Segmented Flow Systems Research Articles

Accelerating Biphasic Biocatalysis through New Process Windows.

Process intensification through continuous flow reactions has increased the production rates of fine chemicals and pharmaceuticals. Catalytic reactions are accelerated through an unconventional and unprecedented use of a high‐performance liquid/liquid counter current chromatography system. Product generation is significantly faster than in traditional batch reactors or in segmented flow systems, which is exemplified through stereoselective phase‐transfer catalyzed reactions. This methodology also enables the intensification of biocatalysis as demonstrated in high yield esterifications and in the sesquiterpene cyclase‐catalyzed synthesis of sesquiterpenes from farnesyl diphosphate as high‐value natural products with applications in medicine, agriculture and the fragrance industry. Product release in sesquiterpene synthases is rate limiting due to the hydrophobic nature of sesquiterpenes, but a biphasic system exposed to centrifugal forces allows for highly efficient reactions.

Scale-up potential of photochemical microfluidic synthesis by selective dimension enlarging with agitation of microbubbles

Selective dimension enlarging integrated with numbering-up is of great importance for microfluidics. However, its feasibility for photochemical processes remains unclear due to the strict requirements of uniform irradiation. Herein, a novel method for selective dimension enlarging in photochemical production was developed by introducing microbubbles. A membrane dispersion microreactor was employed to generate microbubbles for efficient mixing and uniform absorption of photons. With an increased channel size from 0.6 mm to 4 mm, it allowed a 41-fold increase in productivity while maintaining the microscale effect. The yield of was increased by 44–70 % with 83–86% less side products, compared with those of the homogeneous and segmented flow systems. In addition, a theoretical method combining CFD simulation was developed to predict the change of mixing time with device scales, which could be used to assess the practicality by selective dimension enlarging for different photochemical microfluidic processes.

ChemInform Abstract: Continuous‐Flow Synthesis of Functionalized Phenols by Aerobic Oxidation of Grignard Reagents.

Phenols are important compounds in chemical industry. An economical and green approach to phenol preparation by the direct oxidation of aryl Grignard reagents using compressed air in continuous gas-liquid segmented flow systems is described. The process tolerates a broad range of functional groups, including oxidation-sensitive functionalities such as alkenes, amines, and thioethers. By integrating a benzyne-mediated in-line generation of arylmagnesium intermediates with the aerobic oxidation, a facile three-step, one-flow process, capable of preparing 2-functionalized phenols in a modular fashion, is established.

Continuous‐Flow Synthesis of Functionalized Phenols by Aerobic Oxidation of Grignard Reagents

AbstractPhenols are important compounds in chemical industry. An economical and green approach to phenol preparation by the direct oxidation of aryl Grignard reagents using compressed air in continuous gas‐liquid segmented flow systems is described. The process tolerates a broad range of functional groups, including oxidation‐sensitive functionalities such as alkenes, amines, and thioethers. By integrating a benzyne‐mediated in‐line generation of arylmagnesium intermediates with the aerobic oxidation, a facile three‐step, one‐flow process, capable of preparing 2‐functionalized phenols in a modular fashion, is established.

Continuous‐Flow Synthesis of Functionalized Phenols by Aerobic Oxidation of Grignard Reagents

Phenols are important compounds in chemical industry. An economical and green approach to phenol preparation by the direct oxidation of aryl Grignard reagents using compressed air in continuous gas-liquid segmented flow systems is described. The process tolerates a broad range of functional groups, including oxidation-sensitive functionalities such as alkenes, amines, and thioethers. By integrating a benzyne-mediated in-line generation of arylmagnesium intermediates with the aerobic oxidation, a facile three-step, one-flow process, capable of preparing 2-functionalized phenols in a modular fashion, is established.

