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Micro- and nanotechnology in nuclear magnetic resonance

Final Activity Report Summary - MICRO AND NANO-NMR (Micro- and Nanotechnology in Nuclear Magnetic Resonance)

Nuclear magnetic resonance (NMR) spectroscopy is one of the most versatile and powerful analytical techniques available today for the study of, for example, molecular or biomolecular structures, binding kinetics or molecular dynamics. A major limitation of NMR spectroscopy is its intrinsically low sensitivity, resulting in the requirement of relatively large amounts of material.

One particular approach to enhance NMR sensitivity for mass-limited samples utilises small sample volumes and reduced diameter NMR coils since the amplitude of the NMR signal is maximised when the size of the radio frequency (RF) coil matches that of the sample. There are different types of microcoils. In our approach, a planar and circular microcoil was fabricated using photolitography techniques and deposited on the top of a substrate in which the sample channel was defined, viz. NMR-chip. Such an NMR-on-a-chip setup worked at 9.4 T, i.e. at 400 MHz proton frequency, allowing for high resolution hydrogen one NMR (1H-NMR) and fluorine 19-NMR (19F-NMR) spectroscopy at relatively low concentrations. The possibility of working at relatively low concentrations in our NMR chip and the good resolution allowed for the monitoring of small chemical shift variations and enabled the study of, for example, supramolecular interactions. Thus, supramolecular assemblies called rosettes were detected by 1H-NMR inside the NMR chip, as well as the encapsulation of guest molecules inside their cavities. These assemblies were difficult to synthesise, therefore the possibility of detecting a very small amount, i.e. a picomole, proved the utility and good performance of our NMR chip.

On the other hand, the supramolecular interaction between a fluorinated anion, hexafluorophosphate, and alpha-cyclodextrin was followed in the picomole level by monitoring the fluorine peaks chemical shift variation upon changing the concentration of cyclodextrin. The combination of small volumes and the advantages of 19F-NMR spectroscopy, like large chemical shift dispersion and not overlapping spectra, opened up new windows so as to additionally study complicated molecular structures and supramolecular assemblies or complexation inside the NMR chip. Potential applications ranged from microfluidic lab-on-a-chip devices to indicator displacement assay methods and screening of biologically relevant molecules. Last but not least, focusing on 19F signals, NMR measurements could be performed using normal, i.e. protonated, solvents, thus not requiring sample pre-treatment or use of deuterated solvents.