Target-Responsive Structural Switching for Nucleic Acid-Based Sensors

Abstract

Interest in the development of sensitive, selective, rapid, and cost-effective biosensors for biomedical analysis, environmental monitoring, and the detection of bioterrorism agents is rapidly increasing. A classic biosensor directly transduces ligand-target binding events into a measurable physical readout. More recently, researchers have proposed novel biosensing strategies that couple ligand-induced structural switching of biomolecules with advanced optical and electronic transducers. This approach has proven to be a highly general platform for the development of new biosensors. In this Account, we describe a series of electrochemical and optical nucleic acid sensors that use target-responsive DNA structures. By employing surface-confined DNA structures with appropriate redox labels, we can monitor target-induced structural switching of DNA or aptamer-specific small molecule probes by measuring electrochemical currents that are directly associated with the distance between the redox label and the electrode surface. We have also demonstrated significant improvements in sensing performance through optimization of the DNA self-assembly process at electrode surfaces or the introduction of nanomaterial-based signal amplification. Alternatively, gold nanoparticles interact differently with folded and unfolded DNA structures, which provides a visual method for detecting target-induced structural switching based on the plasmonic change of gold nanoparticles. This novel method using gold nanoparticles has proven particularly suitable for the detection of a range of small-molecule targets (e.g., cocaine) and environmentally toxic metal ions (e.g., Hg(2+)). Rational sequence design of DNA aptamers improves the sensitivity and increases the reaction kinetics. Recently, we have also designed microfluidic devices that allow rapid and portable mercury detection with the naked eye. This Account focuses on the use of bulk and nanoscale gold and DNA/aptamer molecules. We expect that researchers will further expand the analyte spectrum and improve the sensitivity and selectivity of nucleic acid sensors using functional biomolecules, such as DNAzymes, peptide aptamers and engineered proteins, and nanomaterials of different sizes, dimensions and compositions, such as carbon nanotubes, graphene, silicon nanowires, and metal nanoparticles or nanorods.

Comprehensive Screen of Metal Oxide Nanoparticles for DNA Adsorption, Fluorescence Quenching, and Anion Discrimination

“…[1][2][3][4][5][6] While DNA has been interfaced with metal and carbon-based nanomaterials, [6][7][8][9] limited work was carried out on metal oxide nanoparticles (MONPs). [10][11][12][13][14][15][16][17][18][19][20] MONPs represent a very important class of material due to their unique electronic, optical, magnetic and catalytic properties.…”

Sensing Parts-per-Trillion Cd2+, Hg2+, and Pb2+ Collectively and Individually Using Phosphorothioate DNAzymes

“…In order to provide on-site analysis, a number of metal sensing platforms have been developed. [2][3][4][5][6][7][8][9][10][11] DNAzymes are DNA-based catalysts obtained through in vitro selection. [12][13][14][15][16] Owing to their high catalytic efficiency and versatility in sensor design, RNA-cleaving DNAzymes have emerged as a unique metal sensing platform.…”

Tandem Phosphorothioate Modifications for DNA Adsorption Strength and Polarity Control on Gold Nanoparticles

“…[7][8][9] In particular, DNA-directed assembly of gold nanoparticles (AuNPs) has tremendously fueled the growth of nanobiotechnology. [10][11][12][13][14][15][16] The dense layer of DNA creates a unique colloidal system with many fundamentally interesting physical properties. 10 End-labeled thiol is the main anchor for linking DNA to AuNPs due to strong Au-thiol interactions.…”