The aim of my current research is the fusion of novel plasmonic nanotechnology with advanced optical imaging techniques for the study of pathological processes in biological tissues, and the refinement of this technology for implementation in a clinical diagnostic environment.
The presence of a metallic surface can dramatically alter the emission properties of a locally situated fluorophore, via the near-field optical interaction of the molecule and plasmon resonances in the metal. This can result in enhanced fluorescence emission and greater photostability by reducing the excited state lifetime. I am investigating these plasmon-induced fluorescence modifications for a wide variety of nanostructured systems, such as metal-island films, individual gold nanospheres, and lithographically patterned nanoparticle arrays. The strong dependence of these effects on fluorophore-metal separation is being explored as a means to increase both lateral and longitudinal resolution in confocal microscopy. This will reveal a level of physical detail in biological systems that is currently inaccessible with conventional technologies
(Left) Atomic force microscope image of an array of Silver nanoparticles formed by nanosphere lithography. Each particle is approximately 100 nm in diameter.
(Middle) Transmitted light image of an array of nanoparticles.
(Right) Fluorescence lifetime image of the same region showing an enhancement in intensity and reduction in lifetime around the nanoparticles.
High-content cellular analysis
Current high-content screening techniques involve the analysis of cellular assays using high-resolution imaging combined with sophisticated algorithms for automated image analysis. Commercially available platforms are invariably highly specialised and expensive. I have developed a novel method of high-content analysis utilising changes in fluorescence lifetime in the vicinity of a rough Au film. A mammary carcinoma cell line has been created expressing EGFP in the membrane, which are plated onto thin gold filmsfilms. FLIM images show a large reduction in lifetime for membrane-bound GFP in close proximity to the Au surface. Addition of a suitable ligand leads to internalization of the GFP with a corresponding increase in lifetime. The degree of internalization can be very quickly and easily checked using standard lifetime analysis techniques.
(Left) Fluorescence lifetime images of cells on glass and Au films, expressing GFP in the membrane (mutant, wildtype), after ligand induced internalization (SDF), and expressed throughout the cytosol.
Curriculum Vitae
Post-doc: Kings College London (2006-)
Post-doc: NTT Basic Research Laboratories,
Japan (2004-2006)
PhD research: Clarendon Laboratory, University of Oxford (2000-2004)
MPhys Physics: Christ Church, University of Oxford (1996-2000)
Other experience: Ultra-fast and near-field optical spectroscopy of semiconductor nanostructures (quantum wires / dots).
Magneto-optics and mK magneto-transport measurements.
Infrared single photon detection and counting techniques. Photon frequency upconversion.
