Article
Biotechnology & Applied Microbiology
Monica Moreno-Gonzalez, Pattra Chuekitkumchorn, Marcelo Silva, Roos Groenewoud, Marcel Ottens
Summary: This study presents a rational methodology using high throughput experimentation for the separation of major proteins in canola meal, resulting in a very good agreement between theoretical model and experimental results. The study identified column operating parameters that lead to >98% yield and purity for both proteins, paving the way for a conceptual downstream processing proposal.
FOOD AND BIOPRODUCTS PROCESSING
(2021)
Article
Chemistry, Multidisciplinary
Hao Xu, Jinglong Lin, Qianyi Liu, Yuntian Chen, Jianning Zhang, Yang Yang, Michael C. Young, Yan Xu, Dongxiao Zhang, Fanyang Mo
Summary: As an important attribute of organic compounds, polarity greatly affects their properties. Thin-layer chromatography (TLC) is commonly used for polarity estimations. However, current TLC techniques lack standardization, resulting in low reproducibility. In this study, an automated system is developed to conduct TLC analysis under standardized conditions, allowing high-throughput data collection. Machine-learning methods are then utilized to establish surrogate models that correlate compound structures with their polarity. These trained models can accurately predict the polarity of organic compounds in different solvent combinations, providing general guidelines for purification conditions and facilitating the generation and analysis of quality TLC data.
Article
Materials Science, Multidisciplinary
Xirui Lv, Yiming Lei, Zhao Zhang, Jie Zhang, Jingyang Wang
Summary: High throughput experimentation is used to establish a ternary system with a compositional range of SiO2, Yb2O3, and Ho2O3, and investigate their phase composition and mechanical properties. The chemical stability and thermal expansion compatibility between SiC and RE silicates with different compositions are also validated. The optimized materials for environmental barrier coating and interphase in SiCf/SiC CMC are screened according to the trends and data. This study accelerates the design and screening of promising optimal candidates for RE2O3-SiO2 compounds.
JOURNAL OF MATERIALS SCIENCE & TECHNOLOGY
(2023)
Article
Chemistry, Physical
Lucas Foppa, Christopher Sutton, Luca M. Ghiringhelli, Sandip De, Patricia Loeser, Stephan A. Schunk, Ansgar Schaefer, Matthias Scheffler
Summary: The design of heterogeneous catalysts is challenging due to the complexity of materials and processes. This study demonstrates how artificial intelligence can be used to identify key physicochemical parameters for catalyst performance. By combining experimental and theoretical data, the researchers identified temperature, phosphorus content, and composition-weighted electronegativity as key parameters for high-yield oxygenate products.
Review
Biotechnology & Applied Microbiology
Manman Sun, Alex Xiong Gao, Xiuxia Liu, Yankun Yang, Rodrigo Ledesma-Amaro, Zhonghu Bai
Summary: The demand for faster and more efficient protein production has increased in the post-genomic era. This review presents a holistic high-throughput process development strategy and discusses the challenges, limitations, and future research directions in recombinant protein production.
MICROBIAL CELL FACTORIES
(2023)
Review
Chemistry, Physical
Anass Benayad, Diddo Diddens, Andreas Heuer, Anand Narayanan Krishnamoorthy, Moumita Maiti, Frederic Le Cras, Maxime Legallais, Fuzhan Rahmanian, Yuyoung Shin, Helge Stein, Martin Winter, Christian Wolke, Peng Yan, Isidora Cekic-Laskovic
Summary: The timely arrival of novel materials is crucial for technological breakthroughs, with high-throughput experimentation and computation strategies accelerating the discovery and optimization of materials. However, adapting algorithms and integrating with machine learning are necessary for optimal data leverage in advanced battery electrolytes development.
