Letter | Published:

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

Nature volume 447, pages 694697 (07 June 2007) | Download Citation

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-coils1, alternative detection schemes2,3 and pre-polarization approaches4. But these strategies cannot be easily used in NMR experiments involving the fast sample spinning essential for obtaining well-resolved spectra5,6 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.

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References

  1. 1.

    , , , & High-resolution microcoil 1H-NMR for mass-limited, nanoliter-volume samples. Science 270, 1967–1970 (1995)

  2. 2.

    , & Optical detection of liquid-state NMR. Nature 442, 1021–1024 (2006)

  3. 3.

    et al. Force detection of nuclear magnetic resonance. Science 264, 1560–1563 (1994)

  4. 4.

    et al. Increase in signal-to-noise ratio of >10,000 times in liquid-state NMR. Proc. Natl Acad. Sci. USA 100, 10158–10163 (2003)

  5. 5.

    , & Nuclear magnetic resonance spectra from a crystal rotated at high speed. Nature 182, 1659 (1958)

  6. 6.

    Free induction decays of rotating solids. Phys. Rev. Lett. 2, 285–287 (1959)

  7. 7.

    & The signal-to-noise ratio of the nuclear magnetic resonance experiment. J. Magn. Reson. 24, 71–85 (1976)

  8. 8.

    Radiofrequency microcoils in magnetic resonance. Prog. Nucl. Magn. Reson. Spectrosc. 31, 1–42 (1997)

  9. 9.

    et al. NMR spectroscopy of single neurons. Magn. Reson. Med. 44, 19–22 (2000)

  10. 10.

    , , , & MR microscopy of multicomponent diffusion in single neurons. Magn. Reson. Med. 45, 1107–1112 (2001)

  11. 11.

    , & Implementing solenoid microcoils for wide-line solid-state NMR. J. Magn. Reson. 167, 87–96 (2004)

  12. 12.

    , & Towards nuclear magnetic resonance μ-spectroscopy and μ-imaging. Analyst 129, 793–803 (2004)

  13. 13.

    , , , & Microcoil high-resolution magic angle spinning NMR spectroscopy. J. Am. Chem. Soc. 128, 8722–8723 (2006)

  14. 14.

    et al. Design, construction, and validation of a 1-mm triple-resonance high-temperature-superconducting probe for NMR. J. Magn. Reson. 179, 290–293 (2006)

  15. 15.

    Electronic and Radio Engineering Ch. 3 (McGraw-Hill, New York, 1955)

  16. 16.

    The development of a thick-film non-contact shaft torque sensor for automotive applications. J. Phys. E 22, 82–88 (1989)

  17. 17.

    , & Powering efficiency of inductive links with inlaid electroplated microcoils. J. Micromech. Microeng. 14, 576 (2004)

  18. 18.

    & Optimization of NMR receiver bandwidth by inductive coupling. Magn. Reson. Imag. 10, 55–65 (1992)

  19. 19.

    & Use of mutually inductive coupling in probe design. Concepts Magn. Reson. B 15, 262–285 (2002)

  20. 20.

    , & High-temperature superconducting surface coil for in vivo microimaging of the human skin. Magn. Reson. Med. 45, 376–382 (2001)

  21. 21.

    , , & Wireless implanted magnetic resonance probes for in vivo NMR. J. Magn. Reson. 68, 161–167 (1986)

  22. 22.

    Cylindrical demagnetization fields and microprobe design in high-resolution NMR. J. Magn. Reson. A 109, 265–269 (1994)

  23. 23.

    , & High-resolution 1H NMR spectroscopy in rat liver using magic angle turning at a 1 Hz spinning rate. Magn. Reson. Med. 47, 829–836 (2002)

  24. 24.

    et al. Quantitative neuropathology by high resolution magic angle spinning proton magnetic resonance spectroscopy. Proc. Natl Acad. Sci. USA 94, 6408–6413 (1997)

  25. 25.

    , & Proton NMR chemical shifts and coupling constants for brain metabolites. NMR Biomed. 13, 129–153 (2000)

  26. 26.

    et al. High-resolution solid-state nuclear magnetic resonance experiments on highly radioactive ceramics. Rev. Sci. Instrum. 75, 5232–5236 (2004)

  27. 27.

    & Picoliter 1H NMR spectroscopy. J. Magn. Reson. 154, 336–343 (2002)

  28. 28.

    , , , , & Isotropic susceptibility shift under MAS: The origin of the split water resonances in 1H MAS NMR spectra of cell suspensions. Magn. Reson. Med. 50, 515–521 (2003)

  29. 29.

    , , , & Using microcontact printing to fabricate microcoils on capillaries for high resolution proton nuclear magnetic resonance on nanoliter volumes. Appl. Phys. Lett. 70, 2464–2466 (1997)

  30. 30.

    et al. Laser-lathe lithography — a novel method for manufacturing nuclear magnetic resonance microcoils. Biomed. Microdevices 5, 21–27 (2003)

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Acknowledgements

We thank J. Virlet for discussions on inductive coupling, H. Desvaux for discussions and help with the manuscript, D. Hoult for discussions on inductive coupling and micro-coils, A. Trabesinger, C. A. Meriles, T. Charpentier and A. Llor for discussions, P. Berthault for help with the manuscript and F. Engelke for help with chip capacitors and hardware.

Author Contributions D.S. and J.-F.J. conceived the technique and carried out the NMR experiments. G.L.G. machined the ceramic and plastic rotor inserts. D.S. wrote the paper.

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Affiliations

  1. Laboratoire de Structure et Dynamique par Résonance Magnétique, Service de Chimie Moléculaire (Laboratoire Claude Fréjacques, CNRS URA 331) DSM/DRECAM/SCM, CEA Saclay, Gif-sur-Yvette 91191, France

    • D. Sakellariou
  2. Service de Physique de l’Etat Condensé (CNRS URA 2464), DSM/DRECAM/SPEC, CEA Saclay, Gif-sur-Yvette 91191, France

    • G. Le Goff
    •  & J.-F. Jacquinot

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Reprints and permissions information is available at www.nature.com/reprints. The authors declare no competing financial interests.

Corresponding author

Correspondence to D. Sakellariou.

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https://doi.org/10.1038/nature05897

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