Direct Production of a Hyperpolarized Metabolite on a Microfluidic Chip

Area of Science:

• Nuclear Magnetic Resonance Spectroscopy
• Microfluidics
• Metabolic Studies

Background:

• Microfluidic systems are valuable for studying microscopic biological samples.
• Quantitative metabolic studies in small volumes require enhanced sensitivity.
• Hyperpolarization techniques can significantly boost NMR signal intensity.

Purpose of the Study:

• To demonstrate the integrated generation and detection of a hyperpolarized metabolite on a microfluidic chip.
• To enable quantitative metabolic studies in volume-limited systems using high-resolution NMR.
• To develop a continuous flow system for hyperpolarized metabolite production.

Main Methods:

• Integration of hyperpolarized agent generation and NMR detection on a single microfluidic chip.
• Utilizing para-enriched hydrogen diffusion, ruthenium-catalyzed reaction, and radiofrequency pulse sequences for hyperpolarization.
• Implementing methods to mitigate singlet-triplet mixing effects to improve polarization levels.

Main Results:

• Successful on-chip generation and detection of hyperpolarized [1-¹³C]fumarate.
• Continuous flow of hyperpolarized material at 2.5 μL/min with a 4% polarization level.
• Demonstration of techniques to overcome polarization loss mechanisms.

Conclusions:

• This work presents the first integrated microfluidic system for producing and detecting hyperpolarized metabolites.
• The developed system facilitates quantitative metabolic analysis in microfluidic settings.
• The approach holds promise for advancing in-situ metabolic studies of cells and tissues.