Hydrophilic Reagents Research Articles

Surface Hydrophilic Modification for Chip of Centrifugal Microfluidic Immunoassay System.

The surface of a centrifugal microfluidic immunoassay system chip such as polymethyl methacrylate (PMMA) is often hydrophobic, which leads to problems such as poor liquid transfer efficiency and easy-to-block siphon channels, leading to bad fluid control. Therefore, surface hydrophilic modification for such chips is necessary to improve the rapidity and sensitivity of the system. Chemical modification is commonly used, but there is little research on the hydrophilic effect of different concentrations of hydrophilic reagents. According to function requirements for different microchannels of the chip (some only need to ensure the liquid can flow into the next chamber, and some also need to ensure the function of “closing the door” during immunoassay incubation), we explored the best combination of hydrophilic reagent and concentration through experiments. Firstly, three hydrophilic reagents were used for modification. Secondly, the hydrophilic effects of different reagents and concentrations were explored by contact angle test, the influence of different modification methods on liquid transfer efficiency was characterized by residual liquid calculation in the chamber. Finally, the effect of different hydrophilic reagents on absorbance was also tested. By experimental results and comprehensively considering the stability of the modification effect and the function requirements, Tween-20 (2.0% v/v) was chosen as the modifying reagents of the first siphon valve and the second siphon valve, and TritonX-100 (2.0% v/v) was chosen for the third siphon valve, which effectively reduces the contact angle and improves the liquid transfer efficiency, leading to further improvement of the rapidity and sensitivity of the centrifugal microfluidic immunoassay system by efficient siphoning and high plasma separation efficiency (99%).

Separation of Americium from a Complex Matrix by Solvent Extraction Using CyMe4BTPhen in a Room Temperature Ionic Liquid Diluent

ABSTRACT The extraction performance and mechanism of 2,9-bis(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-benzo[1,2,4]triazin-3-yl)-1,10-phenanthroline (CyMe4BTPhen) in the room temperature ionic liquid 1-alkyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([C4mim][NTf2]) have been studied and are herein reported. Americium is extracted from nitric acid solutions by cation exchange and is most efficient at low (< 1 M) nitric acid concentrations as opposed to the high (4 M) concentration preferred when using most traditional molecular diluents. The kinetics are slow, taking 24 hours to achieve quantitative extraction of americium but are greatly improved, achieving the same within 8 hours, by dilution with 1-octanol. High SFAm/Eu > 3000 were achieved although decontamination factors for americium from more complex matrices were non-competitive with extraction using traditional molecular diluents. Modest improvements in decontamination factor were attained by the addition of the hydrophilic reagent N,N,N’,N’-tetraethyl diglycolamide (TEDGA).

Solid-Contact pH Sensor with Covalent Attachment of Ionophores and Ionic Sites to a Poly(decyl methacrylate) Matrix.

With a view to improving the sensor lifetime, solid-contact ion-selective electrodes (ISEs) were prepared with a plasticizer-free and cross-linked poly(decyl methacrylate) matrix, to which only the ionic sites, only the ionophore, or both the ionic sites and ionophore were covalently attached. In earlier work with covalently attached ionophores or ionic sites, it was difficult to discount the presence of ionophores or ionic site impurities that were not covalently attached to the polymer backbone because the reagents used to introduce the ionophore or ionic sites had high hydrophobicities. In this work, we deliberately chose readily available hydrophilic reagents for the introduction of covalently attached H+ ionophores with tertiary amino groups and covalently attached sulfonate groups as ionic sites. This simplified the synthesis and made it possible to thoroughly remove ionophores and ionic sites not covalently attached to the polymer backbone. Our results confirm the expectation that hydrophobic ISE membranes with both covalently attached ionophores and ionic sites have impractically long response times. In contrast, ISEs with either covalently attached H+ ionophores or covalently attached ionic sites responded to pH with quick Nernstian responses and high selectivity. Both conventional plasticized poly(vinyl chloride) (PVC)-based ISEs and the new poly(decyl methacrylate) membranes were exposed to 90 °C heat for 2 h, 10% ethanol for 1 day, or undiluted blood serum for 5 days. In all three cases, the poly(decyl methacrylate) ISEs exhibited properties superior to conventional PVC-based ISEs, confirming the advantages of the covalent attachment.

