Periodic Reporting for period 2 - ZULF (Zero and ultra-low field nuclear magnetic resonance)
Reporting period: 2020-02-01 to 2022-07-31
Nuclear magnetic resonance (NMR) is a powerful technique employed in various areas of science and industry, from medicine to quantum computing. Conventional NMR requires very strong magnetic fields, which provide high spectral and spatial resolutions, but also require application of very expensive and bulky magnets and limit the use of the techniques to nonmagnetic materials or patients without endoprosthesis or cardiac pacemakers. Recent progress in physics and chemistry enabled detection of NMR signals at Zero and Ultra-Low magnetic Fields (ZULFs). The ZULF NMR Innovative Training Network (ITN) was dedicated to developing, exploring, and applying methods of NMR in this regime and providing training to 11 Early Stage Researchers (ESRs). The main scientific objective of the project was to go beyond the state-of-the-art in NMR under ZULF conditions by pushing the boundary in hyperpolarization and magnetometry. Combination of the techniques allowed to investigate chemical dynamics, search for physics beyond the Standard Model, or identify unknown substances.
The ZULF NMR ITN had two objectives. The first was the development of a new NMR modality by combining the developments in hyperpolarization and optical magnetometry. In this first context, such techniques as non-hydrogenative parahydrogen-induced polarization, dynamic nuclear polarization, and photochemically-induced dynamic nuclear polarization were used within the project. They allowed a significant increase in the nuclear-polarization level, enabling research previously impossible with ZULF NMR. In the context of magnetometry, a particular progress was made in nanomagnetometry. Using small ensembles of nitrogen-vacancy centers in diamonds or even a single center, NMR signals from single molecules were measured.
A specific example of new NMR capabilities, originating from the combination of hyperpolarization and optical magnetometry, was measurements of spectra of compounds yet uninvestigated under ZULF. Demonstration of the ability of measuring such compounds often led to the creation of a whole novel subfield of NMR. Specifically, spectroscopy of biorelevant molecules (sugars, aminoacids, urea) opened ZULF NMR for biological investigations. Another example of novel research demonstrated within the project is ultralow-field NMR relaxometry. This research allowed reaching a magnetic-field range earlier inaccessible to NMR and hence investigate spin dynamics under yet unexplored conditions. From a more practical perspective, it enabled detection of NMR silent molecules (e.g. glucose), hence opening ZULF NMR toward “medical” diagnostics (e.g. diabetes).
Spectacular examples of the research performed within the project are associated with studies of molecular dynamics. Specifically, real-time monitoring of hyperpolarized-fumarase activity was demonstrated, which opened the path to greatly accelerated preclinical studies using fumarate as a biomarker. Monitoring chemical reactions inside metallic enclosers was yet another example. Such measurements are impossible in conventional NMR and hence operation at ZULF enabled studies of reactions that required such conditions.
The second goal of the ZULF NMR ITN was to educate a group of young scientists in the field yet unavailable in the curriculum of any educational institution. This task was realized by organization of semi-annually weekly workshops, during which the ESRs interact with experts in NMR and magnetometry. Besides the academic lectures, the ESRs were trained in scientific communication and writing, presentations, or interviewing.
Another important aspect of the ZULF NMR project was the secondments. During the project, all ESRs worked in “foreign” laboratories. This exposed them to a different knowledge and working environment, significantly improving their intellectual and interpersonal skills. Due to the pandemic, some of the initially planned in-person secondments were converted into virtual ones, but these Skype/Zoom-based secondments proved to be efficient means of knowledge transfer.
The training of the ESRs also occurred through the dissemination of their results. A prime example of the activity was the organization of the 1st ZULF NMR conference, for which the ESRs prepared the program, invited speakers, and chaired sessions. The online conference turned to be a huge success with about 200 attendees and 15 talks.
The last aspect of the ESRs’ training was broad public dissemination of their research. For that, the website (www.zulf.eu) and blog (blog.zulf.eu) dedicated to ZULF NMR were created. In conjunction with ESR-prepared multinational entry on ZULF NMR at Wikipedia (en.wikipedia.org/wiki/Zero_field_NMR) this offers a good introduction into ZULF NMR basics as well as up-to-date information.
