Friday, November 30, 2018

Saliba, Edward P., Erika L. Sesti, Nicholas Alaniva, and Alexander B. Barnes. “Pulsed Electron Decoupling and Strategies for Time Domain Dynamic Nuclear Polarization with Magic Angle Spinning.” The Journal of Physical Chemistry Letters 9, no. 18 (September 20, 2018): 5539–47.

Magic angle spinning (MAS) dynamic nuclear polarization (DNP) is widely used to increase nuclear magnetic resonance (NMR) signal intensity. Frequency-chirped microwaves yield superior control of electron spins, and are expected to play a central role in the development of DNP MAS experiments. Time domain electron control with MAS has considerable promise to improve DNP performance at higher fields and temperatures. We have recently demonstrated that pulsed electron decoupling using frequency-chirped microwaves improves MAS DNP experiments by partially attenuating detrimental hyperfine interactions. The continued development of pulsed electron decoupling will enable a new suite of MAS DNP experiments which transfer polarization directly to observed spins. Time domain DNP transfers to nuclear spins in conjunction with pulsed electron decoupling is described as a viable avenue toward DNP-enhanced, high-resolution NMR spectroscopy over a range of temperatures from <6K to 320 K.

Wednesday, November 28, 2018

Development of Very-Low-Temperature Millimeter-Wave Electron-Spin-Resonance Measurement System #DNPNMR

Fujii, Y., Y. Ishikawa, K. Ohya, S. Miura, Y. Koizumi, A. Fukuda, T. Omija, et al. “Development of Very-Low-Temperature Millimeter-Wave Electron-Spin-Resonance Measurement System.” Applied Magnetic Resonance 49, no. 8 (August 2018): 783–801.

We report the development of a millimeter-wave electron-spin-resonance (ESR) measurement system at the University of Fukui using a 3He/4He dilution refrigerator to reach temperatures below 1 K. The system operates in the frequency range of 125–130 GHz, with a homodyne detection. A nuclear-magnetic-resonance (NMR) measurement system was also developed in this system as the extension for millimeter-wave ESR/NMR double magnetic-resonance (DoMR) experiments. Several types of Fabry–Pérot-type resonators (FPR) have been developed: A piezo actuator attached to an FPR enables an electric tuning of cavity frequency. A flat mirror of an FPR has been fabricated using a gold thin film aiming for DoMR. ESR signal was measured down to 0.09 K. Results of ESR measurements of an organic radical crystal and phosphorous-doped silicon are presented. The NMR signal from 1H contained in the resonator is also detected successfully as a test for DoMR.

Monday, November 26, 2018

Rossini, Aaron J. “Materials Characterization by Dynamic Nuclear Polarization-Enhanced Solid-State NMR Spectroscopy.” The Journal of Physical Chemistry Letters 9, no. 17 (September 6, 2018): 5150–59.

High-resolution solid-state NMR spectroscopy is a powerful tool for the study of organic and inorganic materials because it can directly probe the symmetry and structure at nuclear sites, the connectivity/bonding of atoms and precisely measure inter-atomic distances. However, NMR spectroscopy is hampered by intrinsically poor sensitivity, consequently, the application of NMR spectroscopy to many solid materials is often infeasible. High-field dynamic nuclear polarization (DNP) has emerged as a technique to routinely enhance the sensitivity of solid-state NMR experiments by one to three orders of magnitude. This perspective gives a general overview of how DNP-enhanced solid-state NMR spectroscopy can be applied to a variety of inorganic and organic materials. DNP-enhanced solid-state NMR experiments provide unique insights into the molecular structure, which makes it possible to form structure-activity relationships that ultimately assist in the rational design and improvement of materials.

Sunday, November 25, 2018

Two Open Postdoc Position in ssNMR and DNP of materials

The Division of Chemical & Biological Sciences at Ames Laboratory, a Department of Energy National Laboratory affiliated with Iowa State University, has two open positions for a postdoctoral associate with a background in solid-state NMRspectroscopy.

Position 1:
The chosen candidate will join a large multidisciplinary team consisting of researchers from both the Ames Laboratory, as well as other national laboratories and universities. The successful candidate will be responsible for conducting investigations of heterogeneous catalysts, polymers, and other materials by conventional as well as dynamic nuclear polarization (DNP) enhanced solid-state NMR spectroscopy. Aside from the aforementioned applications, the new candidate would be expected to also work in fundamental methods development of solid-state NMR and DNP, with main emphasis placed towards the characterization of surfaces and interfaces.

Position 2
The chosen candidate will become a part of a multidisciplinary team, consisting of Ames Laboratory as well as other U.S. DOE labs and universities, working towards the development, and understanding, of next generation supercapacitors. The work will mainly focus on the measurement of charge carrier dynamics and the characterization of electrode materials by both conventional as well as dynamic nuclear polarization (DNP) enhanced solid-state NMR. Studies of electrolyte-ion transport will use pulsed field gradient (PFG) NMR. The candidate will also be encouraged to work in the fundamental development of NMR methods and instrumentation.

Ames Laboratory is equipped with 9.4 and 14.1 T solid-state NMR spectrometers with MAS probes for rotor diameters ranging from 5 to 1.6-mm. The Laboratory is awaiting the delivery of a 110 kHz ultrafast MAS probe. Aside from these instruments, the lab is also equipped with a 9.4 T Bruker MAS-DNP NMR spectrometer with both 3.2 and 1.3-mm MAS-DNP probes. The successful candidate will collaborate with other PIs in the Division of Chemical and Biological Sciences and the Division of Materials Sciences and Engineering for synthetic and additional characterization needs.

