Microflow System Research Articles

Assessment of ionic liquids' toxicity through the inhibition of acylase I activity on a microflow system

Acylase I (ACY I) plays a role in the detoxication and bioactivation of xenobiotics as well in other physiological functions. In this context, an automated ACY I assay for the evaluation of ionic liquids' (ILs) toxicity was developed. The assay was implemented in a sequential injection analysis (SIA) system and was applied to eight commercially available ILs. The SIA methodology was based on the deacetylation of N-acetyl-l-methionine with production of l-methionine, which was determined using fluorescamine. ACY I inhibition in the presence of ILs was monitored by the decrease of fluorescence intensity. The obtained results confirmed the influence of ILs' structural elements on its toxicity and revealed that pyridinium and phosphonium cations, longer alkyl side chains and tetrafluoroborate anion displayed higher toxic effect on enzyme activity.The developed methodology proved to be robust and exhibited good repeatability (RSD < 1.3%, n = 10), leading also to a reduction of reagents consumption and effluents production. Thus, it is expected that the proposed assay can be used as a novel tool for ILs' toxicity screening.

The continuous kilogram-scale process for the synthesis of 2,4,5-trifluorobromobenzene via Gattermann reaction using microreactors

2,4,5-Trifluorobromobenzene is a valuable synthetic intermediate with important applications in pharmaceutical industry. We report a continuous microflow process for the synthesis of 2,4,5-trifluorobromobenzene via Gattermann reaction in this paper. The microflow system is easily assembled by a simple T-micromixer, microchannel reactors and several pumps. The use of this system facilitated the diazotization reaction of 2,4,5-trifluoroaniline with HBr and NaNO2 to produce the thermally unstable 2,4,5-trifluorophenyl diazonium salts in seconds, which then react with HBr at the catalysis of copper powder to obtain 2,4,5-trifluorobromobenzene. The aqueous HBr containing copper powder was added and stirred for 30min at 70°C in the stirred vessel. And then, the CuBr in situ was given and performed a quench-type reaction as catalyst. The influence of the reaction parameters on the diazotization reaction steps was examined and discussed in microreactors. The microflow system had the capacity to promote efficient mass- and heat-transfer and shorten the reaction time. On this basis, the kilogram-scale production of 2,4,5-trifluorobromobenzene was realized in a self-made scale-up microreactor by numbering-up of micromixers and microchannels.

Electroanalytical thread-device for estriol determination using screen-printed carbon electrodes modified with carbon nanotubes

Microflow systems are powerful analytical tools that explore similar principles of typical flow injection analysis driven to in a microfluidic device. Generally, microfluidic devices can promote a low consumption of reagents and samples, high speed of analysis and possibility of portability. Several advances have been reached applying a simple and low cost device based on cotton thread as microfluidic channel where the transportation of solutions is based on capillary force helped by gravity. In the present work, we have demonstrated the versatility of thread-based electroanalytical devices (μTED) constructed using a cotton thread as the solution channel and screen-printed electrodes (SPE) surface modified with carbon nanotubes (CNT) as electrochemical detectors for the amperometric determination of estriol hormone in pharmaceutical samples. The parameters involved in the amperometric detection and microflow system were studied and optimized, using the best experimental conditions (flow rate of 0.50μLs−1, 10mm of analytical path, 2.0μL of volume of injection and potential of detection of 0.75V) a linear response was observed for concentration range (LDR) of 1.0 to 1000μmolL−1 with limits of detection (LOD) and quantification (LOQ) of 0.53μmolL−1 and 1.77μmolL−1, respectively, and frequency of injection of 32 per hour. The proposed methodology was applied for determination of estriol in commercial samples and results were compared with those provided by spectrophotometric method (official methodology). The obtained results are in agreement at a 95% of confidence level.

Development of a Microflow System for In-Cell Footprinting Coupled with Mass Spectrometry.

