Luminescent polymer-PNA optical assays for the detection of nucleotide mutations associated with resistant leukaemia.

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Luminescent polymers are driving forward a new generation of cheap, flexible displays based on their excellent photoluminescence properties combined with high stability and simple chemical tailoring. These properties can be exploited in other fields and, through the advent of water soluble luminescent polymers, applications in the area of biological sciences are now possible. Both anionic and cationic polymers can be synthesised and, via their charged nature, can bind readily electrostatically to DNA. With the addition of appropriate peptide nucleic acid (PNA) it becomes possible to ?detect? the specific nucleotide sequence of a segment of the DNA, using cheap, simple and fast optical detection. The polymer acts as an antenna for the system, strongly absorbing light in the violet, with the exciton thus created able to migrate along the length of the polymer chain. If a complimentary, fluorophore-labelled, PNA is also bound to the DNA strand, rapid and efficient Forster Energy transfer can occur, transferring the excitation energy from the polymer to the PNA label. This emission can then be detected and used to signal that the PNA has specifically bound to its target DNA. Because of the optical properties of the polymer, ?optical? amplification of up to one million-fold is possible for the entire assay. Currently in the Physics Department at Durham we are working to understand and optimise the full photophysics of this complex system. In order to extend the work into real application areas we need to understand the hybridisation interactions between DNA and PNA, how to optimise this in the presence of the luminescent polymer and how we should improve the polymer to optimise it for the assay application. Our initial assay is tailored specifically at tackling well known problems in nucleotide mutation detection so we need to gain experience working with it in a clinical environment. A Discipline Hopping award would be an ideal opporunity to take us on this next step and to maximize the potential of the physics when applied to biological analysis in an area of real clinical need.