Hyperpolarization techniques in general and dynamic nuclear polarization (DNP) in particular have matured as viable methods to boost the NMR signal in various biological and inorganic applications. While in solid-state NMR (ssNMR), DNP is performed routinely in situ at magnetic fields ≥ 9 T, a similar approach in liquids is hampered by strong microwave (mw) absorption and heating of the solvent. Moreover, until recently it was assumed that the polarization transfer mechanism in liquids does not permit large signal enhancements at high magnetic field. However, opposed to 1H, the spin polarization transfer mechanism in liquids for 13C is favored reaching enhancements of up to 600 at 9 T [1-2].
In order to harvest the possible sensitivity gain, we designed a new DNP spectrometer operating at 9.4 T and room temperature that allows for tunable high-power continuous wave mw irradiation, large microliter sample volume (V ≥ 20 μL), and saturation factors up to 40-50 %. The design is based on a commercial NMR setup, in which quasi optical mw components were integrated, thus enabling narrow NMR linewidths during mw irradiation. Each part and the mw pathway in particular was tested and optimized to guarantee an efficient mw penetration of the sample.
We screened a large set of target molecules including pharmaceutical drugs and could quantify signal enhancements of about one order of magnitude in favorable cases. The investigation of different chemical environments also allowed us to gain new insights on the electron-nuclear spin polarization transfer mechanism. The setup further enables the integration of DNP into routine 2D correlation experiments such as 13C-TOCSY and INADEQUATE on 13C enriched as well as natural abundance samples with similar signal enhancements as observed in 1D experiments.