m a te ri a l wo rl d
Nanotubes probe cellular secrets T
here’s strength in numbers, especially for carbon nanotubes. Nikolai Kouklin at the University of Wisconsin, Milwaukee, and colleagues at Bryn Mawr College and Brown University have bundled nanotubes into tiny, robust probes that penetrate living cells without damaging them. The bundles are much stronger than a typical glass probe, and they can be attached to off-the-shelf electrodes for delicate electrical measurements or used to deliver molecules to specific parts of a cell (Appl. Phys. Lett. 2005, 87, doi 10.1063/1.2112183). Kouklin and colleagues aligned two needle-shaped electrodes to point toward each other with a gap between the tips. When the electrodes were placed in an ethanol–water solution of carbon nanotubes and a voltage was applied, the nanotubes in the gap spontaneously bunched into bundles of parallel tubes aligned along the electric field and attached to the electrodes. The size of the bundles could be controlled by adjusting the strength of the electric field and the concentration of nanotubes. To test a new bundle of nanotubes, dubbed a nanoprobe, the investigators ran a current through it. A tightly bound nanoprobe should have a very low electric resistance and be physically robust so that it doesn’t break or easily fall apart. “If you grab a 50-nm glass probe and walk to the [scanning electron microscope] chamber, the tip will be gone,” says Kouklin. With “carbon tubes, you can do whatever you want— they’re not fragile.” The low electric resistance of nanoprobes isn’t just a nifty way to test their structural integrity—it’s a distinct advantage, particularly at the small scales of biological cells. Electrophysiologists have used thin glass probes to measure © 2006 AMERICAN CHEMICAL SOCIETY
20 nm
10 µm
A 20-nm-thick nanoprobe extends from the tip of an electrode. (Adapted with permission. Copyright 2005 American Institute of Physics.)
the electric potential of cell membranes, but the electric resistance of a glass probe rises as the width of the probe shrinks, and the signal grows noisy. The nanoprobes of Kouklin’s group can be made orders of magnitude smaller than glass probes, and they have a much lower electric resistance. Kouklin predicts that the nanoprobes will be able to pick up signals of individual organelles within a cell, something impossible to do with glass probes. The investigators used a carbon nanoprobe to deliver a fluorescent dye into a living cell. When the probe was withdrawn, the still-viable cell was glowing. “One of the important properties we observed is that [the carbon nanoprobes] create a seal with the membrane,” says Kouklin. “So you’re not creating large
holes in the cell membrane. The probe goes inside, and you can access all different parts of the cell.” According to Kouklin, the nanoprobe could be used to deliver drugs, enzymes, or DNA to specific locations within a cell. And it can be readily attached to standard-sized electrodes or metal rods for easy manipulation. “This paper is a beautiful example of the integration of nanotechnology with living systems,” says Charles Martin at the University of Florida. He adds that the researchers have made two significant innovations: the elegantly simple construction of the nanoprobe itself and its use to deliver a molecule into a cell without killing it. Electrophysiologists are excited about the electric sensitivity of the nanoprobes. “We think these nanotube bundles will make new measurements possible,” says Donald Hilgemann at the University of Texas Southwestern Medical Center. “Right now, we have to disrupt the cell a lot in order to really manipulate it electrically. This, if we develop it right, could be really noninvasive.” Hilgemann also notes that it’s possible to change the surface properties of the nanotubes. This might allow researchers to attach enzymes or other molecules that could act as submicroscopic sensors within specific parts of the cell. Kouklin and colleagues point out that the tiny bundles of carbon nanotubes have an advantage beyond their utility. “The more difficult the technique, the more difficult for researchers to use it,” says Kouklin. “We were looking for something easy and robust. The cost to do this in your lab would be only $2,000–3,000. It’s a very accessible technique and very low cost.” a —Kim Krieger
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