Category Archives: Metabolomics

Detecting acetylated aminoacids in blood serum using hyperpolarized 13C-1Η-2D-NMR

Katsikis, Sotirios, Ildefonso Marin-Montesinos, Christian Ludwig, and Ulrich L. Günther. “Detecting Acetylated Aminoacids in Blood Serum Using Hyperpolarized 13C-1Η-2D-NMR.” Journal of Magnetic Resonance 305 (August 2019): 175–79.

Dynamic Nuclear Polarization (DNP) can substantially enhance the sensitivity of NMR experiments. Among the implementations of DNP, ex-situ dissolution DNP (dDNP) achieves high signal enhancement levels owing to a combination of a large temperature factor between 1.4 and 300 K with the actual DNP effect in the solid state at 1.4 K. For sufficiently long T1 relaxation times much of the polarization can be preserved during dissolution with hot solvent, thus enabling fast experiments during the life time of the polarization. Unfortunately, for many metabolites found in biological samples such as blood, relaxation times are too short to achieve a significant enhancement. We have therefore introduced 13C-carbonyl labeled acetyl groups as probes into amino acid metabolites using a simple reaction protocol. The advantage of such tags is a sufficiently long T1 relaxation time, the possibility to enhance signal intensity by introducing 13C, and the possibility to identify tagged metabolites in NMR spectra. We demonstrate feasibility for mixtures of amino acids and for blood serum. In two-dimensional dDNP-enhanced HMQC experiments of these samples acquired in 8 s we can identify acetylated amino acids and other metabolites based on small differences in chemical shifts.

Parahydrogen induced hyperpolarization provides a tool for NMR metabolomics at nanomolar concentrations

Sellies, Lisanne, Indrek Reile, Ruud L. E. G. Aspers, Martin C. Feiters, Floris P. J. T. Rutjes, and Marco Tessari. “Parahydrogen Induced Hyperpolarization Provides a Tool for NMR Metabolomics at Nanomolar Concentrations.” Chemical Communications 55, no. 50 (2019): 7235–38.

An NMR approach based on parahydrogen hyperpolarization is presented to detect and resolve specific classes of metabolites in complex biomixtures at down to nanomolar concentrations. We demonstrate our method on solid phase extracts of urine, by simultaneously observing hundreds of metabolites well below the limits of detection of thermal NMR.

Illuminating the dark metabolome to advance the molecular characterisation of biological systems #DNPNMR

This is a great review showcasing the capabilities of DNP-enhanced NMR spectroscopy for metabolomic studies.

Jones, Oliver A. H. “Illuminating the Dark Metabolome to Advance the Molecular Characterisation of Biological Systems.” Metabolomics 14, no. 8 (August 2018).

Background  The latest version of the Human Metabolome Database (v4.0) lists 114,100 individual entries. Typically, however, metabolomics studies identify only around 100 compounds and many features identified in mass spectra are listed only as ‘unknown compounds’. The lack of ability to detect all metabolites present, and fully identify all metabolites detected (the dark metabolome) means that, despite the great contribution of metabolomics to a range of areas in the last decade, a significant amount of useful information from publically funded studies is being lost or unused each year. This loss of data limits our potential gain in knowledge and understanding of important research areas such as cell biology, environmental pollution, plant science, food chemistry and health and biomedical research. Metabolomics therefore needs to develop new tools and methods for metabolite identification to advance as a field.

Stable Isotope-Resolved Analysis with Quantitative Dissolution Dynamic Nuclear Polarization

Lerche, M. H., D. Yigit, A. B. Frahm, J. H. Ardenkjaer-Larsen, R. M. Malinowski, and P. R. Jensen. “Stable Isotope-Resolved Analysis with Quantitative Dissolution Dynamic Nuclear Polarization.” Analytical Chemistry 90 (January 2, 2018): 674–78.

Metabolite profiles and their isotopomer distributions can be studied noninvasively in complex mixtures with NMR. The advent of dissolution Dynamic Nuclear Polarization (dDNP) and isotope enrichment add sensitivity and resolution to such metabolic studies. Metabolic pathways and networks can be mapped and quantified if protocols that control and exploit the ex situ signal enhancement are created. We present a sample preparation method, including cell incubation, extraction and signal enhancement, to obtain reproducible and quantitative dDNP (qdDNP) NMR-based stable isotope-resolved analysis. We further illustrate how qdDNP was applied to gain metabolic insights into the phenotype of aggressive cancer cells.

