Microfluidic approach for rapid interfacial tension measurement

A novel microfluidic approach to measure interfacial tension of immiscible fluids rapidly is reported. This method rests upon quantitative force balance analysis of drop formation dynamics in a coaxial microfluidic device. The values of interfacial tension for several two liquids without/with surfactants are measured. These measurements compare well with those measured by the commercial interfacial tensiometry. The viscosity of water phase fluid can also be accurately measured in the same microfluidic device. Several model systems with interfacial tension from 1.0 to 10.0 mN/m and water phase viscosity from 1.0 to 10.0 mPa.s are tested in this work.     

Microfluidic Wheatstone bridge for rapid sample analysis

We developed a microfluidic analogue of the classic Wheatstone bridge circuit for automated, real-time sampling of solutions in a flow-through device format. We demonstrate precise control of flow rate and flow direction in the "bridge" microchannel using an on-chip membrane valve, which functions as an integrated "variable resistor". We implement an automated feedback control mechanism in order to dynamically adjust valve opening, thereby manipulating the pressure drop across the bridge and precisely controlling fluid flow in the bridge channel. At a critical valve opening, the flow in the bridge channel can be completely stopped by balancing the flow resistances in the Wheatstone bridge device, which facilitates rapid, on-demand fluid sampling in the bridge channel. In this article, we present the underlying mechanism for device operation and report key design parameters that determine device performance. Overall, the microfluidic Wheatstone bridge represents a new and versatile method for on-chip flow control and sample manipulation.     

Microfluidic baker's transformation device for three-dimensional rapid mixing

We developed a new passive-type micromixer based on the baker's transformation and realized a fast mixing of a protein solution, which has lower diffusion constant. The baker's transformation is an ideal mixing method, but there is no report on the microfluidic baker's transformation (MBT), since it is required to fabricate the complicated three-dimensional (3D) structure to realize the MBT device. In this note, we successfully fabricate the MBT device by using precision diamond cutting of an oxygen-free copper substrate for the mould fabrication and PDMS replication. The MBT device with 10.4 mm mixing length enables us to achieve complete mixing of a FITC solution (D = 2.6 × 10(-10) m(2) s(-1)) within 51 ms and an IgG solution (D = 4.6 × 10(-11) m(2) s(-1)) within 306 ms. Its mixing speed is 70-fold higher for a FITC solution and 900-fold higher for an IgG solution than the mixing speed by the microchannel without MBT structures. The Péclet number to attain complete mixing in the MBT device is estimated to be 6.9 × 10(4).     

Microfluidic pool structure for cell docking and rapid mixing

A microfluidic pool structure for cell docking and rapid mixing is described. The pool structure is defined as a microchamber on one structural layer of a bilayer chip and connects with two or more individual microchannels on the other structural layer. In contrast to the turbulent flow in a macroscale pool, laminar streams enter and exit this microfluidic pool structure with definite and controllable direction that may be influenced by the location and geometry of the pool. A simple microfluidic model was used to validate this hypothesis. In this model, a microscale pool structure was made on the lower layer of a chip and connected with three parallel microchannels in the upper layer. Simulation and experimental results indicated that the flow profile within the pool structure was determined by its geometry and location. This could be used as a flow control method and it was simpler than designs based on microvalve, hydraulic pressure, or electrokinetic force, and has some important applications. For example, controllable streams within this structure were used to immobilize biological cells along the microchannel walls. When different solution streams flowed through the pool, rapid diffusion of analytes occurred for short diffusion distance between vertical flow laminas. Furthermore, desired dilution (mixing) ratio could be obtained by controlling the geometry of the microfluidic pool.     

Oscillating drop/bubble tensiometry: effect of viscous forces on the measurement of interfacial tension

The oscillating drop/bubble technique is increasingly popular for measuring the interfacial dilatational properties of surfactant/polymer-laden fluid/fluid interfaces. A caveat of this technique, however, is that viscous forces are important at higher oscillation frequencies or fluid viscosities; these can affect determination of the interfacial tension. Here, we experimentally quantify the effect of viscous forces on the interfacial-tension measurement by oscillating 100 and 200 cSt poly(dimethylsiloxane) (PDMS) droplets in water at small amplitudes and frequencies ranging between 0.01 and 1 Hz. Due to viscous forces, the measured interfacial tension oscillates sinusoidally with the same frequency as the oscillation of the drop volume. The tension oscillation precedes that of the drop volume, and the amplitude varies linearly with Capillary number, Ca=DeltamuomegaDeltaV/gammaa(2), where Deltamu=mu(D)-mu is the difference between the bulk Newtonian viscosities of the drop and surrounding continuous fluid, omega is the oscillation frequency of the drop, DeltaV is the amplitude of volume oscillation, gamma is the equilibrium interfacial tension between the PDMS drop and water, and a is the radius of the capillary. A simplified model of a freely suspended spherical oscillating-drop well explains these observations. Viscous forces distort the drop shape at Ca>0.002, although this criterion is apparatus dependent.     

