Benchtop NMR-Based Metabolomics: First Steps for Biomedical Application

Nuclear magnetic resonance (NMR)-based metabolomics is a valuable tool for identifying biomarkers and understanding the underlying metabolic changes associated with various diseases. However, the translation of metabolomics analysis to clinical practice has been limited by the high cost and large size of traditional high-resolution NMR spectrometers. Benchtop NMR, a compact and low-cost alternative, offers the potential to overcome these limitations and facilitate the wider use of NMR-based metabolomics in clinical settings. This review summarizes the current state of benchtop NMR for clinical applications where benchtop NMR has demonstrated the ability to reproducibly detect changes in metabolite levels associated with diseases such as type 2 diabetes and tuberculosis. Benchtop NMR has been used to identify metabolic biomarkers in a range of biofluids, including urine, blood plasma and saliva. However, further research is needed to optimize the use of benchtop NMR for clinical applications and to identify additional biomarkers that can be used to monitor and manage a range of diseases. Overall, benchtop NMR has the potential to revolutionize the way metabolomics is used in clinical practice, providing a more accessible and cost-effective way to study metabolism and identify biomarkers for disease diagnosis, prognosis, and treatment.

[1]  D. Raftery,et al.  NMR Metabolomics Methods for Investigating Disease. , 2023, Analytical chemistry.

[2]  P. Bhattacharyya,et al.  Metabolomics of asthma, COPD, and asthma-COPD overlap: an overview , 2022, Critical reviews in clinical laboratory sciences.

[3]  Stefan Kuhn Applications of machine learning and artificial intelligence in NMR. , 2022, Magnetic resonance in chemistry : MRC.

[4]  H. Drexler,et al.  Low-Field Flow 31P NMR Spectroscopy for Organometallic Chemistry: On-Line Analysis of Highly Air-Sensitive Rhodium Diphosphine Complexes , 2022, Organometallics.

[5]  J. Brezmes,et al.  Urine NMR Metabolomics for Precision Oncology in Colorectal Cancer , 2022, International journal of molecular sciences.

[6]  E. von Harbou,et al.  Accurate Measurements of Self-diffusion Coefficients with Benchtop NMR using a QM Model-based Approach. , 2022, Magnetic resonance in chemistry : MRC.

[7]  R. Bowler,et al.  Metabolome Features of COPD: A Scoping Review , 2022, Metabolites.

[8]  N. Jagannathan,et al.  Potential of nuclear magnetic resonance metabolomics in the study of prostate cancer , 2022, Indian journal of urology : IJU : journal of the Urological Society of India.

[9]  A. Dey,et al.  Ultrafast 2D NMR for the analysis of complex mixtures. , 2022, Progress in nuclear magnetic resonance spectroscopy.

[10]  M. Mather,et al.  Preliminary demonstration of benchtop NMR metabolic profiling of feline urine: chronic kidney disease as a case study , 2021, BMC research notes.

[11]  S. Kuhn,et al.  Computational Simulation of 1 H NMR Profiles of Complex Biofluid Analyte Mixtures at Differential Operating Frequencies: Applications to Low-Field Benchtop Spectra. , 2021, Magnetic resonance in chemistry : MRC.

[12]  J. L. Izquierdo-García,et al.  Benchtop nuclear magnetic resonance-based metabolomic approach for the diagnosis of bovine tuberculosis. , 2021, Transboundary and emerging diseases.

[13]  Sangdoo Ahn,et al.  Recent Applications of Benchtop Nuclear Magnetic Resonance Spectroscopy , 2021, Magnetochemistry.

[14]  J. Hunt,et al.  NMR-based metabolomics associated with chronic kidney disease in humans and animals: a one health perspective , 2021, Molecular and Cellular Biochemistry.

[15]  E. McCarney,et al.  Benchtop NMR in Forensic Chemistry. , 2021, Magnetic resonance in chemistry : MRC.

[16]  C. Boutin,et al.  129Xe ultra-fast Z spectroscopy enables micromolar detection of biosensors on a 1 T benchtop spectrometer , 2021 .

[17]  J. L. Izquierdo-García,et al.  Urine NMR-based TB metabolic fingerprinting for the diagnosis of TB in children , 2021, Scientific Reports.

[18]  Jie Pan,et al.  Identification of Metabolic Phenotypes in Young Adults with Obesity by 1H NMR Metabolomics of Blood Serum , 2021, Life.

[19]  D. Suter,et al.  Optimal control pulses for subspectral editing in low field NMR. , 2021, Journal of magnetic resonance.

[20]  L. Tenori,et al.  Precision Oncology via NMR-Based Metabolomics: A Review on Breast Cancer , 2021, International journal of molecular sciences.

