Microfluidic systems for the analysis of blood-derived molecular biomarkers

Biomarkers are relevant indicators of the physiological state of an individual. Although biomarkers can be found in diseased tissue and different biofluids, sampling from blood plasma is relatively easy and less invasive. Among the molecular biomarkers that can be found circulating in plasma are proteins, metabolites, nucleic acids, and exosomes. Some of these plasma-circulating biomarkers are now employed for patient stratification in a broad range of diseases with high sensitivity and specificity and are useful in early diagnosis, initial risk assessment, and therapy selection. However, there is a pressing need to develop novel approaches for biomarker analysis that can be translated into clinical or other settings without complex methodologies or instrumentation. Microfluidics has been touted as a promising technology to carry out this task because it offers high-throughput, automation, multiplexed detection, and portability, possibly overcoming the bottleneck that prevent the translation of novel biomarkers to the point-of-care (POC). Here, we provide a review of the microfluidic systems that have been engineered to detect circulating molecular biomarkers in blood plasma. We also review the different microfluidic approaches for plasma enrichment, which are now being integrated with microfluidic-based biomarker analyzers. Such integration should lead to cost-effective solutions in in vitro diagnostics, with special relevance to POC platforms.     

Ethylbenzene to chemicals: Catalytic conversion of ethylbenzene into styrene over metal-containing MCM-41

Isomorphously substituted (MeDM) and impregnated metal-containing MCM-41 (MeO_x/IM) catalysts, in which Me = Co, Cu, Cr, Fe or Ni, have been prepared. Structural and textural characterizations of the catalysts were performed by means of X-ray diffraction (XRD), chemical analysis, Raman spectroscopy, electron paramagnetic resonance (EPR), N₂ adsorption isotherms and temperature programmed reduction (TPR). Cu²⁺, Co²⁺, and Cr⁴⁺/Cr³⁺ species were found over the catalysts as cations incorporated in the MCM-41 structure (MeDM) or highly dispersed oxides on the surface (MeO_x/IM). The MeDM catalysts exhibited a good performance in the dehydrogenation of ethylbenzene with CO₂. However, MeO_x/IM catalysts had a low performance in styrene production (activity less than 15 × 10^?3 mmol h^?1 and selectivity for styrene less than 80%) due to the high reducibility of the metals species. However, Ni²⁺ or Fe³⁺ coordinated with the MCM-41 framework, as well as NiO_x and Fe₂O₃ extra-framework species, is continuously oxidized by the CO₂ to maintain the active sites for dehydrogenating ethylbenzene. Deactivation studies on the FeDM sample showed that Fe³⁺ species produced active sp² carbon compounds, which are removed by CO₂; the referred sample is catalytically selective for styrene and stable over 24 h of reaction. In contrast, highly active Ni²⁺ and Ni⁰ species produced a large amount of polyaromatic carbonaceous deposits from styrene, as identified by TPO, TG and Raman spectroscopy. An acid–base mechanism is proposed to operate to adsorb ethylbenzene and abstract the β-hydrogen. CO₂ plays a role in furnishing the lattice oxygen to maintain the Fe³⁺ active sites in the dehydrogenation of ethylbenzene to form styrene.     

Characterization and study of microwave activation effects on the polystyrene tacticity

¹³C Nuclear magnetic resonance proved to be an advantageous tool to determine the stereoregularity of polystyrene polymers. The latter was achieved through the analysis of the signal of the quaternary carbon and that of the carbon-p in the aromatic ring too. Styrene was polymerized through microwaves and conventional heating activation using two different polymerization techniques: emulsion and bulk. Microwave activation was performed in a mono-modal type device under the following experimental conditions: various initiator concentrations, an average irradiation power of 50?W, temperature of 70°C, and using a batch reactor for emulsion and bulk experiments. The results obtained in these experiments were compared with those obtained by conventional heating activation polymerization under the same initiator concentration and temperature conditions. Microwave-activated reactions resulted in shorter reaction times and higher yields. The tacticity of the polymer samples was not significantly altered, which lead to the conclusion that, in this case, the stereoregularity of polystyrene was not influenced by microwave irradiation.     

Dynamic Effect of Operational Regulation on the Mesophilic BioMethanation of Grape Marc

Wine production annually generates an estimated 11 million metric tonnes of grape marc (GM) worldwide. The diversion of this organic waste away from landfill and towards its use in the generation of renewable energy has been investigated. This study aimed to evaluate the effectiveness of operational parameters relating to the treatment regime and inoculum source in the extraction of methane from GM under unmixed anaerobic conditions at 35 °C. The study entailed the recirculation of a previously acclimated sludge (120 days) as downstream inoculum, an increased loading volume (1.3 kg) and a low substrate-to-inoculum ratio (10:3 SIR). The results showed that an incorporation of accessible operational controls can effectively enhance cumulative methane yield (0.145 m³ CH₄ kg⁻¹ VS), corresponding to higher amounts of digestible organics converted. The calculated average volumetric methane productivity equalled 0.8802 L CH₄ L_Work⁻¹ d⁻¹ over 33.6 days whilst moderate pollutant removal (43.50% COD removal efficiency) was achieved. Molecular analyses identified Firmicutes and Bacteroidetes phyla as core organisms for hydrolytic and fermentative stages in trophic relationships with terminal electron acceptors from the methane-producing Methanosarcina genus. Economic projections established that the cost-effective operational enhancements were sustainable for valorisation from grape marc by existing wineries and distilleries.     

