Multiplexed DNA-Modified Electrodes

We report the use of silicon chips with 16 DNA-modified electrodes (DME chips) utilizing DNA-mediated charge transport for multiplexed detection of DNA and DNA-binding protein targets. Four DNA sequences were simultaneously distinguished on a single DME chip with 4-fold redundancy, including one incorporating a single base mismatch. These chips also enabled investigation of the sequence-specific activity of the restriction enzyme Alu1. DME chips supported dense DNA monolayer formation with high reproducibility, as confirmed by statistical comparison to commercially available rod electrodes. The working electrode areas on the chips were reduced to 10 μm in diameter, revealing microelectrode behavior that is beneficial for high sensitivity and rapid kinetic analysis. These results illustrate how DME chips facilitate sensitive and selective detection of DNA and DNA-binding protein targets in a robust and internally standardized multiplexed format

DNA charge transport over 34 nm

Molecular wires show promise in nanoscale electronics but the synthesis of uniform, long conductive molecules is a significant challenge. DNA of precise length, by contrast, is easily synthesized, but its conductivity has not been explored over the distances required for nanoscale devices. Here we demonstrate DNA charge transport (CT) over 34 nm in 100-mer monolayers on gold. Multiplexed gold electrodes modified with 100-mer DNA yield sizable electrochemical signals from a distal, covalent Nile Blue redox probe. Significant signal attenuation upon incorporation of a single base pair mismatch demonstrates that CT is DNA-mediated. Efficient cleavage of these 100-mers by a restriction enzyme indicates that the DNA adopts a native conformation that is accessible to protein binding. Similar electron transfer rates are measured through 100-mer and 17-mer monolayers, consistent with rate-limiting electron tunneling through the saturated carbon linker. This DNA-mediated CT distance of 34 nm surpasses most reports of molecular wires

Cationic iridium(III) complexes bearing ancillary 2,5-dipyridyl(pyrazine) (2,5-dpp) and 2,2 ':5 ',2 ''-terpyridine (2,5-tpy) ligands : synthesis, optoelectronic characterization and light-emitting electrochemical cells

Four cationic iridium(III) complexes of the form [Ir(C^N)2(N^N)]+ bearing either a 2,5-dipyridylpyrazine (2,5-dpp) or a 2,2′:5′,2′′-terpyridine (2,5-tpy) ancillary ligand and either 2-phenylpyridine (ppy) or a 2-(2,4-difluorophenyl)-5-methylpyridine (dFMeppy) cyclometalating ligands were synthesized. The optoelectronic properties of all complexes have been fully characterized by UV-visible absorption, cyclic voltammetry and emission spectroscopy. The conclusions drawn from these studies have been corroborated by DFT and TDDFT calculations. The four complexes were assessed as emitters in light-emitting electrochemical cells. Complex 1a, [Ir(ppy)2(2,5-dpp)]PF6, was found to be a deep red emitter (666 nm) both in acetonitrile solution and in the electroluminescent device. Complex 2a, [Ir(ppy)2(2,5-tpy)]PF6 was found to be an orange emitter (604 nm) both in solution and in the LEEC. LEECs incorporating both of these complexes were stable over the course of around 4–6 hours. Complex 1b, [Ir(dFMeppy)2(2,5-dpp)]PF6, was also determined to emit in the orange (605 nm) but with a photoluminescent quantum yield (ΦPL) double that of 2a. Complex 2b, [Ir(dFMeppy)2(2,5-tpy)]PF6 is an extremely bright green emitter (544 nm, 93%). All four complexes exhibited quasireversible electrochemistry and all four complexes phosphoresce from a mixed charge-transfer excited state.PostprintPeer reviewe

Following Anticancer Drug Activity in Cell Lysates with DNA Devices

There is a great need to track the selectivity of anticancer drug activity and to understand the mechanisms of associated biological activity. Here we focus our studies on the specific NQO1 bioactivatable drug, ß-lapachone, which is in several Phase I clinical trials to treat human non-small cell lung, pancreatic and breast cancers. Multi-electrode chips with electrochemically-active DNA monolayers are used to track anticancer drug activity in cellular lysates and correlate cell death activity with DNA damage. Cells were prepared from the triple-negative breast cancer (TNBC) cell line, MDA-MB-231 (231) to be proficient or deficient in expression of the NAD(P)H:quinone oxidoreductase 1 (NQO1) enzyme, which is overexpressed in most solid cancers and lacking in control healthy cells. Cells were lysed and added to chips, and the impact of β-lapachone (β-lap), an NQO1-dependent DNA-damaging drug, was tracked with DNA electrochemical signal changes arising from drug-induced DNA damage. Electrochemical DNA devices showed a 3.7-fold difference in the electrochemical responses in NQO1+ over NQO1− cell lysates, as well as 10–20-fold selectivity to catalase and dicoumarol controls that deactivate DNA damaging pathways. Concentration-dependence studies revealed that 1.4 µM β-lap correlated with the onset of cell death from viability assays and the midpoint of DNA damage on the chip, and 2.5 µM β-lap correlated with the midpoint of cell death and the saturation of DNA damage on the chip. Results indicate that these devices could inform therapeutic decisions for cancer treatment