[21]  James G. Longstaffe,et al.  Developments in benchtop NMR spectroscopy 2015–2020 , 2021 .

[22]  P. Giraudeau,et al.  Recent advances in benchtop NMR spectroscopy and its applications , 2021 .

[23]  J. L. Izquierdo-García,et al.  Discovery and validation of an NMR-based metabolomic profile in urine as TB biomarker , 2020, Scientific Reports.

[24]  P. Hui,et al.  Lithium-7 qNMR as a method to quantify lithium content in brines using benchtop NMR. , 2020, The Analyst.

[25]  M. Grootveld,et al.  Low-Field Benchtop NMR Spectroscopy as a Potential Non-Stationary Tool for Point-of-Care Urinary Metabolite Tracking in Diabetic Conditions. , 2020, Diabetes research and clinical practice.

[26]  Kwanjeera Wanichthanarak,et al.  Deep metabolome: Applications of deep learning in metabolomics , 2020, Computational and structural biotechnology journal.

[27]  P. Giraudeau,et al.  Gradient-based pulse sequences for benchtop NMR spectroscopy. , 2020, Journal of magnetic resonance.

[28]  E. von Harbou,et al.  A comparison of non-uniform sampling and model-based analysis of NMR spectra for reaction monitoring. , 2020, Magnetic resonance in chemistry : MRC.

[29]  G. Bernard,et al.  Lead-207 NMR Spectroscopy at 1.4 T: Application of Benchtop Instrumentation to a Challenging I = ½ Nucleus. , 2020, Magnetic resonance in chemistry : MRC.

[30]  F. Casanova,et al.  Benchtop Low-Frequency 60 MHz NMR Analysis of Urine: A Comparative Metabolomics Investigation , 2020, Metabolites.

[31]  T. V. van Beek Low-field benchtop NMR spectroscopy: status and prospects in natural product analysis. , 2020, Phytochemical analysis : PCA.

[32]  C. Gardana,et al.  Urinary TMAO Levels Are Associated with the Taxonomic Composition of the Gut Microbiota and with the Choline TMA-Lyase Gene (cutC) Harbored by Enterobacteriaceae , 2019, Nutrients.

[33]  C. Butts,et al.  Improving the accuracy of 1H–19F internuclear distance measurement using 2D 1H–19F HOESY , 2019, Magnetic resonance in chemistry : MRC.

[34]  K. Khunti,et al.  The global epidemics of diabetes in the 21st century: Current situation and perspectives , 2019, European journal of preventive cardiology.

[35]  E. von Harbou,et al.  Reaction Monitoring by Benchtop NMR Spectroscopy Using a Novel Stationary Flow Reactor Setup , 2019, Industrial & Engineering Chemistry Research.

[36]  D. Hansen,et al.  Using Deep Neural Networks to Reconstruct Non-uniformly Sampled NMR Spectra , 2019, Journal of Biomolecular NMR.

[37]  A. Bonfigli,et al.  NMR-Based Metabolomic Approach Tracks Potential Serum Biomarkers of Disease Progression in Patients with Type 2 Diabetes Mellitus , 2019, Journal of clinical medicine.

[38]  Di Guo,et al.  Accelerated Nuclear Magnetic Resonance Spectroscopy with Deep Learning , 2019, Angewandte Chemie.

[39]  B. Blümich,et al.  Synthesis of α‐fluoro‐α,β‐unsaturated esters monitored by 1D and 2D benchtop NMR spectroscopy , 2019, Magnetic resonance in chemistry : MRC.

[40]  M. Halse,et al.  Hyperpolarised 1H–13C Benchtop NMR Spectroscopy , 2019, Applied Sciences.

[41]  Olivier Gonçalves,et al.  Highly Resolved Pure-Shift Spectra on a Compact NMR Spectrometer. , 2019, Chemphyschem : a European journal of chemical physics and physical chemistry.

[42]  Laneke Luies,et al.  The application of metabolomics toward pulmonary tuberculosis research. , 2019, Tuberculosis.

[43]  Yue Lang,et al.  1H nuclear magnetic resonance-based metabolic profiling of cerebrospinal fluid to identify metabolic features and markers for tuberculosis meningitis. , 2019, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.

[44]  K. Kazimierczuk,et al.  Monitoring Hydrogenation Reactions using Benchtop 2D NMR with Extraordinary Sensitivity and Spectral Resolution , 2019, ChemistryOpen.

[45]  L. Gladden,et al.  In situ reaction monitoring in heterogeneous catalysts by a benchtop NMR spectrometer. , 2019, Magnetic resonance imaging.