Fast photochemical oxidation of proteins (FPOP) has become a valuable tool for protein structural characterization. The method has recently been demonstrated to oxidatively modify solvent-accessible sites of proteins inside live cells (IC-FPOP). However, the flow system used for in vitro analysis is not well-suited for IC-FPOP as a number of factors can lead to cell aggregation, causing inconsistent labeling and clogging. Here, we present an IC-FPOP flow system that centrally focuses the cells, ensuring consistent radiation exposure. Fluorescence imaging was used to analyze the effectiveness of the system in focusing the cells. Analysis shows the cells flowing individually through the center of the capillary with the buffer visible along the walls and with no aggregation or clogging observed. To ensure the flow system does not disturb oxidative modification, Vero cells were labeled using the flow system and analyzed by liquid chromatography-mass spectrometry (LC-MS). The results demonstrate a 13-fold increase in the number of oxidized proteins and a 2 orders of magnitude increase in the dynamic range of the method.

An efficient etherification of Ginkgol biloba extracts with fewer side effects in a micro-flow system

In this study, etherification of ginkgolide B and dimethylaminoethyl chloride hydrochloride was investigated as a model reaction in a micro-flow system (MFS), providing the resulting ethers in high yield with fewer side effects. Meanwhile, this novel process in MFS worked well for other ginkgolides from Ginkgol biloba and halides, giving moderate yields.

Shear stress activates monovalent cation channel transient receptor potential melastatin subfamily 4 in rat atrial myocytes via type 2 inositol 1,4,5-trisphosphate receptors and Ca(2+) release.

During each contraction and haemodynamic disturbance, cardiac myocytes are subjected to fluid shear stress as a result of blood flow and the relative movement of sheets of myocytes. The present study aimed to characterize the shear stress-sensitive membrane current in atrial myocytes using the whole-cell patch clamp technique, combined with pressurized fluid flow, as well as pharmacological and genetic interventions of specific proteins. The data obtained suggest that shear stress indirectly activates the monovalent cation current carried by transient receptor potential melastatin subfamily 4 channels via type 2 inositol 1,4,5-trisphosphate receptor-mediated Ca(2+) release in subsarcolemmal domains of atrial myocytes. Ca(2+) -mediated interactions between these two proteins under shear stress may be an important mechanism by which atrial cells measure mechanical stress and translate it to alter their excitability. Atrial myocytes are subjected to shear stress during the cardiac cycle under physiological or pathological conditions. The ionic currents regulated by shear stress remain poorly understood. We report the characteristics, molecular identity and activation mechanism of the shear stress-sensitive current (Ishear ) in rat atrial myocytes. A shear stress of ∼16dyn cm(-2) was applied to single myocytes using a pressurized microflow system, and the current was measured by whole-cell patch clamp. In symmetrical CsCl solutions with minimal concentrations of internal EGTA, Ishear showed an outwardly rectifying current-voltage relationship (reversal at -2mV). The current was conducted primarily (∼80%) by monovalent cations but not Ca(2+) . It was suppressed by intracellular Ca(2+) buffering at a fixed physiological level, inhibitors of transient receptor potential melastatin subfamily 4 (TRPM4), intracellular introduction of TRPM4 antibodies or knockdown of TRPM4 expression, suggesting that TRPM4 carries most of this current. A notable reduction in Ishear occurred upon inhibition of Ca(2+) release through the ryanodine receptors or inositol 1,4,5-trisphosphate receptors (IP3 R) and upon depletion of sarcoplasmic reticulum Ca(2+) . In type 2 IP3 R (IP3 R2) knockout atrial myocytes, Ishear was 10-20% of that in wild-type myocytes. Immunocytochemistry and proximity ligation assays revealed that TRPM4 and IP3 R2 were expressed at peripheral sites with co-localization, although they are not localized within 40nm. Peripheral localization of TRPM4 was intact in IP3 R2 knockout cells. The data obtained in the present study suggest that shear stress activates TRPM4 current by triggering Ca(2+) release from the IP3 R2 in the peripheral domains of atrial myocytes.