ADVANCED ENERGY MATERIALS
(2022)
Article
Chemistry, Applied
Xavier Jusseau, Ed Cleator, William M. Maton, Qinghao Chen, Robert Geertman, Yuanyuan Yuan, Xiaowei Wang, Haojuan Wei, Florian Medina, Massimo Giannerini
Summary: This study presents the process optimization for the synthesis of an RSV antiviral agent, which greatly reduces the development time and improves key steps such as the telescoped pyrazolopyrimidine core assembly and the borylation/Suzuki sequence through the use of high-throughput experimentation.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2022)
Article
Biochemical Research Methods
Valentina Marassi, Monica Mattarozzi, Lorenzo Toma, Stefano Giordani, Luca Ronda, Barbara Roda, Andrea Zattoni, Pierluigi Reschiglian, Maria Careri
Summary: This study investigated the potential of asymmetrical flow field-flow fractionation (AF4) with UV detection for the screening of a large number of lysozyme aptamers, including randomized sequences and an interfering agent. The selective monitoring of the evolution of untagged aptamer signal as a result of aptamer-protein binding makes the developed method effective for shortlisting the most promising aptamers for subsequent development of aptamer-based analytical devices.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Chandan L. Barhate, Andrew F. Donnell, Merrill Davies, Ling Li, Yong Zhang, Fukang Yang, Regina Black, Greg Zipp, Yingru Zhang, Cullen L. Cavallaro, E. Scott Priestley, Harold N. Weller
Summary: The successful miniaturization of assays in recent years has enabled the exploration of reducing synthesis scale in pharmaceutical discovery, leading to lower material consumption and shorter timelines without sacrificing data quality. Isolating and purifying compounds is a key step in library synthesis, and an optimized microscale purification system can efficiently purify samples.
CHEMICAL COMMUNICATIONS
(2021)
Article
Engineering, Chemical
Jonathan A. Ouimet, Xinhong Liu, David J. Brown, Elvis A. Eugene, Tylar Popps, Zachary W. Muetzel, Alexander W. Dowling, William A. Phillip
Summary: This study emphasizes the importance of improved characterization techniques in advancing membrane processes. By developing a diafiltration apparatus guided by data science, membrane performance can be rapidly characterized over a broad range of feed solution compositions. The synergy between data analytics and instrumentation, including an inline conductivity probe, allows for accurate determination of membrane transport coefficients and identification of governing phenomena.
JOURNAL OF MEMBRANE SCIENCE
(2022)
Article
Chemistry, Multidisciplinary
Yangang Liang, Heather Job, Ruozhu Feng, Fred Parks, Aaron Hollas, Xin Zhang, Mark Bowden, Juran Noh, Vijayakumar Murugesan, Wei Wang
Summary: This study develops a high-throughput experimental process to collect large-scale and high-quality solubility data, accelerating the development of redox-active materials. The optimized electrolyte formulation and additives in redox flow batteries lead to highly stable performance and increased energy density.
CELL REPORTS PHYSICAL SCIENCE
(2023)
Article
Chemistry, Multidisciplinary
Melody A. Morris, Carolyn E. Mills, Justin M. Paloni, Eric A. Miller, Hadley D. Sikes, Bradley D. Olsen
Summary: Evolution shapes diverse properties of proteins. Incorporating proteins into materials is desired for applications, but high-throughput selection techniques are lacking. This study established a high-throughput platform to assess binding affinity for ordered sensing proteins. Fusion proteins library was constructed, and selected variants showed high binding in films. The assembly of fusion proteins and the functionality of binding protein are key factors in biosensing performance. Integration of directed evolution with assembled systems is necessary for designing better materials.
Article
Chemistry, Multidisciplinary
Jakob Rorbaek Saugbjerg, Thorbjorn Bogh Jensen, Mogens Hinge, Martin Lahn Henriksen
Summary: This study presents a low-cost automated synthesis machine capable of performing up to 45 batch syntheses under controlled atmosphere with the mixing of up to five components. It is tested by performing 13 ring-opening metathesis polymerizations and proved to be reliable and flexible.
REACTION CHEMISTRY & ENGINEERING
(2023)
Article
Chemistry, Applied
Jon A. Jurica, Jonathan P. McMullen
Summary: Automated reactor and sampling technologies were used in process characterization studies of a cyclization reaction using gaseous ammonia, leading to significant improvements in efficiency and experimental reproducibility compared to conventional methods. Data-driven models were established for key reaction responses to create a process fingerprint and evaluate the stability of the process, enabling identification of optimal operating conditions under various constraints.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2021)
Article
Materials Science, Multidisciplinary
Min Wei, Lei Zhao, Liwu Jiang, Lixia Yang, Haizhou Wang
Summary: This article introduces an efficient multi-temperature-field heat treatment method using microwave radiation as the heating source, which can process multiple samples simultaneously. The method incorporates rapid characterization techniques, enabling the acquisition of a large amount of data in a short time. The feasibility of this method was verified through heat treatment experiments on high-carbon, high-chromium steel.
