Multinuclear 1D & 2D NMR with 19F-Photo-CIDNP hyperpolarization in a microfluidic chip with broadband microcoil

Abstract

Nuclear Magnetic Resonance (NMR) spectroscopy is one of the most powerful molecular characterization and quantification techniques available today, yet two major persistent factors limit more wide-spread applications of NMR: the poor sensitivity, and the intricate complex and expensive hardware required for sophisticated NMR experiments. We present a microfluidic NMR-chip in which the 25 nL detection volume can be efficiently illuminated with laser-diode light that enhances the sensitivity by orders of magnitude via the photo-CIDNP hyperpolarization principle, allowing rapid detection of samples in the lower picomole range. The chip is further equipped with a single planar microcoil operating in broadband mode that allows different Larmor frequencies to be addressed simultaneously, permitting advanced hetero-, di- and trinuclear, 1D and 2D NMR experiments. The NMR chips with photo CIDNP and broadband capabilities address two of the major limiting factors of NMR, by enhancing sensitivity as well as reducing cost and hardware complexity, and the performance is compared to state-of-the-art instruments.

Magnetometer-detected Nuclear Magnetic Resonance of Photochemically Hyperpolarized Molecules

“…In low-field photo-CIDNP experiments, susceptibility-induced broadening is small and uniform irradiation can also be achieved by injecting multiple fibres into the sample. We expect that in future, microfluidic implementations of the experiment will offer further improvements in both polarization and experimental control, as has been shown at high field [43][44][45] . Another promising direction is a combination of photo-CIDNP with optical spatial encoding for imaging experiments without gradients as was initially proposed for high-field experiments 46 .…”

Shim-free homebuilt 2 T magnet for NMR spectroscopy with sub-ppm resolution and sub-nanomole sensitivity

“…Commercial NMR probe heads are sophisticated and expensive, but home-built microfluidic NMR coils can be as simple and cheap as about 1 Euro and even show sub-picomole sensitivity 15,39 . Incorporating microcoils in nontuned radiofrequency (RF) circuits allows a further dramatic simplification in the RF circuit design and supporting electronics 16,[40][41][42] . Modern commercial low-field NMR spectrometers use impressively shimmed magnets with field homogeneity in the < 5 ppb range 4,7 , and can be readily integrated in, e.g., advanced machine-learning microfluidic set ups 43 .…”

“…These techniques, however, require sophisticated and complex hardware. Photo-CIDNP is a powerful hyperpolarization technique 35,36 , that is readily integrated in microfluidics and microcoil systems 15,16 , with relatively simple hardware. The space-wound microcoil encompassing a 0.5 uL detection volume in a 1 mm (0.8 mm inner diameter) glass capillary straightforwardly provides photo-CIDNP hyperpolarized spectra.…”

“…This is achieved by concentrating magnetic field lines in a relatively small volume, and exploiting home-built microcoils with field-homogeneity matching detection volumes in the 0.5 µL -40 nL range, 10 3 -10 4 times smaller than the standard NMR tube volume. The sensitivity of the set-up can be boosted with another three orders of magnitude by simply implementing a light-fiber in the open magnet design to allow photochemically-induced dynamic nuclear polarization (photo-CIDNP), a hyperpolarization technique with relatively simple experimental requirements 14 , that is of particular great value combined with microfluidic and small volume NMR [15][16][17] .…”