The MESA+ Research Institute for Nanotechnology is an organization dedicating to providing the supporting infrastructure for a diverse range of research topics. Member groups have interests that encompass everything from laser wakefield acceleration through to the development of novel piezoelectric nanostructures. With such a diverse range of researchers, it can be difficult to keep track of what everyone is up to. To overcome this problem, and to open up more possibilities for collaborative research projects, the MESA+ institute organizes a one-day meeting that provides a snapshot of the institute's research activities, giving us a chance to listen to some of the latest research performed by the invited speakers.

A more extensive article devoted to the work of one of them will appear later—in the mean time, you can get your science fix with this new development in nuclear magnetic resonance spectroscopy (NMR).

NMR is, without doubt, the gold standard in spectroscopy. To put it in perspective, the discovery and subsequent technical developments in (NMR) spectroscopy—including the magnetic resonance imaging used in hospitals—have garnered four Nobel prizes, the last being in 2002. Every hospital, chemistry, and biochemistry lab worthy of the name has at least one of these things.

NMR uses the interaction of the nuclear spin with its environment to determine the properties of that environment. The idea works like this: a hydrogen atom's nucleus, when placed in a magnetic field, will begin to precess—the way a top behaves as it spins—with a certain frequency. However, if the atom it is sitting next to it is a carbon atom, then that will alter the frequency slightly. Likewise, if the next carbon down the chain is bonded differently, then a hydrogen atom attached to it will have a different resonant frequency. In the case of long molecules that folds back on itself, the atoms that end up close to each other will mutually change each other's resonant frequency, even though they are not bonded directly.

All of these frequency shifts will appear in the spectrum in direct proportion to how many atoms are in that particular configuration. By careful calculation, one can do things like figure out the folded structure of a protein complex, which is an absolutely incredible achievement. However, doing NMR on very small samples is difficult. Jacob Bart and co-workers from the MESA+ Institute recently demonstrated NMR on samples as small as 100nl.

The problem is two-fold. First, the signal from the atomic nucleus is very small, so a large sample volume gives you lots of nuclear material to get a signal from. They can't do anything about this—100nl is 100nl, and you can't have small samples and large signals.

The second problem is the magnetic field. The frequency of the signal depends on the strength of the magnetic field, and that strength has to be evenly distributed across the sample. Remember, we interpret NMR data by looking at how the resonance frequency changes, so you had better be damn sure that you know what the magnetic field strength is. This is generally done by using big coils that have a very homogenous field near their center, where the spectroscopy is performed. Once you move to small sample volumes, this becomes a problem because the coil needs to be smaller, making it harder to obtain a homogenous field.

Their solution was to use what is called a strip-line. This is a strip of metal on a printed circuit board with a metallic ground plane underneath. The length of the strip-line was chosen such that it generated electrical standing waves, like the oscillations on a guitar string. The geometry of the strip-line and ground plane produce a nicely confined and homogenous magnetic field. There is a problem here, in that the field is too weak.

In a rush of inspiration, the researchers realized that the field strength is proportional to current density, so they made a center portion of the strip line very narrow. This had the effect of vastly increasing the current density and, consequently, the magnetic field strength. This intense magnetic field is located very close to the wire, but is still quite homogenous. As a result, a tiny sample volume is actually a requirement for doing NMR with this setup.

Bart and coworkers demonstrated this by hooking it up to a microfluidic reactor, where two chemicals were pumped into a chamber to react and form a single product. The flow then continued to the NMR chip, where spectroscopy was performed. They found, as expected, that if the flow rate was low enough, the reaction would go to completion and they would only detect the final product.

As the speed was increased, however, they began detecting the two chemicals originally put into the reaction chamber. Furthermore, they could also detect an intermediate product that is formed as the reaction proceeds. The resolution of the NMR spectrum was also sufficient to perform more complicated forms of molecular identification. (For the chemists among you, the spectrometer could resolve the hydrogen triplets.)

This little development has untold possibilities. It will now be possible to perform generalized "I haven't a clue what this sample is, but I need to find out" spectroscopy on a chip. This is important because microfluidic systems make general spectroscopic methods difficult, leading researchers to resort to specialized devices where you limit the use of the device to situations where you basically know what needs to be detected.

Journal of Chemical Physics, 2008, DOI: 10.1063/1.2833560