A comparative study of exogenous surfactant preparations and tracheal aspirate: interfacial tensiometry and properties of foam films

Surfactant replacement therapy has a vital role in the management of respiratory distress syndrome (RDS). Several techniques and models have been largely used to investigate interfacial physico-chemical properties in vitro and to assist clinical efficiency of exogenous surfactant preparations (ESPs) in vivo. Among them are interfacial tensiometry (Langmuir balance coupled with Wilhelmy plate method for surface tension measurement) and black foam film (BFF) method for measuring the capability of ESPs for bilayer foam film formation.

Here, we report some freshly established data from a comparative study of Exosurf, Survanta, Curosurf, Alveofact and clinical samples of tracheal aspirate (TA) of newborns with RDS treated with Curosurf. New observations concerning the properties of foam films of ESPs are also reported and discussed.

Measured interfacial physico-chemical parameters prove “better” properties in vitro of the SP-B and -C containing preparations Curosurf and Alveofact. Their properties are similar, Alveofact showing a higher surface tension lowering capacity under dynamic conditions.

A comparison with measured interfacial parameters of clinical samples shows that after treatment with Curosurf the phospholipid concentration in tracheal aspirates (367 μg/ml) is higher than the minimum phospholipid concentration for stable black film formation (C_t) of all four ESPs studied, while before treatment this concentration (63 μg/ml) is lower than C_t.

Values of measured “dynamic” parameters of clinical samples after treatment with Curosurf approach those of the exogenous surfactant preparation itself.     

Microfluidic approach for highly efficient synthesis of heparin-based bioconjugates for drug delivery

This paper demonstrates the highly efficient synthesis of amphiphilic heparin-folic acid-retinoic acid (HFR) bioconjugates with a high drug coupling ratio by a microfluidic approach. The microfluidic synthesis enabled the conjugation of 17 molecules of retinoic acid to each heparin chain with 21 possible groups for attachment after reacting for several minutes. In contrast, about 11 molecules of the drug were covalently conjugated to one heparin chain after 4 days in the bulk reaction. The microfluidic based-HFR bioconjugates readily self-assembled in aqueous media to form uniform nanoparticles, while the product from the bulk reaction formed non-uniform nanoparticles with broad size distribution. The HFR nanoparticles with high drug content effectively delivered the drug to folate receptor-positive cancer cells with superior cellular uptake and selective cytotoxicity in vitro compared to HFR nanoparticles synthesized in bulk reaction. With the ability to achieve high drug content in heparin carrier within a short reaction time, the microfluidic technique offers new alternatives for the efficient synthesis of polymer-based conjugates for drug delivery.     

Microfluidic droplet-based liquid/liquid extraction modulated by the interfacial Galvani potential difference

With a microfluidic droplet-based liquid/liquid extraction setup, we demonstrate that the extraction of an ionic analyte from complex matrices can be modulated by the interfacial Galvani potential difference and the extraction equilibrium follows the classical Nernst equation.     

Adsorption behavior of lauric acid at heptane/water interface as studied by second harmonic generation spectroscopy and interfacial tensiometry.

Interfacial tensiometry and second harmonic generation (SHG) spectroscopy were applied to examine the adsorption behavior of lauric acid (LA) at a heptane/water interface. From interfacial tensiometry measurements, the adsorption kinetics of LA was revealed to be diffusion-controlled, and the adsorption constant of LA was estimated to be 9.6 x 10(4) M(-1). The adsorption isotherms obtained by SHG measurements were analyzed by taking account of both the molecular orientation of LA at the interface and a surface electric field generated by the adsorbed LA layer. It was confirmed that the carboxylic groups of adsorbed LA molecules were well ordered at the heptane/water interface and the orientation of the carboxylate group was invariant during the adsorption process.     

