Pushing nuclear magnetic resonance sensitivity limits with microfluidics and photo-chemically induced dynamic nuclear polarization

Abstract

Among the methods to enhance the sensitivity of nuclear magnetic resonance (NMR) spectroscopy, small-diameter NMR coils (microcoils) are promising tools to tackle the study of mass-limited samples. Alternatively, hyperpolarization schemes based on dynamic nuclear polarization techniques provide strong signal enhancements of the NMR target samples. Here we present a method to effortlessly perform photo-chemically induced dynamic nuclear polarization in microcoil setups to boost NMR signal detection down to sub-picomole detection limits in a 9.4T system (400 MHz 1H Larmor frequency). This setup is unaffected by current major drawbacks such as the use of high-power light sources to attempt uniform irradiation of the sample, and accumulation of degraded photosensitizer in the detection region. The latter is overcome with flow conditions, which in turn open avenues for complex applications requiring rapid and efficient mixing that are not easily achievable on an NMR tube without resorting to complex hardware.

Low‐cost LED‐based Photo‐CIDNP Enables Biocompatible Hyperpolarization of 19F for NMR and MRI at 7 T and 4.7 T

“…Photo‐CIDNP also allows a fast and direct spatial encoding by illuminating different parts of the sample . It was recently shown that 19 F photo‐CIDNP allows for the detection of a diluted p‐fluorophenol sample containing only 0.8 pmol/μL of the fluorinated substrate . CIDNP is field dependent but it was shown that hyperpolarization can be achieved over a wide range covering the typical field strengths of clinical MRI scanners between 1.5 and 3 T .…”

Parahydrogen based NMR hyperpolarisation goes micro: an alveolus for small molecule chemosensing

“…For instance, Jiménez-Martínez et al designed an on-chip hyperpolarised Xenon NMR system,16 Causier et al presented a 3D-printed polariser to address hyperpolarisation with different gas species using a hand-wound microcoil,17 Bouchard et al exploited NMR to visualize chemical processes in catalytic microreactors 18. Recently, Lehmkuhl et al demonstrated an in-line flow setup for SABRE on a bench-top NMR spectrometer based on a 3D printed membrane reactor19 while Mompeán et al presented a photo-CIDNP NMR probe for limited-volume samples by leveraging the advantages of microcoils 20…”

Use of dissolved hyperpolarized species in NMR: Practical considerations

“…A number of integrated devices combining microfluidics, micro-detection and hyperpolarization have been described in in the literature. While a few use laser-polarized Xe [105,48] and CIDNP, [106] the majority of them deal with hyperpolarization via parahydrogen, [107,108] the cheapest method, which is becoming more versatile. Recently, Bordonali et al, [40] as already mentioned, proposed a device based on a micro-SABRE platform mounted on the core of a Bruker microimaging probe (a similar mounting was used for the device conceived by Causier et al [48] for hyperpolarized 129 Xe NMR).…”