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DNA sensors: Playing the field

A promising plasmon-based DNA detection technique becomes more sensitive and accurate with the use of an electric field.

Genetic screening technology has advanced at breathtaking speed in recent years, yet techniques such as the sensitive detection of specific DNA remain confined to the laboratory. Taking such measurements into the field, however, could open up an array of possibilities in health science, including the detection of airborne pathogens. Scientists led by Yao-Qun Li from Xiamen University in China have now developed a compact and highly sensitive technology for the detection of specific DNA with the accuracy to reject even single base DNA mutations1. The high sensitivity and strong miniaturization potential of this technology could allow it to be integrated into handheld, lab-on-chip devices for field use.

Fig. 1: Conventional SPCDE (left) is affected by false negative DNA detection (top) due to signal deviation related to the inclination of hybridized complexes, and false positives (bottom) due to the amplified signal from hybridization with DNA having single base mismatches. Electrically assisted SPCDE (right) resolves both issues to improve the sensitivity and accuracy of DNA detection.© 2011 ACS

The researchers based their sensor on a technique called surface plasmon-coupled directional emission (SPCDE), which detects specific target DNA by measuring the distant-dependent signal between a fluorescently labeled ‘hairpin’ DNA probe and a gold surface. The hairpin DNA probes are prepared by depositing a DNA probe onto a gold substrate. When exposed to a sample of single-stranded DNA, strands with probe-matching sequences bond to the probes and form a hybridized duplex that unfolds the hairpin. This moves the fluorescent label a few nanometers off the surface where it interacts with the plasmon surface resonances of gold electrons, which can then be detected with high sensitivity.

However, SPCDE devices can suffer from high false negative detection rates because the hybridized DNA duplexes occasionally form inclined structures that fail to produce the full plasmon response. False positives are also a problem because DNA strands with single base mutations are still able to hybridize to the probe and couple with the surface plasmon to produce a signal.

Li and his co-workers resolved these accuracy issues through the skillful combination of an electric field with SPCDE (see image). Applying an electric field allowed the team to assemble the DNA into systematically oriented layers, eliminating the orientation effect. The electric field also reduces the stability of DNA duplexes containing a single base mismatch, preventing hybridization. These two effects increase the accuracy of SPCDE detection by a factor of ten. “This method amplifies the signal of matches and intelligently suppresses that of mismatches,” explains Li.

The team is now investigating how the densities and sequences of gold-anchored DNA affect sensor behavior.

References

  1. Cao, S.-H., Xie, T.-T., Cai, W.-P., Liu, Q. & Li, Y.-Q. Electric field assisted surface plasmon-coupled directional emission: An active strategy on enhancing sensitivity for DNA sensing and efficient discrimination of single base mutation. J. Am. Chem. Soc. 133, 1787–1789 (2011).

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DNA sensors: Playing the field. NPG Asia Mater (2011). https://doi.org/10.1038/asiamat.2011.53

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  • DOI: https://doi.org/10.1038/asiamat.2011.53

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