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High-Resolution Nuclear Magnetic Resonance Spectroscopy With Picomole\n Sensitivity by Hyperpolarisation On A Chip

2019/01/21 by James Eills, William Hale, Eills, James +9
Chemistry · Medicine · Physics and Astronomy · #Advanced MRI Techniques and Applications #Advanced NMR Techniques and Applications #Applied Physics (physics.app-ph) #Atomic and Subatomic Physics Research #Chemical Physics (physics.chem-ph) #FOS: Physical sciences

paper · pdf · doi:10.48550/arxiv.1901.07065

openalex publication_date 2019/01/21 · openalex created_date 2022/07/30 · openalex updated_date 2026/07/28

Abstract

We show that high-resolution NMR can reach picomole sensitivity for\nmicromolar concentrations of analyte by combining parahydrogen induced\nhyperpolarisation (PHIP)with a high-sensitivity transmission line\nmicro-detector. The para-enriched hydrogen gas is introduced into solution by\ndiffusion through a membrane integrated into a microfluidic chip. NMR\nmicrodetectors, operating with sample volumes of a few \μL or less, benefit\nfrom a favourable scaling of mass sensitivity. However, the small volumes make\nit very difficult to detect species present at less than millimolar\nconcentrations in microfluidic NMR systems. In view of overcoming this\nlimitation, we implement parahydrogen-induced polarisation (PHIP) on a\nmicrofluidic device with 2.5~ μ L detection volume. Integrating the\nhydrogenation reaction into the chip minimises polarisation losses to\nspin-lattice relaxation, allowing the detection of picomoles of substance. This\ncorresponds to a concentration limit of detection of better than\n\1 ,\μ M ,\√(s), unprecedented at this sample volume. The\nstability and sensitivity of the system allows quantitative characterisation of\nthe signal dependence on flow rates and other reaction parameters and permits\nhomo- and heteronuclear 2D NMR experiments at natural 13\C\nabundance.\n

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