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

本项目探索共轭聚合物的合成、设计和在生物检测中的应用，这些检测与生物恐怖主义威胁评估和防御相关。具体地说，重点放在阳离子共轭聚合物上，这种聚合物具有捕光大分子的作用，可以显著提高或“增强”标准荧光检测和识别DNA、RNA和蛋白质结构的灵敏度。通过提高光学灵敏度，人们将能够通过共轭聚合物的分子微调来检查样品，无论是来自环境还是来自潜在受感染的方法，以最大限度地减少导致传感器灵敏度损失的非特异性相互作用。将合成具有特定分子结构的聚合物，以探测聚合物的光学活性部分与单链或双链DNA之间的关联。对聚合物链的大部分进行氟化将减少共轭聚合物和生物底物之间的疏水相互作用。将通过提高和降低共轭链段的电子亲和力来研究共轭聚合物和生物底物富电子位置之间的光诱导电荷转移机制所产生的潜在的浪费荧光猝灭。该提议的智力优势来自于其固有的多学科方法。它汇集了不同的科学领域，如聚合物合成和光物理、生物分子相互作用机制、水化学和分析方法学。从拟议工作产生的信息中，我们不仅能够了解如何改进用于生物恐怖主义评估的生物传感器，而且还能够了解DNA和有机半导体材料之间存在的弱分子间力。这些知识严重缺乏，可以为电活性和光学活性有机材料与生物物质的合理接口提供基础。该奖项由NSF和数学和物理科学局联合支持，支持基础研究和劳动力发展方面的新概念，有可能为国家安全做出贡献。该提案的更广泛影响在于生物传感器在疾病诊断和法医应用中的潜在使用，这为社会带来了明显的好处。应当指出，在发展中国家，阻碍医疗的是诊断费用，而不是治疗费用。有了这项研究中提出的材料，有可能达到灵敏度水平，使DNA检测与自然发生的数量。这样的改进将避免进行聚合酶链式反应扩增的需要，并将显著降低总体诊断成本。参与该项目的学生将接触到一系列跨学科的科学技术和方法，并将接受良好的培训，以利用多个科学领域的接口提供的机会。该奖项由美国国家科学基金会和情报界共同支持。数学和物理科学局的反恐方法方案支持基础研究和劳动力发展方面的新概念，有可能对国家安全作出贡献。

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.