Recombinant drugs-on-a-chip: The usage of capillary electrophoresis and trends in miniaturized systems – A review

We present here a critical review covering conventional analytical tools of recombinant drug analysis and discuss their evolution towards miniaturized systems foreseeing a possible unique recombinant drug-on-a-chip device. Recombinant protein drugs and/or pro-drug analysis require sensitive and reproducible analytical techniques for quality control to ensure safety and efficacy of drugs according to regulatory agencies. The versatility of miniaturized systems combined with their low-cost could become a major trend in recombinant drugs and bioprocess analysis. Miniaturized systems are capable of performing conventional analytical and proteomic tasks, allowing for interfaces with other powerful techniques, such as mass spectrometry. Microdevices can be applied during the different stages of recombinant drug processing, such as gene isolation, DNA amplification, cell culture, protein expression, protein separation, and analysis. In addition, organs-on-chips have appeared as a viable alternative to testing biodrug pharmacokinetics and pharmacodynamics, demonstrating the capabilities of the miniaturized systems. The integration of individual established microfluidic operations and analytical tools in a single device is a challenge to be overcome to achieve a unique recombinant drug-on-a-chip device.     

Non-destructive method for determination of hydroxyl value of soybean polyol by LS-SVM using HATR/FT-IR

This paper presents the use of least-squares support vector machine (LS-SVM) for quantitative determination of hydroxyl value (OHV) of hydroxylated soybean oils by horizontal attenuated total reflection Fourier transform infrared (HATR/FT-IR) spectroscopy. A least-squares support vector machine (LS-SVM) calibration model for the prediction of hydroxyl value (OHV) was developed using the range 1805.1-649.9 cm(-1). Validation of the method was carried out by comparing the OHV of a series of hydroxylated soybean oil predicted by the LS-SVM model to the values obtained by the AOCS standard method. A correlation coefficient equal to 0.989 and RMSEP = 4.96 mg of KOH/g was obtained. This study demonstrates a better prediction ability of the LS-SVM technique to determine OHV in hydroxylated soybean oil samples by HATR/FT-IR spectra.     

High-performance liquid chromatographic separation of rolipram, bupivacaine and omeprazole using a tartardiamide-based stationary phase influence of flow rate and temperature on the enantioseparation

Chromatographic separation of the chiral drugs rolipram, bupivacaine and omeprazole on a tartardiamide-based stationary phase commercially named Kromasil CHI-TBB is shown in this work. The effect of temperature on the chromatographic separation of the chiral drugs using the Kromasil CHI-TBB stationary phase was determined quantitatively so as to contribute toward the design for the racemic mixtures of the named compound by using chiral columns. A decrease in the retention and selectivity factors was observed, when the column temperature increased. Van't Hoff plots provided the thermodynamic data. The variation of the thermodynamic parameters enthalpy and entropy are clearly negative meaning that the separation is enthalpy controlled.     

Controlling the electrophoretic mobility of single-walled carbon nanotubes: a comparison of theory and experiment

The electrophoretic mobilities of single-walled carbon nanotubes (SWNTs) in agarose gels subjected to negatively charged covalent functionalization and noncovalent anionic surfactant adsorption are compared using a simplified hydrodynamic model. Net charges are calculated on the basis of estimated friction coefficients for cylindrical rodlike particles. The effects of functionalization with negatively charged 4-hydroxybenzene diazonium and anionic sodium cholate are quantified and compared with model predictions. The adsorption of Na+ counterions into the nonionic surfactant layer adsorbed on SWNTs (Triton-X-405) is shown to induce a positive charge and reverse the mobility under select conditions. This effect has not been identified or quantified for nanoparticle systems and may be important in the processing of these systems.     

