Label-free electrical detection of DNA hybridization for the example of influenza virus gene sequences

Anal Biochem. 2008 Mar 1;374(1):143-53. doi: 10.1016/j.ab.2007.10.035. Epub 2007 Oct 30.

Abstract

Microarrays based on DNA-DNA hybridization are potentially useful for detecting and subtyping viruses but require fluorescence labeling and imaging equipment. We investigated a label-free electrical detection system using electrochemical impedance spectroscopy that is able to detect hybridization of DNA target sequences derived from avian H5N1 influenza virus to gold surface-attached single-stranded DNA oligonucleotide probes. A 23-nt probe is able to detect a 120-nt base fragment of the influenza A hemagglutinin gene sequence. We describe a novel method of data analysis that is compatible with automatic measurement without operator input, contrary to curve fitting used in conventional electrochemical impedance spectroscopy (EIS) data analysis. A systematic investigation of the detection signal for various spacer molecules between the oligonucleotide probe and the gold surface revealed that the signal/background ratio improves as the length of the spacer increases, with a 12- to 18-atom spacer element being optimal. The optimal spacer molecule allows a detection limit between 30 and 100 fmol DNA with a macroscopic gold disc electrode of 1 mm radius. The dependence of the detection signal on the concentration of a 23-nt target follows a binding curve with an approximate 1:1 stoichiometry and a dissociation constant of KD=13+/-4 nM at 295 K.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biosensing Techniques / methods
  • DNA / chemistry*
  • Electric Impedance
  • Genes, Viral*
  • Gold
  • Hemagglutinin Glycoproteins, Influenza Virus / genetics
  • Influenza A Virus, H5N1 Subtype / genetics*
  • Microelectrodes
  • Nucleic Acid Hybridization*
  • Oligonucleotide Array Sequence Analysis / methods*
  • Oligonucleotide Probes / chemistry
  • Spectrum Analysis

Substances

  • Hemagglutinin Glycoproteins, Influenza Virus
  • Oligonucleotide Probes
  • hemagglutinin, avian influenza A virus
  • Gold
  • DNA