An ultrasonic atomization spray strategy for constructing hydrophobic and hydrophilic synergistic surfaces as gas diffusion layers for proton exchange membrane fuel cells

An effective strategy to construct a gas diffusion layer with hydrophobic and hydrophilic synergistic surfaces using a one-step ultrasonic atomizing spray low surface hydrophilic reagent (aerosol ® ot-75 surfactant: polyacrylic acid: deionized water = 1:1:8) is reported. Higher peak power density is obtained with respect to conventionally prepared gas diffusion layers. The Energy Dispersive Spectrometer (EDS) mapping of the cross section and surface of the gas diffusion layer proves that the hydrophobic and hydrophilic synergistic surfaces is existed in the whole gas diffusion layer. By comparing the contact angle, water breakthrough pressure and pore size distribution of the two kind of gas diffusion layers, the main advantage of this gas diffusion layer with hydrophobic - hydrophilic synergistic surfaces is provide water transfer pathway so that improve the cell performance.

Controlled Oil/Water Partitioning of Hydrophobic Substrates Extending the Bioanalytical Applications of Droplet-Based Microfluidics.

Functional annotation of novel proteins lags behind the number of sequences discovered by the next-generation sequencing. The throughput of conventional testing methods is far too low compared to sequencing; thus, experimental alternatives are needed. Microfluidics offer high throughput and reduced sample consumption as a tool to keep up with a sequence-based exploration of protein diversity. The most promising droplet-based systems have a significant limitation: leakage of hydrophobic compounds from water compartments to the carrier prevents their use with hydrophilic reagents. Here, we present a novel approach of substrate delivery into microfluidic droplets and apply it to high-throughput functional characterization of enzymes that convert hydrophobic substrates. Substrate delivery is based on the partitioning of hydrophobic chemicals between the oil and water phases. We applied a controlled distribution of 27 hydrophobic haloalkanes from oil to reaction water droplets to perform substrate specificity screening of eight model enzymes from the haloalkane dehalogenase family. This droplet-on-demand microfluidic system reduces the reaction volume 65 000-times and increases the analysis speed almost 100-fold compared to the classical test tube assay. Additionally, the microfluidic setup enables a convenient analysis of dependences of activity on the temperature in a range of 5 to 90 °C for a set of mesophilic and hyperstable enzyme variants. A high correlation between the microfluidic and test tube data supports the approach robustness. The precision is coupled to a considerable throughput of >20 000 reactions per day and will be especially useful for extending the scope of microfluidic applications for high-throughput analysis of reactions including compounds with limited water solubility.

Rapid chemical clearing of white matter in the post-mortem human brain by 1,2-hexanediol delipidation.

Three-dimensional (3D) imaging based on chemical tissue clearing in the post-mortem human brain is a promising approach for stereoscopic understanding of central nervous system diseases. Especially, delipidation of lipid-rich white matter (WM) is a rate-determining step in human brain clearing by hydrophilic reagents. In this study, we described the rapid delipidation of WM by a 1,2-hexanediol (HxD)-based aqueous solution. HxD delipidation enabled rapid clearing of a formalin-fixed human brain specimen including the WM. Although harsh HxD delipidation was applied to the brain tissue, conventional pathological staining patterns and various types of antigenicity were sufficiently preserved. Furthermore, HxD delipidation was compatible with 3D imaging of fluorescently-labeled tissue samples. HxD delipidation could be useful in future 3D neuropathological diagnosis.

Vortex assisted in situ ionic liquid dispersive liquid–liquid microextraction for preconcentration of uranyl ion in water samples before spectrophotometric detection

Vortex assisted in situ ionic liquid dispersive liquid–liquid microextraction method was developed for extraction of U(VI) from aqueous solutions using hydrophilic ionic liquid and ion-exchange reagent. Arsenazo III was used as a complexing agent in microextraction process. Under optimized conditions, the proposed method for uranyl ion exhibited good precision, 5.2% for 1 µg L−1 and 5.1% for 4 µg L−1, low limit of detection, 0.06 µg L−1 and high enrichment factor, 91. The accuracy studies were achieved by spiking of 1 and 5 µg L−1 U(VI) into water samples and the recovery was found in the range of 99–111%.

Chemical Landscape for Tissue Clearing Based on Hydrophilic Reagents

We describe a strategy for developing hydrophilic chemical cocktails for tissue delipidation, decoloring, refractive index (RI) matching, and decalcification, based on comprehensive chemical profiling. More than 1,600 chemicals were screened by a high-throughput evaluation system for each chemical process. The chemical profiling revealed important chemical factors: salt-free amine with high octanol/water partition-coefficient (logP) for delipidation, N-alkylimidazole for decoloring, aromatic amide for RI matching, and protonation of phosphate ion for decalcification. The strategic integration of optimal chemical cocktails provided a series of CUBIC (clear,unobstructed brain/body imaging cocktails and computational analysis) protocols, which efficiently clear mouse organs, mouse body including bone, and even large primate and human tissues. The updated CUBIC protocols are scalable and reproducible, and they enable three-dimensional imaging of the mammalian body and large primate and human tissues. This strategy represents a future paradigm for the rational design of hydrophilic clearing cocktails that can be used for large tissues.

