation concentration, gassing supersaturation, cooling rate, and 25 stirrer speed) and compared to normal cooling crystallization. After the application of gassing, 26 metastable zone widths were narrower, median diameters were bigger and reproducibility was 27 enhanced. We found that for process parameters which resulted in broad metastable zone widths 28 the effect of gassing on the median diameter was biggest, independent of crystallizer scale and 29 geometry. Gassing crystallization induces nucleation and affects product crystal properties, 30 which works best for process conditions resulting in broad metastable zone widths.
Design of Median Crystal Diameter Using Gassing Crystallization and Different Process Concepts
Crystal Growth & Design, Feb 10, 2016
The reproducibility of product properties of normal batch cooling crystallizations is often insuf... more The reproducibility of product properties of normal batch cooling crystallizations is often insufficient. For a reliable design of product properties like the median diameter, it is essential to control the nucleation process. An innovative technology to induce nucleation during cooling crystallization is gassing. Therefore, quantification of the influence of gassing and process parameters is important. For this purpose, Design of Experiment approaches were used, investigating a linear cooling profile with constant cooling duration and quadratic cooling profiles with varied cooling duration. Succinic acid/water was used as the model system. The supersaturation where gassing is started was identified as most important design parameter using linear cooling profiles. Using quadratic cooling profiles, the median diameter can be mainly designed by adjusting the cooling duration. By the choice of the cooling profile and gassing supersaturation, it is possible to control the median diameter in a range between 30...
Cooling Crystallization: Does Gassing Compete with Seeding?
Crystal Growth & Design, Aug 2, 2018
Cooling crystallization processes are most often controlled by adding seed crystals within the me... more Cooling crystallization processes are most often controlled by adding seed crystals within the metastable zone to induce nucleation. Seeding is a challenging task and involves the risk of contamination. Its success depends on a lot of aspects, namely seed size and amount, time point and place of addition, and experience of the operator. Gassing to induce nucleation is an innovative technology which has shown in the past that nucleation control and product design is possible. Purpose of this paper is to show that gassing is competitive to seeding during a cooling crystallization process. Two different cooling process concepts with and without a holding time were considered. As model system succinic acid/water was used. Gassing as well as seeding enhances production capacity by shortening the production time by a quarter for product crystals with desired mean crystal size in comparison to a normal cooling crystallization process. Production capacity is slightly higher for seeding than for gassing, but gassi...
Computers & Chemical Engineering, May 1, 2013
An existing model is extended to simulate batch cooling crystallizations with induced nucleation ... more An existing model is extended to simulate batch cooling crystallizations with induced nucleation processes like ultrasound or gassing. All important phenomena such as nucleation, growth, agglomeration and breakage are taken into account. A differentiation between ultrasound and gassing is necessary. Induced nucleation processes also require a modification of crystal growth mechanism. In general, the model parameters required for the kinetics are determined simultaneously by fitting them to experimental data. Mostly a correlation model results without physical basis. Here, the model parameters are sequentially determined by decoupling the mechanisms, saving effort and time, and make it possible to reduce the number of parameters also. The model and the model parameter determination procedure are validated using three different organic solute/solvent systems. The number of simulation runs for parameter fitting was reduced to less than 100 instead of simultaneous parameter determination, which requires several hundreds of thousands runs, resulting in physically reasonable solutions.
Chemical Engineering Science, Dec 1, 2018
h i g h l i g h t s Gassing is a suitable and promising technique to induce nucleation in continu... more h i g h l i g h t s Gassing is a suitable and promising technique to induce nucleation in continuous stirred tank operation. Gassing can enhance product quality control in terms of crystal size and size distribution. Conductivity probes represent cheap and easy-to-build PAT tools. Conductivity probes enable the detection of the onset of the nucleation shower. Conductivity probes enable steady state monitoring.
Applied sciences, Feb 26, 2022
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Quantification of internal crystal defects using image analysis
Powder Technology, 2021
Chemical Engineering & Technology, May 3, 2018
This article has been accepted for publication and undergone full peer review but has not been th... more This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the final Version of Record (VOR). This work is currently citable by using the Digital Object Identifier (DOI) given below. The final VoR will be published online in Early View as soon as possible and may be different to this Accepted Article as a result of editing. Readers should obtain the final VoR from the journal website shown below when it is published to ensure accuracy of information. The authors are responsible for the content of this Accepted Article.
