Benchtop FT-NMR Applied to SARS-CoV-2 and ‘Long COVID’ Research Lowers the Barrier to Clinical Translation

Researchers at the Australian National Phenome Centre (ANPC) at Murdoch University have successfully detected and quantified newly discovered biomarkers of SARS-CoV-2 acute infections and of ‘Long COVID’. They used a benchtop Fourier Transform-nuclear magnetic resonance (FT-NMR) spectrometer with a permanent magnet, thereby lowering the barrier to clinical translation of this epidemiological and diagnostic research technology.

Under the direction of Professor Jeremy Nicholson, the research found that the unique signatures and quantification of the inflammatory biomarkers developed on a 600

MHz Bruker Avance IVDr NMR system could be reproduced on the 80 MHz Bruker Fourier 80 Benchtop FT-NMR spectrometer.

Combining benchtop NMR with high-field NMR enables clinical translation to extend the reach of this powerful technology to suit the differing clinical and research market needs.

The ANPC-Bruker collaboration used a sophisticated J-edited diffusional (JEDI) NMR experiment on the Fourier 80 to obtain quantitative signatures of two biomarker signals from N-acetylated glycoprotein (Glyc) and a novel supramolecular phospholipid composite (SPC) from phospholipids in lipoproteins. This was enhanced by a combination of relaxation, diffusion and J-editing properties of the JEDI experiment that attenuate contributions from other molecular species in plasma. This JEDI experiment also demonstrates excellent discrimination of COVID-19 from control patients.

The novel Glyc/SPC ratio measurement has emerged as a useful molecular biomarker of inflammation in Long COVID, which could significantly improve current clinical and therapeutic understanding of the acute disease and of Long COVID.

Following the recent launch of the Bruker PhenoRisk PACS™ RUO² module on its Avance IVDr 600 MHz NMR system – for molecular phenomics research on ‘Long COVID’ patient blood samples – this latest test further demonstrates that the methodology can be reliably transferred to a compact benchtop FT-NMR system. JEDI helps to overcome the issue of reduced dispersion and enhanced signal overlap typically associated with a lower field spectrometer. The simplified sample preparation developed for benchtop applications also

supports data acquisition in a similar timeframe to high-speed instruments, and further experiments suggest the potential of quantification of the SPC/Glyc ratio in just minutes.

Prof. Jeremy Nicholson, Director of the ANPC, commented: “Our major goal is to detect new disease signatures and translate them into the clinic. This involves developing innovative new technologies that will immediately benefit human health, whilst laying a platform for future scientific discoveries. Quickly and efficiently testing for informative biomarkers in large numbers of human blood samples, with easy-to-use instruments, is a major milestone, proving that NMR analysis could begin to play an important role in patient care. In the case of Long COVID, we need to measure, monitor and mitigate the disease process, and benchtop technologies will be an important part of delivering that translational mission at the population level. We believe these findings will facilitate work in samples from patients with SARS-CoV-2 acute infection and Long COVID using benchtop devices, and we look forward to continuing our strategic partnership with Bruker into other disease areas.”

Dr. Iris Mangelschots, Division President of Bruker BioSpin’s AIC, added: “This is a powerful example of how NMR spectroscopy can help in the development of new epidemiological and clinical research methods. NMR can play a pivotal role in measuring COVID-19 progression quantitatively based on phenomic molecular signatures, and it may therefore be beneficial in the development of Long COVID clinical management and treatment options. The potential of translating biomarker quantification from the high-field Avance IVDr to the benchtop Fourier 80 extends the reach of NMR to laboratories that do not have the high-field NMR infrastructure. This new lab topology can bring the benefits of this solution to a broader medical research community.”

The compact, high-performance Bruker Fourier 80 Benchtop FT-NMR features a novel, ultra-stable 80MHz permanent magnet and operates using standard electrical power. With no need for cryogens or specialized lab infrastructure, installation or operator training, the Fourier 80 delivers the power of FT-NMR in a push-button instrument, paving the way for routine targeted NMR biomarker research in any lab.

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