Highly effective enhancement of waste activated sludge dewaterability by altering proteins properties using methanol solution coupled with inorganic coagulants

Proteins are the dominant organic component of extracellular polymeric substances (EPS) in waste activated sludge (WAS), and play an important role during sludge dewatering processes. Methanol is a polar hydrophilic reagent and can denature proteins, which suggested to us that the modification of protein configurations with methanol could improve sludge dewatering performance.In this study, methanol was used to precondition WAS prior to adding inorganic coagulants for dewatering enhancement. The morphology and EPS properties (especially of proteins) were investigated to analyze and explain the effects of methanol in the sludge conditioning process. The results show that methanol performed much better than traditional inorganic coagulants in improving sludge dewaterability in term of specific resistance to filtration (SRF) and cake solid content (CSC). Extractable proteins in EPS increased to a maximum when the concentration of methanol reached 40% (w/w) because cell membranes were destroyed and intracellular substances and water were released. Floc protein content was reduced with the further increase in methanol concentration due to protein precipitation. Confocal laser scanning microscopy analysis indicated that proteins precipitated and formed larger aggregates because methanol destroyed both the hydration shell and the hydrophobic clusters of proteins and expanded the protein tertiary structure to release interstitial water and bound water. The combination treatment of methanol and inorganic coagulants (PAC or FeCl3) showed significant synergetic effects on enhancing sludge dewatering and cake drying. In practical applications, methanol from the dewatering sludge can be returned to the biochemical pool and used as the carbon source for nitrogen removal in the denitrification process. This integrated process is appropriate for sludge final disposal technologies that have high energy demands, such as incineration and pyrolysis. This paper describes a novel approach to improving sludge dewaterability through the alteration of protein properties by use of physiochemical techniques.

Cross-talk between emulsion drops: how are hydrophilic reagents transported across oil phases?

Emulsion drops are frequently used as vessels, for example, to conduct biochemical reactions in small volumes or to perform screening assays at high throughputs while consuming minimal sample volumes. These applications typically require drops that do not allow exchange of reagents such that no cross-contamination occurs. Unfortunately, in many cases, reagents are exchanged between emulsion drops even if they have a low solubility in the surrounding phase, resulting in cross-contaminations. Here, we investigate the mechanism by which hydrophilic reagents are transported across an oil phase using water-oil-water double emulsion drops as a model system. Remarkably, even large objects, including 11 000 base pair double-stranded circular DNA are transported across oil shells. Importantly, this reagent transport, that is to a large extent caused by aqueous drops that spontaneously form at the water-oil interface, is not limited to double emulsions but also occurs between single emulsion drops. We demonstrate that the uncontrolled reagent transport can be decreased by at least an order of magnitude if appropriate surfactants that lower the interfacial tension only moderately are employed or if the shell thickness of double emulsions is decreased to a few hundreds of nanometers.

Synergistic effect of quercetin and pH-responsive DEAE-chitosan carriers as drug delivery system for breast cancer treatment

Amphiphilic chitosans, which may self-assemble in aqueous solution to form nanoaggregates with different conformations depending to the environmental pH, can be used as drug transport and delivery agents, when the target pH differs from the delivery medium pH. In this study, quercetin, a bioactive flavonoid, was encapsulated in a pH-responsive system based on amphiphilic chitosan. The hydrophilic reagent 2-chloro-N,N-diethylethylamine hydrochloride (DEAE), also known to inhibit the proliferation of cancer cells, was used as a grafting agent. Drug loading experiments (DL ∼5%) showed a quercetin entrapment efficiency of 73 and 78% for the aggregates. The sizes of blank aggregates measured by dynamic light scattering (DLS) varied from 169 to 263nm and increased to ∼410nm when loaded with quercetin. The critical aggregation concentration, zeta potential and morphology of the aggregates were determined. pH had a dominant role in the release process and Fickian diffusion was the controlling factor in drug release according to the Korsmeyer-Peppas mathematical model. In vitro studies indicated that the DEAE-modified chitosan nanoaggregates showed a synergistic effect with quercetin on the control of the viability of MCF-7 cells. Therefore, DEAE-modified chitosan nanoaggregates with pH-sensibility can be used as optimized nanocarriers in cancer therapy.