[46]  E. McCarney,et al.  Evaluation of benchtop NMR Diffusion Ordered Spectroscopy for small molecule mixture analysis. , 2019, Magnetic resonance imaging.

[47]  F. Casanova,et al.  Progress in low-field benchtop NMR spectroscopy in chemical and biochemical analysis. , 2019, Analytica chimica acta.

[48]  J. Konzuk,et al.  Practical application of 1H benchtop NMR spectroscopy for the characterization of a nonaqueous phase liquid from a contaminated environment , 2019, Magnetic resonance in chemistry : MRC.

[49]  J. Sýkora,et al.  Diagnosis of pancreatic cancer via1H NMR metabolomics of human plasma. , 2018, The Analyst.

[50]  Jean-Nicolas Dumez,et al.  Spatial encoding and spatial selection methods in high-resolution NMR spectroscopy. , 2018, Progress in nuclear magnetic resonance spectroscopy.

[51]  M. Malet‐Martino,et al.  Diffusion‐ordered spectroscopy on a benchtop spectrometer for drug analysis , 2018, Journal of pharmaceutical and biomedical analysis.

[52]  Gaëlle Lefort,et al.  ASICS: an R package for a whole analysis workflow of 1D 1H NMR spectra , 2018, bioRxiv.

[53]  F. Felpin,et al.  Flow reactors integrated with in-line monitoring using benchtop NMR spectroscopy , 2018 .

[54]  Alimuddin Zumla,et al.  Tuberculosis: advances and challenges in development of new diagnostics and biomarkers. , 2018, The Lancet. Infectious diseases.

[55]  P. Adriaensens,et al.  Identification of metabolic phenotypes in childhood obesity by 1H NMR metabolomics of blood plasma , 2018, Future science OA.

[56]  G. Remaud,et al.  High-throughput authentication of edible oils with benchtop Ultrafast 2D NMR. , 2018, Food chemistry.

[57]  Randy W. St. Germain,et al.  Fluorescent Dyes: A New Weapon for Conquering DNAPL Characterization , 2018 .

[58]  Josep Gómez,et al.  rDolphin: a GUI R package for proficient automatic profiling of 1D 1H-NMR spectra of study datasets , 2018, Metabolomics.

[59]  J. Eriksson,et al.  AQuA: An Automated Quantification Algorithm for High-Throughput NMR-Based Metabolomics and Its Application in Human Plasma. , 2018, Analytical chemistry.

[60]  P. Giraudeau,et al.  Ultrafast 2D NMR: Methods and Applications , 2018 .

[61]  S. Moore,et al.  1H and 31P benchtop NMR of liquids and solids used in and/or produced during the manufacture of methamphetamine by the HI reduction of pseudoephedrine/ephedrine. , 2017, Forensic science international.

[62]  K. Khunti,et al.  Type 2 diabetes , 2017, The Lancet.

[63]  J. Adamski,et al.  Metabolomics for clinical use and research in chronic kidney disease , 2017, Nature Reviews Nephrology.

[64]  M. Bernstein,et al.  A robust, general automatic phase correction algorithm for high‐resolution NMR data , 2017, Magnetic resonance in chemistry : MRC.

[65]  S. Akoka,et al.  Gradient‐based solvent suppression methods on a benchtop spectrometer , 2017, Magnetic resonance in chemistry : MRC.

[66]  H. Stark,et al.  Introducing Students to NMR Methods Using Low-Field 1H NMR Spectroscopy to Determine the Structure and the Identity of Natural Amino Acids , 2017 .

[67]  F. Felpin,et al.  Ultrafast 2D NMR on a benchtop spectrometer: Applications and perspectives , 2016 .

[68]  G. Leskowitz,et al.  Benchtop NMR spectrometers in academic teaching , 2016 .

[69]  Meden F. Isaac-Lam Determination of Alcohol Content in Alcoholic Beverages Using 45 MHz Benchtop NMR Spectrometer , 2016 .

[70]  Martin R. M. Koos,et al.  Differentiation of enantiomers by 2D NMR spectroscopy at 1 T using residual dipolar couplings , 2016, Magnetic resonance in chemistry : MRC.

[71]  S. Radford,et al.  Mechanisms of amyloid formation revealed by solution NMR , 2015, Progress in nuclear magnetic resonance spectroscopy.

[72]  S. Akoka,et al.  Optimizing water suppression for quantitative NMR-based metabolomics: a tutorial review , 2015, Metabolomics.

[73]  David S. Wishart,et al.  Accurate, Fully-Automated NMR Spectral Profiling for Metabolomics , 2014, PloS one.

