Revolutionary Advance in Sensitivity

Under the coordination of the University of Stuttgart, researchers are working on a technology, which will open up entirely new possibilities for nuclear magnetic resonance spectroscopy. Thanks to the quantum properties of certain impurities in diamonds, the sensitivity of the method can be increased by a factor of 1000. Pharmaceutical companies, laboratories, doctor’s practices and, not least of all, personalized medicine will all benefit from this development.

The fields in which any technology finds application is determined by the price. If it costs a six- or seven-figure sum to procure it then it will remain a niche technology however well it performs. However, if the same technology were cheaper by a factor of 100 and the cost were to sink even lower to just a few hundred euro within a decade then that would amount to a revolutionary development: suddenly the technology in question would be available to anyone.

This is precisely the sort of revolutionary development Professor Jens Anders, Director of the Institute of Smart Sensors (IIS) at the University of Stuttgart, has in mind when he talks about nuclear magnetic resonance spectroscopy. The electrical engineer is the coordinator of the EU’s “Nanospin” research project, which is due to start imminently and will involve interdisciplinary teams from five European countries.

The project participants have set themselves the goal of enhancing the sensitivity of nuclear magnetic resonance spectroscopy by a factor of 1000. “This will enable the development of systems that are either far more powerful than their predecessors or much smaller and cheaper than contemporary devices” Anders points out. To understand how this works, one needs to follow his train of thought from the extremely large – today’s devices – to the extremely small, i.e., quantum effects.

Ordinarily, the only contact most people have with nuclear magnetic resonance is when they're sent to the hospital for an MRI scan. Being “put in the tube” for a diagnostic scan involves lying in a device with a diameter of around two metres that generates images of one’s tissues and organs. In some cases, patients are injected with a contrast substance. Apart from its use in medical practice, nuclear magnetic resonance is also used in the field of analytics, in which context the technology is used to probe materials and active agents with extreme accuracy, so accurately in fact that individual molecules can be identified with ease. This method is referred to as nuclear magnetic resonance spectroscopy and it is this application that Project “Nanospin” is all about.

“It uses one of the quantum mechanical properties of atomic nuclei – their so-called nuclear spin”, Anders explains. Each atomic nucleus behaves like a miniature magnet. A state of resonant excitation can be induced in these nuclear spins by exposing a material sample to a strong magnetic field and radiating energy into it via an alternating electromagnetic field after which they can be “read out” via a coil. Based on the resulting data, scientists can then draw conclusions about the structure and dynamics as well as the concentration of the molecules in questions. It is a powerful analytical tool – with large, powerful devices. “The most sensitive ones occupy entire hangars and achieve magnetic field strengths of 28 Tesla” explains Anders. That’s about 3000 times stronger than a fridge magnet. Such powerful magnetic fields require correspondingly large currents in refrigerated magnetic coils. Whilst such gigantic machines are only found in a few specialized laboratories around the world, systems operating at around seven Tesla are relatively common, for example, in research institutes and pharmaceutical enterprises.

“The main drawback of this technology”, says Anders, “is its low sensitivity. Determining the composition of the molecules in a given sample, for example, takes the entire night”. High turnover measurements of the type commonly used in pharmacological research are, therefore, often not cost-effective. Such measurements involve, for instance, the systematic evaluation of the efficacy of as many variants of pharmaceutical substances as possible. “Using nuclear magnetic resonance spectroscopy for this task is only possible if other methods have already been used to reduce the number of potential variants to the bare minimum”, says Anders. “Only then will their number be small enough to subject them to time-consuming NMR-spectroscopic analyses”. If, on the other hand, it proved possible to increase their sensitivity by a factor of 1000, then the time needed to complete the analyses would be dramatically reduced: what used to take all night could then be completed in just a few minutes.

Unfortunately, it is hardly possible to increase the sensitivity of the process, as currently implemented, as the construction of magnets with even higher field strengths is subject to technical limitations. “Which is why we're taking a completely different approach in our project”, says Anders. The scientists exploit a quantum mechanical effect based on F-centres in artificial diamonds, the so-called dynamic nuclear polarization effect. F-centres are deliberately created impurities, produced, for example, by inserting nitrogen atoms, which absorb specific light wavelengths thus giving the inherently colorless diamond a specific hue. Ultimately, this makes it possible to align more atomic nuclei in the sample under analysis than would ordinarily have been possible. The more aligned atomic nuclei, the higher the sensitivity of the NMR-spectroscopic measurements, indeed by the factor of 1000 cited by Anders.

An interdisciplinary team of researchers from five European countries are collaborating in the “Nanospin” project to achieve this ambitious-sounding goal. The groups headed by Professors Fedor Jelezko and Martin Plenio from Ulm University include proven experts in the study of the dynamic nuclear polarisation effect. In the course of the project, the Ulm-based researchers will work to advance the current understanding of the underlying physical principles to move the subject “from the realm of theoretical physics to the application laboratory” as Anders puts it. Also onboard is NVision Imaging Technologies, a spin-off company co-managed by Jelezko and Plenio, which will contribute to the industrial implementation of the nuclear magnetic resonance spectroscopy research results. Jens Anders’ Stuttgart-based group will in turn be responsible for the sensor-related implementation. In addition, with the Belgian University of Hasselt and the Czech Academy of Sciences two institutes are involved in the project that will focus on the materials-science perspectives.

They have many years of experience with imperfections in diamonds and create them in a targeted manner. The Wigner Research Center for Physics will complement this materials-science expertise with a theoretical component: physicists at the institute are using simulations to investigate the properties of the diamonds. And finally, the Wageningen University & Research augments the “Nanospin” project team with experts in nuclear magnetic resonance. “Within their respective disciplines”, says Anders, “all project participants are among the world’s leading experts and, through the University of Stuttgart, for the first time, the engineering side is represented in a research project of this kind, which focuses on so-called hyperpolarized nuclear magnetic resonance spectroscopy. That's a unique configuration made possible through intra-European collaboration”. Project “Nanospin” is part of a European network known as “QuantERA”, in which 32 organizations from 26 countries have banded together to advance research in the field of quantum technology.

The “Nanospin” project partners have set themselves three objectives, which they want to achieve within the three-year project period. First, they want to prove that by exploiting imperfections in diamonds, NMR spectroscopic measurements are possible even at the level of single molecules. That would deliver new insights in the field of molecular biology. Second, the researchers want to implement hyperpolarization technology on chips to enable the production of portable devices. This would limit the magnetic field strength to around one Tesla but this would be compensated for by the one-thousand-fold increase in sensitivity.

“Our vision for the medium term”, explains Anders, “is to enable the production of affordable NMR spectrometers that would sell for less than 10,000 euro, which would make them economically viable for, for example, blood analysis in GP surgeries”. Within a decade, the electronic engineer hopes, chip-based devices could become so miniaturized and simplified that they could be acquired for just a few hundred euro. “That would be of interest in the field of personalized medicine. For example, patients could screen their own blood for specific disease markers in the same way that diabetics currently measure their own blood sugar levels”. The third objective involves high-end NMR spectrometers that currently occupy entire hangars. The researchers want to develop an add-on system for these with which existing operational devices can be retrofitted to shorten the mensuration times for typical experiments by far more than a thousandfold. Achieving any one of these objectives would be an enormous step forward by itself.

Michael Vogel