(Invited) Microfluidic Synthesis of Functional Nanomaterials

The controlled synthesis of functional nanoparticles with tunable structures and properties has been extensively investigated for cancer treatment and diagnosis. Among a variety of methods for fabrication of nanoparticles, microfluidics-based synthesis enables enhanced mixing and precise fluidic modulation inside microchannels, thus allowing for the flow-mediated production of nanoparticles in a controllable manner. We present a hollow-structured rigid nanoparticle fabricated by a multi-stage microfluidic chip in one step, to effectively entrap various hydrophilic reagents inside, without complicated synthesis, extensive use of emulsifiers and stabilizers, and laborious purification procedures. The nanoparticle contains a hollow water core, a rigid poly (lactic-co-glycolic acid) (PLGA) shell, and an outermost lipid layer. The entrapment efficiency of hydrophilic reagents such as calcein, rhodamine B and siRNA inside hollow water core is ~ 90 %. In comparison with the combination of free Dox and siRNA, the hollow-structured rigid nanoparticle that co-encapsulates siRNA and doxorubicin (Dox) reveals a significantly enhanced anti-tumor effect for a multi-drug resistant tumor model. Lipid-covered PLGA NPs or liposomes of the same size and surface properties, but different rigidity by controlling the interfacial water layer, can be realized using a two-stage microfluidic chip. It enables us to explore how rigidity of NPs regulates the cellular uptake and elucidate the intrinsic mechanism. Given the only significant difference between those two types of NPs is the rigidity, the experiments suggest that rigidity could dramatically alter the cellular uptake efficiency, with rigid NPs being easier to get through members than soft ones. The mechanisms revealed here suggest that tuning of rigidity of NPs is one appealing way in improving therapeutic efficiency.

Selective hydrophilic modification of hydrophobic POSS nanoparticles

Hydrophobicity of polyhedral oligomeric silsesquioxane was selectively improved by simple amidiation reaction with hydrophilic colour reagent (carboxyazo-p-COOH, PCAC) at ambient temperature. The molecular structure, thermal properties and absorption features of the resulting PCAC-POSS were characterised by Fourier transform infrared, thermal gravimetric analyses, differential scanning calorimetry and visible absorption spectra. Modified polyhedral oligomeric silsesquioxane nanoparticles exhibit excellent solubility in ethanol, and keep insoluble in aqueous solution. The solubility is selectively controlled by proper hydrophilic modification using a simple and mild amidation reaction.

Development of a gas-diffusion microfluidic paper-based analytical device (μPAD) for the determination of ammonia in wastewater samples.

An inexpensive, disposable and highly selective microfluidic paper-based analytical device (μPAD) is described for the determination of ammonia (molecular ammonia and ammonium cation) in wastewaters which implements for the first time a gas-diffusion separation step on a paper-based platform. Its hydrophilic reagent zones were defined by printing filter paper with a hydrophobic paper sizing agent using a conventional inkjet printer. The sample was introduced into the sodium hydroxide impregnated sample zone of the μPAD. This allowed the quantitative conversion of the ammonium ion to molecular ammonia which diffused across the hydrophobic microporous Teflon membrane of the device into an adjacent hydrophilic reagent zone containing the acid-base indicator 3-nitrophenol or bromothymol blue. The change in indicator color was measured using a desktop scanner for ammonia quantification. Under optimal conditions, the μPAD is characterized by a limit of detection of 0.8 and 1.8 mg N L(-1) and repeatability of 3.1 and 3.7% (n ≥ 10, 20 mg N L(-1)), expressed as relative standard deviation, in the case of 3-nitrophenol or bromothymol blue, respectively. This μPAD was used successfully for the determination of ammonia in sewage and soil water samples. The small dimensions, minimal reagent consumption, low cost, simplicity of operation, and possibility of using a portable scanner make the proposed μPAD suitable for on-site ammonia monitoring in contaminated environmental waters and domestic, agricultural and industrial wastewaters. The successful implementation of the gas-diffusion approach on a paper-based platform is expected to result in the development of other μPADs for volatile analytes.

Microreactor mediated deoxygenation of benzylic alcohols in a biphasic organic-aqueous medium

Safe and efficient deoxygenation of benzylic alcohols was accomplished using a droplet-based microreactor, which induced rapid mixing of the hydrophilic reagents (HI and H3PO2) in the aqueous phase and the alcohols in the organic phase. We investigated the relationship between the surface-to-volume ratio of the organic droplets and the reaction rate, and examined the effect of temperature and concentration of HI and H3PO2 in the reaction. The deoxygenated product was separated from the strongly acidic aqueous solution, and HI in the aqueous solution could be recycled. The reaction afforded 99% yield at 120°C with HI (3.4M HI) and H3PO2 (4.8M).

