Modular microfluidic reactor and inline filtration system for the biocatalytic synthesis of chiral metabolites

O’Sullivan, Brian; Al-Bahrani, H; Lawrence, James; Campos, María Elena; Cázares, Armando; Baganz, Frank; Wohlgemuth, Roland; Hailes, Helen C.; Szita, Nicolas

doi:10.1016/j.molcatb.2011.12.010

Cited by 40 publications

(37 citation statements)

References 44 publications

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“…This simple colored food dye perfusion experiment demonstrated that the perfusion functionality of the cellular acetate membrane was retained after 3D printing; demonstrating the feasibility of using the FDM-based 3D printing and embedding method to fabricate porous membrane-based microfluidic devices. The first 3D printed perfusion fluidic device is applicable to continuous microcarrier-based cell culture or biocatalytic synthesis applications similar to the one described by Abeille et al 29 and O'Sullivan et al, 30 respectively, but without the need for any postdevice assembly and finishing.…”

Section: Resultsmentioning

confidence: 99%

Embedding objects during 3D printing to add new functionalities

Yuen

2016

Biomicrofluidics

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A novel method for integrating and embedding objects to add new functionalities during 3D printing based on fused deposition modeling (FDM) (also known as fused filament fabrication or molten polymer deposition) is presented. Unlike typical 3D printing, FDM-based 3D printing could allow objects to be integrated and embedded during 3D printing and the FDM-based 3D printed devices do not typically require any post-processing and finishing. Thus, various fluidic devices with integrated glass cover slips or polystyrene films with and without an embedded porous membrane, and optical devices with embedded Corning V R Fibrance TM Light-Diffusing Fiber were 3D printed to demonstrate the versatility of the FDMbased 3D printing and embedding method. Fluid perfusion flow experiments with a blue colored food dye solution were used to visually confirm fluid flow and/or fluid perfusion through the embedded porous membrane in the 3D printed fluidic devices. Similar to typical 3D printed devices, FDM-based 3D printed devices are translucent at best unless post-polishing is performed and optical transparency is highly desirable in any fluidic devices; integrated glass cover slips or polystyrene films would provide a perfect optical transparent window for observation and visualization. In addition, they also provide a compatible flat smooth surface for biological or biomolecular applications. The 3D printed fluidic devices with an embedded porous membrane are applicable to biological or chemical applications such as continuous perfusion cell culture or biocatalytic synthesis but without the need for any post-device assembly and finishing. The 3D printed devices with embedded Corning V R Fibrance TM Light-Diffusing Fiber would have applications in display, illumination, or optical applications. Furthermore, the FDMbased 3D printing and embedding method could also be utilized to print casting molds with an integrated glass bottom for polydimethylsiloxane (PDMS) device replication. These 3D printed glass bottom casting molds would result in PDMS replicas with a flat smooth bottom surface for better bonding and adhesion. Published by AIP Publishing. [http://dx

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Section: Resultsmentioning

confidence: 99%

Embedding objects during 3D printing to add new functionalities

Yuen

2016

Biomicrofluidics

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“…[33][34][35][36] These systems have been used extensively to study upstream bioprocessing steps, [37][38][39][40][41] but the number of reports of microfluidic devices developed to study process optimisation of downstream processing steps, such as purification and separation of biomolecules, is still limited. 27,[42][43][44][45][46][47][48] In downstream bioprocessing, flocculation has attracted renewed interest but suitable analytical tools to comprehensively understand the flocculation mechanism have been absent. The precise control over the microenvironment afforded by microfluidic devices opened up an opportunity to investigate, for the first time, the formation and growth of flocs independently from floc breakage and ageing phases.…”

Section: Discussionmentioning

confidence: 99%

Flocculation on a chip: a novel screening approach to determine floc growth rates and select flocculating agents

et al. 2018

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Flocculation is a key purification step in cell-based processes for the food and pharmaceutical industry where the removal of cells and cellular debris is aided by adding flocculating agents. However, finding the best suited flocculating agent and optimal conditions to achieve rapid and effective flocculation is a nontrivial task. In conventional analytical systems, turbulent mixing creates a dynamic equilibrium between floc growth and breakage, constraining the determination of floc formation rates. Furthermore, these systems typically rely on end-point measurements only. We have successfully developed for the first time a microfluidic system for the study of flocculation under well controlled conditions. In our microfluidic device (μFLOC), floc sizes and growth rates were monitored in real time using high-speed imaging and computational image analysis. The on-line and in situ detection allowed quantification of floc sizes and their growth kinetics. This eliminated the issues of sample handling, sample dispersion, and end-point measurements.We demonstrated the power of this approach by quantifying the growth rates of floc formation under forty different growth conditions by varying industrially relevant flocculating agents (pDADMAC, PEI, PEG), their concentration and dosage. Growth rates between 12.2 μm s −1 for a strongly cationic flocculant (pDADMAC) and 0.6 μm s −1 for a non-ionic flocculant (PEG) were observed, demonstrating the potential to rank flocculating conditions in a quantitative way. We have therefore created a screening tool to efficiently compare flocculating agents and rapidly find the best flocculating condition, which will significantly accelerate early bioprocess development.

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“…The recovery and reuse of enzymes has been achieved using bio-microreactors with immobilized enzymes, a topic discussed later in this paper. Nevertheless, some interesting results were also obtained for continuous flow systems, as in the case of the synthesis of a chiral compound using transketolase [82], where the separation of the enzyme from the other substances was achieved by coupling a tangential flow filtration system to a microfluidic reactor.…”

Section: Bio-microreactors With Free Enzymesmentioning

confidence: 99%

“…A lower yield with respect to a typical chemical synthesis was observed with high substrate concentrations, which was attributed to inhibition and denaturation effects induced by the presence of an excess of substrate molecules in the proximity of the enzyme [82]. To overcome this problem, an interesting strategy incorporating a multi-input microfluidic reactor, capable of substrate feeding at multiple points, was designed and successfully applied to the transketolase-catalyzed synthesis of L-erythrulose [83].…”

Section: Bio-microreactors With Free Enzymesmentioning

confidence: 99%

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Enzymatic microreactors in biocatalysis: history, features, and future perspectives

Laurenti¹,

Vianna²

2016

Biocatalysis

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Microfluidic reaction devices are a very promising technology for chemical and biochemical processes. In microreactors, the micro dimensions, coupled with a high surface area/volume ratio, permit rapid heat exchange and mass transfer, resulting in higher reaction yields and reaction rates than in conventional reactors. Moreover, the lower energy consumption and easier separation of products permit these systems to have a lower environmental impact compared to macroscale, conventional reactors. Due to these benefits, the use of microreactors is increasing in the biocatalysis field, both by using enzymes in solution and their immobilized counterparts. Following an introduction to the most common applications of microreactors in chemical processes, a broad overview will be given of the latest applications in biocatalytic processes performed in microreactors with free or immobilized enzymes. In particular, attention is given to the nature of the materials used as a support for the enzymes and the strategies employed for their immobilization. Mathematical and engineering aspects concerning fluid dynamics in microreactors were also taken into account as fundamental factors for the optimization of these systems.

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Modular microfluidic reactor and inline filtration system for the biocatalytic synthesis of chiral metabolites

Cited by 40 publications

References 44 publications

Embedding objects during 3D printing to add new functionalities

Embedding objects during 3D printing to add new functionalities

Flocculation on a chip: a novel screening approach to determine floc growth rates and select flocculating agents

Enzymatic microreactors in biocatalysis: history, features, and future perspectives

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