Very First Application of Compact Benchtop NMR Spectrometers to Complex Biofluid Analysis and Metabolite Tracking for Future Metabolomics Studies: A Retrospective Decennial Report from November 2014

Herein we report the very first experiments which were conducted in an attempt to demonstrate the ability of low-field (LF), compact benchtop NMR spectrometers to provide spectral profiles of whole human biofluids, which took place in September–November 2014, and this paper represents a 10-year (decennial) anniversary of this work. LF 1H NMR analysis was performed on 2H2O-reconstituted lyophilizates of urine samples (pH 7.00) collected from untreated Niemann-Pick type C1 (NPC1) disease patients and their heterozygous carrier controls (n = 3 in each case). 1H NMR spectra were acquired on a 60 MHz Oxford Instruments Pulsar compact benchtop spectrometer with spectral filter widths of 5000 Hz, using 1000–1600 scans, and relaxation delays of 15 or 30 s. Further, 400 MHz spectra were also obtained on these samples. Following parameter optimisation, the benchtop system generated reasonable quality urinary 1H NMR profiles containing ca. 30 signals. Benchtop 1H NMR analysis confirmed the abnormal urinary metabolic signature of NPC1 disease, and also revealed a gastric permeability disorder in one patient (detection of upregulated urinary sucrose, verified by 400 MHz NMR analysis). Early LF NMR experiments also demonstrated that glucose was trackable in control urine samples pre-spiked with this metabolite. This paper continues with further developments made on LF NMR-based metabolomics technologies, which are systematically discussed for related investigations conducted since 2014. In conclusion, such ‘first-time’ bioanalytical information regarding spectral quality served to pave the way forward for benchtop NMR-based metabolomics investigations of biofluids, which could provide invaluable disease-engendered ‘snapshots’ of disturbances to metabolic pathways and activities, along with those of any co-linked or unlinked comorbidities.