Evaluating Suppliers of Complex Systems: A Multiple Criteria Approach

Organizations are frequently required to make long-term strategic choices regarding the design and manufacture of innovative process equipment and systems which address future needs. An important consideration in such choices is the evaluation of the unique capabilities of available suppliers. Typically, such evaluations must be made relative to multiple attributes or criteria. This paper examines one such supplier evaluation process in the context of a major international manufacturer of telecommunication equipment. The ad hoc method used by the organization to evaluate the multiple factors involved is presented, and an alternative, structured approach to deal with the multiple factors is then discussed.     

Assay development and high-throughput screening of caspases in microfluidic format

Caspase proteases are familiar targets in drug discovery. A common format for screening to identify caspase inhibitors employs fluorogenic or colorimetric tetra-peptide substrates in 96, 384, or 1536 -well microtiter plates. The primary motivation for increasing the number of wells per plate is to reduce the reagent cost per test and increase the throughput of HTS operations. There are significant challenges, however, to moving into or beyond the 1536-well format, such as submicroliter liquid handling, liquid evaporation, increased surface area-to-volume ratios, and the potential for artifacts and interference from small air-borne particles such as lint. Therefore, HTS scientists remain keenly interested in technologies that offer alternatives to the ever-shrinking microtiter plate well. Microfluidic assay technology represents an attractive option that, in theory, consumes only subnanoliter volumes of reagents per test. We have successfully employed a microfluidic assay technology in fluorogenic screening assays for several caspase isoforms utilizing the Caliper Technologies Labchip platform. Caspase-3 is used as a representative case to describe microfluidic assay development and initial high-throughput screening results. In addition, microfluidic screening and plate-based screening are compared in terms of reagent consumption, data quality, and ease of operation.     

A L-RNA aptamer chiral stationary phase for the resolution of target and related compounds

In this paper, we report for the first time an aptamer-based chiral stationary phase (CSP) able to resolve racemates of both target and various related compounds. The enantiomers of tyrosine and analogues (11 enantiomeric pairs) were separated using an immobilized tyrosine-specific L-RNA aptamer as CSP and an aqueous buffer (8 mM Tris-HCl buffer, 25 mM NaCl, 5 mM MgCl2; pH 7.4) as mobile phase, at a column temperature of 10 degrees C. It appeared that the carboxylic and amino groups as well as the aromatic side chain of amino acid controlled the stereospecific recognition. Modifications on the polar groups were strongly detrimental for enantioselectivity while the replacement of the phenolic group by some bicyclic aromatic residues of different polarity, size or shape did not impair the enantioselective interaction. In addition, the effects of the mobile phase composition and column temperature upon the retention and stereoselective properties of the CSP were assessed. Finally, it was found that the immobilized RNA aptamer could be used under hydro-organic mobile phase conditions without alteration of the stationary phase stability.     

Solvothermal syntheses of Cu3P via reactions of amorphous red phosphorus with a variety of copper sources

Polycrystalline Cu₃P was successfully prepared under a wide variety of solvothermal conditions. The reaction of red phosphorus with several copper sources (copper metal, copper (I) iodide, copper (I) chloride and copper (II) chloride) at 150-200 °C for 1-2 days in water produced Cu₃P. Products were examined with powder X-ray diffraction, scanning electron microscopy and energy dispersive spectroscopy. Thermal analyses and optical spectroscopy were also performed. A detailed list of reaction conditions, products and impurity phases (where applicable) are reported.     

Rearrangement of epoxynitriles: a convenient homologation of acyclic and cyclic ketones to carboxylic acids

A convenient two-step homologation of both aliphatic and aromatic ketones to the corresponding carboxylic acid has been developed. First ketones were converted to epoxynitriles with the Darzens reaction. Second, a Lewis acid mediated rearrangement of these epoxynitriles with lithium bromide was achieved to give homologated secondary alkanoic acids (as well as aryl-alkanoic) in good yields. The mechanism and the scope of the rearrangement reaction were investigated. This strategy constitutes a two-step homologation of ketones to secondary carboxylic acids.     

Electrostatically stabilized metal oxide particle dispersions in carbon dioxide

We report electrostatic stabilization of micrometer-sized TiO(2) particles at long range (several micrometers) in liquid and supercritical CO(2) despite the ultralow dielectric constant, as low as 1.5. The counterions were solubilized in dry reverse micelles, formed with a low-molecular weight cationic perfluoropolyether trimethylammonium acetate surfactant, to prevent ion pairing with the particle surface. Dynamic light scattering and settling velocities indicate a particle diameter of 620-740 nm. The electrophoretic mobility of -2.3 x 10(-8) m(2)/V s indicated a particle charge on the order of -1.7 x 10(-17) C, or 105 elementary negative charges per particle. The balance of particle compression by an electric field versus electrostatic repulsion generated an amorphous arrangement of particles with 5-9 mum spacing, indicating Debye lengths greater than 1 mum. Scattering patterns also indicate that chains of particles may be achieved in CO(2) by dielectrophoresis with alternating fields. The electrostatic stabilization has been achieved by solubilizing a small concentration of counterions in only a small fraction of the reverse micelles in the double layer. Whereas many low-molecular weight surfactants have been shown to form reverse micelles in CO(2), very few polymers are able to stabilize micrometer-sized colloids sterically. Thus, electrostatic stabilization has the potential to expand markedly the domain of colloid science in apolar supercritical fluids.     

Synthesis and Circular Dichroism of Both Enantiomers of 2-deuterofluoroacetic acid ( Fluoro[2H1]acetic acid)

Sharpless epoxidation of (E)-1-(trimethylsilyl)[1-²H₁]oct-1-en-3-o1 ( 3a ) yielded (1S,2S,3S)- and (1R,2R,3R)-1-(trimethylsilyl)-1,2-epoxy[1-²H₁]octan-3-ols ( 4a and 4b , resp.) which were converted in three steps into (S)- and (R)-fluoro[ ²H₁]acetic acid ( 7a and 7b , resp.) in good yields. Their high isotopic and optical purity was established by ¹H- and ¹⁹F-NMR, mass, and circular-dichroism spectroscopy.     

Use of a native affinity ligand for the detection of G proteins by capillary isoelectric focusing with laser-induced fluorescence detection

Affinity probe capillary isoelectric focusing (CIEF) with laser-induced fluorescence was explored for detection of Ras-like G proteins. In the assay, a fluorescent BODIPY FL GTP analogue (BGTPgammaS) and G protein were incubated resulting in formation of BGTPgammaS-G protein complex. Excess BGTPgammaS was separated from BGTPgammaS-G protein complex by CIEF using a 3-10 pH gradient and detected in whole-column imaging mode. In other cases, a single point detector was used to detect zones during the focusing step of CIEF using a 2.5-5 pH gradient. In this case, analyte peaks passed the detector in approximately 5 min at an electric field of 350 V/cm. Detection during focusing allowed for more reproducible assays at shorter times but with a sacrifice in sensitivity compared to detection during mobilization. Resolution was adequate to separate BGTPgammaS-Ras and BGTPgammaS-Rab3A complexes. Formation of specific complexes was confirmed by adding GTPgammaS to samples containing BGTPgammaS-G protein. GTPgammaS competed with BGTPgammaS for G protein binding sites resulting in decreased BGTPgammaS-G protein peak heights. The concentrating effect of CIEF enabled detection limits of 30 pM.