Functionalized Conjugated Polymers for Signal Amplifying Biosensors and Sensor Arrays.

Conjugated Polymers;Biosensors;Microarrays;Materials Science and Engineering;Engineering;Materials Science and Engineering

Lee, KangwonMartin, David C. ;

University of Michigan

关键词: Conjugated Polymers;    Biosensors;    Microarrays;    Materials Science and Engineering;    Engineering;    Materials Science and Engineering;   

Others  :  https://deepblue.lib.umich.edu/bitstream/handle/2027.42/60834/kangwonl_1.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

Conjugated polymers (CPs) are great alternatives to the conventional fluorescencedyes as signaling reporters in biosensor design due to the fluorescent signal amplificationproperty of CPs. Two series of CPs, poly(p-phenyleneethynylene) (PPE) and poly(poxadiazole-co-phenylene) (POX) derivatives, have been systematically designed,developed, and studied in this thesis to devise highly sensitive and selective novelmolecular biosensors and sensor arrays for the detection of clinically important biologicalmolecules. The key concept developed in the thesis work was the molecular designprinciples to combine biological receptor molecules for specific detection of targetoligonucleotides and CPs as the signal transduction and amplification unit. To achievethis goal, a series of completely water-soluble and highly emissive conjugatedpolyelectrolytes (CPEs) were first developed through systematic investigation on thexxiicorrelation between the polymer structure and its water-solubility. We also developed amethod to bioconjugate CPEs to peptides and DNA by end-modification of the CPEswith a carboxylic acid group to develop hybrid bio/-synthetic sensory CPs and to achieveselective detection of target with amplified fluorescence signal in aqueous solution. DNAdetection results using the CPE-DNA hybrid system confirmed large signal amplificationby means of efficient Förster energy transfer from the energy harvesting CPEs to thefluorescent dye attached to the complementary analyte DNA. To apply the signalamplification scheme to practically more useful solid-state microarray novel conjugatedpolymers, POXs, having unique photochemical stabilities were developed. By applyingon-chip DNA synthesis on the POXs and achieving efficient Förster energy transfer fromPOXs to the dye-labeled target DNA we successfully developed signal amplifying DNAmicroarrays. The signal amplifying scheme was combined with a self-signaling conceptby means of introducing intercalating dyes and molecular beacon into the CPs for labelfreedetection. As a result of sensitive and selective prostate specific antigen detection hasbeen demonstrated. In addition to the biosensor development, the developedbioconjugation technique between biological molecules and CPEs was uniquely appliedto the development of CPE-antibody for live cell imaging. Selective live cell imaging ofhuman B-cell lymphoma and human T-cell leukemia having largely enhanced sensitivityand excellent selectivity was demonstrated by using the CPE-antibody.