Coupling spectroscopy and chromatography: Microfluidic portability

Coupling

A US team has paired the remote-detection version of NMR/MRI spectroscopy with a chromatography technique used in microfluidic devices. The work opens the way to portable and highly sensitive multi-dimensional chemical analysis.

Alexander Pines of the University of California Berkeley and his team have demonstrated for the first time how their pioneering remote detection NMR/MRI expertise can be used to perform analyses in a microscale monolithic chromatograph column and so rapidly identify the chemical constituents of samples in a microfluidic "lab-on-a-chip" device. The chromatography can separate components of the sample quickly enough so that NMR/MRI detection is possible. Pines and colleagues Vikram Bajaj, Thomas Teisseyre, Jiri Urban, Nicholas Halpern-Manners, Stuart Chambers and Frantisek Svec, report details in the journal Analytical Chemistry.

Chromatography is one of the key tools used in analytical chemistry and separation science but coupling it to remote NMR/MRI in a microfluidic device allows the researchers to obtain high-resolution, velocity-encoded images of the chromatographic mobile phase as it flows through the stationary phase. "Our technique provides both real-time peak detection and chemical shift information for small aromatic molecules, and demonstrates the unique power of magnetic resonance, both direct and remote, in studying chromatographic processes," explains Bajaj.

Monolithic spectroscopic

The polymer monolithic column at the centre of the new technology was developed by chemist Svec who works in the Organic and Macromolecular Synthesis facility at Berkeley Lab's Molecular Foundry. In standard chromatography, the stationary phase column is usually filled with porous polymer beads or another discrete medium with physical and chemical properties that modulate the diffusion rates of the analytes as they pass through. Svec's stationary phase is instead monolithic, meaning it contains solid, but porous, polymer.

"Polymer monoliths as a separation media can be compared to a single large particle that does not contain inter-particular voids," explains Svec. "As a result, all the mobile phase must pass through the stationary phase as convective flow rather than diffusion during chromatographic processes. This convective flow greatly accelerates the rate of analyte separation."

"With our remote NMR/MRI technology and the polymer monoliths of Svec's group, we were able to look inside optically opaque microfluidic columns and measure the velocity of the flowing fluid during a chromatographic separation,? Bajaj adds. "We were also able to demonstrate in-line monitoring of chromatographic separations of small molecules at high flow rates."

Multidimensional portability

The team has now demonstrated how the use of the remote NMR/MRI technique with the polymer monoliths can give much better discrimination between different, but related, analytes at the molecular level, Bajaj says. It is an improvement on mass spectrometry and optical spectroscopic techniques, he adds. Indeed, the research paves the way for multidimensional analysis, in which the result of a chromatographic separation would be encoded into an NMR/MRI signal by charge, size or some other factor and stored. The encoded fluid would then be run through a second separation and those results would also be encoded into an NRM/MRI signal and stored.

"This would allow us to create a multidimensional chromatography experiment that does not require the fluid volume to be physically partitioned," Bajaj says. "The fluid would, quite literally, be partitioned in the magnetic degrees of freedom instead."

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