Small-Volume and High-Sensitivity NMR Probes

Abstract

Aside from efforts to develop capillary nuclear magnetic resonance (NMR) probes during the 1970s, most NMR samples were traditionally examined using 5 mm probes. Due to low gyromagnetic ratio and/or natural abundance, some larger format NMR probes were developed, these including 8 and 12 mm, and large volume probes of 18 and 22 mm. Large format probes addressed the difficulties of acquiring NMR data for insensitive nuclides when an investigator was not sample limited or dealing with highly insoluble materials. In contrast, for the characterization of scarce samples of natural products, impurities or degradants of pharmaceuticals, metabolites, forensic samples, and other severely sample-limited applications, even conventional 5 mm probes were not well suited to the task of acquiring data for such samples. These considerations led to the development of the first of the 3 mm NMR probes in the early 1990s followed by a succession of progressively smaller format NMR probes down to the 1 mm tube format probes currently available. In parallel, μCoil probes were also developed allowing the use of still smaller sample volumes, albeit in a flow cell rather than a “tube” format, as were magic angle sideways spinning liquids probes such as the Varian Nano-probe ™ . In the late 1990s, the first examples of cryogenic NMR probe technology became available, and these extremely high-sensitivity NMR probes are now becoming more readily available to investigators faced with undertaking the structural characterization of scarce samples. The development of small-volume and high-sensitivity NMR probes is described in this contribution and examples of the application of these probe technologies are reviewed.