Design of a Continuous Tubular Cooling Crystallizer for Process Development on Lab‐Scale

Hohmann, Lukas; Gorny, Ramona; Klaas, Oliver; Ahlert, Jonas; Wohlgemuth, Kerstin; Kockmann, Norbert

doi:10.1002/ceat.201600072

Cited by 55 publications

(73 citation statements)

References 51 publications

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“…Microstructured CFI (MCFI) setups have been reported, combining the advantages of a narrow RTD with intensified heat and mass transfer characteristics [76, 83,88,89]. A cooling crystallization application of the CFI concept was recently reported by our group [75]. The concept will be introduced in the following.…”

Section: Coiled Flow Inverter For Crystallizationmentioning

confidence: 99%

“…A prototype was constructed from polymeric tube material (both polyvinyl chloride [PVC] and fluorinated ethylene propylene [FEP]), with an inner tube diameter of d i = 4 mm and a tube length of l = 6.5 m [75,83] (see Figure 8).…”

Section: Coiled Flow Inverter For Crystallizationmentioning

confidence: 99%

“…Bodenstein numbers of Bo = 110-170 were measured for various mass flow rates in the range of 1 to 10 g/min [75]. To adjust desirable temperature profiles, the CFI was equipped with a jacket pipe and baffles for countercurrent cooling with a gaseous cooling agent.…”

Section: Coiled Flow Inverter For Crystallizationmentioning

confidence: 99%

“…Unseeded cooling crystallization processes proved poor suitability for continuous operation, as the transfer of measured primary nucleation kinetics from batch to continuous process can lead to unstable operation [75]. The metastable zone width (MSZW), Liquid-liquid slug flow…”

Section: Coiled Flow Inverter For Crystallizationmentioning

confidence: 99%

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Separation Units and Equipment for Lab-Scale Process Development

Hohmann¹,

Kurt²,

Soboll³

et al. 2016

J Flow Chem

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For complete chemical processes, downstream operation steps are essential, but on a miniaturized scale, they are not so far developed as the microreactors. This contribution presents three different unit operations for phase and component separation. Liquid-liquid extraction is often performed in columns, which were miniaturized for higher separation efficiency and flow rates suitable for processes in flow chemistry. Two-phase mass transfer processes in capillaries benefit from rapid final phase separation, which can be performed in an in-line phase splitter based on different surface wetting behavior. Crystallization is often a final purification step, which is performed in a continuously operated helical tube setup with narrow residence time distribution. For all unit operations, design criteria are shown with typical applications. The methodology of downscaling of known equipment and employing typical microscale phenomena such as good flow control, laminar flow, or dominant surface forces leads to successful equipment design.

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Section: Coiled Flow Inverter For Crystallizationmentioning

confidence: 99%

Section: Coiled Flow Inverter For Crystallizationmentioning

confidence: 99%

Section: Coiled Flow Inverter For Crystallizationmentioning

confidence: 99%

Section: Coiled Flow Inverter For Crystallizationmentioning

confidence: 99%

See 2 more Smart Citations

Separation Units and Equipment for Lab-Scale Process Development

Hohmann¹,

Kurt²,

Soboll³

et al. 2016

J Flow Chem

Self Cite

View full text Add to dashboard Cite

show abstract

“…Continuous crystallization has the advantage of reduced breakage caused by stirring and avoids batch-to-batch variability, although tubular crystallizers may be affected by blocking. Typical continuous tubular setups include straight tubes as presented by Borchert and Sundmacher for crystal aggregation [1], helically coiled flow tubes (HCTs) as studied with respect to flow profiles by Vashisth and Nigam [2], and coiled flow inverters (CFIs) as applied for crystallization by Hohmann et al [3]. The mixing properties of the previously mentioned tubular crystallizers increase from straight tubes to CFIs as shown by Klutz et al [4].…”

Section: Introductionmentioning

confidence: 99%

Crystal Population Growth in a Continuous Helically Coiled Flow Tube Crystallizer

2017

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A helically coiled flow tube crystallizer was investigated as a novel device for the shape-selective generation of crystals with potassium alum as the model solid. The shape evolution of the crystal population was analyzed for growth-dominated seeded cooling crystallization. The macro-mixing behavior was characterized by residence time distribution measurements for the fluid phase and the crystals. At the crystallizer outlet, a flow-through microscope was used to analyze the crystal size and shape distribution, where the 3D shape of individual crystals was estimated from 2D projections. The experiments showed a separation of the particle population according to the crystal size. This process allows the controlled shaping of crystals under continuous operating conditions.

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Simulation of continuous low pH viral inactivation inside a coiled flow inverter

David

Bayer

Lobedann

et al. 2020

Biotech & Bioengineering

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Continuous production of monoclonal antibodies is gaining more and more importance. To ensure continuous flow through the entire process as well as viral safety, continuous viral clearance needs to be investigated as well. This study focuses on low pH viral inactivation inside a coiled flow inverter (CFI). Computational fluid dynamics (CFD) simulation is used to gain further insight into the inactivation process inside the apparatus. The influence of viruses in comparison to different tracer elements on the residence time distribution (RTD) behavior is investigated. Finally, the viral inactivation kinetics are implemented into the CFD simulation and real process conditions are simulated. These are compared to experimental results. To the authors' knowledge, this study represents the first successful simulation of continuous viral inactivation inside a CFI. It allows the detailed analysis of processes inside the apparatus and the prediction of experimental virus study results and will therefore contribute to the effective planning of future validation studies.

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Design of a Continuous Tubular Cooling Crystallizer for Process Development on Lab‐Scale

Cited by 55 publications

References 51 publications

Separation Units and Equipment for Lab-Scale Process Development

Separation Units and Equipment for Lab-Scale Process Development

Crystal Population Growth in a Continuous Helically Coiled Flow Tube Crystallizer

Simulation of continuous low pH viral inactivation inside a coiled flow inverter

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