Limited-Sample NMR Using Solenoidal Microcoils, Perfluorocarbon Plugs, and Capillary Spinning

Abstract

This study demonstrates three improvements to mass-limited NMR using solenoidal microcoils as detectors: (1) sample confinement using liquid perfluorocarbon plugs to increase the observe factor, (2) design and incorporation of a capillary spinner to improve spectral line widths, and (3) facile sample changing via the use of a capillary insert. The probe is constructed to spin a fused silica capillary of 530 microns i.d., 700 microns o.d. inside a solenoidal coil wound around a 0.8 mm i.d., 1 mm o.d. glass capillary. The smaller capillary contains the sample, and capillaries with different samples can be exchanged easily. In high-resolution limited sample microcoil NMR studies published thus far, the length of the sample plug has been 7-10 times the length of the solenoid to avoid line broadening from volume magnetic susceptibility (chi v) mismatches at both ends of the sample. This arrangement is not efficient since it places most of the sample volume outside of the coil observe volume. It is shown here that the observe factor cannot exceed 23% if the sample plug is bracketed by air, without substantial line broadening occurring. However, if the sample is bracketed by two liquid perfluorocarbon plugs, the observe factor can be increased to 70% while maintaining high spectral resolution. This is equivalent to improving the limit of detection by a factor of 3, or reducing the total data acquisition time for a given signal-to-noise by a factor of 9. It is also shown that, for the 440-nL sample plug used in this study (bracketed by the perflurocarbon plugs), sample spinning can improve the spectral resolution from 1.5 (nonspinning) to 0.6 Hz (spinning). This corresponds to a further improvement in the limit of detection of 2.5, or just over a factor of 6 decrease in data acquisition time.

Silicon cylinder spiral coil for nuclear magnetic resonance spectroscopy of nanoliter samples

“…As described in (1) and in other publications (2)(3)(4)(5), the main challenge of using microcoils is the low spectral resolution. Commonly, the linewidth LW is compromised by a nonhomogeneous distribution of the static magnetic field (B 0 -field) within the sample.…”

“…Commonly, the linewidth LW is compromised by a nonhomogeneous distribution of the static magnetic field (B 0 -field) within the sample. These field variations originate from the different magnetic susceptibilities of the materials from which the detector is constructed (6) or of the interface between the sample plug and the confinement applied (3,7).…”

NMR probes for measuring magnetic fields and field dynamics in MR systems

“…In the present implementation this is accomplished with another liquid, forming two plugs between which the probe droplet is suspended (15). Similarly to the sample container, the plug liquid must not give any NMR signal at the observation frequency.…”

Dissolution DNP NMR with solvent mixtures: Substrate concentration and radical extraction

“…Such commercially-available liquids have a number of distinct advantages including thermal properties that are similar to those of water, the possibility of controlling their density to make them slightly "heavier or lighter" than water (so as to better target the mixture to the observation of hydrophilic or hydrophobic substrates), and biological inertness. From the spectroscopic standpoint they also exhibit important added values in their absence of major NMR-active nuclides other than 19 F, and of suitable susceptibility matching vis-à-vis aqueous solutions (16,17). Another interesting option to consider involves combining the present approach with suitable radical quenchers, in the hope of bypassing the shortening of the hyperpolarization's T 1 should this problem be exacerbated by the use of a solvent mixture.…”