Small Volume NMR Probes

There are probes specifically designed for small volumes of sample (e.g., the Bruker microprobe, which handles 80 pL volumes and the Varian nanoprobe, which handles 40 pL volumes), but these probes suffer from problems with either low spectral resolution and/or low throughput, not to mention the order-of-magnitude-plus higher cost associated with sample vessels versus conventional NMR tubes. Nonetheless, if our application requires and benefits from the use of one of these small-sample-volume probes, we will be glad that these probes exist. 

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Smaller diameter probes reduce sample volumes from 500 to 600 pi typical with a 5 mm probe down to 120-160 pi with a 3 mm tube. By reducing the sample volume, the relative concentration of the sample can be correspondingly increased for non-solubility limited samples. This dramatically reduces data acquisition times when more abundant samples are available or sample quantity requirements when dealing with scarce samples. At present, the smallest commercially available NMR tubes have a diameter of 1.0 mm and allow the acquisition of heteronuclear shift correlation experiments on samples as small as 1 pg of material, for example in the case of the small drug molecule, ibu-profen [5]. In addition to conventional tube-based NMR probes, there are also a number of other types of small volume NMR probes and flow probes commercially available [6]. Here again, the primary application of these probes is the reduction of sample requirements to facilitate the structural characterization of mass limited samples. Overall, many probe options are available to optimize the NMR hardware configuration for the type and amount of sample, its solubility, the nucleus to be detected as well as the type and number of experiments to be run. 

To overcome the problem of sample availability, smaller volume NMR probes, nanoprobes , have been introduced for structure elucidations of samples that were previously considered too small for NMR analysis. 43 ... 

As techniques for chemical analysis are used in continually smaller domains, experimental challenges for inherently insensitive methods such as NMR spectroscopy become increasingly severe. Among the various schemes to boost the intrinsic sensitivity of an NMR experiment, the development of small-volume RF probes has experienced a renaissance during the past decade. Commercial NMR probes now allow analyses of nanomole quantities in microliter volumes from natural product extracts and combinatorial chemical syntheses. Figure 7.3.1.9 illustrates the range of volumes that can be examined by NMR probes and accessories such as microsample tubes and inserts. With recently reported advances in sample preconcentration for microcoil NMR analysis [51], dilute microliter-volume samples can now be concentrated into nanoliter-volume... 

NMR spectroscopy provides a noninvasive way to quantitate solution- and solid-phase library eompounds while also permitting total struetural elucidation, which aids in determining structure-activity relationships for rational drug design. The mass sensitivity and resolution of NMR eontinue to improve with the development of small-volume flow probes for solution-... 

Haner RL, Llanos W, Mueller L. Small volume flow probe for automated direct-injection NMR analysis design and performance. J Magn Reson 2000 143 69-78. 

Fig. 2 shows the spectrum as a function of time of HP xenon diffusing into porous Vycor glass, which has interconnecting pores of 42A diameter. The experiment in this case was done in batch mode, where a previously collected volume of HP xenon is passed into the sample space in a static NMR probe containing the Vycor sample. The spectrum was collected with a series of pulses with small tip angles so as not to destroy the magnetization of the HP xenon. The experiment is started even before there is gas in the sample space so that... 

Relaxation can be probed in inhomogeneous fields, so that the homogeneous polarization field B0 is not a necessity for successful applications of soft-matter imaging. Based on this fact, small portable NMR sensors can be built, which provide NMR data from a single volume element with the same specificity as the contrast in an NMR image [12]. Such... 

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