We present a phase decomposition approach to deal with the generalized Rankine–Hugoniot relations and then the Riemann problem for a model of two-phase flows. By investigating separately the jump ...relations for equations in conservative form in the solid phase, we show that the volume fractions can change only across contact discontinuities. Then, we prove that the generalized Rankine–Hugoniot relations are reduced to the usual form. It turns out that shock waves and rarefaction waves remain on one phase only, and the contact waves serve as a bridge between the two phases. By decomposing Riemann solutions into each phase, we show that Riemann solutions can be constructed for large initial data. Furthermore, the Riemann problem admits a unique solution for an appropriate choice of initial data.
▸ Automated concurrent determinations of anions and cations were made possible. ▸ Sample plugs were manipulated with a sequential injection analysis manifold. ▸ Contactless conductivity detection ...(C4D) was used for narrow capillaries of 10μm. ▸ Simultaneous separations at different pH with capillary electrophoresis were achieved.
Different schemes for simultaneous separations of both cations and anions were implemented in capillary electrophoresis employing a sequential injection analysis manifold for flexible manipulation of the background electrolyte and samples. The utilization of contactless conductivity allowed sensitive detection in narrow capillaries of 10μm internal diameter, which in turn enabled the use of hydrodynamic pumping without significant penalty in dispersion otherwise caused by the laminar nature of the flow. This allowed to position sample plugs at a desired place along the entire length of the capillary prior to electrophoretic separation or to carry out concurrent pumping during the separation itself for optimization of resolution. Also implemented was dual single-end injection, the injection of two sample plugs from one end of the capillary, and the small size of the contactless conductivity detector allowed the concurrent use of two cells at different points along the capillary for added flexibility. Equally considered was the effect of the pH-value of the background electrolyte as this strongly influences the electroosmotic flow, which also has bearing on the protocol to be used. For dual single-end injection reproducibilities in separation time of about 1–3% were obtained and the peak areas could be reproduced to within about 3–5% (both standard deviations). The detection limits for inorganic ions were all about 1μM.
A novel electrokinetic preconcentration approach, so-called multiple pressure-assisted large-volume sample stacking with an electroosmotic flow pump (M-PA-LVSEP), was developed to allow in-capillary ...enrichment and separation of analytes from unlimited sample volumes. With this approach, the inherent limitation of in-capillary electrokinetic preconcentrations to the separation capillary volume can be overcome. The M-PA-LVSEP protocol relies on repeated cycles of pressure-assisted electroosmotic pumping and injection of extremely large sample volumes for analyte stacking and sample matrix removal. This technique was developed to address the challenge of sensitive and simultaneous determination of several amyloid β (Aβ) peptides, which are biomarkers for the molecular diagnosis of Alzheimer’s disease (AD). For the first time, reliable quantification of different species of fluorescently derivatized Aβ peptides, that is, Aβ 1–42, Aβ 1–40, and Aβ 1–38 down to subnanomolar ranges in cerebrospinal fluids (CSF) from AD and non-demented patients (healthy controls) was made possible without recourse to immunoassay, immunoprecipitation, or mass spectrometry approaches. Based on the stacking from a sample plug representing up to 400% of the total capillary volume, sensitive enhancement factors up to 170 could be achieved with this “antibody free” approach. Quantification limits for these Aβ peptides down to 0.05 nM with capillary electrophoresis coupled with laser-induced fluorescent detection could be obtained. Excellent agreement between results from M-PA-LVSEP and the gold standard ELISA method was achieved for measurements of Aβ 1–42 in CSF, with a determination correlation (r 2) better than 0.993.
We have synthesized 50 benzimidazole (BMZ) derivatives with 1,2‐phenylenediamines and aromatic aldehydes under mild oxidation conditions by using inexpensive, nontoxic inorganic salt sodium ...metabisulfite in a one‐pot condensation reaction and screened their ability to interfere with Zika virus (ZIKV) infection utilizing a cell‐based phenotypic assay. Seven BMZs inhibited an African ZIKV strain with a selectivity index (SI=CC50/EC50) of 9–37. Structure‐activity relationship analysis demonstrated that substitution at the C‐2, N‐1, and C‐5 positions of the BMZ ring were important for anti‐ZIKV activity. The hybrid structure of BMZ and naphthalene rings was a structural feature responsible for the high anti‐ZIKV activity. Importantly, BMZs inhibited ZIKV in human neural stem cells, a physiologically relevant system considering the severe congenital anomalies, like microcephaly, caused by ZIKV infection. Compound 39 displayed the highest antiviral efficacy against the African ZIKV strain in Huh‐7 (SI>37) and neural stem cells (SI=12). Compound 35 possessed the highest activity in Vero cells (SI=115). Together, our data indicate that BMZs derivatives have to be considered for the development of ZIKV therapeutic interventions.
