<?xml version="1.0" encoding="UTF-8"?><?xml-stylesheet type="text/xsl" href="../nsu_article.xsl"?><!DOCTYPE nsuarticle PUBLIC "-//NPG//DTD NSU//EN" "../nsu_article.dtd"><nsuarticle type="news"><articleidlist><articleid type="uid">991202</articleid><storyno>-3</storyno><articleid type="doi">10.1038/nsu991202</articleid><storyno>-3</storyno></articleidlist><pubfm><pubdate><dayofweek name="Monday"></dayofweek><day>29</day><month>November</month><year>1999</year></pubdate><category>cells &amp; molecules</category></pubfm><fm><title>Showing the way to DNA</title><aug><fnm>Philip</fnm><snm>Ball</snm></aug></fm><body><p>US scientists have constructed a microscopic machine for moving and sorting short strands of DNA. The surprising thing about the device is that it doesn't push or pull the DNA molecules in any particular direction &ndash; it just lets them wander.</p><p>Efforts to read the entire genetic code of humans and other organisms typically use biological catalysts or 'enzymes' to snip DNA into manageable fragments. These fragments are then separated according to their size using a technique called 'gel electrophoresis'. New ways of automating or increasing the efficiency of this sorting process, involving techniques for manipulating DNA fragments, could accelerate the rate at which the message of the genomes can be read.</p><p>Joel Bader of the CuraGen Corporation in Connecticut, USA, and colleagues describe one such device-built on a silicon wafer that acts as a pump to transport DNA-in the <emphasis>Proceedings of the National Academy of Sciences</emphasis><bibr rid="b1">1</bibr>. The researchers say that their pump, just two thousandths of a millimetre wide, could form part of a laboratory-on-a-chip, in which pieces of DNA are sorted, moved around and sequenced on a single chip, all under computer control.</p><p>The pump is basically a 'Brownian ratchet'. A Brownian ratchet extracts directional motion from aimless wandering. This seemingly miraculous feat is achieved because wandering takes place in a non-uniform landscape. In essence, the landscape consists of a series of ramp-like hills that slope sharply on one side but less steeply on the other side.</p><p>Imagine a group of listless, wandering fish moving over a rippled seabed with this shape. The fish alternate between bursts of aimless swimming over peaks and periods of inactivity when they sink into troughs. Swimming doesn't itself take them any further in one direction than another. But because at any moment a swimming fish will be more likely to be over the broad, gentle slopes than the narrow, steep slopes, when it sinks back to the sea bed it is more likely to slide down the shallow slope and so be carried in that direction. Therefore each burst of swimming takes the fish from one trough to another in predominantly the downhill direction of the shallow slope. So the very asymmetry of the underlying landscape acts as a kind of ratchet, transporting the fish preferentially in one direction.</p><p>A molecular thermal ratchet is like this, except that the aimless swimming corresponds to random Brownian motion owing to the molecules' thermal energy, and the ramped landscape corresponds to an underlying 'field', such as an electric field, with a sawtooth shape.</p><p>In the Brownian DNA ratchet proposed by Bader's group, the sawtooth field is provided by tiny electrodes engraved into the silicon wafer, in alternating positive-and-negative pairs. The electrodes are arranged asymmetrically, with alternately large and small gaps between them. The DNA fragments in a solution placed on top of the device are negatively charged, and so attracted to the positive electrodes.</p><p>As the electric field is alternately switched on (to 'trap' the DNA molecules in 'troughs' at the positive electrodes) and off (to let them wander randomly through Brownian motion), the researchers say that fluorescently labelled fragments make their way through the device. Because fragments of different length are trapped with different strength by the sawtooth field, they travel at different rates and so can be separated. Bader's team estimates that DNA fragments made up of 24 and 25 base pairs (the basic building blocks of DNA) could be separated within five and a half seconds on a 1.25-centimetre chip.</p></body><bm><refgrp><bib id="b1" arturl="http://www.pnas.org/cgi/content/abstract/96/23/13165"><refau><snm>Bader</snm>, <fnm>J.</fnm> <inits>S.</inits></refau>, <refau><snm>Hammond</snm>, <fnm>R.</fnm> <inits>W.</inits></refau>, <refau><snm>Henck</snm>, <fnm>S.</fnm> <inits>A.</inits></refau>, <refau><snm>Deem</snm>, <fnm>M.</fnm> <inits>W.</inits></refau>, <refau><snm>McDermott</snm>, <fnm>D.</fnm> <inits>A.</inits></refau>, <refau><snm>Bustillo</snm>,<fnm>J.</fnm> <inits>M.</inits></refau>, <refau><snm>Simpson</snm>, <fnm>J.</fnm> <inits>W.</inits></refau>, <refau><snm>Mulhern</snm>, <fnm>G.</fnm> <inits>T.</inits></refau> &amp; <refau><snm>Rothberg</snm>, <fnm>J.</fnm> <inits>M.</inits></refau> <atl>DNA transport by a micromachined Brownian ratchet device</atl> <jtl>PNAS</jtl>  <vol>96</vol>, <spn>13165</spn><epn>13169</epn> <pubyear>1999</pubyear>.</bib></refgrp></bm></nsuarticle>