Design and construction of a microcoil NMR probe for the routine analysis of 20-μL samples

Recent advances in microcoil NMR have provided commercially available, robust methodologies for analyzing mass and volume limited samples in the low microliter regime, and the technology has been applied in a number of areas. Unfortunately, due to constraints on sample size and the limited solubility of some compounds of interest, the application of this approach to certain areas of development, such as the structural analysis of chromatography eluates, is restricted. A current challenge is to provide an option within a previously unexplored sample size regime (tens of microliters) while still taking advantage of the increase in mass sensitivity afforded by solenoidal microcoil NMR. In this article, we present the design and construction of a microcoil NMR probe with a custom detection cell for the routine analysis of 20-μL samples. The detection cell is comprised of a CO2-laser-heated HF-etched borosilicate active volume with fused silica transfer lines added to provide sample input and output. This setup produces an enlarged sample bubble within the detection coil and provides easy connection with 1/16 in. standard LC connections, lending itself to applications with HPLC-NMR, online SPE and similar separation techniques, as well as higher-throughput robotic automation. NMR performance characteristics determined using standard compounds showed the probe exhibited reasonable resolution (<0.01 ppm), although sensitivity was less than optimal due to tuning constraints. Future improvements and opportunities are also discussed. © 2008 Wiley Periodicals, Inc. Concepts Magn Reson Part B (Magn Reson Engineering) 33B: 1–8, 2008