Selective and inexpensive: 1,2‐Disubstituted BMZs were synthesized in an efficient, environmentally friendly one‐pot condensation. Screening showed that they interfere with ZIKV infection in human neural stem cells. The top compound had the highest efficacy against the African ZIKV strain; the bottom compound possessed the highest activity against the Asian strain. A time‐of‐addition study indicated that BMZs inhibit ZIKV RNA replication.
•Capillaries of 10μm ID were employed.•Superimposed hydrodynamic pumping is possible without penalty in band broadening with such narrow capillaries.•Analysis times of less than 3min were ...possible.•The use of a computer controlled sequential analysis system allows flexible optimization of injection volumes and pumping rates.•Detection limits in the low μM range were achieved.
The common sweeteners aspartame, cyclamate, saccharin and acesulfame K were determined by capillary electrophoresis with contactless conductivity detection. In order to obtain the best compromise between separation efficiency and analysis time hydrodynamic pumping was imposed during the electrophoresis run employing a sequential injection manifold based on a syringe pump. Band broadening was avoided by using capillaries of a narrow 10μm internal diameter. The analyses were carried out in an aqueous running buffer consisting of 150mM 2-(cyclohexylamino)ethanesulfonic acid and 400mM tris(hydroxymethyl)aminomethane at pH 9.1 in order to render all analytes in the fully deprotonated anionic form. The use of surface modification to eliminate or reverse the electroosmotic flow was not necessary due to the superimposed bulk flow. The use of hydrodynamic pumping allowed easy optimization, either for fast separations (80s) or low detection limits (6.5μmolL−1, 5.0μmolL−1, 4.0μmolL−1 and 3.8μmolL−1 for aspartame, cyclamate, saccharin and acesulfame K respectively, at a separation time of 190s). The conditions for fast separations not only led to higher limits of detection but also to a narrower dynamic range. However, the settings can be changed readily between separations if needed. The four compounds were determined successfully in food samples.
We present in this study a new microfluidic droplet platform, named Lab-in-Droplet, for multistep glycoprotein sample treatment. Several operations are required for the sample treatment of a given ...glycoprotein to profile its N-glycans. In our case, all preparation steps for the analysis of N-glycans from glycoproteins could be realized in an automatic manner and without cross contamination. This could be achieved through several features that are not met in previous droplet setups, notably full automation, droplet sensing and heating. The magnetic tweezer technology was employed to manipulate (capture and release) coated magnetic beads used as analyte cargos over droplets. Droplets ranging from 1 to 10 μL play the role of confined microreactors, allowing to realize several steps that involve advanced functions such as heating and mixing with organic solvents. A complex sample treatment protocol that has been feasible so far only in batchwise mode can now be converted into a novel microfluidic version. With this Lab-in-Droplet, we can enzymatically release and fluorescently label N-linked oligosaccharides from Human Immuglobulin G and then off-line analyze the labeled glycans by capillary electrophoresis with laser induced fluorescent detection. We demonstrated the superiority of this Lab-in-Droplet over the conventional batchwise protocol, with 10-fold less reagent consumption, 3-fold less time, and 2-fold improvement of glycan labeling yield, without degradation of glycan separation profile obtained by capillary electrophoresis. The platform with the developed droplet protocol was applied successfully for mapping N-linked glycans released from human sera, serving for diagnostic screening of congenital disorders of glycosylation.
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•A novel microfluidic droplet-based platform for high performance multistep glycoprotein sample treatment was developed.•Positive features not available in previous droplet setups, notably automation, droplet sensing and heating were developed.•A complex sample treatment protocol feasible so far only in batchwise mode can be converted into a microfluidic version.•Mapping of N-linked glycans from human sera was made for diagnostic screening of congenital disorders of glycosylation.