FT-IR Spectroscopic Imaging of Reactions in Multiphase Flow in Microfluidic Channels

Rapid, in situ, and label-free chemical analysis in microfluidic devices is highly desirable. FT-IR spectroscopic imaging has previously been shown to be a powerful tool to visualize the distribution of different chemicals in flows in a microfluidic device at near video rate imaging speed without tracers or dyes. This paper demonstrates the possibility of using this imaging technology to capture the chemical information of all reactants and products at different points in time and space in a two-phase system. Differences in the rates of chemical reactions in laminar flow and segmented flow systems are also compared. Neutralization of benzoic acid in decanol with disodium phosphate in water has been used as the model reaction. Quantitative information, such as concentration profiles of reactant and products, can be extracted from the imaging data. The same feed flow rate was used in both the laminar flow and segmented flow systems. The laminar flow pattern was achieved using a plain wide T-junction, whereas the segmented flow was achieved by introducing a narrowed section and a nozzle at the T-junction. The results show that the reaction rate is limited by diffusion and is much slower with the laminar flow pattern, whereas the reaction is completed more quickly in the segmented flow due to better mixing.

Miniaturizing Biocatalysis: Enzyme‐Catalyzed Reactions in an Aqueous/Organic Segmented Flow Capillary Microreactor

AbstractA segmented flow capillary microreactor was used to perform the enzyme‐catalyzed conversion of 1‐heptaldehyde to 1‐heptanol in a two liquid‐liquid phase system. These reactor formats are established for chemical reactions but so far data describing the relevant system parameters for enzymatic catalysis are lacking. This work now addresses the impact of important parameters such as capillary diameter, flow velocity, phase ratio, and enzyme as well as substrate concentration on the performance of the enzymatic reaction under segmented flow conditions. All key parameters governing reaction performance have been correlated in a novel operational window for an easy assessment of the various system constraints. Such systems are characterized by high productivities and easy phase separation facilitating downstream processing. This work underscores the importance of segmented flow systems as a promising tool to perform multiphasic enzymatic catalysis. Abbreviations/Nomenclature: Da: Damköhler number; kcat: turnover number (s−1); eo: enzyme concentration (mM); φ: phase ratio; kL: mass transfer coefficient (m s−1); a: interfacial area per volume (m−1); CAe: equilibrium substrate concentration in the aqueous phase (mM); CAL: substrate concentration in the bulk aqueous phase (mM); rA: rate of reaction in the aqueous phase; mA: substrate mass transfer into the aqueous phase; STY: space time yield.

Microfluidic Chemical Analysis Systems

The field of microfluidics has exploded in the past decade, particularly in the area of chemical and biochemical analysis systems. Borrowing technology from the solid-state electronics industry and the production of microprocessor chips, researchers working with glass, silicon, and polymer substrates have fabricated macroscale laboratory components in miniaturized formats. These devices pump nanoliter volumes of liquid through micrometer-scale channels and perform complex chemical reactions and separations. The detection of reaction products is typically done fluorescently with off-chip optical components, and the analysis time from start to finish can be significantly shorter than that of conventional techniques. In this review we describe these microfluidic analysis systems, from the original continuous flow systems relying on electroosmotic pumping for liquid motion to the large diversity of microarray chips currently in use to the newer droplet-based devices and segmented flow systems. Although not currently widespread, microfluidic systems have the potential to become ubiquitous.

Generation of Chemical Movies: FT-IR Spectroscopic Imaging of Segmented Flows

We have previously demonstrated that FT-IR spectroscopic imaging can be used as a powerful, label-free detection method for studying laminar flows. However, to date, the speed of image acquisition has been too slow for the efficient detection of moving droplets within segmented flow systems. In this paper, we demonstrate the extraction of fast FT-IR images with acquisition times of 50 ms. This approach allows efficient interrogation of segmented flow systems where aqueous droplets move at a speed of 2.5 mm/s. Consecutive FT-IR images separated by 120 ms intervals allow the generation of chemical movies at eight frames per second. The technique has been applied to the study of microfluidic systems containing moving droplets of water in oil and droplets of protein solution in oil. The presented work demonstrates the feasibility of the use of FT-IR imaging to study dynamic systems with subsecond temporal resolution.

