ACT/SGER: Novel Conjugated Polymer Structures for Use in Bioterrorism Threat Assays

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This project explores the synthesis, design and application of conjugated polymers in biological assays that are relevant for bioterrorism threat assessment and defense. Specifically, the focus is on cationic conjugated polymers which behave as light harvesting macromolecules and which substantially improve, or "boost", the sensitivity of standard fluorometric detection and identification of DNA, RNA and protein structures. By improving optical sensitivity one will be able to examine samples, whether from the environment or from potentially infected methods to minimize non-specific interactions, which lead to sensor sensitivity losses, by molecular fine-tuning of the conjugated polymer. Polymers will be synthesized with specific molecular structures that probe the association between the optically active portion of the polymer and single stranded- or double stranded-DNA. Fluorinating substantial portions of the polymer chains will diminish hydrophobic interactions between the conjugated polymer and biological substrates. Potentially wasteful fluorescence quenching by photoinduced charge transfer mechanisms between the conjugated polymer and the electron rich sites of biological substrates will be examined by raising and lowering the electron affinity of the conjugated segments.The proposal's intellectual merit stems from its inherent multidisciplinary approach. It brings together distinct scientific fields, such as polymer synthesis and photophysics, mechanisms of biomolecular interactions, aqueous chemistry and analytical methodology. From the information generated by the proposed work we will be able to obtain insight not only on how to improve biosensors for bioterrorism assessment, but also on the weak intermolecular forces that exist between DNA and organic semiconducting materials. Such knowledge is woefully lacking and could provide the basis for a rational interfacing of electrical and optically active organic materials with biological matter. This award is supported jointly by the NSF and Directorate for Mathematics and Physical Sciences supports new concepts in basic research and workforce development with the potential to contribute to national security.The broader impact of the proposal rests on the potential use of biosensors in disease diagnostics and forensic applications, which provide society with obvious benefits. It should be noted that in developing countries it is the cost of diagnostics, not treatment, which prevents medical treatment. With the materials proposed in this study, it may be possible to reach sensitivity levels that allow DNA examination with naturally occurring quantities. Such an improvement would circumvent the need to do polymerase chain reaction amplification and would substantially lower overall diagnostic costs. Students involved in the project are exposed to an interdisciplinary range of scientific techniques and approaches and will be well trained to capitalize on the opportunities offered at the interface of multiple scientific fields.This award is supported jointly by the NSF and the Intelligence Community. The Approaches to Combat Terrorism Program in the Directorate for Mathematics and Physical Sciences supports new concepts in basic research and workforce development with the potential to contribute to national security.