Skip to main content

Ultra-sensitive NMR in liquids

Periodic Reporting for period 3 - BetaDropNMR (Ultra-sensitive NMR in liquids)

Reporting period: 2018-10-01 to 2020-03-31

Nuclear Magnetic Resonance (NMR) is an extremely sensitive technique used in many fields of research, including chemistry and biology where is is used to determine the structure and interactions of many different biomolecules. However, its main limitation is a very poor sensitivity. The aim of the betaDropNMR project is to transfer an ultrasensitive version of NMR, namely beta-detected NMR, from nuclear physics applications to chemistry and biology and to investigate with it the interaction of essential metal ions with biomolecules. Because beta-(detected) NMR requires up to a billion times fewer probe nuclei, studies which suffered from low NMR sensitivity might be now possible, e.g. investigation of zinc interaction with different proteins or interaction of Na+ and K+ ions with DNA G-quadruplex structures, which all play roles in the correct functioning of our organisms, and their malfunctioning, or are believed to be related to different diseases, including Parkinson's and Alzheimer’s.
At this stage of the project we have built the dedicated experimental setup at the CERN-ISOLDE facility allowing us to laser-polarize radioactive isotopes in their atomic form and to perform beta-asymmetry and beta-NMR studies with them. We have commissioned it using beta-asymmetry studies on short-lived Na isotopes. Since then we performed 3 beta-NMR experiments using the same Na isotopes in solid and liquid samples. We have also tested the liquid-vacuum interface which is required when working with some liquids, e.g. water. We have also identified the first biomolecules to study (DNA G-quadruplex structures), got them syntesized and studied with complementary methods by our collaborators, and very recently have performed first beta-NMR experiments using these systems as solid and liquid hosts. Very preliminary analysis shows that the recorded signals change when DNA is added to the samples. Thorough analysis and complementary studies are now under way.
State of the art of conventional ultrasensitive NMR is based mostly on the Dynamic Nuclear Polarization approach, where the sensitivity can be increased by several orders of magnitude. Our liquid beta-NMR resonances required only about 1e8 Na nuclei, thus increasing the sensitivity of the technique by 8 to 9 orders of magnitude. No other present approach can achieve such an improvement.
As next steps we plan to measure chemical shifts and relaxation times on G-quadruplex sequences in liquid environment. Then, during the 2-year period with no short-lived isotopes at CERN we will prepare a setup for checking the degree of polarization by fluorescence detection or conventional NMR and will work on laser-polarization schemes for K, Cu or Zn. We will also attempt to record conventional NMR spectra from stable, but hyperpolarized nuclei of these elements (and Na). If the latter works, until the end of the project we will put all efforts to study the interaction of different biomolecules with stable NMR isotopes of those elements with up to 1e5 improved sensitivity compared to conventional NMR, since the radioactive nuclei should be back at CERN only after the end of the project.
First 26Na beta-NMR in a liquid sample and DNA-G quadruplex to be studies with this technique