[NMR] DNP NMR postdoc position at NHMFL, Tallahassee, FL #DNPNMR

Postdoctoral Position:

Development of High-Field Solution-State Overhauser DNP NMR Spectroscopy

Location: National High Magnetic Field Laboratory, Tallahassee, FL

Application Deadline: Until the position is filled 

A postdoctoral position is available, starting Fall 2018, at the U.S. National High Magnetic Field Laboratory (NHMFL) in Tallahassee Florida to carry out research on Overhauser Dynamic Nuclear Polarization (ODNP) NMR at high field (14.1 T). This position is fully funded for a period of 3 years by the National Science Foundation. For this research project, the NHMFL facility is equipped with a 600 MHz solution-state NMR spectrometer and a matching 395 GHz Gyrotron. We seek highly motivated applicants to work with the NHMFL DNP group to develop and implement new methods and experimental applications needed for enabling ODNP NMR spectroscopy of small to medium-sized molecules. The resulting solution-state ODNP NMR experiments will have applications in chemistry and biochemistry, particularly for characterizing limited quantities of molecules from natural product and pharmaceutical chemistry, from petroleum and polymer analytical chemistry, from food and environmental sciences, and from metabolomics.

The successful candidate will be involved in collaborative research with other experts at the NHMFL working in chemical and physical applications of ODNP NMR, as well as advanced microwave and RF instrumentation and technology. He/she will work within a team that consists of the faculty and engineers in the NMR and EPR divisions. Minimum qualifications include a Ph.D. in Chemistry, Physics or a related discipline related to advanced NMR. Experience in experimental NMR methods is essential and in DNP and/or EPR is expected. 

This position will remain available until filled. To apply, please send a CV, a cover letter describing your experience and research interests, and contact information for three references to:

Sungsool Wi

National High Magnetic Field laboratory

1800 E. Paul Dirac Drive, Tallahassee, FL 32310, USA


Tel: 850-645-2770

The NHMFL is operated for the National Science Foundation by a collaboration of institutions comprising Florida State University, the University of Florida, and Los Alamos National Laboratory.

Florida State University (FSU) is an Equal Opportunity/Access/Affirmative Action/Pro Disabled & Veteran Employer.


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[NMR] NMR position at the University of Florida

The lab of Dr. Matthew Merritt has an immediate opening for a post-doctoral research associate in NMR and metabolism. The position is funded through a newly awarded NIH P41 grant (Project title: National Resource for Advanced NMR Technology, 1P41GM122698) with pay according to the NIH scale. 

Project Description

High Temperature Superconducting (HTS) cold probes provide gains in signal to noise ratio that exceed current cold probe technology by a factor of two at least. In collaboration with Dr. Bill Brey at the NHMFL, the research team will commission newly built HTS probes at 600 and 800 MHz. The probes will focus on X-detection, with potential applications in 13C and 2H based methods for studying intermediary metabolism. Other possible applications include 15N detected methods for structural biology. In addition to these goals, the Merritt lab has an active program in hyperpolarization for the study of metabolic turnover in perfused organs and in vivo. Synchronization of hyperpolarization and traditional isotope methods for measuring metabolic flux is part of a long term strategy for developing new insights into metabolic control and intermediary metabolism.


The University of Florida (Gainesville) is part of the National High Magnetic Field Laboratory, and hosts a diverse array of state of the art MR and MRI equipment. The site includes 2 horizontal bore imaging systems operating at 4.7 T and 11 T. The 11 T is a 40 cm bore system, and was recently upgraded to the latest Bruker imaging console. We also host multiple vertical bore NMR systems, including a widebore 750 MHz system for imaging and spectroscopy, three 600 MHz NMR systems, and 2 dynamic nuclear polarization instruments operating at 3.35 T (HyperSense) and 5 T (a homebuilt system). An 800 MHz NMR system will be commissioned this year; this system will serve as a primary instrument for development of the new HTS probes.

