By precisely measuring tiny fluctuations in mass, carbon nanotubes will allow chemists to follow reactions of individual proteins atom by atom, predict Spanish researchers. Their recently published nanotube device, which can weigh protein molecules to a resolution of around 1 zeptogram (10^-21 g), or three atoms of gold, is the latest in a glut of ultra-sensitive mass detectors that may perform better than mass spectrometers - but aren't yet ready for real-world application.

Adrian Bachtold, who leads the Spanish team at Barcelona's research centre for nanoscience and nanotechnology, notes that mass spectrometers can already detect the mass of a single hydrogen atom, but get less sensitive with larger molecules such as proteins.

His group's protein weighing machine consists of a carbon nanotube pinned between two electrodes in a vacuum. The nanotube is a resonator; it vibrates like a guitar string, at a constant frequency. When an atom or molecule hits it, the speed at which it vibrates changes. By relating vibration frequency to mass the team are able to weigh very tiny particles, as they demonstrate in their latest study by evaporating chromium atoms onto the nanotube. The weighing scale only hits maximum sensitivity at 5 K and 0.1 millibar pressure, however. 

Using nanotube resonators, Bachtold says, it will eventually be possible to engineer devices that can discriminate between isotopes of the same element and follow the reactions of single proteins: 'We could place one haemoglobin molecule on one nanotube and look at how it changes as a function of time, so for example, if it releases some oxygen atoms or not.' Right now, he is hoping to match the sensitivity of mass spectrometers over a wider mass range.

Similarly ambitious goals are held by Kenneth Jensen and colleagues at the University of California, Berkeley, who earlier this year fashioned vibrating nanotube cantilevers - pinned at one end instead of two - with a record mass resolution as small as two fifths of a gold atom (1.3 x 10^-25  kg) at room temperature. 'One of the eventual goals of this research is to detect proteins and viruses by their mass signature,' he says. The method could be used in the clinical diagnosis of blood samples, he suggests, or in high throughput drug screening to detect a binding interaction by mass sensing. Nanotube scales are also small enough to be incorporated onto chips.

'Carbon nanotube resonators are proving to be exquisite mass sensors,' says Jensen. 'Bachtold's approach has the advantage that there is already a large body of research on doubly clamped nanotube resonators, which might make large-scale fabrication easier.' 

Weighing up the options

According to Michael Roukes, who studies nanoelectromechanical systems at the California Institute of Technology, real advances in mass sensing technology will only be achieved with large, organised assemblies of such devices. The ability of individual nanodevices to capture molecules, he says, is 'infinitesimal', simply because they are so small. 

The trouble with nanotubes is that because they are grown by chemical catalysis it is very difficult to routinely control their position. But Roukes  points out that it is already possible to precisely assemble very large arrays of silicon nanowires. In 2007, his team demonstrated silicon carbide cantilevers capable of detecting around 1 attogram (1 x 10^-18 g), which functioned at ambient temperature and pressure. He believes they offer the only viable solution for the foreseeable future.

Bachtold admits that positioning of the carbon nanotubes is currently one of the biggest problems his team face in developing their technology. But he says their relative lightness compared to silicon nanowires makes them more sensitive materials for mass detection. 'The nanotube has a very low mass,' he explains, 'So if you evaporate one atom on a nanotube, it's a more important fraction of the number of atoms.'

Nanotube devices could eventually provide a cheap, compact alternative to mass spectrometry, agrees  Ashwin Seshia, a sensors expert at the University of Cambridge. 'The question is really: can you measure mass with the repeatability and the robustness that's required to run these for a practical application?' he asks.

Bachtold thinks so. He says that the incredible mechanical strength of nanotubes means they can be used again and again, although so far the team have only reused their devices a maximum of half a dozen times.

'The fact is that there are interesting tools that are being made now but we are still some way from assembling them into useful devices,' Seshia says. 'That's not often talked about in all these papers.'

Hayley Birch

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