In this study, the employment of purpose-made dual-channel compact capillary electrophoresis (CE) instrument with capacitively coupled contactless conductivity detection (C4D) as a simple and ...inexpensive solution for screening determination of various pharmaceutical pollutants frequently occurring in surface water and hospital wastewater in Hanoi, Vietnam is reported. Five negatively charged pharmaceutically active compounds, namely ibuprofen, diclofenac, bezafibrate, ketoprofen and mefenamic acid were determined using the first channel whereas three positively charged ones, namely diphenhydramine, metoprolol and atenolol were determined with the second channel of the CE-C4D instrument. Two different background electrolytes (BGEs) were used in these two CE channels independently. The best detection limits achieved were in the range of 0.2–0.8mg/L without sample pre-concentration. Enrichment factors up to 200 were obtainable with the inclusion of a solid phase extraction step. Good agreement between results obtained from CE-C4D and those with the standard confirmation method (HPLC-DAD) was achieved, with correlation coefficients higher than 0.98.
Screening determination of pharmaceutical pollutants in different water matrices using dual-channel capillary electrophoresis coupled with contactless conductivity detection.
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•A new approach for screening determination of pharmaceutical pollutants in water.•Pharmaceutical pollutants in different water matrices in Hanoi were determined.•A dual-channel CE-C4D instrument with two individual running buffers was developed.
The cytokine interleukin 6 (IL-6) is involved in the pathogenesis of different inflammatory diseases, including cancer, and its monitoring could help diagnosis, prognosis of relapse-free survival and ...recurrence. Here, we report an innovative microfluidic approach that uses the fluidization of magnetic beads to specifically extract, preconcentrate and fluorescently detect IL-6 directly on-chip. We assess how the physical properties of the beads can be tuned to improve assay performance by enhancing mass transport, reduce non-specific binding and multiply the detection signal threefold by transitioning between packed and fluidization states. With the integration of a full ELISA protocol in a single microfluidic chamber, we show a twofold reduction in LOD compared to conventional methods along with a large dynamic range (10 pg/mL to 2 ng/mL). We additionally demonstrate its application to IL-6 detection in undiluted serum samples.
The portable capillary electrophoresis instrument is automated and features three independent channels with different background electrolytes to allow the concurrent optimized determination of three ...different categories of charged analytes. The fluidic system is based on a miniature manifold which is based on mechanically milled channels for injection of samples and buffers. The planar manifold pattern was designed to minimize the number of electronic valves required for each channel. The system utilizes pneumatic pressurization to transport solutions at the grounded as well as the high voltage side of the separation capillaries. The instrument has a compact design, with all components arranged in a briefcase with dimensions of 45 (w) × 35 (d) × 15 cm (h) and a weight of about 15 kg. It can operate continuously for 8 h in the battery-powered mode if only one electrophoresis channel is in use, or for about 2.5 h in the case of simultaneous employment of all three channels. The different operations, i.e. capillary flushing, rinsing of the interfaces at both capillary ends, sample injection and electrophoretic separation, are activated automatically with a control program featuring a graphical user interface. For demonstration, the system was employed successfully for the concurrent separation of different inorganic cations and anions, organic preservatives, additives and artificial sweeteners in various beverage and food matrices.
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•The use of parallel channels allows the concurrent separation of different classes of analytes.•Separate background electrolytes allow individual optimization.•The instrument is compact and field portable.
We complete a well-balanced numerical method by introducing computing correctors to an earlier scheme for a model of two-phase flows. Each improvement based on a corrector to the scheme is designed ...to reduce the size of the errors across the interface of each node when using the solid contact to absorb the nonconservative terms. Three correctors of two kinds are presented. One corrector of the first kind is designed to correct the states on both side of the solid contact at each node and the corresponding numerical flux before applying the iterative scheme. Two correctors of the second kind are designed to correct the state given by the iterative scheme depending on the sign of the velocity of the solid contact. These improvements are still well-balanced schemes. Tests show that the improvement by using the corrector of the first kind gives relatively better results, and the improvements by using one corrector of the second kind give much better results. Interestingly, we find that improvements by using a corrector of second kind can resolve the accuracy problem of the existing scheme when its approximate solutions might converge to the solution slightly different from the exact solution.
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