Reaction screening

Using enzymes to drive a reaction is often preferred to chemical catalysts. A clear advantage of using enzymes is the high substrate specificity, which generally gives rise to high yields and high reaction rates, as well as products free from unwanted biproducts. Due to both technical and economic benefits, the enzymes used to catalyse reactions are often immobilized on the surface of different insoluble materials. The immobilization will lead to easier recycling, manipulation and separation of the enzyme, as well as an increase in its thermal and operational stability.

The most common applications for immobilized enzymes include esterifications, transesterifications, amidations and the modification of fats and oils. To identify the enzyme best suited for the conversion of a certain substrate, the candidate enzymes are put through a screening process. As the reaction conditions must ensure the stability of the enzyme and substrate, parameters such as solvent, temperature and pH should also be optimized to guarantee a high and pure product yield. In processes including enzyme development, there is also a need for screening of different methods of immobilization, as well as potential carrier materials, to ensure preserved enzyme activity.

As evaluation is generally needed for several different factors when developing an enzyme-catalysed process, easy screening of multiple reaction parameters will allow for easier and faster design of experiments. By being able to examine several parameters simultaneously in a multidimensional parameter space, the process can quickly be optimized. Through this, high parameter robustness can be achieved, thus also providing the process with high reproducibility, validity and reliability.

Magnetic rotating bed reactors

The SpinChem® magnetic rotating bed reactor (MagRBR), carries 0.5 mL solid phase resin, and is designed for screening of biocatalysts and biocatalytic reactions in liquid phase volumes of 5-100 mL. The SpinChem® MagRBR retains the solid phase particles, and conducts the mass transfer by impelling the movement of the liquid phase.

No preparations are required prior to implementing the MagRBR in screening applications, and the downstream processing is greatly minimized or completely cut out due to the lack of filtration steps. The SpinChem® MagRBR is delivered pre-packed with a variety of resins for catalysis and adsorption screening. As the SpinChem® MagRBR is spun by means of magnetic coupling, solution is continuously passed through the packed bed within, allowing the reactants in the different phases to interact. By running the reactions in minimized liquid volumes, the amount of enzyme and substrate needed is reduced, thus significantly increasing the rate of enzyme development. For even further streamlined screening, the SpinChem® magnetic stirrer with multiple positions can be used to run several reactions in parallel.

Application 1007
Automated semi-continuous batch processing system with rotating bed reactor

Video showing the principle of an automated rotating bed reactor system capable of filling a solution, neutralizing it by ion exchange and draining it. By microcomputer control, unattended semi-continuous batch processing was accomplished for many cycles until the ion exchanger was completely saturated.  Keywords: Automation, Ion exchange, Seamless scaleup, Technology

Application 1023
Biocatalysis in rotating bed reactors – from screening to production

Poster describing the screening of resins with immobilized enzymes for esterification reactions. The screening was performed with prepacked cartridges inside a SpinChem® rotating bed reactor (RBR) and compared to parallel screening with prototype disposable magnetic RBR (MagRBR) in 10 mL volume. Both approaches were very quick, required minimum preparation and no filtration. Up-scaled processes enabled quick enzyme recycling, opening for the possibility of semi-continuous processes with attractive production economy.

Application 9005
Chemical Catalysis with MagRBR and EasyMax – Quick and Convenient Suzuki couplings

This application note demonstrates how the combination of a SpinChem MagRBR custom-filled with heterogenous Pd(II)-catalyst and the controlled conditions in a Mettler-Toledo EasyMax™ 102 Advanced Synthesis Workstation allows for quick and convenient generation of C-C coupled products.  Keywords: Chemical catalysis, Easy handling, Mettler-Toledo

Application 1028
Enzyme immobilization screening using magnetic rotating bed reactors

The SpinChem® MagRBR ECR screening kit, pre-packed with Purolite® Lifetech™ resins, was used to screen six different enzyme carrier resins in parallel for the immobilization of lipase CalB. Easy sampling and monitoring of the process, together with effortless handling, established the MagRBR as a time and labour efficient screening device. Keywords: Biotransformation, Easy handling, Immobilized enzymes, Rapid screening

Application 9001
Recycling of Immobilized Enzymes – Simple and Streamlined Biocatalysis

Immobilized catalyst recycling using a SpinChem® rotating bed reactor (RBR) and a Mettler-Toledo EasyMax™ 102 Advanced synthesis workstation. The process proved very time efficient as no filtration steps were needed between cycles, or for the samples extracted for analysis during each run. Washing of the resin between runs was fast, simple and robust, without running the risk of material loss. Keywords: Biotransformation, Immobilized enzymes, Mettler-Toledo, Organic molecules, Preserved activity, Quick recycling

Application 1032
Rotating bed reactor for immobilized enzymatic reactions

Poster on a case study of applying the rotating bed reactor for the lipase-mediated stereoselective acetylation of a racemate amine as a model reaction for the manufacturing of pharmaceutical building blocks. The results showed that enzyme recycling and synthesis scale up was easy to achieve with preserved yield, enantioselectivity and catalytic activity.   Keywords: Biotransformation, Easy handling, Immobilized enzymes, Quick recycling, Seamless scaleup

Application 1036
Screening of activated carbon using the SpinChem® RBR S2

In co-operation with ZHAW, two students screened various types and sizes of activated carbon using the SpinChem® RBR S2. Five different carbons were screened by decolorizing solutions of methylene blue in distilled water. The decolorization process was monitored using inline UV-Vis spectrometry (PAT). The results show the importance of choosing the correct media for your application. In this case of activated carbon, the source and type of the activation was shown to have a major impact on performance.  Keywords: Activated carbon, Decolouration, Fast reaction, Rapid screening, Technology

Application 9002
Screening of Immobilized Enzymes – Fast and Convenient Reaction Optimization

The stable reaction environment in the EasyMax™ 102 Advanced synthesis workstation and the high flow rates through the SpinChem® RBR allowed for quick and convenient screening of different immobilized lipases to find the enzyme most suitable for further reaction optimization.   Keywords: Biotransformation, Immobilized enzymes, Mettler-Toledo, Organic molecules, Rapid screening

Application 1027
Screening of immobilized lipases using magnetic rotating bed reactors

Six different immobilized lipases were screened in parallel for the esterification of lauric acid into propyl laurate using the pre-packed SpinChem® MagRBR Lipase screening kit. The process proved fast and simple, as efficient sampling and monitoring of the process was achieved without filtration steps, by keeping the immobilized catalyst confined inside the MagRBR.   Keywords: Biotransformation, Easy handling, Immobilized enzymes, Organic molecules, Rapid screening

Application 1022
Transfer hydrogenation with catalyst recycling in a rotating bed reactor

Convenient transfer hydrogenation catalysed by palladium-containing beads was performed using a SpinChem® rotating bed reactor (RBR). The set-up resulted in high product conversions throughout more than 10 consecutive batches without any need for filtration to recycle the catalyst.  Keywords: Easy handling, Organic molecules, Palladium on carbon, Quick recycling, Synthesis

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