Caltech Researchers Weigh Individual Molecules

karvind writes "PhysOrg reports that physicists at the California Institute of Technology have created the first nanodevices capable of weighing individual biological molecules. This technology may lead to new forms of molecular identification that are cheaper and faster than existing methods, as well as revolutionary new instruments for proteomics. The Caltech devices are 'nanoelectromechanical resonators' -- essentially tiny tuning forks about a micron in length and a hundred or so nanometers wide that have a very specific frequency at which they vibrate when excited. Slashdot covered earlier the effort by Cornell for measuring attogram objects which also employs NEMS cantilevers."

Re:Cool tech. Some issues

[RWerp]

You're right that the bonds make the total mass smaller. But we're talking about stable molecules here, which bonded in one specific way. If their mass were to change, they would have to decay or interact with the environment. If the molecule is stable, it's energy is very well defined. The only limiting factor is the principle of uncertainty, which basically tells here, that the longer you measure the mass, the more precise you are. So the deviation of the measurement may change, but not its expectation value. It would be very interesting, however, if we could apply this -- or other -- technique to measuring masses of unstable molecules and watch how it changes in time.

Mass spectroscopy

[FirienFirien]

This is the next step from a process called mass spectroscopy, where a molecule is given + or - one electron, then fired through a calibrated magnet to hit a target. If the magnet is calibrated so that a single charge on a molecule of weight W deflects by exactly n degrees, then if the molecule weighs W it will hit the target, and you know the mass of your molecule.

It's more trial-and-error than TFA, but with a sweep across the calibration settings you get lovely graphs showing how much of a mixture is which compound. It's fast (seconds for a full-range mass chart), which I somehow doubt TFA is quite up to yet - maybe for a single molecule, but something in the description rankles of a slow process.

Re:uhh... so what?

[FirienFirien]

We know the masses of a lot of the atoms (though there's a lot more than 1000 isotopes). Molecules are a completely different matter; there's an infinite range of possible molecules, because you can put them together in a lot of different ways; chain molecules (like DNA (hey, there's 5 billion different molecules - and that's only counting humans!)) are difficult to untangle and sort out; when you can weigh them, you can use the masses of atoms to try to calculate how many of each atom is in the molecule, and from there you can try and work out which configurations of atoms are possible.

Re:uhh... so what?

[mamladm]

As I understand it, one of the more useful applications envisaged for the technique is not to find out what the actual weight of a given molecule is, but to detect the presence of a particular molecule, such as certain proteins which are present in blood in the very early stages of cancer and which are very difficult to detect with today's methods.

Re:Resolution

[operon]

proteins does not have a typical mass. They have a wide range of masses, with molecules having few aminoacids to large and complex quaternary strucutures.

Actually it's called mass spectrometry

[Anonymous Coward]

This is the next step from a process called mass spectroscopy, where a molecule is given + or - one electron

A molecule can not be "given" an electron is mass spec. Ions are generated by ejecting an electron or breaking a bond forming a positive species and a negative radical. Only postive species are detected.

then fired through a calibrated magnet to hit a target.

What you're describing is a magnetic sector mass spec but there are many other types.

If the magnet is calibrated so that a single charge on a molecule of weight W deflects by exactly n degrees, then if the molecule weighs W it will hit the target, and you know the mass of your molecule.

Close. What you're actually detecting is the mass to charge ratio (m/z). The way it works is that the +'ve ions are accelerated by a constant voltage that gives all ions the same kinetic energy. The molecule then continues though the instrument where it encounters a magnetic field which causes it to deflect. Only ions with the correct m/z ratio will be deflected perfectly around a bend and reach the detector. Other ions will be deflected too much or not enough. The spectrum is swept by altering the field strength For most peaks in a mass spectrum the charge (z) is +1 so the m/z ratio is in fact just m however species with greater charge are generated. In this case the peak appears to arise from a lighter ion but in reality that ion just experienced a greater force from the deflecting field due to the higher charge. For the analysis or proteins you generally interested in the molecular ion (the intact molecule less an electron) as this directly reviles the mass of the protein. To do this "soft" ionization methods such as electrospray and MALDI mass spec are used. This is different from "hard" ionization which breaks apart molecules into many ions which are detected individually. Structural information can be gained by examining how the molecule fragments. This isn't as useful for proteins because they are so large.

No it's not

[Mr. Underbridge]

It's an April Fool's joke you idiot. Weighing molecules, what idiocy. Like you can make a molecule-sized set of scales to weight it on. Not to mention that molecules don't weight straight down like objects, they float about, so wouldn't press down on the scales. The rest of the article is filled with pseudo-science drivel to try to look clever and hide the fact that they're making the whole thing up.

I'm familiar with his research, half my group collaborated with him, and I think I met him once. It's real. MEMS-based cantilever technology has been getting progressively better, this isn't particularly surprising.

I don't know why you're surprised that New Scientist is pseudoscience, but you can find similar results with real science in journals. Look up Roukes, M in "web of science" or something.

Nice troll, but I can't have you confusing the n00bs on matters scientific.

Re:Cool tech. Some issues

[fearofcarpet]

You're right that the bonds make the total mass smaller. But we're talking about stable molecules here, which bonded in one specific way. If their mass were to change, they would have to decay or interact with the environment. If the molecule is stable, it's energy is very well defined. The only limiting factor is the principle of uncertainty, which basically tells here, that the longer you measure the mass, the more precise you are. So the deviation of the measurement may change, but not its expectation value. It would be very interesting, however, if we could apply this -- or other -- technique to measuring masses of unstable molecules and watch how it changes in time.

Huh? You're going to have to explain to me how you bonds change the mass of a molecule... Especially decreasing it. I'm really curious where you heard this. Perhaps there is some nuance to this statement that I'm missing? Are you saying that the mass of the constituent atoms is different than that of a molecule? This can certianly be true if electrons are gained or lost, but chemical bonds don't affect anything beyond the valence electrons of the atoms. As for uncertainty - I'm not buying it. Even if there was a teeny tiny mass "change" over time, you'd be hard pressed to observe it, especially when you're talking about molecules weighing thousands of Daltons... The difference in scale would be like trying to measure the mass you loose from expelling carbon dioxide while standing on your bathroom scale - and having to take into account mass loss to water evaporation, skin exfoliation, etc. Macromolecules, especially biological molecules, have static charge build up, hydration, aggregation, etc. all contributing to a very dynamic system.

At any rate the "mass of a molecule" is an average of all the weights based on the natrual abundance of isotopes because that is the only factor that affects the mass of two molecules with the same empirical formula. "Unstable" molecuels loose mass by becoming different molecules. It is incorrect to say that a molecule's weight changes - that is impossible (save radioactive decay) because when the empirical formula changes, you no longer have the same molecule.

At any rate, it is an interesting challenge to identify biological molecules by weighing them one at a time, as the horrific isotope distribution in the mass spec of any macromolecule demonstrates.