Continuous synthesis of ginkgolide B derivatives in a micro-flow system

In this study, etherification process of ginkgolide B in a micro-flow system was investigated. With calcium carbonate as an acid-binding agent, the optimal result was obtained in such conditions: residence time 3min, temperature 85°C, molar ratio of ginkgolide B to dimethylamino ethyl chloride hydrochloride 1:2, molar ratio of ginkgolide B to potassium iodide 1:0.2, and molar ratio of ginkgolide B to calcium carbonate 1:2.5. Meanwhile, this novel process in MFS could proceed well for the etherification reaction between ginkgolide B and other halides, to afford the target products in moderate yields. Besides, salification reaction was conducted in a valve assisted micromixer by reacting dimethylaminoethyl ginkgolide B with methane sulfonic acid. Compared with conventional drugs, enhanced bioavailability was obtained when nano-scale drugs were dosed.

Flow synthesis of medium molecular weight polyisobutylene coinitiated by AlCl3

In this work, we established a microflow reaction system, and systematically investigates the flow synthesis of medium molecular weight polyisobutylene (MPIB, 10,000–100,000gmol−1) coinitiated by neat AlCl3 in the mixture of hexane and CH2Cl2. It includes (1) revealing the effects of mixing conditions and the evolution of polymer products, (2) proposing chain transfer dominated polymerization mechanism with considerations on the possibilities or rates of various chain reactions, (3) exploring the effects of diluent from the viewpoint of active species transformation to guide for the selection of diluent, (4) evaluating the effects of temperature to find a window capable of producing MPIBs with adjustable molecular weight, and (5) testing the polymerization process in high monomer concentration to enhance the productivity. Exploiting the perfect performances of a microflow system in mixing and residence time control, the adjustable molecular weight in the range from 20,000 to 100,000gmol−1 was afforded at relative high temperatures (−30°C to −10°C). The reaction time for quantitative conversion could be decreased to 6s. It potentially leads to a breakthrough for high efficiency MPIBs production.

Fast flow synthesis of highly reactive polyisobutylene co-initiated by an AlCl3/isopropyl ether complex

In this work, with AlCl3 addition in the range from 4 to 10 mmol L−1 and enough isopropyl ether (iPr2O) addition, we successfully synthesized highly reactive polyisobutylene (HRPIB) using a microflow system within 12 s or less.

ChemInform Abstract: Supramolecular Chemistry in Microflow Fields: Toward a New Material World of Precise Kinetic Control

AbstractReview: [22 refs.

Shear stress induces a longitudinal Ca(2+) wave via autocrine activation of P2Y1 purinergic signalling in rat atrial myocytes.

Atrial myocytes are exposed to shear stress during the cardiac cycle and haemodynamic disturbance. In response, they generate a longitudinally propagating global Ca(2+) wave. Here, we investigated the cellular mechanisms underlying the shear stress-mediated Ca(2+) wave, using two-dimensional confocal Ca(2+) imaging combined with a pressurized microflow system in single rat atrial myocytes. Shear stress of ∼16 dyn cm(-2) for 8 s induced ∼1.2 aperiodic longitudinal Ca(2+) waves (∼79 μm s(-1)) with a delay of 0.2-3 s. Pharmacological blockade of ryanodine receptors (RyRs) or inositol 1,4,5-trisphosphate receptors (IP3 Rs) abolished shear stress-induced Ca(2+) wave generation. Furthermore, in atrial myocytes from type 2 IP3R (IP3R2) knock-out mice, shear stress failed to induce longitudinal Ca(2+) waves. The phospholipase C (PLC) inhibitor U73122, but not its inactive analogue U73343, abolished the shear-induced longitudinal Ca(2+) wave. However, pretreating atrial cells with blockers for stretch-activated channels, Na(+)-Ca(2+) exchanger, transient receptor potential melastatin subfamily 4, or nicotinamide adenine dinucleotide phosphate oxidase did not suppress wave generation under shear stress. The P2 purinoceptor inhibitor suramin, and the potent P2Y1 receptor antagonist MRS 2179, both suppressed the Ca(2+) wave, whereas the P2X receptor antagonist, iso-PPADS, did not alter it. Suppression of gap junction hemichannels permeable to ATP or extracellular application of ATP-metabolizing apyrase inhibited the wave. Removal of external Ca(2+) to enhance hemichannel opening facilitated the wave generation. Our data suggest that longitudinally propagating, regenerative Ca(2+) release through RyRs is triggered by P2Y1-PLC-IP3R2 signalling that is activated by gap junction hemichannel-mediated ATP release in atrial myocytes under shear stress.

