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
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
Biochemical Research Methods
Xiaotong Fu, Asher Williams, Meisam Bakhshayeshi, John Pieracci
Summary: Utilizing high throughput (HTP) strategies and automation technologies for gene therapy process development can help overcome unique challenges in early-stage development, but further exploration is needed due to the unique challenges related to viral vector purification.
JOURNAL OF CHROMATOGRAPHY A
(2022)
Article
Chemistry, Multidisciplinary
Felicia D. Cannavacciuolo, Rinku Yadav, Alec Esper, Antonio Vittoria, Giuseppe Antinucci, Francesco Zaccaria, Roberta Cipullo, Peter H. M. Budzelaar, Vincenzo Busico, Georgy P. Goryunov, Dmitry Uborsky, Alexander Z. Voskoboynikov, Keith Searles, Christian Ehm, Adam S. Veige
Summary: Efficient and economical upcycling of plastic waste relies on the development of catalysts capable of polymer degradation. Through a systematic high-throughput screening, important structure-activity correlations were revealed in the degradation of cis-1,4-polybutadiene (PB) using various polymerization catalyst precursors. The ability to degrade PB was found to be a general reactivity profile of neutral group 4 metal hydrides, with improved degradation ability associated with increased steric congestion and lower electrophilicity.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
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, Applied
Jennifer M. Crawford, Tobias Gensch, Matthew S. Sigman, Jennifer M. Elward, Janelle E. Steves
Summary: Modern high-throughput experimentation is crucial for accelerating the development of key synthetic steps in pharmaceutical processes. However, the selection of experiments and the analysis of reaction outcomes require careful consideration. This article presents a method to holistically analyze reaction results and quantify reagent diversity using computational featurization and multivariate linear regression modeling.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2022)
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, Physical
Sriram Vijayakrishnan, John W. Ward, Andrew I. Cooper
Summary: In this study, a novel photocatalyst CTF-2 was discovered for decarboxylative conjugate addition under visible-light irradiation. CTF-2 showed the ability to couple with various other reactions and can be prepared on a large scale with recyclability.
Article
Chemistry, Physical
Sriram Vijayakrishnan, John W. Ward, Andrew I. Cooper
Summary: Photoredox catalysis is an important development in organic synthesis, but the current use of homogeneous metal complexes or organic dyes raises issues of cost, recyclability, and waste production. In this study, a covalent triazine framework photocatalyst (CTF-2) was discovered, which enables decarboxylative conjugate addition of carboxylic acids under visible-light irradiation. CTF-2 can be prepared on a large scale and recycled without loss of catalytic efficiency.
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
Chemistry, Applied
Jason M. Stevens, Eric M. Simmons, Yichen Tan, Alina Borovika, Junying Fan, Robert Forest, Peng Geng, Carlos A. Guerrero, Sha Lou, Dimitri Skliar, Sarah E. Steinhardt, Neil A. Strotman
Summary: This study describes the invention of a commercial route to the Bruton's tyrosine kinase inhibitor branebrutinib (BMS-986195) in four total chemical steps. By utilizing high-throughput experimentation and a first-principles approach, a novel indolization reaction that rapidly generated high synthetic complexity was identified as the centerpiece of the synthesis.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2022)
Article
Multidisciplinary Sciences
M. Ali Al-Radhawi, Michael Margaliot, Eduardo D. Sontag
Summary: This study explores the synchronization of dynamical systems to periodic inputs, investigates the maximization of a weighted average of the system's output along the periodic attractor, and formulates it as a periodic optimal control problem. It is found that constant inputs are optimal in some architectures, suggesting that non-constant periodic signals may indicate optimization of an underlying time-varying objective functional.
ROYAL SOCIETY OPEN SCIENCE
(2021)
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)
Article
Engineering, Multidisciplinary
Jonas B. Weber, Michael Hartisch, Alexander D. Herbst, Ulf Lorenz
Summary: The research focuses on developing software tools to support human-driven design processes through modern mathematical methods. It involves model extension and algorithmic method development for a selected class of thermofluid systems to achieve practical optimization.
OPTIMIZATION AND ENGINEERING
(2021)
Article
Chemistry, Multidisciplinary
Yoshio Hato, Timothy F. Jamison
Summary: Efficient and robust synthesis of active pharmaceutical ingredients (APIs) requires the use of continuous flow chemistry. This study investigates continuous synthetic approaches to ondansetron, an essential medicine. Continuous condensation and Mannich reactions were established, along with a continuous work-up and purification process. A batch process was employed for an elimination and Michael addition step, showing the complementary advantages of flow and batch chemistry in API synthesis.