Green chemical multicomponent approach for the synthesis of C3-pyranopyrazole-substituted coumarins

An efficient and rapid method was developed for the synthesis of C3-pyranopyrazole-substituted coumarins from one-pot five-component reaction of β-keto ester, hydrazine, O-hydroxy aromatic aldehydes, 6-methyl, 4-hydroxy pyranone and aromatic aldehyde in the presence of tri-ethylamine in solvent-free conditions. The microwave-assisted method reported herein offers advantageous shorter reaction times, higher yields and cleaner reaction compared with conventional heating methods.     

A rapid and simple approach for glycoform analysis

Fast glycoform analysis is important for quality control of glycoproteins that account for over 40% of the approved biopharmaceuticals. Herein, we realized an Au nanoparticle-based lectin affinity chromatography (LAC) using simple standard laboratory equipment for fast glycoform analysis. Pisum sativum agglutinin (PA), a lectin derived from P. sativum, was covalently conjugated to Au nanoparticles via naturally formed carboxylic groups onto the surface of Au nanoparticles and amino groups of PA. Each model glycoprotein was separated into several fractions including the unbound, weakly bound, modestly bound, and strongly bound glycoforms based on affinity strength of the glycoform toward PA. A single run of Au nanoparticle-based LAC was finished within 18 min, which could be further decreased by centrifuging the mixture of the PA functionalized Au nanoparticles and the glycoproteins at a higher speed. To our knowledge, we are the first to use Au nanoparticles as LAC matrix.     

A new multicomponent approach to highly functionalized 2,3-dihydroisoxazoles

The synthesis of highly functionalized 2,3-dihydroisoxazoles by a one-pot multicomponent reaction of an aldehyde, hydroxamic acid, and malononitrile or methyl cyanoacetate is described.     

A combinatorial scaffold approach based upon a multicomponent reaction

A combinatorial scaffolding procedure for the synthesis and spatial arrangement of tripartite structures was developed. [reaction: see text]     

Surface hydrophilization for polypropylene microporous membranes: A facile interfacial crosslinking approach

A hydrophilic surface is very important for hydrophobic separation membranes such as polypropylene microporous membranes (PPMMs). In this work a facile and effective method, interfacial crosslinking combined with pretreatment by dielectric barrier discharge plasma at atmospheric pressure, was developed for endowing PPMMs with a hydrophilic and charged surface. Poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) and p-xylylene dichloride were selected for quaternization crosslinking to form a positively charged coating layer, which was characterized with FT-IR/ATR, XPS, and FESEM. Water contact angle and pure water flux measurements were conducted to evaluate the surface hydrophilicity. The influence of surface charges on protein filtration was also investigated. It is found that the mass gain of interfacial crosslinking increases almost linearly with increasing the PDMAEMA concentration from 0.5 to 10 g/L. The crosslinking degree is larger than 80% according to the XPS results, ensuring the stability of the crosslinking layer. The surface hydrophilicity is demonstrated by the sharp decrease of water contact angle from 145° to 20°. The pure water flux also increases 3 times under the optimized conditions. Furthermore, the results of protein filtration suggest that these highly hydrophilic and charged surfaces can effectively resist the fouling of proteins.     

A multicomponent approach to substituted benzenes involving sequential nickel-catalyzed reactions

Two sequential nickel-catalyzed reactions allow the preparation of highly functionalized alkylidene cyclohexenols. Dehydration of the resulting cycloadducts allows the preparation of densely functionalized aromatic ring systems, whereas a simple sequence involving oxidation followed by carbonyl addition or enolization allows additional diversity incorporation.     

Synthesis of C3-dihydrofuran substituted coumarins via multicomponent approach

An efficient method was developed for the synthesis of dihydrofuran substituted coumarin from a one-pot, four-component reaction of 2-hydroxy aromatic aldehydes, 6-methyl, 4-hydroxy pyranone, aromatic aldehyde, and pyridinium ylide in the presence of tri-ethylamine under microwave irradiation. The reaction proceeds under solvent-free conditions to afford C3-dihydrofuran substituted coumarin in a diastereoselective manner in good yields (71–89%).     

Straightforward stereoselective synthesis of polyfunctionalised cyclohexenols using a multicomponent approach

An intramolecular Ugi 5-centre-4-component reaction (U-5C-4CR) followed by a palladium-catalysed ring-opening has been employed to transform oxabicycloheptene-based β-amino acids into two families of regioisomeric polyfunctionalised cyclohexenols. The whole process is completely stereoselective and enantiomerically pure products are obtained in high overall yields.