[74]  Josep Gómez,et al.  Dolphin: a tool for automatic targeted metabolite profiling using 1D and 2D 1H-NMR data , 2014, Analytical and Bioanalytical Chemistry.

[75]  Meden F. Isaac-Lam Analysis of Bromination of Ethylbenzene Using a 45 MHz NMR Spectrometer: An Undergraduate Organic Chemistry Laboratory Experiment , 2014 .

[76]  Mathias Nilsson,et al.  Ultrahigh-Resolution NMR Spectroscopy , 2014, Angewandte Chemie.

[77]  E. K. Kemsley,et al.  60 MHz 1H NMR spectroscopy for the analysis of edible oils , 2014, Trends in analytical chemistry : TRAC.

[78]  P. Karakousis,et al.  Application of (1)h NMR spectroscopy-based metabolomics to sera of tuberculosis patients. , 2013, Journal of proteome research.

[79]  M. Foroozandeh,et al.  Simultaneously Enhancing Spectral Resolution and Sensitivity in Heteronuclear Correlation NMR Spectroscopy , 2013, Angewandte Chemie.

[80]  K. Laukens,et al.  Getting Your Peaks in Line: A Review of Alignment Methods for NMR Spectral Data , 2013, Metabolites.

[81]  L. Azadbakht,et al.  Socio-economic factors and diabetes consequences among patients with type 2 diabetes , 2013, Journal of education and health promotion.

[82]  G. Pfyffer,et al.  Incubation Time of Mycobacterial Cultures: How Long Is Long Enough To Issue a Final Negative Report to the Clinician? , 2012, Journal of Clinical Microbiology.

[83]  Nele Friedrich,et al.  Metabolomics in diabetes research. , 2012, The Journal of endocrinology.

[84]  Maria De Iorio,et al.  BATMAN - an R package for the automated quantification of metabolites from nuclear magnetic resonance spectra using a Bayesian model , 2012, Bioinform..

[85]  Cheng Zheng,et al.  Identification and quantification of metabolites in 1H NMR spectra by Bayesian model selection , 2011, Bioinform..

[86]  Vitor Sousa,et al.  Metabolic signatures of lung cancer in biofluids: NMR-based metabonomics of urine. , 2011, Journal of proteome research.

[87]  E. Danieli,et al.  Small magnets for portable NMR spectrometers. , 2010, Angewandte Chemie.

[88]  Elaine Holmes,et al.  Evaluation of full-resolution J-resolved 1H NMR projections of biofluids for metabonomics information retrieval and biomarker identification. , 2010, Analytical chemistry.

[89]  S. Duckett,et al.  A theoretical basis for spontaneous polarization transfer in non-hydrogenative parahydrogen-induced polarization. , 2009, The Journal of chemical physics.

[90]  Lynn F. Gladden,et al.  Comparing Strengths of Surface Interactions for Reactants and Solvents in Porous Catalysts Using Two-Dimensional NMR Relaxation Correlations , 2009 .

[91]  K. D. Atkinson,et al.  Reversible Interactions with para-Hydrogen Enhance NMR Sensitivity by Polarization Transfer , 2009, Science.

[92]  Daniel Raftery,et al.  Comparing and combining NMR spectroscopy and mass spectrometry in metabolomics , 2007, Analytical and bioanalytical chemistry.

[93]  Manuel Martín-Pastor,et al.  A new general-purpose fully automatic baseline-correction procedure for 1D and 2D NMR data. , 2006, Journal of magnetic resonance.

[94]  Wen Wu,et al.  Peak Alignment of Urine NMR Spectra Using Fuzzy Warping , 2006, J. Chem. Inf. Model..

[95]  Cécile Canlet,et al.  Metabonomic assessment of physiological disruptions using 1H-13C HMBC-NMR spectroscopy combined with pattern recognition procedures performed on filtered variables. , 2002, Analytical chemistry.

[96]  J. Kasperczyk HETCOR NMR study of poly(rac-lactide) and poly(meso-lactide) , 1999 .

[97]  K. Zangger,et al.  Homonuclear Broadband-Decoupled NMR Spectra , 1997 .

[98]  F J Snoek,et al.  Development of a Type 2 Diabetes Symptom Checklist: a Measure of Symptom Severity , 1994, Diabetic medicine : a journal of the British Diabetic Association.

[99]  Richard R. Ernst,et al.  Homonuclear broad band decoupling and two-dimensional J-resolved NMR spectroscopy , 1976 .

[100]  R. R. Ernst,et al.  Two‐dimensional spectroscopy. Application to nuclear magnetic resonance , 1976 .

[101]  D. Hoult Solvent peak saturation with single phase and quadrature fourier transformation , 1976 .