Low-Field, Benchtop NMR Spectroscopy as a Potential Tool for Point-of-Care Diagnostics of Metabolic Conditions: Validation, Protocols and Computational Models

Abstract

Novel sensing technologies for liquid biopsies offer promising prospects for the early detection of metabolic conditions through omics techniques. Indeed, high-field nuclear magnetic resonance (NMR) facilities are routinely used for metabolomics investigations on a range of biofluids in order to rapidly recognise unusual metabolic patterns in patients suffering from a range of diseases. However, these techniques are restricted by the prohibitively large size and cost of such facilities, suggesting a possible role for smaller, low-field NMR instruments in biofluid analysis. Herein we describe selected biomolecule validation on a low-field benchtop NMR spectrometer (60 MHz), and present an associated protocol for the analysis of biofluids on compact NMR instruments. We successfully detect common markers of diabetic control at low-to-medium concentrations through optimised experiments, including α-glucose (≤2.8 mmol/L) and acetone (25 µmol/L), and additionally in readily accessible biofluids, particularly human urine. We present a combined protocol for the analysis of these biofluids with low-field NMR spectrometers for metabolomics applications, and offer a perspective on the future of this technique appealing to ‘point-of-care’ applications.

Chemical Constituents with GNMT-Promoter-Enhancing and NRF2-Reduction Activities from Taiwan Agarwood Excoecaria formosana

“…Comparing with (24R) 24-ethyl-7β-hydroperoxy-cholest-5-en-3β-ol and (24R) 24-ethyl-7α-hydroperoxy-cholest-5en-3β-ol [27], the chemical shift of C-6 was (δ C 126.0) in 7-β-stereoisomer, while the chemical shift of C-6 was (δ C 119.9) in 7-α-stereoisomer. Thus, the structure of Compound 1 was further confirmed by COSY and ROESY data ( 33.9 23 25.9 24 45.8 25 29.3 26 19.8 0.81 (d, 6.2) 27 19.0 0.82 (d, 6.2) 28 23.1 29 12.0 0.88 (t, 7.2)…”

“…From a biosynthetic point of view, the monomeric lignin precursors (6)(7)(8)(9)(10)(11), coumarins (17)(18)(19), and the condensation of lignin with coumarins-coumarinolignans (20)(21)(22)(23)(24)(25) were successively isolated from this plant. Therefore, we regarded Compounds 2 and 3 as natural plant constituents.…”

Benchtop Low-Frequency 60 MHz NMR Analysis of Urine: A Comparative Metabolomics Investigation

“…We also present results regarding improvements in spectral resolution, which are achievable via the acquisition of 2D NMR urinary profiles through LF 1 H-1 H correlation (COSY) spectra. This paper complements the preliminary metabolomics results reported by Percival et al [11], and describes for the first time the fully assigned 2D spectra acquired at LF, in addition to a robust comparison between metabolomics studies performed at both operating frequencies. Results presented in this manuscript are therefore sub-divided into three sections.…”

“…However, HF NMR analysis also presents a number of disadvantages, such as cost, size, and transportation limitations, and often the requirement for specialist technical staff for instrumental operation. Moreover, the size of such high-resolution NMR facilities limits their accessibility to many researchers, and therefore precludes regular use outside of university-based NMR-dedicated laboratories, along with those in large industrial centres.Low-frequency (LF) applications of NMR have previously been explored in some detail [8][9][10], and the future of NMR-based metabolomics has also been recently discussed, with an emphasis on this approach providing a convincing solution for metabolic fingerprinting at 'point-of-care' sites or prospectively, even for personal use [11][12][13]. Moreover, LF 1 H NMR applications have recently been shown to distinguish between control and type 2 diabetic (T2D) participants, with potential use for point-of-care applications in a metabolomics study using a near-portable benchtop NMR spectrometer as a novel bioanalytical tool [11].…”

“…Moreover, LF 1 H NMR applications have recently been shown to distinguish between control and type 2 diabetic (T2D) participants, with potential use for point-of-care applications in a metabolomics study using a near-portable benchtop NMR spectrometer as a novel bioanalytical tool [11]. The advantages of this technique included fast acquisition time, ease-of-use and low limits of detection [11]. Moreover, LF benchtop NMR facilities do not require expensive cryogens, nor a Gauss safety line for the magnetic field, and much less power is required for operation, achieving desirable low running costs for potential applications in clinical chemistry.…”