Donoso Barrera, A.;
(2009)
Nanomechanical sensor arrays for antibiotic drug analysis.
Doctoral thesis , UCL (University College London).
Abstract
The increasing emergence of antibiotic-resistant bacterial strains, such as methicillin-resistant Staphylococci aeurus (MRSA) is driving the development of new technologies to investigate antibiotics. This thesis describes the use of BioMEMS cantilever technology for the label-free detection of glycopeptide antibiotics in solution, at concentrations as low as ~ 1 nM. Multiple cantilever arrays were used to detect the antibiotics vancomycin, ristomycin, chloroeremomycin and oritavancin, which are often considered as the ‘last line of resistance’ to bacterial infections. Cantilevers wee coated with thiolated mucopeptide analogues found in antibiotic-sensitive bacteria and mutated peptides found in resistant strains. Drug-mucopeptide binding was found to generate a compressive surface stress and could discriminate the deletion of a single hydrogen bond associated with resistant peptides. Measured binding constant were in close agreement with reported data. Building on these findings, a new model is proposed to describe the propagation of surface stress on cantilevers and considers two factors – a chemical binding factor describing local drug-target interactions and a factor describing the mechanical connectivity –percolation – of the system. These findings and underlying concepts will simplify the design of new coating and devices to significantly enhance drug detection sensitivity. The second part of this thesis describes two novel approaches to optimise microcantilever technology. The first approach investigates the role of the gold adhesion layer by comparing silane self-assembled monolayers with conventional chromium/titanium layers. The second approach describes finite element simulations of a novel silicon-metal hybrid strain gauge with gauge factors of up to 800 that could be used as an alternative to optical cantilever bending detection. Prototype strain gauges were fabricated and tested, where the measurements were shown to agree remarkably well with the simulations.
| Type: | Thesis (Doctoral) |
|---|---|
| Title: | Nanomechanical sensor arrays for antibiotic drug analysis |
| Language: | English |
| Additional information: | Authorisation for digitisation not received |
| UCL classification: | UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Computer Science > CoMPLEX: Mat&Phys in Life Sci and Exp Bio UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > London Centre for Nanotechnology |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/17276 |
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