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

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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).