Shape-independent particle classification for discrimination of single crystals and agglomerates
Powder Technology, Mar 1, 2019
Abstract While agglomeration has significant effects on particulate products, quantification is s... more Abstract While agglomeration has significant effects on particulate products, quantification is still a time-consuming process. Particle classification using multivariate analysis can help gain an understanding of these agglomeration processes, but the necessary classifiers are often applicable to one type of particles only. This study focuses on the generation of a particle classifier for the discrimination of single particles/agglomerates which is applicable to a variety of particulate systems of a different shape. This might be of importance for solids that change their shape, e.g., crystalline systems that may change their aspect ratio or habit according to different process parameters, impurity concentrations, or polymorphic form. It was found that artificial neural networks can perform the discrimination task of single crystal/agglomerate for several crystalline systems when the training set with whose help the classifier is generated contains a selection of crystals that cover a wide range of possible crystal shapes. Variable selection using proportional similarity generated a highly accurate classifier while only a little time needed to be invested. Proportional similarity not only proved helpful for the discrimination task of single crystal/agglomerate but differentiation of the α and β polymorphs of l -glutamic acid as well. Using the information from particle classification, a more in-depth characterization of how single particles, agglomerates, or different particle shapes are distributed can be given.
Chemie Ingenieur Technik, Aug 29, 2016
Crystals, Jan 19, 2022
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Archimedes tube crystallizer: Design and characterization for small-scale continuous crystallization
Chemical engineering research & design, Feb 1, 2022
Processes, Dec 3, 2021
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Chemical Engineering & Technology, May 3, 2018
This article has been accepted for publication and undergone full peer review but has not been th... more This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the final Version of Record (VOR). This work is currently citable by using the Digital Object Identifier (DOI) given below. The final VoR will be published online in Early View as soon as possible and may be different to this Accepted Article as a result of editing. Readers should obtain the final VoR from the journal website shown below when it is published to ensure accuracy of information. The authors are responsible for the content of this Accepted Article.
The Way to an Efficient Operation of a Continuous Taylor‐Couette Cooling Crystallizer
Chemie Ingenieur Technik, Aug 25, 2022
Crystals, Dec 16, 2022
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Biochemical Engineering Journal, Jun 1, 2017
Precipitation with polyelectrolytes is a promising alternative to conventional methods for purifi... more Precipitation with polyelectrolytes is a promising alternative to conventional methods for purification of monoclonal antibodies (mAb). This study focuses on clarification of a monoclonal antibody by precipitation of the model impurity bovine serum albumin (BSA) with cationic polyelectrolytes. Different types of cationic polyelectrolytes with different functional amine groups and molecular weights are screened for their capability to precipitate BSA in mixture with mAb. Due to the high BSA depletion and mAb recovery achieved, two cationic polyelectrolytes, polyethyleneimine (PEI) and polyallylamine (PAA) with a molecular weight of 65 kDa were selected as most suitable precipitation agents. Additionally, influences of different parameters (polyelectrolyte, BSA and NaCl concentration and pH value) were analyzed by the use of Design of Experiments (DoE). Herewith, a fast identification of influencing factors and factor interaction was achieved. With DoE, two regression models for the analysis of BSA depletion in dependence of influencing factors were established. This enabled the analysis of the robustness of precipitation as initial clarification step of Downstream Process of mAb.
Population balance modeling of unstirred cooling crystallization on an integrated belt filter
Computers & Chemical Engineering, Nov 1, 2022
Separation and Purification Technology, May 1, 2015
In order to meet the growing demand for monoclonal antibodies (mAbs), many research studies focus... more In order to meet the growing demand for monoclonal antibodies (mAbs), many research studies focus on the development of new purification technologies to overcome disadvantages of conventional methods. The precipitation of mAbs with anionic polyelectrolytes is a promising alternative offering advantages like e.g. low additive consumption. The antibody-polyelectrolyte interaction depends on numerous factors. While the influence of factors like pH value, ionic strength and polyelectrolyte concentrations was already examined in different studies, this study focuses on the influence of different properties of impurity proteins on the precipitation of a monoclonal antibody with the anionic polyelectrolyte polyanetholesulfonic acid. For this purpose, five model impurity proteins, bovine serum albumin, ovalbumin, a-Lactalbumin, b-Lactoglobulin, and myoglobin, were selected with regard to their isoelectric points and molecular weights. Additionally, the surface charge distribution of these proteins was simulated. The experimental results provide a better insight in the electrostatic interactions taking place between proteins and polyelectrolyte molecules.
Influence of Gassing Crystallization Parameters on Induction Time and Crystal Size Distribution
Crystal Growth & Design, Oct 31, 2016
Gassing in combination with linear cooling profiles is an innovative technology to induce nucleat... more Gassing in combination with linear cooling profiles is an innovative technology to induce nucleation and control product properties. Previous work found that among gassing parameters like gassing supersaturation, gassing duration, and gas volume flow, gassing supersaturation has an effect on product properties only. This paper investigates why gassing duration and volume flow cannot be used to control product properties. Therefore, the influence of gassing parameters on induction time and final crystal size distributions were evaluated. Experiments were performed using succinic acid/water as model system in a 1 L crystallizer. Compared to normal cooling crystallization, induction time could be reduced by about 60 min by gassing. The difference in the specific bubble surface areas during gassing with the gas volume flows applied was too low to create an effect on the amount of nuclei induced and thus on induction time. Only gassing at different supersaturations resulted in different amounts of nuclei induc...
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Papers by Kerstin Wohlgemuth