221. Low-Cost High-Pressure Clinical-Scale 50% Parahydrogen Generator Using Liquid Nitrogen at 77 K

Benjamin Chapman, Baptiste Joalland, Collier Meersman, Jessica Ettedgui, Rolf E. Swenson, Murali C. Krishna, Panayiotis Nikolaou, Kirill V. Kovtunov, Oleg G. Salnikov, Igor V. Koptyug, Max E. Gemeinhardt, Boyd M. Goodson, Roman V. Shchepin, and Eduard Y. Chekmenev; Analytical Chemistry; (2021); DOI: 10.1021/acs.analchem.1c00716

We report on a robust and low-cost parahydrogen generator design employing liquid nitrogen as a coolant. The core of the generator consists of catalyst-filled spiral copper tubing, which can be pressurized to 35 atm. Parahydrogen fraction >48% was obtained at 77 K with three nearly identical generators using paramagnetic hydrated iron oxide catalysts. Parahydrogen quantification was performed on the fly via benchtop NMR spectroscopy to monitor the signal from residual orthohydrogen–parahydrogen is NMR silent. This real-time quantification approach was also used to evaluate catalyst activation at up to 1.0 standard liter per minute flow rate. The reported inexpensive device can be employed for a wide range of studies employing parahydrogen as a source of nuclear spin hyperpolarization. To this end, we demonstrate the utility of this parahydrogen generator for hyperpolarization of concentrated sodium [1-13C]pyruvate, a metabolic contrast agent under investigation in numerous clinical trials. The reported pilot optimization of SABRE-SHEATH (signal amplification by reversible exchange–shield enables alignment transfer to heteronuclei) hyperpolarization yielded 13C signal enhancement of over 14,000-fold at a clinically relevant magnetic field of 1 T corresponding to approximately 1.2% 13C polarization—if near 100% parahydrogen would have been employed, the reported value would be tripled to 13C polarization of 3.5%.