This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The inherent sensitivity of NMR conventionally restricts its use to compounds where significant quantities can be produced for analysis. Consequently mass limited samples cannot be examined successfully. These mass limited samples are often proteins where the extraction of significant quantities for analysis can be difficult, time consuming and costly. Coupled with the use of higher magnetic field strengths to improve the signal, the development of small and sensitive microcoils for NMR spectroscopy offers the promise of high quality spectra on mass limited samples. As described in Highlights, we have made a 750 MHz solenoidal microcoil with an active volume of approximately 1 ml and a total volume of just over 4 ml. This coil is very sensitive, and we have obtained good quality 1D NMR spectra of a 1 mM protein in 8 scans. These results were obtained by using rectangular wire rather than the more common round wire. We have constructed an eight-coil NMR probe at 600 MHz and have demonstrated simultaneous 1H COSY and TOCSY spectra for eight small molecule samples. This probe is the first multiple channel solenoid probe to utilize 4 channel receivers; each receiver collected two staggered acquisition datasets. The data are high quality and represent a significant step towards high-throughput analysis. One of the aims of this core is to develop high-throughput NMR using microcoil arrays in the 11.1 T/40 cm magnet. We have started to collect 1H 1D data on water samples using a rather large (1.2 mm) diameter coil. Our findings are that the lineshape with this relatively large volume is not good, and we are unable to get significantly more shimming power. We anticipate that this will improve as we go to smaller coils, so we are now preparing coils with 75 mm inner diameter. Based on previous work with small molecules, coils this size can produce acceptable S/N for fairly concentrated samples with narrow line-widths. If the data are still not acceptable with the smaller size, we will explore two options. First, we might be able to apply a spectral deconvolution protocol that was developed at the NHMFL for data collected in a very inhomogeneous resistive magnet. The idea is to record simultaneous 1H and 2H spectra, where the 2H spectrum has a single resonance (e.g. D2O). The D2O data are then fit to a function which leads to a single line, and that function is applied to the more complicated 1H spectrum. Second, if the data manipulation does not work, we might explore the possibility of constructing very small shim sets that would give us more shimming power at the sample.
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