DNA origami-based reconfigurable chiral plasmonic nanodevices for analytical applications

Abstract

DNA origami folds DNA into complex nanostructures, which can serve as templates for assembly of various hetero element components with nanometre precision. By accurately attaching metal nanoparticles to DNA origami templates, controlled coupling of plasmonic resonances is enabled. In the coupled plasmonics system, optical responses are sensitive to the relative positioning of the metal nanoparticles. Particularly, the circular dichroism (CD) responses can be readily correlated with the structural configurations of the chiral plasmonic assemblies. With rational design, CD signals can be altered by molecular stimuli through configurational change. The thesis explored two analytical applications of the DNA origami-based reconfigurable chiral plasmonic nanodevices: I) detecting biomolecules; II) characterizing aptamers. Aptamers are single-stranded DNA and RNA strands, which specifically bind to targets with high affinities. Aptamers have emerged as promising alternatives to protein antibodies for molecular detection, drug delivery, and therapeutics due to low production cost and low batch-to-batch variabilities. The successful applications of aptamers lie in the capabilities of the aptamers to differentiate the target (specificities) and to capture the target (affinities), represented by the dissociation constant (KD) of the binding reactions. However, the characterization of aptamers, that is, the measurement of affinities and specificities of the aptamers remains problematic as partitioning bound and unbound aptamers typically relies on specific characteristics of a particular aptamer-target complex (size, charge, and fluorescent change etc.). Often, the choice of characterization method is not optimal due to limited lab resources. By developing a competitive hybridization-based strategy, we engineered the reconfigurable chiral plasmonic assemblies to enable the reliable characterization of versatile aptamers, including aptamers targeting small molecules and macromolecules, as well as aptamers with high and low affinities. Aptamers are common receptors in biosensors, which play important roles in environmental monitoring, food safety, and diagnostics. Taking advantage of the high CD signal-to-noise ratio of the reconfigurable chiral plasmonic assemblies serving as the transducers, we developed biosensors that allowed selective and sensitive detection of targets. The CD-based biosensors can perform even in strongly light-absorbing environments, demonstrating that the reconfigurable chiral plasmonic transducers are promising alternatives to traditional fluorescent probes. We expect the results may address the discrepancy in the aptamer characterization and provide a practical route to molecular detection.