REACTION CHEMISTRY & ENGINEERING
(2023)
Article
Chemistry, Multidisciplinary
Catalina A. Suarez Ruiz, Jennifer Kwaijtaal, Oriol Cabau Peinado, Corjan van den Berg, Rene H. Wijffels, Michel H. M. Eppink
ACS SUSTAINABLE CHEMISTRY & ENGINEERING
(2020)
Article
Biotechnology & Applied Microbiology
Catalina A. Suarez Ruiz, Santiago Zarate Baca, Lambertus A. M. van den Broek, Corjan van den Berg, Rene H. Wijffels, Michel H. M. Eppink
ALGAL RESEARCH-BIOMASS BIOFUELS AND BIOPRODUCTS
(2020)
Article
Biotechnology & Applied Microbiology
Deborah C. Gernat, Renzo Rozenbroek, Eric R. Brouwer, Luuk A. M. van der Wielen, Marcel Ottens
JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY
(2020)
Article
Agricultural Engineering
Razieh Shafiei Alavijeh, Keikhosro Karimi, Rene H. Wijffels, Corjan van den Berg, Michel Eppink
BIORESOURCE TECHNOLOGY
(2020)
Article
Biotechnology & Applied Microbiology
Petronella M. Slegers, Giuseppe Olivieri, Elke Breitmayer, Lolke Sijtsma, Michel H. M. Eppink, Rene H. Wijffels, Johannes H. Reith
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2020)
Review
Biotechnology & Applied Microbiology
Michel H. M. Eppink, Sonia P. M. Ventura, Joao A. P. Coutinho, Rene H. Wijffels
Summary: Ionic liquids are used for the extraction and separation of biomolecules, allowing for the valorisation of biomass in biorefinery processes. Aqueous biphasic systems and emulsions can effectively fractionate microalgal biomass, with different components obtained through mechanical disruption.
TRENDS IN BIOTECHNOLOGY
(2021)
Review
Biotechnology & Applied Microbiology
Tiago Castanheira Silva, Michel Eppink, Marcel Ottens
Summary: Process development in the biotech industry requires significant investments, and automation and miniaturization are crucial tools for achieving efficient and cost-effective processes. Liquid-handling stations and microfluidics play important roles in enabling high-throughput process development, while continuous processing is seen as the next frontier for cost reduction and quality control improvements.
JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY
(2022)
Review
Biotechnology & Applied Microbiology
Mariana N. Sao Pedro, Marieke E. Klijn, Michel H. M. Eppink, Marcel Ottens
Summary: The transition to continuous biomanufacturing aims to reduce costs and improve process robustness in the biopharmaceutical industry by utilizing miniaturized biosensors for real-time measurement of mAb aggregation during downstream processing.
JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Catalina A. Suarez Ruiz, Oriol Cabau-Peinado, Corjan van den Berg, Rene H. Wijffels, Michel H. M. Eppink
Summary: This study successfully investigated the fractionation of lipids from other microalgal components using polymers and IL solutions in aqueous two-phase systems, showing potential applications for multiproduct microalgal biorefineries. The research also demonstrated that by combining polypropylene glycol 400 solution with subsequent ATPS, most of the microalgae biomolecules could be fractionated.
ACS SUSTAINABLE CHEMISTRY & ENGINEERING
(2022)
Article
Agricultural Engineering
Iulian Zoltan Boboescu, Antoinette Kazbar, Lars Stegemuller, Piet Lazeroms, Thanasis Triantafyllou, Fengzheng Gao, Calvin Lo, Maria J. Barbosa, Michel H. M. Eppink, Rene H. Wijffels
Summary: Cellular agriculture offers a more sustainable option for food production, and Tisochrysis lutea microalgae is a valuable source of nutrients. Mild targeted acoustic treatment has been found to disrupt cells and reduce energy requirements.
BIORESOURCE TECHNOLOGY
(2022)
Article
Biochemical Research Methods
Tiago Castanheira Silva, Michel Eppink, Marcel Ottens
Summary: Biopharmaceuticals, especially monoclonal antibodies (mAb), play a critical role in the treatment of diseases such as cancer and autoimmune diseases. However, the purification step using chromatography is costly and time-consuming. This paper presents a microfluidic chip approach that offers a more cost-effective alternative for chromatographic process development. The microfluidic chip shows comparable performance to other miniaturized techniques, with significantly reduced liquid and resin volume.
JOURNAL OF CHROMATOGRAPHY A
(2022)
Article
Biochemical Research Methods
Mariana N. Sao Pedro, Mafalda S. Santos, Michel H. M. Eppink, Marcel Ottens
Summary: This research presents the development of a real-time process analytical technology tool for monitoring the formation of antibody aggregates. By using miniaturized sensors and a zigzag microchannel structure, fast and efficient mixing is achieved, providing important real-time feedback and process control for fluorescence-based protein aggregate detection.
BIOTECHNOLOGY JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Edgar Suarez Garcia, Carlota F. Miranda, M. Teresa Cesario, Rene H. Wijffels, Corjan van den Berg, Michel H. M. Eppink
Summary: A novel extraction and fractionation concept using Ionic Liquids (ILs) was proposed to extract and recover proteins and carbohydrates from macroalgae. The process involved IL-assisted mechanical shear for initial extraction and two-phase partitioning or ultrafiltration for fractionation. The selective extraction of proteins and the preservation of their native structure were demonstrated. The potential application of this approach in the biorefinery of macroalgae was highlighted.
ACS SUSTAINABLE CHEMISTRY & ENGINEERING
(2023)
Article
Chemistry, Multidisciplinary
Calvin Lo, Jeltzlin Semerel, Corjan van den Berg, Rene H. Wijffels, Michel H. M. Eppink
Summary: This study proposed a method to change the hydrophobicity spectrum of a semi-hydrophobic solvent, which can induce phase separation between oil and solvent by adding imidazole to the solution, achieving high efficiency in lipid recovery.
Article
Engineering, Environmental
C. A. Suarez Ruiz, M. Martins, J. A. P. Coutinho, R. H. Wijffels, M. H. M. Eppink, C. van den Berg, S. P. M. Ventura
CHEMICAL ENGINEERING JOURNAL
(2020)