Analysis of Samples Stored as Individual Plugs in a Capillary by Electrospray Ionization Mass Spectrometry

Droplets or plugs within multiphase microfluidic systems have rapidly gained interest as a way to manipulate samples and chemical reactions on the femtoliter to microliter scale. Chemical analysis of the plugs remains a challenge. We have discovered that nanoliter plugs of sample separated by air or oil can be analyzed by electrospray ionization mass spectrometry when pumped directly into a fused silica nanospray emitter tip. Using leucine-enkephalin in methanol and 1% acetic acid in water (50:50 v:v) as a model sample, we found carry-over between plugs was <0.1% and relative standard deviation of signal for a series of plugs was 3%. Detection limits were 1 nM. Sample analysis rates of 0.8 Hz were achieved by pumping 13 nL samples separated by 3 mm long air gaps in a 75 microm inner diameter tube. Analysis rates were limited by the scan time of the ion trap mass spectrometer. The system provides a robust, rapid, and information-rich method for chemical analysis of sample in segmented flow systems.

Sampling and Electrophoretic Analysis of Segmented Flow Streams Using Virtual Walls in a Microfluidic Device

A method for sampling and electrophoretic analysis of aqueous plugs segmented in a stream of immiscible oil is described. In the method, an aqueous buffer and oil stream flow parallel to each other to form a stable virtual wall in a microfabricated K-shaped fluidic element. As aqueous sample plugs in the oil stream make contact with the virtual wall, coalescence occurs and sample is electrokinetically transferred to the aqueous stream. Using this virtual wall, two methods of injection for channel electrophoresis were developed. In the first, discrete sample zones flow past the inlet of an electrophoresis channel and a portion is injected by electroosmotic flow, termed the "discrete injector". With this approach at least 800 plugs could be injected without interruption from a continuous segmented stream with 5.1% RSD in peak area. This method generated up to 1,050 theoretical plates, although analysis of the injector suggested that improvements may be possible. In a second method, aqueous plugs are sampled in a way that allows them to form a continuous stream that is directed to a microfluidic cross-style injector, termed the "desegmenting injector". This method does not analyze each individual plug but instead allows periodic sampling of a high-frequency stream of plugs. Using this system at least 1000 injections could be performed sequentially with 5.8% RSD in peak area and 53,500 theoretical plates. This method was demonstrated to be useful for monitoring concentration changes from a sampling device with 10 s temporal resolution. Aqueous plugs in segmented flows have been applied to many different chemical manipulations including synthesis, assays, sampling processing and sampling. Nearly all such studies have used optical methods to analyze plug contents. This method offers a new way to analyze such samples and should enable new applications of segmented flow systems.

Fully automatic flow injection system for the determination of uranium at trace levels in ore leachates

An automatic flow injection system is described for the determination of uranium in ore leachates. Following injection from an autosampler, the leachate is extracted with a solution of tributyl phosphate in heptane, which removes uranium, and the organic phase is separated. The extract is reacted with an ethanolic solution of 2-(5-bromo-2-pyridylazo)-5-diethylaminophenol (BrPADAP) and benzyldimethyltetradecylammonium chloride (zephiramine) and the resulting ternary complex with U(VI) is measured spectrophotometrically at 579 nm. The lower limit of determination is 0.1 p.p.m. of uranium and up to 50 samples per hour can be analysed. In terms of speed and sensitivity this improves significantly on published procedures using segmented flow systems. The technique is ideal for process control and can be applied to the analysis of ores following mineralisation.

Evaluation and comparison of reaction detectors

Post-column reaction detectors are becoming increasingly popular as specific, dedicated detection systems in column liquid chromatographs. Three types of reactor are currently used: open-tubular reactors, packed-bed reactors and segmented-flow systems. The performance of these reactors was studied theoretically and investigated experimentally. A comparison was made of the performance of the various reactor types for a standard reaction. It is demonstrated that for short reaction times ( ca. 1 min) the dispersion in each type of reactor can be reduced by an optimum design to a level that is compatible with the requirements set by modern liquid chromatographics. It is demonstrated that packed-bed reactors are preferable to open-tubular reactors with regard to dispersion and pressure drop. For gas segmented-flow reactors, optimum performance can be obtained only when conventional debubblers are omitted.