Article
Engineering, Chemical
A. A. M. Abusultan, J. A. Wood, T. Sainio, A. J. B. Kemperman, W. G. J. van der Meer
Summary: Reverse osmosis (RO) membrane technology is increasingly used for large-scale production of potable water. However, the acidic and unbuffered RO permeate can damage water piping networks. Remineralization using an ion exchange resin - bipolar membrane electrodialysis hybrid process can protect the water distribution network. This study investigates the use of preparative ion exchange chromatography principles for monovalent-divalent ion separation.
SEPARATION AND PURIFICATION TECHNOLOGY
(2023)
Article
Biophysics
Joao Carlos Simoes-Cardoso, Nanako Hoshino, Yusuke Yoshimura, Chyi-Shin Chen, Cristina Dias-Cabral, Noriko Yoshimoto, Shuichi Yamamoto
Summary: This study investigates the thermodynamics of bovine serum albumin monomer adsorption onto chromatographic surfaces with grafted ligands, revealing clear differences in the driving forces of adsorption caused by different ligand architectures. Additionally, a new relation between the salt required for protein elution and the change in adsorption enthalpy is found, intrinsically connecting both adsorption and desorption mechanisms.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2021)
Article
Chemistry, Analytical
Agnieszka Kamedulska, Lukasz Kubik, Julia Jacyna, Wiktoria Struck-Lewicka, Michal J. Markuszewski, Pawel Wiczling
Summary: In this study, a mechanistic model based on liquid chromatography retention data was proposed to explain the relationship between pH, organic modifier type, temperature, gradient duration, and analyte retention. The model utilized a Bayesian multilevel framework and provided interpretable summaries of complex data and decision support.
ANALYTICAL CHEMISTRY
(2022)
Article
Biochemical Research Methods
Szabolcs Fekete, Amarande Murisier, Matthew Lauber, Davy Guillarme
Summary: This article presents a practical solution to improve the linearity of effluent pH response in pH gradient cation exchange chromatography (CEX) by converting pH to mobile phase volume fraction and generating an inverse response function in the time domain. By setting the inverse function as the gradient program, an ideally linear pH response can be achieved.
JOURNAL OF CHROMATOGRAPHY A
(2021)
Article
Biochemical Research Methods
Baubek Spanov, Bas Baartmans, Oladapo Olaleye, Simone Nicolardi, Natalia Govorukhina, Manfred Wuhrer, Nico C. van de Merbel, Rainer Bischoff
Summary: We have developed a method using pH gradient cation-exchange chromatography to reveal the charge heterogeneity of stressed trastuzumab at the subunit level. This approach can be used for charge variant analysis of therapeutic antibodies with two or more modification sites in the Fab region.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2023)
Article
Biochemical Research Methods
Izabela Poplewska, Patrycja Zimoch, Dorota Antos
Summary: This study demonstrates the occurrence of pH excursion in pH gradient elution of monoclonal antibodies (mAbs) on strong cation exchange resins under high overloading conditions. The presence of the proteins affects the pH profiles in both liquid and adsorbed phases, and this effect is enhanced with higher initial pH of the binding buffer and protein concentration. The observed pH transitions for different mAbs on the resins predominantly depend on their adsorption affinity.
JOURNAL OF CHROMATOGRAPHY A
(2022)
Article
Biochemistry & Molecular Biology
Bastiaan Laurens Duivelshof, Thomas Bouvarel, Sebastian Pirner, Vincent Larraillet, Alexander Knaupp, Hans Koll, Valentina D'Atri, Davy Guillarme
Summary: Charge heterogeneity among therapeutic monoclonal antibodies is an important quality attribute that requires careful characterization. The use of solvent-enriched mobile phase composition can improve selectivity for the analysis of various antibody products.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Analytical
Yu Cheng, Tianpei Cai, Jing Feng, Wei Yu, Dongping Yu, Yongzheng Zhou, Dongping Su, Quan Gan, Banghong Liang, Zhimou Guo
Summary: This study presents an efficient method for sequentially separating lanthanides and uranium using a high-performance ion exchange chromatographic column, achieving continuous elution of uranyl and lanthanides, which was validated by the separation of simulated spent nuclear fuel.
JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY
(2023)
Article
Biochemical Research Methods
Leon E. Niezen, Bastiaan B. P. Staal, Christiane Lang, Harry J. A. Philipsen, Bob W. J. Pirok, Govert W. Somsen, Peter J. Schoenmakers
Summary: This study demonstrates that the influence of molecular weight distribution on chemical composition distribution analysis can be reduced using recycling gradient liquid chromatography. The method shows high accuracy and usefulness in determining the chemical composition distribution and evaluating critical conditions of polymers.
