Development of a ¹³C-optimized 1.5-mm high temperature superconducting NMR probe

We report a 1.5-mm NMR probe based on high temperature superconductors operating at 14.1T optimized for (13)C detection. The probe has a total sample volume of about 35 microliters (μL) with an active volume of 20 μL and provides exceptional mass sensitivity for (13)C detection. The probe also has excellent (1)H sensitivity and employs a (2)H lock; (15)N irradiation capability can be added in the future. The coils are cooled to about 20K using a standard Agilent cryogenic refrigeration system, and the sample temperature is regulated near room temperature. The coil design considerations are discussed in detail. This probe is ideal for directly detected (13)C NMR experiments for natural products chemistry and metabolomics applications, for which 35 μL is an optimal sample volume. The outstanding (13)C sensitivity of this probe allowed us to directly determine the (13)C connectivity on 1.1mg of natural abundance histidine using an INADEQUATE experiment. We demonstrated the utility of this probe for (13)C-based metabolomics using a synthetic mixture of common natural abundance metabolites whose concentrations ranged from 1 to 5mM (40-200 nmol).