Article
Biotechnology & Applied Microbiology
Dennis Weber, Juergen Hubbuch
Summary: In biopharmaceutical production processes, freeze-thaw operations are conducted to maintain product integrity during long hold times, but they may introduce additional stresses such as freeze concentration gradients that affect protein activity. Current process characterization methods often rely on limited temperature probes, but a new method utilizing Fiber-Bragg-Grating sensors for detecting freezing times shows promise. The study also highlights the importance of freezing time and boundary effects in ensuring product stability throughout the process and in process development.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Dominik Stein, Volkmar Thom, Juergen Hubbuch
Summary: This paper presents a mechanistic model case study for the separation of two different two-component solutions, confirming prior evidence. A novel HTS screening procedure was developed, incorporating competitive adsorption-based displacement effects and key parameter identification. The screening procedure, using an overload bind and elute mode, was applied to a case study dealing with IgG aggregate removal, resulting in significant improvements in binding capacities.
BIOTECHNOLOGY AND APPLIED BIOCHEMISTRY
(2022)
Article
Biotechnology & Applied Microbiology
Dennis Weber, Christian Sittig, Juergen Hubbuch
Summary: Freezing of cell culture supernatant in mAb platform process development helps concentrate certain proteins and particles, leading to better removal of host cell proteins during purification steps. The freezing temperature also affects the concentrations of HCP and mAb dimers in the eluate during protein A chromatography. Rapid freezing of CCS in process development is crucial for maintaining comparability and transferability to manufacturing.
BIOTECHNOLOGY AND BIOENGINEERING
(2021)
Article
Biotechnology & Applied Microbiology
Dennis Weber, Juergen Hubbuch
Summary: This study demonstrates the use of Raman spectroscopy as a process analytical technology for monitoring freeze concentration profiles in model formulations containing mAbs or BSA. Freeze concentration was found to be dependent on freezing temperature and formulation, with convection currents observed at the bottom of the freezing container. The study also showed correlation between freeze concentration and sucrose concentration in the formulation, indicating diffusion from the bottom to the top of the container.
BIOTECHNOLOGY AND BIOENGINEERING
(2021)
Article
Biochemical Research Methods
Johannes Winderl, Stephan Buerkle, Juergen Hubbuch
Summary: An automated high-throughput screening system for fiber-based adsorbents was successfully established, with optimized screening parameters enabling fast characterization and integration of these novel adsorbents.
JOURNAL OF CHROMATOGRAPHY A
(2021)
Article
Chemistry, Multidisciplinary
Christina H. Wegner, Ines Zimmermann, Juergen Hubbuch
Summary: This study aimed to develop a low-volume, quantitative analytical tool based on UV-visible spectroscopy and partial least squares modeling for faster development of crystallization processes. The developed tool successfully quantified different species in the supernatant with high precision, achieving a sensitivity of 96.23% and a short analysis time of 3 minutes per sample.
CRYSTAL GROWTH & DESIGN
(2022)
Article
Biotechnology & Applied Microbiology
Narmin Suvarli, Lukas Wenger, Christophe Serra, Iris Perner-Nochta, Juergen Hubbuch, Michael Woerner
Summary: Increasing the shelf life and reusability of enzymes is a crucial topic in biotechnology. This study presents a method to immobilize beta-galactosidase on polymer nanoparticles and then encapsulate them inside hydrogel microparticles using a microfluidic device and UV-LEDs. The encapsulation in acrylamide microparticles caused a loss of enzymatic activity, while encapsulation in PEG-diacrylate microparticles preserved some activity. Storage at -26 degrees C resulted in a complete loss of enzymatic activity. The presence of a photoinitiator exposed to UV-irradiation also influenced the enzyme activity.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Engineering, Chemical
Till Briskot, Nils Hillebrandt, Simon Kluters, Gang Wang, Joey Studts, Tobias Hahn, Thiemo Huuk, Juergen Hubbuch
Summary: The Gibbs-Donnan effect causes uneven distribution of ions across semipermeable membranes, leading to discrepancies in pH and excipient concentrations in protein ultrafiltration and diafiltration processes. This study introduces a model that describes the composition of retentate and permeate in combined UF/DF processes, taking into account volume exclusion effects and electrostatic interactions between ions and proteins.