A semiconductor-based, frequency-stabilized mode-locked laser using a phase modulator and an intracavity etalon

We report a frequency-stabilized semiconductor-based mode-locked laser that uses a phase modulator and an intracavity Fabry-Perot etalon for both active mode-locking and optical frequency stabilization. A twofold multiplication of the repetition frequency of the laser is inherently obtained in the process. The residual timing jitter of the mode-locked pulse train is 13 fs (1 Hz to 100 MHz), measured after regenerative frequency division of the photodetected pulse train.     

Detonation structure under chain-branching kinetics with small initiation rate

The structure of ZND waves under simple three step chain-branching kinetics is analyzed, assuming a slow initiation rate but arbitrary chain-branching activation energy. The analysis allows for a complete solution for the ZND wave in all cases, inside or outside the chain-branching explosion region, or close to the explosion limit. Results show that even when the von Neumann point is inside the explosion region, chain-branching effectively stops and the chain-branching radical concentration reaches a small near-steady value before all the reactant is consumed. Beyond that point, chemistry proceeds slowly, at a rate of the order of the initiation rate. For a von Neumann point relatively close to the limit, the reactant concentration is still quite significant when chain-branching stops, but diminishes for von Neumann points deeper inside the explosion region. The assumption that initiation is much slower than chain-branching is often quite accurate, in which case the length required for complete burn is orders of magnitude longer than the chain-branching length, so that as a practical matter, combustion never completes. In contrast, numerical simulation shows that under the same conditions, the cellular wave results in a more complete burn.     

Ultrasound effect used as external stimulus for viscosity change of aqueous carrageenans

Ultrasound (US) serves as a stimulus to change shear viscosity of aqueous polysaccharides of ι-carrageenan, κ-carrageenan and, agar. The US effect was compared in their aqueous solutions at 60 °C for the US frequency of 23, 45, and 83 kHz. Under the US condition with 50 W at 45 kHz, the shear viscosity of each aqueous solution was decreased significantly. Subsequently, when the US was stopped, the shear viscosity returned back to the original value. In addition, the US showed different effects of the US frequency over the viscosity change in the three kinds of polysaccharides. When the US frequency was changed, the US effects were less at 83 kHz and 28 kHz for the shear viscosity change. In addition, as NaCl was present in the aqueous solution, the viscosity change decreased by the US exposure. These results suggest that the US effect on the viscosity reduction was influenced by the condition of polymer coil conformation, which was expanded or shrank by electrostatic repulsion of the SO₃^? groups. FT-IR analysis supported that the hydrogen bonds of carrageenans were broken during the US exposure. Using Fourier self-deconvolution for the FT-IR spectra without and with US exposure suggests that the US influenced the hydrogen bonds of water and the OH group of polysaccharides.     

New crystals in the lithium sulfate family

The preparation and structures of caesium lithium sulfate, Cs_1.15Li_2.85(SO₄)₂, and caesium lithium rubidium sulfate, Cs_0.90Li_2.88Rb_0.22(SO₄)₂, are described and discussed in the context of simple and double sulfate polymorphism. The latter structure is related to the former through the substitution of Rb for Cs. In both crystals, the sulfate ions occupy two non‐equivalent sites, but the ions are disordered in Cs_1.15Li_2.85(SO₄)₂.     

Use of N‐methyliminodiacetic acid boronate esters in suzuki‐miyaura cross‐coupling polymerizations of triarylamine and fluorene monomers

Polytriarylamine copolymers can be prepared by Suzuki‐Miyaura cross‐coupling reactions of bis N‐methyliminodiacetic acid (MIDA) boronate ester substituted arylamines with dibromo arenes. The roles of solvent composition, temperature, reaction time, and co‐monomer structure were examined and (co)polymers prepared containing 9, 9‐dioctylfluorene (F8), 4‐sec‐butyl or 4‐octylphenyl diphenyl amine (TFB), and N, N′‐bis(4‐octylphenyl)‐N, N′‐diphenyl phenylenediamine (PTB) units, using a Pd(OAc)₂/2‐dicyclohexylphosphino‐2′,6′‐dimethoxybiphenyl (SPhos) catalyst system. The performance of a di‐functionalized MIDA boronate ester monomer was compared with that of an equivalent pinacol boronate ester. Higher molar mass polymers were produced from reactions starting with a difunctionalized pinacol boronate ester monomer than the equivalent difunctionalized MIDA boronate ester monomer in biphase solvent mixtures (toluene/dioxane/water). Matrix‐assisted laser desorption/ionization mass spectroscopic analysis revealed that polymeric structures rich in residues associated with the starting MIDA monomer were present, suggesting that homo‐coupling of the boronate ester must be occurring to the detriment of cross‐coupling in the step‐growth polymerization. However, when comparable reactions of the two boronate monomers with a dibromo fluorene monomer were completed in a single phase solvent mixture (dioxane + water), high molar mass polymers with relatively narrow distribution ranges were obtained after only 4 h of reaction. © 2017 The Authors. Journal of Polymer Science Part A: Polymer Chemistry Published by Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 2798–2806