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 complex biological sample analysis, e.g., biofluids and liquid biopsies, are constrained by the low sensitivity of NMR and by the somewhat limited resolution of 1H NMR, the most sensitive NMR active nucleus. A large portion of relevant analytes in biological matrices cannot be detected because they appear below the Limit of Detection (LoD), 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 NMR spectra [2]. 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 [3].
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. Ausmees, K.; Reimets, N.; Reile, I. Understanding Parahydrogen Hyperpolarized Urine Spectra: The Case of Adenosine Derivatives. Molecules 2022, 27, 802, doi:10.3390/molecules27030802.