JOURNAL OF MEMBRANE SCIENCE
(2022)
Article
Biotechnology & Applied Microbiology
Svenja Strauss, Bianca Schroth, Juergen Hubbuch
Summary: Bioprinting is considered a suitable additive manufacturing method in biopharmaceutical process development. To achieve industrial application, higher levels of reproducibility and a standardized bioprinting process are necessary. This study investigates the effect of different processing modes (set pressure vs. set flow rate) on printing reproducibility. The results show that a set flow rate controlled printing process improves accuracy and the filling level also affects the accuracy of printing.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Biochemical Research Methods
Federico Rischawy, Till Briskot, Adrian Schimek, Gang Wang, David Saleh, Simon Kluters, Joey Studts, Juergen Hubbuch
Summary: A fundamental process understanding of an entire downstream process is essential for achieving and maintaining high-quality standards demanded for biopharmaceutical drugs. A holistic process model based on mechanistic insights could support process development by identifying dependencies between process parameters and critical quality attributes across unit operations to design a holistic control strategy.
JOURNAL OF CHROMATOGRAPHY A
(2022)
Article
Biotechnology & Applied Microbiology
David Saleh, Rudger Hess, Michelle Ahlers-Hesse, Federico Rischawy, Gang Wang, Jan-Hendrik Grosch, Thomas Schwab, Simon Kluters, Joey Studts, Juergen Hubbuch
Summary: The development of downstream processes in biopharmaceuticals relies on experimental studies, but the relationship between the protein structure of mAbs and their macroscopic process behavior is poorly understood. This study introduces a multiscale in silico model that allows the development of chromatography processes before protein material is available for experimental studies. The model leverages the mAbs' structural characteristics and experimental data to predict elution profiles and improve the development of chromatography processes for novel antibodies.
BIOTECHNOLOGY AND BIOENGINEERING
(2023)
Article
Biotechnology & Applied Microbiology
Sandra Haas, Saskia Koerner, Laura Zintel, Juergen Hubbuch
Summary: Hydrogels based on renewable resources are promising materials for pharmaceuticals, drug delivery, and personalized medicine. The mechanical properties of these hydrogels, such as storage modulus and elasticity, can be adjusted by changing the accessibility of tyrosine residues and the composition of buffer systems and protein concentration.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Biochemical Research Methods
Laura Rolinger, Juergen Hubbuch, Matthias Ruedt
Summary: Monitoring the protein concentration and buffer composition during UF/DF step is crucial for biopharmaceutical production automation and real-time release testing. This study demonstrates the advantages of combining Raman spectroscopy with EKF for monitoring the UF/DF step, showing improved sensitivity and faster measurement speed.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2023)
Article
Biotechnology & Applied Microbiology
Robin Schiemer, Jan Tobias Weggen, Katrin Marianne Schmitt, Juergen Hubbuch
Summary: In the production of antibody-drug conjugates (ADCs), real-time monitoring of the conjugation reaction is crucial for ensuring product safety and efficacy. This study successfully combined a sensor model and a kinetic reaction model using an extended Kalman filter (EKF), which improved the accuracy of predictions and enhanced robustness against experimental noise or model errors. The developed framework provides a reliable method for monitoring ADC conjugation reactions and has the potential to be implemented in process control and applied to other ADC conjugation reaction types.
BIOTECHNOLOGY AND BIOENGINEERING
(2023)
Article
Biochemical Research Methods
Rudger Hess, Jan Faessler, Doil Yun, David Saleh, Jan-Hendrik Grosch, Thomas Schwab, Juergen Hubbuch
Summary: This study introduces a method for predicting the elution behavior of antibodies in multimodal chromatography based on their amino acid sequences. By analyzing the data of 64 full-length antibodies, the study identifies key structural features and establishes a predictive model for pH gradient elution. The developed model can inform process development and enable in silico manufacturability assessment for target antibodies adhering to standardized purification conditions.
JOURNAL OF CHROMATOGRAPHY A
(2023)
