Liquid crystals that detect DNA sequence could be developed into cheap, portable detectors as small as a wristwatch
Liquid crystals that realign in response to DNA can reveal subtle sequence alterations, even a single base mutation, report US chemists. The finding could lead to cheap, portable alternatives to current lab-based analytical detectors, say the researchers.
Daniel Schwartz at the University of Colorado showed that liquid crystals, which naturally align themselves perpendicular to the surface of a surfactant-coated glass slide, tilt slightly following the addition of short lengths of single stranded DNA. The addition of complementary strands of DNA - with a base sequence that would bind to the strands on the slide - triggers the tilted crystals to return to their perpendicular alignment. However, adding a non-complementary DNA strand - with a sequence that differed by just one base - causes no such response. These differing responses of the liquid crystals were visible to the naked eye.
Fluorescence-based detection is the current state-of-the-art for DNA microarrays, but Schwartz notes that his technology does not require labelling of sample DNA with fluorescent probes, and doesn’t need ’expensive, bulky’ lasers or photodetectors.
Single-base mismatches are used as control experiments in conventional DNA microarray technology, so it was important for Schwartz’s team to show that this was possible with their technology.
’The relevance of a one-base-pair mismatch is that it relates to the degree of precision with which this technology can identify a DNA sequence,’ says Schwartz, professor of chemical and biological engineering. ’If two closely-related bacteria had similar DNA sequences in a certain gene, one might need to distinguish a single base difference in order to make a correct diagnosis,’ he says, ’similarly, some genetic defects which cause genetic disease in humans are related to a single changed base.’
The study is only an initial demonstration of the technology, and more work is needed before a consumer product can be considered.
Nevertheless, says Schwartz, ’In principle, a device based on this technology could be very similar in size and cost to a digital wristwatch with an LCD display - compact, inexpensive, and battery powered. These properties make it well suited to point-of-use applications.’
The LC interface has attracted much attention for its potential to amplify molecular level interactions into signals visible by the naked eye, says Jay Groves, associate professor of chemistry at the University of California, Berkeley. Groves has a paper in press in ChemPhysChem using similar LC arrays to look at membrane-cell junctions, though he says that Schwartz’s technique with DNA hybridization, which he hadn’t seen before, works rather better.
’The fundamental problem with all of these types of technology is that they really are very advanced and expensive to produce,’ says Groves. ’A typical DNA microarray will have tens of thousands of spots, each with a unique DNA strand. It took decades for LC arrays with this many pixels to be developed (for flat panel display), and surely no method of printing DNA on such a complex substrate currently exists.’
From a business side, he adds, DNA printing technology is widely accepted and robust. For a new detection method to have much chance of success it needs either to read traditional arrays or offer a capability so far beyond current capabilities that people are induced to switch, he says.
As well as his work with LC arrays, Groves recently published work on a DNA microarray device based on electrostatic repulsion. The technique uses negatively charged silica beads to detect spots on DNA microarrays where single-stranded DNA hybridizes to form double-stranded DNA.
’The LC technique is indeed elegant but (like our bead technology) it faces many challenges to break through to a commercial product,’ he concluded.Bea Perks
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J. Am. Chem. Soc54, 391 (DOI: 10.1021/ja0774055)