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V I Dyukova

Publications and source records attributed to V I Dyukova.

4 recordsLinked to original sources

Design of carbohydrate multiarrays.

Recently, microarray technology has increasingly been widely applied in glycobiology. This technology has rather evident potential advantages: unlimited number of carbohydrate ligands coated onto one small sized chip, enormously low consumption of both carbohydrate ligands and carbohydrate-binding proteins to be tested, etc. Literature data demonstrate that three approaches are used for glycoarray design. The first one is based on the physical adsorption of glycomolecules on a surface (as in a common ELISA), the second one-on covalent immobilization, and the third one-on a streptavidin-biotin system. In all of the described methods, carbohydrate ligands were placed on chips as a 2D monolayer and high sensitivity was achieved due to fluorescent detection. Notably, a tendency of stepping from model chips toward real multiarrays, where the number of carbohydrate ligands can be up to two hundred, has been observed the last 2 years, this already producing a number of interesting findings when studying carbohydrate-binding proteins. In 2005 new construction, 3D glycochip was described, where 150 mum diameter polyacrylamide gel elements serve as microreactors instead of 2D dots. As a result of the 3D placement of a ligand, two orders of magnitude increase of its density is possible, this providing principal signal improvement during fluorescent detection and increasing method sensitivity. At the same time, carbohydrate consumption is low, i.e., approximately 1 pmol per gel element. Copolymerization chemistry enables the immobilization of several glycomolecule classes to the gel, in particular, aminospacered oligosaccharides, polyacrylamide conjugates, and even 2-aminopyridine derivatives of oligosaccharides, which are widely used in the structural analysis of glycoprotein N-chains.

Carbohydrates↗

Hydrogel glycan microarrays.

The technology of hydrogel microchips manufacturing, which was developed previously for covalent immobilization of DNA and proteins, was applied for the preparation of glycochips and combined glyco/protein chips. Microchips consist of hydrogel drops separated with hydrophobic surface. Spacered amino-saccharides and polyacrylamide glycoconjugates were used for immobilization. Gel elements were approximately 1 nl in volume (150 microm in diameter and 25 microm in height), and the amount of covalently immobilized saccharide in the glycoarray was 0.4-1.7 pmol per gel element. Hydrogel glycan microchips were used for quantitative assay of antibodies against blood group antigens and assay of lectins with fluorescent detection. In all cases, only specific interaction with chip-immobilized saccharides was observed, whereas the background signal was very low. The detection limit of on-chip assays was comparable to that of the standard 96-well plate assays. Mixing of reaction solution allowed us to decrease the duration of the assays significantly: 2-3 h for incubation and development steps and 10 min for washing. A method for determination of association constants for binding of compounds with chip-immobilized ligands from the kinetics of their binding is proposed. Combined microchips containing different types of biomolecules can be designed and used for simultaneous detection of different compounds.

ABO Blood-Group System↗

Quantitative immunoassay of biotoxins on hydrogel-based protein microchips.

Three-dimensional gel-based microchips with immobilized proteins were used for quantitative immunoassay of a series of plant (ricin and viscumin) and bacterial (staphylococcal enterotoxin B, tetanus and diphtheria toxins, and lethal factor of anthrax) toxins. It was shown that different types of immunoassays (direct, competitive, and sandwich type) could be carried out on gel microchips. As shown by confocal microscope studies, antigen-antibody interactions involving the formation of tertiary antibody-antigen-antibody complex occur in the whole volume of microchip gel elements. Sandwich assay on microchips with immobilized antibodies provided the highest sensitivity of detection (0.1 ng/ml for ricin). Antibodies labeled with fluorescent dyes, horseradish peroxidase conjugates, or biotinylated antibodies with subsequent treatment with labeled avidin were used as developing antibodies. The results of immunoassays were recorded using fluorescence, chemiluminescence, or matrix-assisted laser desorption ionization mass spectrometry directly from microchip gel elements. Gel microchips with immobilized capture antibodies were used to analyze the sample simultaneously for the presence of all six biotoxins with the same sensitivity as that for any single toxin.

Animals↗