High-Resolution Nuclear Magnetic Resonance Spectroscopy with Picomole Sensitivity by Hyperpolarization on a Chip

Abstract

We show that high-resolution NMR can reach picomole sensitivity for micromolar concentrations of analyte by combining parahydrogen induced hyperpolarisation (PHIP) with a high-sensitivity transmission line micro-detector. The para-enriched hydrogen gas is introduced into solution by diffusion through a membrane integrated into a microfluidic chip.NMR microdetectors, operating with sample volumes of a few µL or less, benefit from a favourable scaling of mass sensitivity. However, the small volumes make it very difficult to detect species present at less than millimolar concentrations in microfluidic NMR systems.In view of overcoming this limitation, we implement parahydrogen-induced polarisation (PHIP) on a microfluidic device with 2.5 µL detection volume. Integrating the hydrogenation reaction into the chip minimises polarisation losses to spin-lattice relaxation, allowing the detection of picomoles of substance. This corresponds to a concentration limit of detection of better than 1 µM √ s, unprecedented at this sample volume. The stability and sensitivity of the system allows quantitative characterisation of the signal dependence on flow rates and other reaction parameters and permits homo-( 1 H-1 H) and heteronuclear( 1 H-13 C) 2D NMR experiments at natural 13 C abundance.

Use of dissolved hyperpolarized species in NMR: Practical considerations

“…conceived an integrated device that combines PHIP hyperpolarization with a high-sensitivity transmission-line micro-detector. [109] In their setup the hydrogenation reactor is integrated into the microfluidic chip itself, in order to reduce the polarization losses arising from T 1 relaxation.…”

Chemical Reaction Monitoring using Zero‐Field Nuclear Magnetic Resonance Enables Study of Heterogeneous Samples in Metal Containers

“…[12] To overcome this drawback online NMR reaction monitoring was introduced, which involves transfer of ah omogeneous reaction mixture from ar eactor to the NMR magnet for the detection of the flowing sample without the need for discrete sampling or exposing the reaction mixture to the external atmosphere. [13][14][15][16][17][18][19] At the same time,t he studies of heterogeneous reactors and reacting systems [20,21] require different experimental approaches.…”

Chemical Reaction Monitoring Using Zero-Field Nuclear Magnetic Resonance Enables Study of Heterogeneous Samples in Metal Containers

“…However, these approaches are generally incompatible with operando analyses [12]. Recently, online NMR reaction monitoring was introduced, which involves transfer of a reaction mixture from a reactor to the NMR magnet for the detection of the flowing sample without the need for discrete sampling or exposing the reaction mixture to the external atmosphere [13][14][15][16][17][18][19]. At the same time, the studies of heterogeneous reactors and reacting systems [20,21] require different experimental approaches.…”