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Chip and solution detection of DNA hybridization using a luminescent zwitterionic polythiophene derivative

Abstract

Electronic polymers in aqueous media may offer bioelectronic detection of biospecific interactions. Here we report a fluorometric DNA hybridization detection method based on non-covalent coupling of DNA to a water-soluble zwitterionic polythiophene derivative. Introduction of a single-stranded oligonucleotide will induce a planar polymer and aggregation of the polymer chains, detected as a decrease of the intensity and a red-shift of the fluorescence. On addition of a complementary oligonucleotide, the intensity of the emitted light is increased and blue-shifted. The detection limit of this method is at present 10−11 moles. The method is highly sequence specific, and a single-nucleotide mismatch can be detected within five minutes without using any denaturation steps. The interaction with DNA and the optical phenomena persists when the polymer is deposited and patterned on a surface. This offers a novel way to create DNA chips without using covalent attachment of the receptor or labelling of the analyte.

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Figure 1: Absorption and emission data for POWT/DNA complexes.
Figure 2: The formation of POWT/DNA complexes.
Figure 3: Circular dichroism spectra of POWT/DNA complexes.
Figure 4: Fluorescence images of POWT/DNA complexes.

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Acknowledgements

We thank Mats R. Andersson and co-workers, Chalmers University, Sweden, for synthesis of the POWT. We wish to thank Xiangjun Wang for help in the studies of time evolution of photoluminescence in an integrating sphere, and Marilla Lilja for her contributions to microcontact printing of polymers. Per Björk and Gustav Axehult contributed to development of chip-based methods.

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Correspondence to K. Peter R. Nilsson.

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Nilsson, K., Inganäs, O. Chip and solution detection of DNA hybridization using a luminescent zwitterionic polythiophene derivative. Nature Mater 2, 419–424 (2003). https://doi.org/10.1038/nmat899

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