Practical Continuous‐Flow Controlled/Living Anionic Polymerization

Nakahara, Yuko; Furusawa, Mai; Endo, Yuta; Shimazaki, Toshiya; Ohtsuka, Keita; Takahashi, Yusuke; Jiang, Yiyuan; Nagaki, Aiichiro

doi:10.1002/ceat.201900160

Cited by 10 publications

(7 citation statements)

References 87 publications

(82 reference statements)

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“…As defined in (6), the grid resolution is refined to λ conc to obtain a grid independent species solution. The first esterification of the di-isocyanate follows the scheme (11) where the first cyanate group forms a carbamate (urethane) link with the alcohol. The product is termed mono-urethane for simplicity.…”

Section: Reactive Mixingmentioning

confidence: 99%

“…The FOURIER number (4) is F o 1, suggesting that the mixing time is smaller than the residence time. Therefore, enhanced micro mixing effects due to the different injection positions can affect the yield and the selectivity of both reactions (11) and (12).…”

Section: Reactive Mixingmentioning

confidence: 99%

“…While these concepts work well in the lab, industry applications are interested in scale-up and handling. The group around Yoshida has worked on several studies to enhance throughput in capillary reactors using the numbering up philosophy [9][10][11]. The group achieved a service time of several hours, limited by fouling and the consequent increasing pressure drop.…”

Section: Introductionmentioning

confidence: 99%

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CFD analysis of asymmetric mixing at different inlet configurations of a split-and-recombine micro mixer

et al. 2021

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In the scope of the ENPRO II initiative (Energy Efficiency and Process Intensification for the Chemical Industry), a major challenge of process intensification of polymer synthesis in continuous systems is fouling. Pre-mixing is a key aspect to prevent fouling and is achieved through milli and micro structured devices (Bayer et al. 1). While equal volume flow ratios are well investigated in milli and micro systems, asymmetric mixing tasks have received less attention. This paper investigates the dependency of mixing phenomena on different flow rate ratios and modified inlet geometries. A split-and-recombine (SAR) mixer is modified by means of an injection capillary to facilitate the asymmetric mixing task. Asymmetric volume flows of ratios between 1:15 and 1:60 are investigated; the velocity ratios range from 0.5 to 2. The setup is simulated with the Computational Fluid Dynamics (CFD) tool ANSYS®;Fluent. The species equation is solved directly without the use of micro mixing models. The simulation is validated by means of a concentration field in a mixing Tee using Laser-Induced Fluorescence (LIF) with a Confocal Laser Scanning Microscope (CLSM). The three dimensional flow structures and the mixing quality are analyzed as a measure for micro mixing. The calculated concentration fields show good agreement with the experimental results and reveal the secondary flow structures and chaotic advection within the channel. The injection of the small feed stream is found to be very efficient when drawn into the secondary structures, increasing the potential of diffusive mixing. CFD simulations help to understand and locate such structures and improve the mixing performance.

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Section: Reactive Mixingmentioning

confidence: 99%

Section: Reactive Mixingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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CFD analysis of asymmetric mixing at different inlet configurations of a split-and-recombine micro mixer

et al. 2021

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“…16 Rapid mixing and precise residence time control have enabled previously challenging reactions, such as generating unstable lithium species for protecting group-free reactions. 17 Recent studies have explored FMR technology for next-generation protein therapeutics, including antibody−drug conjugate production 12 and PEGylation processes. 13 Expanding upon these foundational studies, this study presents an advancement with the successful implementation of a cascaded-mixer system, enabling FMR-mode protein refolding.…”

Section: ■ Introductionmentioning

confidence: 99%

Spatiotemporal Control of Protein Refolding through Flash-Change Reaction Conditions

Nakahara,

Kawaguchi,

Matsuda

et al. 2024

Langmuir

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Recombinant protein production is an essential aspect of biopharmaceutical manufacturing, with Escherichia coli serving as a primary host organism. Protein refolding is vital for protein production; however, conventional refolding methods face challenges such as scale-up limitations and difficulties in controlling protein conformational changes on a millisecond scale. In this study, we demonstrate the novel application of flow microreactors (FMR) in controlling protein conformational changes on a millisecond scale, enabling efficient refolding processes and opening up new avenues in the science of FMR technology. FMR technology has been primarily employed for small-molecule synthesis, but our novel approach successfully expands its application to protein refolding, offering precise control of the buffer pH and solvent content. Using interleukin-6 as a model, the system yielded an impressive 96% pure refolded protein and allowed for gram-scale production. This FMR system allows flash changes in the reaction conditions, effectively circumventing protein aggregation during refolding. To the best of our knowledge, this is the first study to use FMR for protein refolding, which offers a more efficient and scalable method for protein production. The study results highlight the utility of the FMR as a highthroughput screening tool for streamlined scale-up and emphasize the importance of understanding and controlling intermediates in the refolding process. The FMR technique offers a promising approach for enhancing protein refolding efficiency and has demonstrated its potential in streamlining the process from laboratory-scale research to industrial-scale production, making it a game-changing technology in the field.

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“…Organic synthesis has traditionally been performed in a batch system; however, in recent years, flow-type organic synthesis has attracted attention for its reaction selectivity, scalability, safety, and space efficiency. , Flow synthetic reactions increase production by extending the reaction time. , …”

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confidence: 99%

Highly Productive Flow Synthesis for Lithiation, Borylation, and/or Suzuki Coupling Reaction

Soutome,

Maekawa,

Ashikari

et al. 2024

Org. Process Res. Dev.

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The efficient synthesis of aromatic boronic acids was achieved by increasing the concentration, flow rate, and mixer diameter to prevent clogging. A 1 h synthesis actually produced 180 g of boronic acid. The real-time analysis of the reaction solution was investigated using in-line analyzers suitable for high flow rates. Additives were also studied to accelerate the Suzuki coupling reaction of the boronic acids. Integrated one-flow reactions combining boronic acid synthesis and Suzuki coupling produced pharmaceutical precursors in 97−143 s.

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Practical Continuous‐Flow Controlled/Living Anionic Polymerization

Cited by 10 publications

References 87 publications

CFD analysis of asymmetric mixing at different inlet configurations of a split-and-recombine micro mixer

CFD analysis of asymmetric mixing at different inlet configurations of a split-and-recombine micro mixer

Spatiotemporal Control of Protein Refolding through Flash-Change Reaction Conditions

Highly Productive Flow Synthesis for Lithiation, Borylation, and/or Suzuki Coupling Reaction

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