Seminar Pr Indreek REILE

Pr Indreek REILE

National Institute of Chemical Physics and Biophysics, Tallinn, Estonia

Increasing NMR sensitivity in biological sample analysis by three orders of magnitude with parahydrogen hyperpolarization

NMR spectroscopy is one of the workhorse analytical techniques in natural sciences. It is renowned for its robustness, non-discriminative nature and quantitative properties. However, applications of NMR in detection of small quantities of dilute analytes are somewhat limited even in 1H NMR, the most sensitive NMR active nucleus. In complex biological sample analysis, e.g., biofluids and liquid biopsies, also the spectral resolution of 1H NMR limits the ability to resolve and detect lower concentration components. As a result, a large portion of relevant analytes in biological matrices cannot be measured because they appear below the Limit of Detection (LoD) of NMR, because of spectral overlap with more abundant analytes, or frequently for both reasons.

The talk will give an overview of our work towards addressing these challenges with NMR signal enhancement by parahydrogen hyperpolarization. We have demonstrated NMR detection of low concentration metabolites in a human biofluid at three-orders-of-magnitude below the LoD of regular high field NMR. A proof-of-concept application of hyperpolarized NMR to pharmacokinetics reached mid-nanomolar concentration analyte detection in urine samples [1]. The approach addresses both the resolution and sensitivity challenges and is compatible with minimally altered urine samples, producing highly information rich hyperpolarized spectra [2]. We have recently expanded the scope of this NMR signal enhancement technique from small molecules [1,2] to oligopeptides [3]. Data from below the LoD of regular NMR is robust enough for compiling spectral libraries for assignment of hyperpolarized signals and can be considered for metabolomics applications [4]. 

References:

1. Reimets, N.; Ausmees, K.; Vija, S.; Reile, I. Developing Analytical Applications for Parahydrogen Hyperpolarization: Urinary Elimination Pharmacokinetics of Nicotine. Anal. Chem. 2021, 93, 9480–9485, doi:10.1021/acs.analchem.1c01281.
2. Ausmees, K.; Reimets, N.; Reile, I. Parahydrogen hyperpolarization of minimally altered urine samples for sensitivity enhanced NMR metabolomics. Chem. Commun. 2022, 58, 463–466, doi:10.1039/D1CC05665D.
3. Reimets, N.; Ausmees, K.; Vija, S.; Trummal, A.; Uudsemaa, M.; Reile, I. Parahydrogen hyperpolarized NMR detection of underivatized short oligopeptides. Analyst 2023, 148, 5407–5415, doi:10.1039/D3AN01345F.
4. Ausmees, K.; Reimets, N.; Reile, I. Understanding Parahydrogen Hyperpolarized Urine Spectra: The Case of Adenosine Derivatives. Molecules 2022, 27, 802, doi:10.3390/molecules27030802.