A technology that pushes the boundaries of the invisible by revealing the intimate structure of matter.
Magnetic resonance imaging most often evokes medical scanners that allow visualization of our internal organs without any surgical intervention. But behind this well-known medical application lies a much broader scientific world: that of solid-state NMR, an investigation tool capable of revealing the atomic structure of materials. For decades, this technique has faced a major challenge: its lack of sensitivity. Today, a minuscule but revolutionary innovation—the microcoil—is transforming this field by enabling the study of infinitesimal amounts of matter, opening new perspectives in biology, materials science, and medicine.
Nuclear magnetic resonance, discovered sixty years ago, has become an essential analysis tool in many scientific fields, ranging from condensed matter physics to structural biology and materials chemistry. The fundamental principle of this technique relies on detecting variations in the magnetization of atomic nuclei under the action of a powerful magnetic field and an exciting electromagnetic wave4 .
Nevertheless, NMR suffers from an intrinsic weakness: its lack of sensitivity. This problem is particularly acute in the solid phase, where analyses traditionally require substantial amounts of matter—generally between 30 and 400 mg depending on the samples3 . Such quantity is often difficult, if not impossible, to obtain in many modern research contexts, whether for the study of thin layers elaborated by sol-gel process, biological calcifications like kidney stones, or tissue biopsies in medical investigations3 7 .
Faced with this challenge, the scientific community has explored several approaches to increase the sensitivity of NMR experiments.
The MACS (Magic Angle Coil Spinning) technology represents a major conceptual and technical advance in the field of solid-state NMR. Originally developed by Sakellariou and his team, this ingenious approach combines two fundamental principles of NMR1 3 .
At the heart of the MACS system is a microcoil of millimeter dimensions that surrounds a capillary containing the sample to be analyzed. This microcoil is itself placed inside a classic rotor of an NMR spectrometer, allowing its use without modification of the standard probe3 . The true genius of the approach lies in the combination of magic angle spinning (MAS)—a well-established technique in solid-state NMR—with the advantages of micro-detectors.
The principle of magic angle spinning (typically 54.74°) allows averaging the anisotropic interactions that broaden spectral lines in solid-state NMR. By rotating the sample at high speed under this particular angle, high-resolution spectra comparable to those obtained in liquid phase are obtained. MACS technology pushes this principle further by rotating the detection coil itself, thus improving detection limits by at least one order of magnitude compared to the conventional MAS method1 .
Millimeter-scale coil surrounding sample capillary
Rotation at 54.74° to average anisotropic interactions
At least 10x improvement in detection limits
Only 30-100 µg needed versus 30-400 mg conventionally
Sample required with MACS
Sample required conventionally
Sensitivity improvement
Proton line widths achieved
| NMR Technique | Sample Quantity Required | Typical Resolution | Main Application Areas |
|---|---|---|---|
| Conventional Solid NMR | 30-400 mg | Variable, depending on sample | Bulk materials, polymers, glasses |
| MACS | 30-100 µg | Proton line widths ~5 Hz | Tissue biopsies, thin films, kidney stones |
A particularly demonstrative experiment of the power of microcoils was conducted as part of the HRMACS project (High-Resolution Magic-Angle Coil Spinning), a project supported by the French National Research Agency and coordinated by Alan Wong1 . This project specifically aimed to develop new generations of MACS detectors for the study of metabolism, with potential applications in medical diagnosis.
The central objective of the experiment was twofold: improve the homogeneity of the static field B0 around the coil to obtain spectra with resolution comparable to that observed on liquids, and develop a sample preparation procedure on the order of the nanoliter without tissue degradation1 . These advances were to allow for the first time a microscopic study of biopsies by NMR, particularly in the context of chemotherapy treatment for breast cancer and the study of metabolic activities of metastases in the lungs1 .
Development of microscopic coils adapted to fast rotation at the magic angle.
Development of delicate preparation protocols for tissue samples.
Placement of microcoils in standard NMR spectrometer rotor.
Processing of obtained spectra to extract relevant metabolic information.
The obtained results were convincing: HRMACS technology allowed obtaining very high resolution NMR spectra with proton line widths of about 5 Hz, a remarkable performance for heterogeneous samples of low mass1 .
| Parameter | Improvement |
|---|---|
| Sample Quantity | Reduction of 3-4 orders of magnitude |
| Sensitivity | Improvement of at least one order of magnitude |
| Resolution | Proton line widths ~5 Hz |
The implementation of microcoil technologies in solid-state NMR relies on a set of specialized components and advanced methodologies that constitute the essential toolkit for researchers in this field.
One of the most promising developments in this field is the combination of microcoils with dynamic nuclear polarization (DNP), an approach explored in the MicrogramNMR project coordinated by Christian Bonhomme7 .
The microcoil revolution in solid-state NMR is only just beginning. Current developments foreshadow major advances in the coming years, with potentially transformative implications for several scientific and medical fields.
Microcoils will allow the study of rare or precious synthesis samples, functional thin layers, and nanostructured materials that were previously inaccessible to NMR characterization7 .
This technology opens the way to metabolic analysis of very small biopsies, with applications in oncology for personalized treatment monitoring or the study of fundamental metabolic mechanisms1 .
Further reduction in detector size for even smaller samples
Combination with DNP and other sensitivity enhancement methods
Creation of portable and economical systems for varied environments
While the magnetic resonance coil market is expected to experience significant growth in the coming years, reaching nearly $23 billion by 2035 according to projections8 , innovations in the field of microcoils for fundamental research are likely to find unexpected applications in the clinical domain.
Projected market by 2035
These tiny detectors are opening a gigantic world of scientific possibilities, proving once again that in contemporary science, it is often by miniaturizing that we access the greatest discoveries.