A specific example of new NMR capabilities, originating from the combination of hyperpolarization and optical magnetometry, was measurements of spectra of compounds yet uninvestigated under ZULF. Demonstration of the ability of measuring such compounds often led to the creation of a whole novel subfield of NMR. Specifically, spectroscopy of biorelevant molecules (sugars, aminoacids, urea) opened ZULF NMR for biological investigations. Another example of novel research demonstrated within the project is ultralow-field NMR relaxometry. This research allowed reaching a magnetic-field range earlier inaccessible to NMR and hence investigate spin dynamics under yet unexplored conditions. From a more practical perspective, it enabled detection of NMR silent molecules (e.g. glucose), hence opening ZULF NMR toward “medical” diagnostics (e.g. diabetes).
Spectacular examples of the research performed within the project are associated with studies of molecular dynamics. Specifically, real-time monitoring of hyperpolarized-fumarase activity was demonstrated, which opened the path to greatly accelerated preclinical studies using fumarate as a biomarker. Monitoring chemical reactions inside metallic enclosers was yet another example. Such measurements are impossible in conventional NMR and hence operation at ZULF enabled studies of reactions that required such conditions.
The second goal of the ZULF NMR ITN was to educate a group of young scientists in the field yet unavailable in the curriculum of any educational institution. This task was realized by organization of semi-annually weekly workshops, during which the ESRs interact with experts in NMR and magnetometry. Besides the academic lectures, the ESRs were trained in scientific communication and writing, presentations, or interviewing.
Another important aspect of the ZULF NMR project was the secondments. During the project, all ESRs worked in “foreign” laboratories. This exposed them to a different knowledge and working environment, significantly improving their intellectual and interpersonal skills. Due to the pandemic, some of the initially planned in-person secondments were converted into virtual ones, but these Skype/Zoom-based secondments proved to be efficient means of knowledge transfer.
The training of the ESRs also occurred through the dissemination of their results. A prime example of the activity was the organization of the 1st ZULF NMR conference, for which the ESRs prepared the program, invited speakers, and chaired sessions. The online conference turned to be a huge success with about 200 attendees and 15 talks.
The last aspect of the ESRs’ training was broad public dissemination of their research. For that, the website (www.zulf.eu) and blog (blog.zulf.eu) dedicated to ZULF NMR were created. In conjunction with ESR-prepared multinational entry on ZULF NMR at Wikipedia (en.wikipedia.org/wiki/Zero_field_NMR) this offers a good introduction into ZULF NMR basics as well as up-to-date information.
Within the project, novel scientific and practical capabilities of ZULF NMR were developed. Besides described above (bio)chemical achievements, the project also contributed to physics and technology. For instance, ZULF NMR was used to search for the so-called spin-gravity coupling. Although the project did not reveal any spin-gravity coupling, it allowed to significantly improve the limit on such an interaction, bringing closer the discovery of physics beyond the Standard Model. Other achievement of the project is the creation of a ZULF NMR library. Since each compound possesses unique ZULF NMR spectrum, the library can be used for chemical fingerprinting and hence can find applications in agriculture and home-land security. Significant efforts were also out in detection of NMR signals of single molecules. Within the project, such spectra were measured at high field and significant progress toward ZULF nanoNMR was made. This goal will be realized in the future by the further development of nanoscopic magnetometry but also developed-within-the-project means of selective addressing of specific spins and manipulation of intramolecular interactions.
The great success of the project lies in training ESRs in ZULF NMR. Our ESRs got educated in the cross-disciplinary field, enabling research on the interface between physics, chemistry, and biology. In conjunction in soft skills developed within the project, this unique expertise made them great candidates to undertake scientific and industrial challenges (most ESRs stayed in academia, but a few decided to get into industry).
In summary, the project turned out to be very successful. It allowed to form close collaborations between many groups in Europe. These collaborations have already proven to generate interesting results and have led to several breakthroughs in the field of ZULF NMR, with many links to other disciplines. Importantly, the collaboration, both between the PIs and ESRs will continue in the future (including future grants), which is yet another measure of the success of the project.
The great success of the project lies in training ESRs in ZULF NMR. Our ESRs got educated in the cross-disciplinary field, enabling research on the interface between physics, chemistry, and biology. In conjunction in soft skills developed within the project, this unique expertise made them great candidates to undertake scientific and industrial challenges (most ESRs stayed in academia, but a few decided to get into industry).
In summary, the project turned out to be very successful. It allowed to form close collaborations between many groups in Europe. These collaborations have already proven to generate interesting results and have led to several breakthroughs in the field of ZULF NMR, with many links to other disciplines. Importantly, the collaboration, both between the PIs and ESRs will continue in the future (including future grants), which is yet another measure of the success of the project.