Speed Bump: Tip’s tricks sort DNA, write at nanoscale

Using an old tool in surprising new ways, scientists in California are making molecules race down the sloping sides of a minuscule silicon spike ordinarily reserved for poking at atoms. The novel role for the spike, which is the tip of an instrument known as an atomic-force microscope, or AFM, could lead to advances in DNA sequencing, nanofabrication of devices, and other technologies, the scientists say.

TRAVEL TIP. Electrically driven molecules of different sizes and charges separate on the way from the base (upper-left image) of an atomic-force microscope tip toward its point (upper right). After some molecules are deposited on a surface (lower left), a voltage reversal drives others upward (lower right) for later deposit. K. Unal, et al./Applied Physics Letters

About 10 micrometers long, an AFM’s tip protrudes from the end of a cantilever. Scientists usually drag it or tap it on a surface to discern an object’s topography down to the atomic level (SN: 2/18/06, p. 101: Available to subscribers at New View: Speedy microscope takes fuller look at the nanoworld). Now, H. Kumar Wickramasinghe and his colleagues at IBM Almaden Research Center in San Jose, Calif., have demonstrated that DNA molecules separate according to their lengths as they move along a spike’s wetted surface. Moreover, the scientists have used the spike’s point to lay down a nanoscale pattern of molecules.

For both feats, the IBM researchers first wired an AFM tip to accept up to 10 volts. The electric fields thus produced then made molecules move up or down the spike’s surface inside the thin film of water that forms naturally in humid air.

In their experiments, the scientists showed that a voltage propels a strand of DNA made of 16 chemical building blocks, or bases, more quickly than a strand that’s only 5 bases long. In this way, the electrified spike separated the molecules by size and electric charge—a process known as electrophoresis.

Automated machines today decipher the genomes of people and other organisms by carrying out electrophoresis of DNA pieces within fine glass tubes (SN: 8/6/05, p. 85: Available to subscribers at Speed Reader: Gene sequencing gets a boost). Other systems under development use microchannels etched in glass plates. The AFM-tip procedure could achieve separations 10,000 to 100,000 times as quickly as such capillary systems, the IBM team asserts in the May 1 Applied Physics Letters.

For example, a 15-base DNA segment that travels through a microchannel in 170 seconds could traverse an AFM tip in just 5 milliseconds.

The new work offers “a very promising approach for fast electrophoretic differentiation of molecules,” comments Narayana R. Aluru of the University of Illinois at Urbana–Champaign.

“It provides a new way to think about separating and manipulating DNA molecules,” adds Jeffrey A. Schloss of the National Human Genome Research Institute in Bethesda, Md. However, a practical gene sequencer must handle molecules hundreds of bases in length, he notes.

Wickramasinghe says that so far, 40-base DNA segments are the largest that his team’s AFM tip has transported.

Showcasing another capability of the modified AFM tip, the researchers used voltage pulses to eject droplets of DNA molecules from the spike onto a silicon substrate. By moving the tip, scientists formed the nanoscale letters IBM.

Besides its potential as a DNA sequencer, Wickramasinghe says, the electrified AFM tip could also be a “nano inkjet printer.”

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