Direct Production of A Hyperpolarized Metabolite on a Microfluidic Chip

TL;DR

This paper reports the first integrated microfluidic system that produces and detects hyperpolarized metabolites, enabling high-resolution NMR studies of small biological samples with continuous flow and significant polarization levels.

Contribution

It introduces a novel microfluidic chip that combines hyperpolarization, chemical reaction, and detection of metabolites in a single device, advancing metabolic studies in microscale systems.

Findings

Achieved 4% polarization of hyperpolarized 1-$^{13}$C-fumarate.

Successfully integrated hyperpolarization, reaction, and detection on a microfluidic chip.

Demonstrated continuous flow delivery of hyperpolarized material at 2.5 μL/min.

Abstract

Microfluidic systems hold great potential for the study of live microscopic cultures of cells, tissue samples, and small organisms. Integration of hyperpolarisation would enable quantitative studies of metabolism in such volume limited systems by high-resolution NMR spectroscopy. We demonstrate, for the first time, the integrated generation and detection of a hyperpolarised metabolite on a microfluidic chip. The metabolite 1-$^{13}$C-fumarate is produced in a nuclear hyperpolarised form by (i) introducing para-enriched hydrogen into the solution by diffusion through a polymer membrane, (ii) reaction with a substrate in the presence of a ruthenium-based catalyst, and (iii) conversion of the singlet-polarised reaction product into a magnetised form by the application of a radiofrequency pulse sequence, all on the same microfluidic chip. The microfluidic device delivers a continuous flow of hyperpolarised material at the 2.5 $\mu\text{L}/\text{min}$ scale, with a polarisation level of 4%. We demonstrate two methods for mitigating singlet-triplet mixing effects which otherwise reduce the achieved polarisation level.