Block copolymer based hybrid materials for direct electrochemical biosensing of nucleic acids and hemoproteins

基于嵌段共聚物的杂化材料，用于核酸和血红素蛋白的直接电化学生物传感

• 批准号: 379950571
• 负责人: Professor Dr. Felix H. Schacher
• 金额: --
• 依托单位: Institut für Organische Chemie und Makromolekulare Chemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/379950571?language=en
• 关键词: Block; copolymer; based; hybrid; materials

The project aims at the development of experimentally available reagentless electrochemical methods for identification and quantification of nucleic acids and hemoproteins. The level of circulating tumor DNA, RNA, or micro RNA can be taken as a measure for diagnostic and prognostic approaches to different types of cancer. Simultaneously, a considerable release of hemoprotein cytochrome c occurs during the treatment of cancer cells with anti-cancer drugs, and this level can then be taken as measure for the efficiency of a certain drug, the screening of new potential drug candidates or, in turn, as an indicator for cell resistance towards anti-cancer therapy. Simultaneous detection and quantification of both these biomarkers could considerably increase the efficiency of anti-cancer therapy with respect to (subtle) differences between different patients and help in developing strategies for personalized medicine.The sensitivity of direct electrochemical analysis strictly depends on the degree of integration of the analyte within the working electrode, in our case a nanocomposite material. For this purpose, a combination of carbon nanomaterials (carbon nanotubes or graphene oxide), noble metal nanoparticles (gold or silver nanoparticles), and amphiphilic block copolymers will be used. Therefore, we first focus on principles of organic/inorganic nanocomposite fabrication based on uniformly solubilized carbon nanomaterials and, eventually, noble metal nanoparticles. The employed amphiphilic diblock copolymers will serve a triple role. First, they are used as dispersing agent for the carbon nanomaterial due to hydrophobic interactions between the latter and the hydrophobic block. Further, the hydrophilic (and ionic) part of the material can be used to complex metal ions, followed by reduction to metal nanoparticles. Finally, after deposition on suitable substrates the diblock copolymer serves as matrix material for specific interaction with target biomolecules. The role of the carbon nanomaterial is to improve conductivity of the entire composite and the efficiency of electron transfer. Finally, the presence of metal nanoparticles is expected to catalyze electrochemical reactions. In total, these effects will synergistically provide a considerable improvement of biosensor sensitivity and selectivity for direct electrochemical analysis of both nucleic acids and cytochrome c.During the course of this project, a thorough examination of bioanalytical properties will involve a systematic investigation towards optimal construction and composition of the block copolymer/carbon nanomaterial/metal nanoparticle hybrid material. Subsequently, best working constructs will be used to assess biosensor characteristics, followed by the development of application strategies for direct electrochemical analysis of real samples (whole blood, plasma or serum).

该项目旨在开发实验可用的无试剂电化学方法，用于核酸和血红素蛋白的鉴定和定量。循环肿瘤DNA、RNA或微小RNA的水平可以作为不同类型癌症的诊断和预后方法的量度。同时，在用抗癌药物治疗癌细胞的过程中，发生血红素蛋白细胞色素c的大量释放，然后可以将该水平作为某种药物的效率的量度，筛选新的潜在药物候选物，或者反过来作为细胞对抗癌疗法的抗性的指标。这两种生物标志物的同时检测和定量可以大大提高抗癌治疗的效率，相对于不同患者之间的（细微）差异，并有助于制定个性化medicine.The直接电化学分析的灵敏度严格取决于工作电极内的分析物的集成程度，在我们的情况下，纳米复合材料。为此，将使用碳纳米材料（碳纳米管或氧化石墨烯）、贵金属纳米颗粒（金或银纳米颗粒）和两亲嵌段共聚物的组合。因此，我们首先专注于有机/无机纳米复合材料制造的基础上均匀溶解的碳纳米材料，并最终，贵金属纳米粒子的原则。所采用的两亲性二嵌段共聚物将起到三重作用。首先，由于碳纳米材料与疏水嵌段之间的疏水相互作用，它们被用作碳纳米材料的分散剂。此外，材料的亲水性（和离子）部分可用于络合金属离子，然后还原为金属纳米颗粒。最后，在合适的基底上沉积后，二嵌段共聚物用作与靶生物分子特异性相互作用的基质材料。碳纳米材料的作用是提高整个复合材料的导电性和电子转移效率。最后，金属纳米颗粒的存在有望催化电化学反应。总的来说，这些影响将协同提供一个相当大的改进的生物传感器的灵敏度和选择性的直接电化学分析的核酸和细胞色素c。在这个项目的过程中，生物分析性能的彻底检查将涉及到一个系统的调查，对最佳的结构和组合物的嵌段共聚物/碳纳米材料/金属纳米颗粒混合材料。随后，最好的工作结构将被用来评估生物传感器的特性，其次是直接电化学分析的真实的样品（全血，血浆或血清）的应用策略的发展。