Candidates with a background in chemistry, physics, or experience in NMR or MRI will be considered. A strong interest in hardware development and troubleshooting ability is strongly encouraged in the applicant.

For applications, please send a CV and a letter of motivation to

Matthew E. Merritt

Associate Professor

Department of Biochemistry and Molecular Biology

University of Florida

PO Box 100245

Gaineville, FL 32610-0245

(352) 294-8397


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Application of flow sensitive gradients for improved measures of metabolism using hyperpolarized (13) c MRI

Gordon, J.W., et al., Application of flow sensitive gradients for improved measures of metabolism using hyperpolarized (13) c MRI. Magn Reson Med, 2016. 75(3): p. 1242-8.

PURPOSE: To develop the use of bipolar gradients to suppress partial-volume and flow-related artifacts from macrovascular, hyperpolarized spins. THEORY AND METHODS: Digital simulations were performed over a range of spatial resolutions and gradient strengths to determine the optimal bipolar gradient strength and duration to suppress flowing spins while minimizing signal loss from static tissue. In vivo experiments were performed to determine the efficacy of this technique to suppress vascular signal in the study of hyperpolarized [1-(13)C]pyruvate renal metabolism. RESULTS: Digital simulations showed that in the absence of bipolar gradients, partial-volume artifacts from the vasculature were still present, causing underestimation of the apparent reaction rate of pyruvate to lactate (kP). The addition of a bipolar gradient with b = 32 s/mm(2) sufficiently suppressed the vascular signal without a substantial decrease in signal from static tissue. In vivo results corroborate digital simulations, with similar peak lactate signal to noise ratio (SNR) but substantially different kP in the presence of bipolar gradients. CONCLUSION: The proposed approach suppresses signal from flowing spins while minimizing signal loss from static tissue, removing contaminating signal from the vasculature and increasing kinetic modeling accuracy without substantially sacrificing SNR or temporal resolution.

Imaging metabolism with hyperpolarized (13)c-labeled cell substrates

Brindle, K.M., Imaging metabolism with hyperpolarized (13)c-labeled cell substrates. J Am Chem Soc, 2015. 137(20): p. 6418-27.

Non-invasive (13)C magnetic resonance spectroscopy measurements of the uptake and subsequent metabolism of (13)C-labeled substrates is a powerful method for studying metabolic fluxes in vivo. However, the technique has been hampered by a lack of sensitivity, which has limited both the spatial and temporal resolution. The introduction of dissolution dynamic nuclear polarization in 2003, which by radically enhancing the nuclear spin polarization of (13)C nuclei in solution can increase their sensitivity to detection by more than 10(4)-fold, revolutionized the study of metabolism using magnetic resonance, with temporal and spatial resolutions in the seconds and millimeter ranges, respectively. The principal limitation of the technique is the short half-life of the polarization, which at approximately 20-30 s in vivo limits studies to relatively fast metabolic reactions. Nevertheless, pre-clinical studies with a variety of different substrates have demonstrated the potential of the method to provide new insights into tissue metabolism and have paved the way for the first clinical trial of the technique in prostate cancer. The technique now stands on the threshold of more general clinical translation. I consider here what the clinical applications might be, which are the substrates that most likely will be used, how will we analyze the resulting kinetic data, and how we might further increase the levels of polarization and extend polarization lifetime.

Hyperpolarization of deuterated metabolites via remote cross-polarization and dissolution dynamic nuclear polarization

Vuichoud, B., et al., Hyperpolarization of deuterated metabolites via remote cross-polarization and dissolution dynamic nuclear polarization. J Phys Chem B, 2014. 118(5): p. 1411-5.

In deuterated molecules such as [1-(13)C]pyruvate-d3, the nuclear spin polarization of (13)C nuclei can be enhanced by combining Hartmann-Hahn cross-polarization (CP) at low temperatures (1.2 K) with dissolution dynamic nuclear polarization (D-DNP). The polarization is transferred from remote solvent protons to the (13)C spins of interest. This allows one not only to slightly reduce build-up times but also to increase polarization levels and extend the lifetimes T1((13)C) of the enhanced (13)C polarization during and after transfer from the polarizer to the NMR or MRI system. This extends time scales over which metabolic processes and chemical reactions can be monitored.

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