Chemical modification of polymeric microchip devices

Analytical polymeric microchips in both fluidic and array formats offer short analysis times, coupling of many sample processing and chemical reaction steps on one platform with minimal sample and reagent consumption, as well as low cost, minimal fabrication times and disposability. However, the invariable bulk properties of most commercial polymers have driven researchers to develop new modification strategies. This article critically reviews the scope and development of chemical modifications of such polymeric chips since 2003. Surface modifications were based on chemical derivatization or activation of surface layers with reagent solutions, reactive gases and irradiation. Bulk modification of polymer chips used newly incorporation of monomers with selective chemical functionalities throughout the bulk polymer material and integrated the chip modification and fabrication into a single step. Such modifications hold a great promise for establishing a true ‘lab-on-chip’ as can be seen from many novel applications for modulating electroosmosis, suppressing protein adsorption in microchip capillary electrophoretic separations, extraction of analytes and for zone-specific binding of enzymes and other biomolecules.     

High quality drug screening by capillary electrophoresis: A review

High quality assays are needed in drug discovery to reduce the high attrition rate of lead compounds during primary screening. Capillary electrophoresis (CE) represents a versatile micro-separation technique for resolution of enzyme-catalyzed reactions, including substrate(s), product(s), cofactor(s) and their stereoisomers, which is needed for reliable characterization of biomolecular interactions in free solution. This review article provides a critical overview of new advances in CE for drug screening over the past five years involving biologically relevant enzymes of therapeutic interest, including transferases, hydrolases, oxidoreductases, and isomerases. The basic principles and major configurations in CE, as well as data processing methods needed for rigorous characterization of enzyme inhibition are described. New developments in functional screening of small molecules that modulate the activity of disease-related enzymes are also discussed. Although inhibition is a widely measured response in most enzyme assays, other important outcomes of ligand interactions on protein structure/function that impact the therapeutic potential of a drug will also be highlighted, such as enzyme stabilization, activation and/or catalytic uncoupling. CE offers a selective platform for drug screening that reduces false-positives while also enabling the analysis of low amounts of complex sample mixtures with minimal sample handling.     

Room temperature phosphorescence in the liquid state as a tool in analytical chemistry

A wide-ranging overview of room temperature phosphorescence in the liquid state (RTPL¹) is presented, with a focus on recent developments. RTPL techniques like micelle-stabilized (MS)-RTP, cyclodextrin-induced (CD)-RTP, and heavy atom-induced (HAI)-RTP are discussed. These techniques are mainly applied in the stand-alone format, but coupling with some separation techniques appears to be feasible. Applications of direct, sensitized and quenched phosphorescence are also discussed. As regards sensitized and quenched RTP, emphasis is on the coupling with liquid chromatography (LC) and capillary electrophoresis (CE), but stand-alone applications are also reported. Further, the application of RTPL in immunoassays and in RTP optosensing—the optical sensing of analytes based on RTP—is reviewed. Next to the application of RTPL in quantitative analysis, its use for the structural probing of protein conformations and for time-resolved microscopy of labelled biomolecules is discussed. Finally, an overview is presented of the various analytical techniques which are based on the closely related phenomenon of long-lived lanthanide luminescence. The paper closes with a short evaluation of the state-of-the-art in RTP and a discussion on future perspectives.