The development of circularly polarised luminescence microscopy and responsive CPL probes

Polarised light is made up by adding together right handed and left handed circularly polarised components. Certain metal ions can emit light when they are raised into a high energy state. If the environment around that metal ion is chiral, i.e. left or right handed, then the emitted light can be enriched in the left or right handed component. This phenomenon is called circularly polarised luminescence. It is most well-defined in the emission of red or green light from chiral europium and terbium complexes, and has been observed for several complexes of these metal ions. When a chiral metal complex is located in the presence of other species that are right or left-handed, the emitted light may change its circular polarisation and this change can be tracked with time using a spectrometer that records these changes. Thus, the local chiral environement of the 'probe' metal complex is reported by changes to the circular polarisation of its emission.In this project, we seek to track such changes while observing the spatial localisation of the light-emitting metal complex using a microscope. We will build for the first time, a microscope that is able to monitor changes in the circular polarisation of emitted light from complexes of the emissive europium and terbium metal ions. In parallel, we shall make a series of left and right handed metal complexes that are not only emissive and resist degradation, but also can bind to important bioactive species that are themselves chiral, such as the protein, serum albumin, or the common chiral molecule, vitamin C. We have already shown that related emissive metal complexes can be engineered to be cell-permeable and can be designed to reside preferentially in certain compartments within a living cell. Thus, we shall pioneer the tracking or mapping of these bioactive chiral probes inside a living cell, using the new microscope to monitor their unique optical signal that reports on their local surroundings.

In the commercial sector, the research outputs are of interest to the pharmaceutical and fine chemical industries (GSK, Pfizer, Astra-Zeneca, Organon) who are interested in defining and understanding the role of key bioactive species (albumin in liver cells, various nucleic acids, location of key anti-oxidants like ascorbate) in cellular models. Several former group members and undergraduate tutees hold key research positions in these organisations, so that direct contact can be made should an important finding be revealed. The PI is a Director and founder of an award-winning spin-out company, launched in 2009 (FScan Ltd). This company would consider and assess any commercial opportunities linked to advances associated with new probe technology, in consultation with Durham University Technology Transfer Office. The PI holds over 30 patents and is familiar with issues of patenting, and the licensing of IP. The translational research activity in which the PI is involved currently has regional support from ONE-NE and North Star Finance, and links to a related translational research project, recently supported (March 2010) by 'METRC' as part of the Northern Universities 'N8 Molecular Engineering' initiative. The PI has links to several charities, and is currently a co-I on a CRCUK-led 2m programme grant on cancer imaging (with Newcastle University and the North East Cancer Research Centre). In the longer term (>10 years), the information on protein or metabolite (e.g., citrate) mapping may be of benefit to the wider health sector. Intracellular metabolite changes in certain cell types can offer a signature to disease progression, aiding early diagnosis. This could increase the quality of life for large cohorts of diseased patients. Communication and collaboration Towards the end of the grant period, a general science article will be written (e.g. Chemistry World) that can be given wider prominence, when coupled to a carefully constructed press release issued by the University Press Office and Media Team. We have experience of this form of dissemination. For example, in May 2009 articles appeared (via AP and Reuters) in over 25 national and international newspapers including the front-page lead article in the Daily Express. We shall work closely with the named advisers, engaging in quarterly meetings (either 'webinar' or face-to-face) to assess progress and consider the wider impact of the new work. The advisers themselves could also serve as disciples to spread the good news of any outstanding results to their peer group. The development of the CPL microscope would also be highlighted by the microscope equipment manufacturer, Leica, allowing dissemination of such a breakthrough to the commercial sector. Finally, the students will be encouraged to support Dr Palsson in schools based liaison activities, e.g. via the annual April science week locally. In addition, they will be encouraged to participate in the itinerant 'Spectroscopy in a Suitcase' road-show for schools, that our colleague Dr Beeby leads and to which Dr Palsson has contributed strongly over the past 4 years, as part of his long-term commitment to Outreach activity.