JOURNAL OF CHROMATOGRAPHY A
(2022)
Article
Biochemical Research Methods
Baubek Spanov, Oladapo Olaleye, Nico Lingg, Arthur E. H. Bentlage, Natalia Govorukhina, Jos Hermans, Nico van de Merbel, Gestur Vidarsson, Alois Jungbauer, Rainer Bischoff
Summary: The study evaluated the application of optimized pH gradient systems in the separation of charge variants of trastuzumab, which resulted in high-resolution separation of multiple charge variants without significant impact on the binding properties and Fc gamma receptors.
JOURNAL OF CHROMATOGRAPHY A
(2021)
Article
Chemistry, Analytical
Szabolcs Horvath, Diana Lukacs, Evelin Farsang, Krisztian Horvath
Summary: In this study, the impact of ion-exchange capacity gradient stationary phases combined with eluent concentration gradient on the separation efficiency of liquid chromatography was investigated. Results showed that gradient columns had a significant advantage over uniform columns in separating ions with different charges, due to the increased retention time difference of solutes.
Article
Metallurgy & Metallurgical Engineering
Atefeh Azizitorghabeh, Harshit Mahandra, Juliana Ramsay, Ahmad Ghahreman
Summary: This study investigates the selective recovery of gold over copper from synthetic and real thiocyanate pregnant leach solution (PLS) using ion exchange resins. The results demonstrate that 100 g/L MTA 5011 resin can achieve 99% gold extraction and 12% copper extraction, while a solution of 0.01 M thiourea (TU) and 0.1 M H2SO4 is the most efficient for gold elution with 70% gold and 4% copper recovery.
Article
Biochemical Research Methods
Kamiyar Rezvani, Andrew Smith, Jannat Javed, William R. Keller, Kevin D. Stewart, Logan Kim, Kelcy J. Newell
Summary: The biopharmaceutical industry relies on high-throughput systems and strategies for biologics manufacturing process development. While these systems provide valuable data, their interpretation often requires complex data transformation and time-intensive system characterization. The use of Tecan automated liquid handling systems with RoboColumns for purification development has shown promising results, but the lack of an optimized liquid delivery system limits their performance. This study introduces a Tecan Freedom EVO high-throughput purification tool that enables continuous gradient elution capability, leading to improved performance and consistency between RoboColumns and larger column formats.
JOURNAL OF CHROMATOGRAPHY A
(2023)
Article
Biochemical Research Methods
Ryan Dickerson, Christopher Argento, John Pieracci, Meisam Bakhshayeshi
Summary: This study presents a novel anion exchange chromatography process for enriching full rAAV2 particles, with an identified operating design space to ensure process robustness. Isocratic chromatography offers advantages over traditional shallow linear gradient elution, including lower buffer consumption, smaller intermediate pool volumes, and more robust manufacturing.
BIOTECHNOLOGY JOURNAL
(2021)
Article
Chemistry, Analytical
Honorine Lardeux, Szabolcs Fekete, Matthew Lauber, Valentina D'Atri, Davy Guillarme
Summary: Ion-pairing reversed-phase liquid chromatography (IP-RPLC) is the reference separation technique for characterizing oligonucleotides (ONs) and their related impurities. This study aimed to understand the retention mechanism of ONs, evaluate the applicability of the linear solvent strength (LSS) retention model, and explore ultra-short columns for ONs separation. It was found that 5-35 mm column lengths were appropriate for most gradient separation conditions. Baseline separation of three model ONs mixtures was achieved in as little as 30 seconds on the 5 mm column. This proof-of-concept work paves the way for future investigations using more complex therapeutic ONs and their related impurities.
ANALYTICAL CHEMISTRY
(2023)
Article
Biochemical Research Methods
Yi Feng Lee, Michael Schmidt, Heiner Graalfs, Mathias Hafner, Christian Frech
JOURNAL OF CHROMATOGRAPHY A
(2015)
Article
Chemistry, Analytical
Simon Kluters, Felix Wittkopp, Matthias Joehnck, Christian Frech
JOURNAL OF SEPARATION SCIENCE
(2016)
Article
Biochemical Research Methods
Yi Feng Lee, Heiner Graalfs, Christian Frech
JOURNAL OF CHROMATOGRAPHY A
(2016)
Article
Chemistry, Analytical
Yi Feng Lee, Simon Kluters, Mirjam Hillmann, Thomas von Hirschheydt, Christian Frech
JOURNAL OF SEPARATION SCIENCE
(2017)
Article
Biotechnology & Applied Microbiology
Yi Feng Lee, Matthias Joehnck, Christian Frech
BIOTECHNOLOGY PROGRESS
(2018)
Article
Biochemical Research Methods
Felix Wittkopp, Lars Peeck, Mathias Hafner, Christian Frech
JOURNAL OF CHROMATOGRAPHY A
(2018)
Article
Chemistry, Analytical
Gabriela Sanchez-Reyes, Heiner Graalfs, Mathias Hafner, Christian Frech
Summary: Ion exchange chromatography is a commonly used unit operation for the purification of therapeutic proteins, but its performance is influenced by a complex interplay of various parameters. Batch variations in ion exchange resins play a significant role in the robustness of downstream processing steps, with ligand density being a key factor affecting protein adsorption and separation performance. Using a model-based approach can help in understanding the impact of parameter variations, like ligand density, on the overall process.
