Recent trends in ultra‐fast HPLC: New generation superficially porous silica columns

New generation columns, i.e. packed with superficially porous silica particles are available as trade names with following manufacturers: Halo, Ascentis Express, Proshell 120, Kinetex, Accucore, Sunshell, and Nucleoshell. These provide ultra‐fast HPLC separations for a variety of compounds with moderate sample loading capacity and low back pressure. Chemistries of these columns are C₈, C₁₈, RP‐Amide, hydrophilic interaction liquid chromatography, penta fluorophenyl (PFP), F5, and RP‐aqua. Normally, the silica gel particles are of 2.7 and 1.7 μm as total and inner solid core diameters, respectively, with 0.5‐μm‐thick of outer porous layer having 90 Å pore sizes and 150 m²/g surface area. This article describes these new generation columns with special emphasis on their textures and chemistries, separations, optimization, and comparison (inter and intra stationary phases). Besides, future perspectives have also been discussed.     

Diffusion of dextran within poly(methacrylic acid) hydrogels

We describe an investigation of fluorescence correlation spectroscopy into the diffusion of fluorescein‐tagged dextran (FDEX) in a poly(methacrylic acid) (PMAA) hydrogel. The temperature dependence of FDEX diffusion is shown to follow Zimm behavior in pure water, and the decrease in the diffusion coefficient when in the PMAA hydrogel has been modeled. The addition of acid and alkali (HCl and NaOH, respectively) not only control the swelling and collapse of the hydrogel but also reveal a strong pH dependence of the dextran diffusion coefficient, which shows a (nonmonatonic) increase with pH. The addition of NaCl and CaCl₂ salts similarly showed evidence of network swelling, most notably at low salt concentration, but also that the diffusion coefficient within the gel at these low concentrations is larger than that in the equivalent solution without the hydrogel, indicating that the combination of hydrogel and salt works to increase the diffusion coefficient above that in pure water. © 2012 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2012     

Transparent Rule Based CAS to Support Formalization of Knowledge

The complexity of computer algebra systems hinders many students to develop an adequate mental model of such a system. As a result, they are often suspicious about the results and the didactical benefit is limited. The paper suggests that it is possible to design a transparent version of a computer algebra system that gives students a transparent access to the inner working of such a system. Didactical uses of such a system are discussed.     

High throughput sonication: evaluation for compound solubilization

Dissolution of organic compounds in DMSO in HTS plate or tube format is a difficult problem as users move to higher compression plate formats. Precipitation of compounds from DMSO screening stocks is a recognized problem in the HTS materials management process. The adverse effect of freeze thaw cycles on DMSO stock solutions stored in plate format as a result of cherry picking operations has led to the gradual replacement of plate-based storage with tube-based storage so as to minimize the number of freeze thaw cycles. Compound solubility in DMSO is markedly decreased by uptake of small quantities of water. We attribute this effect to the non ideal properties of DMSO water mixtures such that cavity formation in solvent, a necessary step in dissolution, is more difficult in wet DMSO than in dry DMSO or in pure water. We report here that efficient compound dissolution is possible even in 384 well format by the use of in-well plate-based sonication. Surprisingly, compounds precipitated from DMSO stocks either by water uptake or repeated freeze thaw cycles can be re-dissolved by low energy sonication. Finally, we demonstrate that precipitation of compound from DMSO stock solutions is synergistically enhanced by water uptake into DMSO compound stock solutions as well as by increasing the number of freeze thaw cycles.     

Confirmation of primary active substances from high throughput screening of chemical and biological populations: a statistical approach and practical considerations

Many biologically important substances are discovered through screening of relevant chemical or biological libraries. The ability to find the active substances ("hits") from any random collection is largely determined by the quality of the assay and screening conditions. When a large population is screened for a specific characteristic, each member of that population is usually tested only once. Errors in the measurements require additional follow-up tests to confirm that each hit from the primary screen is truly active. In this report, we present a statistical model system that predicts the reliability of hits from a primary test as affected by the error in the assay and the choice of the hit threshold (hit limit). The hit confirmation rate, as well as false positive (representing substances that initially fall above the hit limit but whose true activity are below the hit limit) and false negative (representing substances that initially fall below the hit limit but whose true activity are in fact greater than the hit limit) rates have been analyzed with this model by computational simulation. This model can also be used in screen validation and post-screening data analysis. The statistical analysis presented here has broad implications and is applicable to screening of any large population for any specific characteristic. Obvious applications include drug discovery, gene chip analysis, population biology, directed molecular evolution, biological panning, and combinatorial material sciences.