High-resolution, high-sensitivity NMR of nanolitre anisotropic samples by coil spinning

Abstract

Nuclear magnetic resonance (NMR) can probe the local structure and dynamic properties of liquids and solids, making it one of the most powerful and versatile analytical methods available today. However, its intrinsically low sensitivity precludes NMR analysis of very small samples-as frequently used when studying isotopically labelled biological molecules or advanced materials, or as preferred when conducting high-throughput screening of biological samples or 'lab-on-a-chip' studies. The sensitivity of NMR has been improved by using static micro-coils, alternative detection schemes and pre-polarization approaches. But these strategies cannot be easily used in NMR experiments involving the fast sample spinning essential for obtaining well-resolved spectra from non-liquid samples. Here we demonstrate that inductive coupling allows wireless transmission of radio-frequency pulses and the reception of NMR signals under fast spinning of both detector coil and sample. This enables NMR measurements characterized by an optimal filling factor, very high radio-frequency field amplitudes and enhanced sensitivity that increases with decreasing sample volume. Signals obtained for nanolitre-sized samples of organic powders and biological tissue increase by almost one order of magnitude (or, equivalently, are acquired two orders of magnitude faster), compared to standard NMR measurements. Our approach also offers optimal sensitivity when studying samples that need to be confined inside multiple safety barriers, such as radioactive materials. In principle, the co-rotation of a micrometre-sized detector coil with the sample and the use of inductive coupling (techniques that are at the heart of our method) should enable highly sensitive NMR measurements on any mass-limited sample that requires fast mechanical rotation to obtain well-resolved spectra. The method is easy to implement on a commercial NMR set-up and exhibits improved performance with miniaturization, and we accordingly expect that it will facilitate the development of novel solid-state NMR methodologies and find wide use in high-throughput chemical and biomedical analysis.

Recent technique developments and applications of solid state NMR in characterising inorganic materials

“…An alternative strategy using inductive coupling enabling wireless transmission of the rf pulses and detection of the signal from the sample under fast MAS also holds a lot of promise [14]. Although still not widely available the specific advantages offered by such microcoils should see more application in the area of inorganic materials in the future.…”

Magnetic Resonance Detection of Individual Proton Spins Using Quantum Reporters

“…Nuclear magnetic resonance and magnetic resonance imaging are essential tools for both the physical and life sciences [1,2], but have been limited to the detection of large ensembles of spins due to their low sensitivity [3,4], or the macroscopic nature of sensors [5,6]. Over the past decades, significant efforts [7][8][9][10][11] have been directed toward pushing this sensitivity to its ultimate physical limit, the detection of individual nuclear spin signals localized in a small volume.…”

Evaluation of High Resolution Magic-Angle Coil Spinning NMR Spectroscopy for Metabolic Profiling of Nanoliter Tissue Biopsies

“…The metabolic profile of sucrose is very well defined. Signals belonging to the glucose protons present a clear multiplicity with measurable J-couplings (see Table 1 and Figure 2 Figure 2 is a marked improvement over that of the currently available approaches to micro-detection with MAS, either using inductively coupled spinning microcoils (MACS) 11,13 or using a static microcoil in a piggy-back MAS approach. 18 Since the microcoil is static in the latter approach, the coil susceptibility is not averaged by the sample spinning.…”

“…The MACS approach has already applied to tissues using a solid-state CP-MAS probe, which is not optimal for high-resolution spectroscopy, and a tremendous mass sensitivity gain was demonstrated -up to two orders of magnitude -for nanoliter samples. 11,13 However, the spectral resolution limit has yet to be investigated for metabonomic studies.…”

“…Recently, a rotating micro-NMR detector has been developed for solid materials. 11,12 It has been called a Magic Angle Coil Spinning (MACS) microcoil. It is a small selfresonant solenoid coil, and can be wirelessly excited and detected using resonant-inductive coupling to commercial CP-MAS or HR-MAS probes.…”