Paradoxical vocal fold motion: Presentation and treatment options

Paradoxical vocal fold motion is a rare disorder in which adduction of the folds occurs on inspiration. The disorder presents with signs of airway obstruction and often airway distress, so proper diagnosis by the otorhinolaryngologist is critical to subsequent management. We present a retrospective review of 10 patients with the diagnosis of paradoxical vocal fold motion seen over a 6-year period. Eight patients were females, and 6 required an acute airway intervention at presentation; 3 patients eventually underwent tracheotomy for respiratory decompensation. Six patients had a prior diagnosis of asthma, and this was determined to contribute to their respiratory status. Five patients were treated with botulinum toxin and 2 with flexible nasolaryngoscopic biofeedback, which improved the outcome. A review of the literature confirms a female predominance of patients presenting with paradoxical adduction and airway distress, often with a history of asthma and psychopathology. Our experience with botulinum toxin and biofeedback suggests that these procedures are viable treatment options in the management of patients with this disorder.     

On the global structure and asymptotic stability of low-stretch diffusion flame: Forced convection

The present work analyzes cylindrical diffusion flames (Tsuji burner) under low stretch condition, considering fuel injection also from the backward region of the burner. To highlight the fundamental aspects of this flame, some assumptions are imposed, like constant thermodynamic and transport coefficients, unitary Lewis number and no radiative heat loss. It is also considered potential flow model and incompressible Navier–Stokes model. Despite the simplicity of the former model, results from both models show good agreement. Also, an asymptotic analysis describing the problem far from the burner is able to capture the most important mechanisms controlling the flame, then the flame shape is determined and the dependence of the characteristic length scales on Peclet number (based on the burner properties), free stream velocity and stoichiometry is revealed. The results show that the flame width is proportional to the mass stoichiometric coefficient and reciprocal to the Peclet number the 1/4 power and free stream velocity the 3/4 power, and that the flame height is proportional to the square of the mass stoichiometric coefficient and to the square root of the ratio of Peclet number to free stream velocity. In addition, an asymptotic stability analysis reveals low-stretch flame extinction to be caused by reduction in fuel and oxidizer concentrations, which provides the range of the stoichiometric coefficient for stable regime, and at the same time the range of heat released.     

Characterization of O2 (1Δg)-derived oxidation products of tryptophan: A combination of tandem mass spectrometry analyses and isotopic labeling studies

The fragmentation mechanisms of singlet oxygen [O(2) ((1)Delta(g))]-derived oxidation products of tryptophan (W) were analyzed using collision-induced dissociation coupled with (18)O-isotopic labeling experiments and accurate mass measurements. The five identified oxidized products, namely two isomeric alcohols (trans and cis WOH), two isomeric hydroperoxides (trans and cis WOOH), and N-formylkynurenine (FMK), were shown to share some common fragment ions and losses of small neutral molecules. Conversely, each oxidation product has its own fragmentation mechanism and intermediates, which were confirmed by (18)O-labeling studies. Isomeric WOH lost mainly H(2)O + CO, while WOOH showed preferential elimination of C(2)H(5)NO(3) by two distinct mechanisms. Differences in the spatial arrangement of the two isomeric WOHs led to differences in the intensities of the fragment ions. The same behavior was also found for trans and cis WOOH. FMK was shown to dissociate by a diverse range of mechanisms, with the loss of ammonia the most favored route. MS/MS analyses, (18)O-labeling, and H(2)(18)O experiments demonstrated the ability of FMK to exchange its oxygen atoms with water. Moreover, this approach also revealed that the carbonyl group has more pronounced oxygen exchange ability compared with the formyl group. The understanding of fragmentation mechanisms involved in O(2) ((1)Delta(g))-mediated oxidation of W provides a useful step toward the structural characterization of oxidized peptides and proteins.     

Production of slow protonium in vacuum

We descrbe how protonium, the quasi-stable antiproton-proton bound system, has been synthesized following the interaction of antiprotons with the molecular ion in a nested Penning trap environment. From a careful analysis of the spatial distributions of antiproton annihilation events in the ATHENA experiment, evidence is presented for protonium production with sub-eV kinetic energies in states around n = 70, with low angular momenta. This work provides a new two-body system for studies using laser spectroscopic techniques.