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A high-resolution NMR flow probe for microfluidic systems based on a new type of stripline detector chip has been developed by researchers in The Netherlands. The tool could be useful in direct monitoring of chemical reactions performed in so-called lab-on-a-chip devices.
Jacob Bart and Han Gardeniers of the Mesa Institute for Nanotechnology, at the University of Twente, Enschede, and Ard Kolkman, Anna Oosthoek-de Vries, Kaspar Koch, Pieter Nieuwland, Hans Janssen. Jan van Bentum, Kirsten Ampt, Floris Rutjes, Sybren Wijmenga, and Arno Kentgens of the Institute for Molecules and Materials, at Radboud University, in Nijmegen, The Netherlands, provide details in the Journal of the American Chemical Society.
As we all know, NMR spectroscopy is an indispensable technique in chemistry, biology, and medicine. But, its intrinsically low sensitivity means it is rarely used with samples of very low mass, such as those likely to be present in microfluidic devices. Researchers have spent a decade reducing the size of the detector coils in instruments to improve absolute sensitivity, the Dutch team explains, but this comes at a price in terms of lower resolution.
To overcome the problems of resolution, sensitivity and interference from coils, the team has devised a new type of NMR "coil", a stripline, which they have previously tested in microfluidic-based studies. The stripline is a flat "coil" produced in single layer lithographic process and is fully scalable to smaller dimensions, the team explained previously in the Journal of Magnetic Resonance (2007, 189, 104-113). "The sensitivity of such a planar structure can be superior to that of a conventional 3D helix," they explained.
"A microfluidic chip based on this resonator showed superior spectral resolution (line width of less than 1 Hertz) in pure ethanol without the use of additional susceptibility matching," the researchers say.
Now, they have demonstrated proof of principle with this stripline probe in a microfluidic flow device. They position the chip vertically in an aluminium tube and connect it to the radio frequency circuit. They connect the NMR chip "fluidically" to a 200 mm fused silica capillary with an internal diameter of 100 micrometres and then carried out the acetylation of benzyl alcohol with acetyl chloride as a test reaction with very promising results.
An analysis of a very small sample of human cerebrospinal fluid they also suggest that the uncompromised, sub-Hz, resolution, of this probe could hold great promise for metabolomics and others kinds of related studies, although it was not designed specifically for the task. Analysis of cerebrospinal fluid is important in understanding and diagnosing central nervous system diseases as well as metabolic problems.
"With the microfabrication toolbox available nowadays, a completely integrated platform in one chip that can handle and detect raw samples without preparative laboratory work is within reach," the team asserts.
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Article by David Bradley
The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.
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