July 13th, 2008
Miniaturized DNA sewing machines
Japanese researchers have found a way to build long threads of DNA using miniaturized hooks and bobbins. In fact, they’ve demonstrated how to manipulate delicate DNA chains without breaking them. They’ve designed these laser-directed microdevices to pick up and manipulate individual molecules of DNA. The scientists have used optical tweezers to catch and move these microdevices, which could be used in the future to detect genetic disorders such as Down’s syndrome. But read more…
You can see above two diagrams showing the chromosomal DNA manipulation methods used by the scientists to build long DNA strands. The top part shows manipulation using the microhook. “The optically driven microhook physically captures a DNA molecule at any desired point on the molecule.” The bottom part illustrates manipulation using microbobbins. “One bobbin revolves around the other in order to wind a DNA molecule. The molecule is held between the bobbins and can be transferred to any desired location along with the bobbins.” (Credit: Kyohei Terao et al.)
This research work has been led by Kyohei Terao of the Department of Micro Engineering at Kyoto University. He worked with Masao Washizu and Hidehiro Oana of the Department of Mechanical Engineering at the University of Tokyo.
Here is an excerpt from the Royal Society of Chemistry (RCS)news release mentioned above. “Scientists can diagnose genetic disorders such as Down’s syndrome by using gene markers, or ‘probes,’ which bind to only highly similar chains of DNA. Once bound, the probe’s location can be easily detected by fluorescence, and this gives information about the gene problem. Detecting these probes is often a slow and difficult process, however, as the chains become tightly coiled. The new method presented by Kyohei Terao from Kyoto University, and colleagues from The University of Tokyo, uses micron-sized hooks controlled by lasers to catch and straighten a DNA strand with excellent precision and care.”
Now, let’s turn to Chemical Science, a RCS journal. On June 23, 2008, it published “Miniaturised sewing machines.” In this article, Sarah Corcoran gave first a description of how Terao got the idea for this new way to build long DNA strands. “Thinking of a strand of DNA as a piece of sewing thread, Terao developed microhooks to pick up the DNA, just like we would use our fingers to pick up thread. When thread is very long it becomes tiresome to manipulate it just with our fingers and instead we wind it around bobbins to make it compact. This is what inspired us to use microbobbins, says Terao.”
And here are some additional details about how the researchers worked to manipulate DNA strands. “Optical tweezers — where tightly focused laser beams trap and hold tiny objects — are used to catch and move these microdevices. The z-shaped microhook is directed by the tweezers to pick up a single strand of DNA, and barbs in the openings of the hook prevent the caught DNA unhooking. In the case of bobbins, two focused laser beams are used to revolve one bobbin around the other. The revolving motion winds the DNA molecule between the two bobbins.”
For more information, this research work has been published in another RCS journal, Lab on a Chip, under the title “On-site manipulation of single chromosomal DNA molecules by using optically driven microstructures” (Advance article posted online on June 23, 2008).
Here is a link to the abstract. “We report a novel method for manipulation of single giant DNA molecules under a video microscope. Using optically driven microstructures, we manipulated chromosomal DNA of length in the order of millimetres, extended by electroosmotic flow without DNA breakage in aqueous solution: we picked up DNA, using microfabricated hooks and wound it around microfabricated bobbins.”
And here is another link to the full paper — which might change in the future. Anyway, here are the conclusions of the scientists. “We have demonstrated the method and device for on-site single-molecule manipulation of giant DNA molecules, using optically driven microstructures for picking up and separating a DNA fibers from a bundle. We used a microfabricated hook together with winding/unwinding of the DNA fiber onto microfabricated bobbins. This method enables the manipulation of DNA molecules in the order of mega base pairs under a microscope without fragmentation. The method is purely mechanical, and requires no chemical modifications; moreover, it can manipulate any desired part of the targeted DNA in the microscope view. This method will create avenues for space-resolved single molecule assays of large chromosomal DNA, along with its applications in gene location and epigenetic studies.”
Finally, while I was writing this post, New Scientist decided to write about these DNA sewing machines. Please read “Tiny fishing reel gets DNA researchers out of a tangle” (Colin Barras, July 13, 2008) for more details.
Sources: Royal Society of Chemistry (RSC) Press Release, July 10, 2008; and various websites
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