Single-Step Synthesis of Onion-Like Au-Pd-PtNPs Nanoparticles Using Microflow System

This paper describes the method of onion-like nanoparticles synthesis in a microflow. As the core of a material, platinum nanoparticles were used. The first shell consists of metallic palladium, and the second one is metallic gold, respectively. The synthesis of onion-like nanostructure was performed using microflow reactors system, which consists of 3 independent elements. As the reducing agent of precious metals ions, vitamin C was used. To prevent NPs from the aggregation, a polyvinyl alcohol as the stabilizing agent was applied.

Supramolecular Chemistry in Microflow Fields: Toward a New Material World of Precise Kinetic Control.

Constructing new and versatile self-assembling systems in supramolecular chemistry is much like the development of new reactions or new catalysts in synthetic organic chemistry. As one such new technology, conventional supramolecular assembly systems have been combined with microflow techniques to control intermolecular or interpolymer interactions through precise regulation of a flowing self-assembly field. The potential of the microflow system has been explored by using various simple model compounds. Uniform solvent diffusion in the microflow leads to rapid activation of molecules in a nonequilibrium state and, thereby, enhanced interactions. All of these self-assembly processes begin from a temporally activated state and proceed in a uniform chemical environment, forming a synchronized cluster and resulting in effective conversion to supramolecules, with precise tuning of molecular (or polymer) interactions. This approach allows the synthesis of a variety of discrete microstructures (e.g., fibers, sheets) and unique supramolecules (e.g., hierarchical assemblies, capped fibers, polymer networks, supramolecules with time-delayed action) that have previously been inaccessible.

Finite Element Analysis on Vibration of a Piezoelectric Micro Pump

Due to the rise of biological and MEMS technology in recent years, some micro flow system components have been paid attentions to developed by many investigators. The importance of micro-pumps manufactured is higher than the other part of micro flow system since it is the power source of the entire micro-flow system and responsible for driving working fluid in the microfluidic system. In actual operation, the instability and bad dynamic characteristics of the micro-pump will cause larger fluid flow mobility error, such as transport behavior and response procedures failure, etc., and even damage the microfluidic system. Therefore, to investigate the stability and dynamic characteristics of a micro pump is necessary. The miniature piezoelectric film micro-pump, made by Microjet Technology Co., Ltd., is employed to study in this work. The computer graphics software SolidWorks is used to build the model of the micro pump. Then, The Finite element analysis (FEA), ANSYS Workbench, is also employed to analyze the dynamic characteristics of this micro pump.

Two-stage continuous flow synthesis of epoxidized fatty acid methyl esters in a micro-flow system

A new protocol combining transesterification reaction with epoxidation process was reported. Besides, a novel continuous extraction device was employed in the integrated process to realize the automatic continuous flow synthesis of epoxidized fatty acid methyl esters (FAMEs). Furthermore, a capillary column containing desiccants was used in the post-processing, leading to dry product.