Microfluidic Synthesis of Rigid Nanovesicles for Hydrophilic Reagents Delivery

AbstractWe present a hollow‐structured rigid nanovesicle (RNV) fabricated by a multi‐stage microfluidic chip in one step, to effectively entrap various hydrophilic reagents inside, without complicated synthesis, extensive use of emulsifiers and stabilizers, and laborious purification procedures. The RNV contains a hollow water core, a rigid poly (lactic‐co‐glycolic acid) (PLGA) shell, and an outermost lipid layer. The formation mechanism of the RNV is investigated by dissipative particle dynamics (DPD) simulations. The entrapment efficiency of hydrophilic reagents such as calcein, rhodamine B and siRNA inside the hollow water core of RNV is ≈90 %. In comparison with the combination of free Dox and siRNA, RNV that co‐encapsulate siRNA and doxorubicin (Dox) reveals a significantly enhanced anti‐tumor effect for a multi‐drug resistant tumor model.

Microfluidic synthesis of rigid nanovesicles for hydrophilic reagents delivery.

We present a hollow-structured rigid nanovesicle (RNV) fabricated by a multi-stage microfluidic chip in one step, to effectively entrap various hydrophilic reagents inside, without complicated synthesis, extensive use of emulsifiers and stabilizers, and laborious purification procedures. The RNV contains a hollow water core, a rigid poly (lactic-co-glycolic acid) (PLGA) shell, and an outermost lipid layer. The formation mechanism of the RNV is investigated by dissipative particle dynamics (DPD) simulations. The entrapment efficiency of hydrophilic reagents such as calcein, rhodamine B and siRNA inside the hollow water core of RNV is ≈90 %. In comparison with the combination of free Dox and siRNA, RNV that co-encapsulate siRNA and doxorubicin (Dox) reveals a significantly enhanced anti-tumor effect for a multi-drug resistant tumor model.

ChemInform Abstract: Solid‐Phase Glycan Isolation for Glycomics Analysis

AbstractReview: 108 refs.

Solid-phase glycan isolation for glycomics analysis.

Glycosylation is one of the most significant protein PTMs. The biological activities of proteins are dramatically changed by the glycans associated with them. Thus, structural analysis of the glycans of glycoproteins in complex biological or clinical samples is critical in correlation with the functions of glycans with diseases. Profiling of glycans by HPLC-MS is a commonly used technique in analyzing glycan structures and quantifying their relative abundance in different biological systems. Methods relied on MS require isolation of glycans from negligible salts and other contaminant ions since salts and ions may interfere with the glycans, resulting in poor glycan ionization. To accomplish those objectives, glycan isolation and clean-up methods including SPE, liquid-phase extraction, chromatography, and electrophoresis have been developed. Traditionally, glycans are isolated from proteins or peptides using a combination of hydrophobic and hydrophilic columns: proteins and peptides remain on hydrophobic absorbent while glycans, salts, and other hydrophilic reagents are collected as flowthrough. The glycans in the flowthrough are then purified through graphite-activated carbon column by hydrophilic interaction LC. Yet, the drawback in these affinity-based approaches is nonspecific binding. As a result, chemical methods by hydrazide or oxime have been developed for solid-phase isolation of glycans with high specificity and yield. Combined with high-resolution MS, specific glycan isolation techniques provide tremendous potentials as useful tools for glycomics analysis.

A paper-based device for measurement of reactive phosphate in water

The preparation and evaluation of a simple paper-based device for the determination of reactive phosphate in natural and soil waters based on the formation of phosphomolybdenum blue is reported. Hydrophilic reagent zones were defined by printing filter paper with a hydrophobic paper-sizing agent using an inkjet printer. The molybdate/potassium antimony(III)-tartrate reagent and ascorbic acid reductant merged together from adjacent hydrophilic zones after spotting the liquid sample onto the paper. The colour intensity of the phosphoantimonylmolybdenum blue complex produced was measured using a flat bed scanner. Under optimal conditions, the paper-based device is characterised by a working range of 0.2–10mgL−1 P, limits of detection and quantitation of 0.05 and 0.16mgL−1 P, respectively, and repeatability of less than 2% RSD at 1 and 5mgL−1 P (n=10 and 8). There was no significant difference between the results obtained using the paper-based device and reference methods (t=0.0135, P (T≤t) two-tail=0.9892, df=38). In its optimum form, the paper-based device was stable for up to 15 day under ambient conditions, and up to 122day when stored at ≤−20°C. The small dimensions, minimal reagent consumption, low cost (a few cents), ease of operation and favourable analytical performance make the proposed paper-based device attractive for on-site environmental monitoring and analysis.