JOURNAL OF SEPARATION SCIENCE
(2021)
Article
Biochemical Research Methods
Carolin Stange, Supriyadi Hafiz, Christoph Korpus, Romas Skudas, Christian Frech
Summary: The study explores the impact of excipients with stabilizing abilities on the purification of monoclonal antibodies and Fc fusion proteins.
Results indicate that these excipients can influence antibody elution behavior and host-cell protein elution behavior, as well as stabilize antibodies during virus inactivation.
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
(2021)
Article
Chemistry, Analytical
Jonas Koch, Daniel Scheps, Matthias Gunne, Oliver Boscheinen, Mathias Hafner, Christian Frech
Summary: This study presents a mechanistic model for the complex elution behavior of a polypeptide in preparative liquid chromatography, incorporating activity coefficients for accurate parameter estimation. The activity coefficient of the solute polypeptide is crucial in both linear and nonlinear ranges of the isotherm, affecting model parameters significantly.
JOURNAL OF SEPARATION SCIENCE
(2022)
Article
Biochemical Research Methods
Felix Seelinger, Felix Wittkopp, Thomas von Hirschheydt, Christian Frech
Summary: The application of a model-based approach for industrial chromatography development requires the capability to describe protein elution under high loading and overloading conditions. New experiments show that discrepancies between simulated and experimental data are primarily caused by intraparticle diffusion effects and conformational changes of the bsAb under different pH conditions. Extending the model to consider multi-component elution can help predict complex peak shapes that arise from charge variants of the bsAb.
JOURNAL OF CHROMATOGRAPHY A
(2022)
Article
Biochemical Research Methods
Felix Seelinger, Felix Wittkopp, Thomas von Hirschheydt, Mathias Hafner, Christian Frech
Summary: In this study, the pH-dependence of model parameters in ion exchange chromatography, including the shielding factor, was investigated and implemented into the SMA model. The experiments revealed that an increasing buffer pH resulted in a higher shielding factor. A correlation describing the relationship between the shielding factor and pH was established, and the accuracy of the model was demonstrated through experimental validation.
JOURNAL OF CHROMATOGRAPHY A
(2022)
Article
Biochemical Research Methods
Carolin Stange, Gabriela Sanchez-Reyes, Heiner Graalfs, Christian Frech
Summary: Cation exchange chromatography is a mild polishing technique used in monoclonal antibody purification. However, recent studies have shown unusual elution behavior, which is caused by on-column unfolding and aggregation of the predominantly mAb molecules. The stability of the protein plays a significant role in this phenomenon.
JOURNAL OF CHROMATOGRAPHY A
(2022)
Article
Biochemical Research Methods
Felix Seelinger, Felix Wittkopp, Thomas von Hirschheydt, Christian Frech
Summary: The objective of this work was to model and simulate the anti-Langmuir elution behavior of a bispecific monoclonal antibody (bsAb) on a strong cation exchange resin. A Self-Association SMA (SAS-SMA) model was applied to describe the protein-protein interactions and the uncommon retention and peak shapes observed in the elution behavior. Experimental data from linear gradient elution and high loading experiments were used to determine the model parameters, and the pH-dependent SAS-SMA model successfully simulated the anti-Langmuir behavior under a wide range of conditions. The model was confirmed by experimental verification. (c) 2022 Elsevier B.V. All rights reserved.
JOURNAL OF CHROMATOGRAPHY A
(2023)
Article
Biochemical Research Methods
Jonas Koch, Daniel Scheps, Matthias Gunne, Oliver Boscheinen, Christian Frech
Summary: The effect of salt modulators on the elution behavior of insulin in reversed-phase chromatography was investigated. Chloride and sulfate salts changed the monomer-multimer equilibrium and prevented the formation of multiple peaks. The elution behavior could be influenced by varying the concentration ratio of chloride and sulfate salts.
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
(2023)
Article
Chemistry, Analytical
Jonas Koch, Daniel Scheps, Matthias Gunne, Oliver Boscheinen, Christian Frech
Summary: In the process development and characterization, scaling up chromatographic steps is challenging due to the assumptions of constant column properties. This work demonstrates the scalability to larger column volumes by applying a mechanistic model calibrated with a pre-packed 1 ml column. The model's relationship between the normalized gradient slope and the eluting salt concentration enables successful scaling with similar eluting salt concentrations, peak heights, and shapes. Improved predictions are achieved by considering radial inhomogeneities in packing quality in scale-up simulations.
JOURNAL OF SEPARATION SCIENCE
(2023)