Unique resonance technology to study cellular metabolism

By March 11, 2022July 21st, 2022IBEC

A Dynamic Nuclear Polarisation (DNP) Polariser for Nuclear Magnetic Resonance (NMR) has been installed at the BIST centre IBEC. The equipment, which is the only one of its kind in operation in Spain and one of very few in Europe, allows for the study of cellular metabolism in real time. Dr Irene Marco, “la Caixa” Foundation – BIST Chemical Biology group leader and former BIST Mothers of Science grantee, leads the laboratory at IBEC.

Following an agreement made with the University of Barcelona (UB), the HyperSense™ equipment, from the company Oxford Instruments Molecular Biotools, has been installed in the Molecular Imaging for Precision Medicine laboratory (MIPMED) at the BIST centres IBEC. The laboratory is led by Dr Irene Marco, who took up the position as group leader in 2021 through the “la Caixa” Foundation – BIST Chemical Biology programme. Dr Marco was also awarded in the 2020 edition of the BIST To the Mothers of Science programme, which aims to support women scientists on their way to becoming leaders in their fields.

The in vitro polariser can provide a signal-to-noise ratio not reachable by conventional NMR equipment, increasing sensitivity more than 10,000 fold. As a result, this technique can be used to study rapid metabolic processes either in vivo or in vitro, in a non-invasive way and in real time, providing information on the mechanistic and biochemical changes that occur in a diseased organ. This powerful technique can open new areas of research and has the potential to change the field of NMR.

The equipment performs dynamic nuclear polarisation of samples in the fluid-form, such as sugars, that are then used to monitor cellular metabolism with conventional NMR equipment. The sample is transferred to the centre of the HyperSense™, where it is submerged in liquid helium at the core of the magnetic field. Everything is done under extremely low temperature (-271,75 ºC) which allows the sample carbon atoms to be nearly fully polarised.

Researchers at IBEC use hyperpolarised pyruvic acid, a sugar that is used to study the metabolism of different cellular types. Inside the NMR, the cells are supplied with this sample and, for about 75 seconds, researchers can follow its absorption by the cells and all the metabolic steps that use this sugar as an energy source. This short time is sufficient to see several enzymatic reactions and transient metabolic reaction intermediates. In other words, this remarkable boost allows researchers to see molecular processes of different biological systems in real time, in situ, and in a non-invasive way, in just few minutes. Moreover, as it is a very fast procedure, problems such as temperature and oxygen changes, cell death and cellular alterations during the experiment are avoided, allowing researchers to reliably compare results among different experiments.

The hyperpolarised magnetic resonance technique allows us to observe in a couple of minutes what we could only see in hours with a conventional NMR, and moreover with a sensitivity that can be up to 10,000 times higher,” explains Dr Irene Marco.

A project coordinated by Dr Marco’s research group, the European BLOC project, will strongly benefit from this recently installed equipment. This project aims to develop a benchtop spectrometer based on magnetic resonance spectroscopy and imaging using dynamic nuclear polarisation (DNP-MR) to monitor diseases and evaluate responses to different stimuli. As a proof-of-concept, this project will fabricate a biomimetic model composed of liver cells and pancreatic islets and develop the necessary DNP-MR hardware and software to study metabolic diseases such as diabetes and non-alcoholic fatty liver disease (NAFLD).

The time-lapse video below shows the entire installation process of the HyperSense™ equipment, which took three days and a number of highly-skilled technicians.

Learn more:
IBEC news
To the Mothers of Science Programme
“la Caixa” Foundation – BIST Chemical Biology Programme