Synthesis of Soy-Polyols Using a Continuous Microflow System and Preparation of Soy-based Polyurethane Rigid Foams

A soy-polyol labeled Polyol-m was synthesized directly from soybean oil in a continuous microflow system equipped with self-designed oil–water separators and using a reported scheme for epoxidation under following the optimized conditions for hydroxylation: sulfuric acid concentration of 10 wt %, residence time of 13 min, and temperature of 75 °C. Another soy-polyol labeled Polyol-f was also synthesized in a conventional flask from commercially available epoxidized soybean oil as a raw material for the purpose of comparison. Polyol-f had a wider molecular weight distribution, higher viscosity, and lower hydroxyl number than Polyol-m because of the more substantial oligomers introduced by oligomerization, which was confirmed by Fourier transform infrared (FTIR) and gel permeation chromatography (GPC). In addition, the corresponding soy-based polyurethane rigid foams labeled PU-m and PU-f were prepared. PU-m had fine, uniform, and closed-cell morphology, and it contained higher cross-linking due to such characteristics as lower viscosity and higher hydroxyl number; these characteristics were beneficial for the foam properties, including compression strength, thermal insulation, dimensional stability, and thermostability.

Establishment of a finite element model for extracting chemical reaction kinetics in a micro-flow injection system with high throughput sampling

Numerical simulation can provide valuable insights for complex microfluidic phenomena coupling mixing and diffusion processes. Herein, a novel finite element model (FEM) has been established to extract chemical reaction kinetics in a microfluidic flow injection analysis (micro-FIA) system using high throughput sample introduction. To reduce the computation burden, the finite element mesh generation is performed with different scales based on the different geometric sizes of micro-FIA. In order to study the contribution of chemical reaction kinetics under non-equilibrium condition, a pseudo-first-order chemical kinetics equation is adopted in the numerical simulations. The effect of reactants diffusion on reaction products is evaluated, and the results demonstrate that the Taylor dispersion plays a determining role in the micro-FIA system. In addition, the effects of flow velocity and injection volume on the reaction product are also simulated. The simulated results agree well with the ones from experiments. Although gravity driven flow is used to the numerical model in the present study, the FEM model also can be applied into the systems with other driving forces such as pressure. Therefore, the established FEM model will facilitate the understanding of reaction mechanism in micro-FIA systems and help us to optimize the manifold of micro-FIA systems.

Two-Stage Flow Synthesis of Coumarin via O-Acetylation of Salicylaldehyde

Continuous-flow synthesis of coumarin was realized in a tandem microflow system containing two microreactors in this study. Generally, better reaction yield (91%) and less side reaction were obtained in the flow system compared with conventional method. Interestingly, different reaction pathways were observed between continuous-flow system and batch methods.

Using Finite Element Analysis and Experimental Analysis on Vibration of a Piezoelectric Micro Pump

Due to the rise of biological and MEMS technology in recent years, some micro flow system components have drawn attention and been developed by many investigators. The importance of micro-pumps manufactured is higher than the other part of micro flow system since it is the power source of the entire micro-flow system and responsible for driving working fluid in the microfluidic system. In actual operation, the instability and bad dynamic characteristics of the micro-pump will cause larger fluid flow mobility error, such as transport behavior and response procedures failure, etc., and even damage the microfluidic system. Therefore, to investigate the stability and dynamic characteristics of a micro pump is necessary. The Finite element analysis (FEA), ANSYS Workbench, is employed to analyze the dynamic characteristics of this micro pump, and experiment is also considered in this study.

A Facile Preparation of α-Aryl Carboxylic Acid via One-Flow Arndt–Eistert Synthesis

An efficient, one-flow Arndt–Eistert synthesis was demonstrated. A sequence of acid chloride formation–nucleophilic acyl substitution–Wolff rearrangement–nucleophilic addition was performed in a microflow system without isolating any intermediates, which included a potentially explosive compound. The microflow system was made from simple, inexpensive, and readily available instruments and tubes. α-Aryl esters 2a and 2b were prepared in yields of 33 and 23 % (three steps) respectively.