Direct Production of a Hyperpolarized Metabolite on a Microfluidic Chip

Abstract

Microfluidic systems hold great potential for the study of live microscopic cultures of cells, tissue samples, and small organisms. Integration of hyperpolarization 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 hyperpolarized metabolite on a microfluidic chip. The metabolite [1- 13 C]fumarate is produced in a nuclear hyperpolarized 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-polarized reaction product into a magnetized form by the application of a radiofrequency pulse sequence, all on the same microfluidic chip. The microfluidic device delivers a continuous flow of hyperpolarized material at the 2.5 μL/min scale, with a polarization level of 4%. We demonstrate two methods for mitigating singlet–triplet mixing effects which otherwise reduce the achieved polarization level.

Metabolic Reactions Studied by Zero- and Low-Field Nuclear Magnetic Resonance

“…Although the microfluidic chip used did not involve fluidic complexity, this is a strength of lab-on-a-chip devices, and indeed it has been shown that the chemical reaction to hyperpolarize fumarate can be carried out on a chip. 40 Microfluidic NMR is hindered in widespread use in part due to the need for specially-designed probes for high-field implementation, as well as limited resolution due to magnetic field gradients at the interface between the chip and sample; ZULF NMR does not suffer from these limitations, and might prove to be a useful spectroscopic technique in this field.…”

Microfluidic quantum sensing platform for lab-on-a-chip applications

“…Here, we demonstrate a generalized microfluidic quantum sensing platform that incorporates the broad challenges posed by NV center-based quantum sensing and LOC applications. As example applications, we have chosen one of the most promising but challenging applications of NV centers in microfluidics: magnetic resonance spectroscopy [27], enabling non-invasive and quantitative analysis for chemical and biochemical applications on the nano-and microscale, complementing the existing NMR spectroscopy capabilities within microfluidics [28][29][30]. Importantly, our platform promotes quantum sensing for other applications as well, such as temperature measurements [15,31], bioassays [32,33], biomagnetism [21], or velocimetry [34],…”

Microfluidic quantum sensing platform for lab-on-a-chip applications

“…As example applications, we have chosen one of the most promising but challenging applications of NV centers in microfluidics: magnetic resonance spectroscopy, 27 enabling non-invasive and quantitative analysis for chemical and biochemical applications on the nano-and microscale, complementing the existing NMR spectroscopy capabilities within microfluidics. [28][29][30] Importantly, our platform promotes quantum sensing for other applications as well, such as temperature measurements, 15,31 bioassays, 32,33 biomagnetism, 21 or velocimetry, 34 making this technology accessible to numerous research communities.…”