Award details

Measurement and identification of glycans on arrays and nanoparticles

Reference	BB/I015582/1
Principal Investigator / Supervisor	Professor Morgan Alexander
Co-Investigators / Co-Supervisors	Professor Martyn Davies, Professor Ian Gilmore
Institution	University of Nottingham
Department	Sch of Pharmacy
Funding type	Skills
Value (£)	91,932
Status	Completed
Type	Training Grants
Start date	01/10/2011
End date	30/09/2015
Duration	48 months

Abstract

unavailable

Summary

The aim of this project is to develop reliable and quantifiable measurements of the surface chemistry of printed glycan arrays. The printing process leads to a multi-component surface either through diluents, contaminants or additives in the printing solution or through incomplete surface coverage after printing owing to differences in surface energies and wettability. Secondary ion mass spectrometry (SIMS) is a powerful technique to image the surface chemistry at high spatial resolution (200 nm is possible) however the mass spectrum is highly complex making it very difficult to separate out the chemical contributions. We propose to use the spatial chemical heterogeneity with discriminant multivariate analytical techniques to separate out the chemical components as well as develop novel approaches with G-SIMS (developed at NPL) to identify the separate chemical components. Once chemical components have been separated the challenge is then todeduce structural information about the molecule from the mass spectrum and consequently identify the molecule. Recently, we have developed a novel informatics approach based on the SMILES molecular structure format to develop a database, G-DB1, of fragmentation ions for mass spectrometry. This has proved to be very effective for the identification of molecules in other surface analytical areas. This project will develop the approach for glycans using an informatics approach to search through relevant publicly available databases of chemical structures such as KEGG and PubChem and the FunctionalGlycomicsGateway. Nanoparticles may be used for both diagnostic and delivery mechanisms for glycan binding proteins. For example, gold nanoparticles functionalised with lectin exhibit specific interactions with glycans which may be measured using a variety of transduction methodologies including electrochemical. Also, gold nanoparticles functionalised with glycans may bind to viruses such as HIV providing a steric barrier to cell entry. For correct correlation with measured activity it is important to know what is at the nanoparticle surface. This project will develop methods to chemically characterise the surface of gold nanoparticles using C60 SIMS. Whilst SIMS is powerful and has high resolution it necessitates the use of vacuum which slows the rate of analysis and sample throughput. Over the last few years the field of ambient surface mass spectrometry has advanced rapidly especially for desorption electrospray ionisation (DESI) and plasma assisted desorption ionisation (PADI). In this project we will investigate the effectiveness of these techniques for the identification of glycans at surfaces and bound proteins (DESI). The two ionisations sources will be coupled to an Orbitrap mass spectrometer providing a mass resolution of > 100,000 and a mass accuracy of better than 3 ppm which will significantly help structural elucidation.

Committee	Not funded via Committee
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	Training Grant - Industrial Case

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