CapNMR Probe. A new, capillary-based probe offers a unique approach to performing high-sensitivity NMR spectroscopy. The flow cell of the CapNMR probe has a volume of just 5 microL, and the entire probe has an inlet-to-outlet volume of only 10 microL. Mass sensitivity is about 10 times more than a conventional-scale 5 mm tube probe, and nearly the same as NMR cryoprobes. A typical figure of merit is that an injection of 1 nmol of sample dissolved in 3 microL of solvent yields a high-resolution, stopped-flow, proton spectrum in about 10 minutes on a 500 MHz spectrometer, with a S/N greater than 10. For a compound of 500 MW, this is 0.5 microg of sample at 0.33 mM. Capillary fluidic design throughout greatly reduces the rate of deuterated solvent consumption and expense.

Sample Injection Options. Manual sample injection is performed with a hand-held syringe connected directly to the probe. Assisted flow injection is performed by loading a valve-mounted sample loop with a hand-held syringe followed by delivery to the NMR flow cell by a micropump. Automated flow injection consists of the Gilson Micro 215, which loads the sample loop of the micropump.

Capillary LC-NMR. The CapLC offers non-split flow, three-channel programmable solvent gradients, a very sensitive, photo-diode array UV-Vis detector, and peak-parking and resume-flow capability for seamless interruption of separation runs, including during solvent gradients. Sample loading volumes for the CapLC are as low at 0.2 microL and total sample volumes as low as 1 microL.

From structural biology and proteomics to metabolite identification and natural products discovery, the amounts of material necessary to do structure elucidation has always been the slow process in moving research forward. With NMR being a pivotal tool in this process, substantial amounts of material are necessary relative to other analytical techniques.

Recent technological advancements in NMR has alleviated some of these problems. With the introduction of very high field NMR spectrometers and the increased sensitivity from cryoprobe technology along with new NMR acquisition techniques, the needs for larger quantities of small molecules or proteins has not been less of a problem. Only a limited budget has been the limiting factor. The latest introduction of the CapNMR(tm) probe technology has made another significant reduction in the necessary quantities of sample needed and softened the budgetary impact.

With the CapNMR(tm) probe, scientists can now very easily acquire complete NMR data sets on as little as 50 micrograms of small molecule unknowns and routine proton spectra on 5 micrograms or less. Preliminary results on proteins has also shown that with less than 10 micrograms of material one can acquire fabulous data. Without the need for NMR tubes and requiring minimal solvent consumption, the CapNMR(tm) probe will pave the way for the future of NMR sample submission and data acquisition.