More details can be found here:

Friday, November 23, 2018

NMR Studies of Protic Ionic Liquids

Overbeck, Viviane, and Ralf Ludwig. “NMR Studies of Protic Ionic Liquids.” In Annual Reports on NMR Spectroscopy, 95:147–90. Elsevier, 2018.

This review presents recent developments in the application of nuclear magnetic resonance (NMR) spectroscopy for studying the structure and dynamics of ionic liquids. We in particular focus on protic ionic liquids which are characterized by strong hydrogen bonding and proton transfer. Thus, the most relevant NMR-active nucleus is the proton, which undergoes rapid exchange on the NMR time scale. Also, other nuclei are considered if they provide information beyond simple characterization of this unique liquid material. We addressed several NMR techniques which are traditionally or just recently used in the field of ionic liquids research: relaxation time experiments, pulsed-field gradient NMR, fast-field-cycling NMR, electrophoretic NMR, and solid state NMR. Also, novel experiments such as dynamic nuclear polarization NMR are discussed.

Wednesday, November 21, 2018

Post-doc position in MAS DNP, Marseille, France

Postdoctoral position on “DNP NMR crystallography of functional organic materials at natural isotopic abundance”. 

The solid-state NMR group of the Institut de Chimie Radicalaire (ICR) at Aix-Marseille University is seeking motivated candidates for a postdoctoral position to work on an exciting project for excellent research funded by the European Research Council (ERC) in solid-state NMR and DNP of organic materials.

Project: The project, lead by Giulia Mollica, will combine methodological developments in dynamic nuclear polarisation solid-state NMR (MAS DNP), X-ray diffraction and computational methods (first principle calculations of NMR observable, crystal structure prediction) to develop an innovative analytical approach to solve the structure of functional organic powders at natural isotopic abundance. The work will mainly concern the study of organic systems of interest for pharmaceutical applications, electronic devices and energy. Computational work complementing experiments will be supported through collaborations with theoretical chemists in France and abroad.

The candidate will:

  • conceive new DNP NMR experiments to access spin-spin interactions on natural abundance spin systems
  • optimise the methods through numerical and analytical simulations
  • implement the newly devised experiments on the DNP NMR spectrometer
  • realise DFT calculations to help interpret the experimental results

Host institution/group: The Institut de Chimie Radicalaire (ICR) of Aix-Marseille University (AMU) is internationally recognised as a leader in the field of MAS DNP both for the development of new DNP-based analytical methods for the characterisation of organic solids and for the ideation of the most efficient polarising agents for MAS DNP. ICR provides a unique environment bringing together complementary expertise in fields like radical chemistry, MAS DNP, and materials science. The Solid-state NMR group of the ICR lab is interested in the characterisation of organic materials (pharmaceutical compounds, synthetic and natural polymeric materials) by a combination of NMR methods and computation. Computational work complementing experiments will be supported through collaborations with theoretical chemists in France and abroad.

The successful candidate will have access to a large range of liquid and SSNMR spectrometers via the analytical facility of AMU Spectropole ( located on the St. Jérôme Campus in Marseille. Two SSNMR 9.4 T spectrometers equipped with the latest developed hardware and numerous MAS probes (for rotor diameters of 1.3, 2.5, 3.2, 4 and 7 mm) are available on site. Solid-state DNP NMR experiments will be initially performed at the Bruker application center located near Strasbourg. A MAS DNP spectrometer will be installed in our laboratory in Marseille in 2019.

Requirements: Applicants are expected to have a degree in physical chemistry or physics, and a doctoral experience in solid-state NMR/DNP and/or computational methods on materials. Knowledge in computational methods for NMR is a clear asset, as it is experience with diffraction methods and crystallography.

The successful candidate will be initially recruited for 12 months (renewable). The net monthly salary will be between 2000 and 3000 €, depending on experience.

Preferred starting date: February 2019.

To apply through the CNRS portal: 

For informal queries about the position and/or the lab, please send an email to Giulia Mollica:

Recent selected publications:
-P. Cerreia-Vioglio, G. Mollica, M. Juramy, C.E. Hughes, P.A. Williams, S. Viel, P. Thureau, K.D.M. Harris, Insights into the Crystallization and Structural Evolution of Glycine Dihydrate by In Situ Solid-State NMR Spectroscopy, Angew. Chem. Int. Ed. 57, 6619 (2018).
-M. Dekhil, G. Mollica, T. Texier-Bonniot, F. Ziarelli, P. Thureau, S. Viel, Determining carbon–carbon connectivities in natural abundance organic powders using dipolar couplings, Chem. Commun. 52, 8565 (2016)
-G. Mollica, M. Dekhil, F. Ziarelli, P. Thureau, S. Viel, Quantitative Structural Constraints for Organic Powders at Natural Isotopic Abundance Using Dynamic Nuclear Polarization Solid-State NMR Spectroscopy, Angew. Chem. Int. Ed. 54, 6028 (2015).

Giulia Mollica - Chargée de Recherche CNRS - ICR Institut de Chimie Radicalaire (UMR CNRS 7273)
Aix-Marseille Université - Service 511 - ST JEROME - Avenue Escadrille Normandie Niemen - 13013 Marseille
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Magic angle spinning spheres

This article is indirectly related to DNP. It describes an exciting new idea from the Barnes lab how to spin samples in a MAS-NMR experiments and the perspective of integrating DNP.

Chen, Pinhui, Brice J Albert, Chukun Gao, Nicholas Alaniva, Lauren E Price, Faith J Scott, Edward P Saliba, et al. “Magic Angle Spinning Spheres.” SCIENCE ADVANCES, 2018, 8.

Magic angle spinning (MAS) is commonly used in nuclear magnetic resonance of solids to improve spectral resolution. Rather than using cylindrical rotors for MAS, we demonstrate that spherical rotors can be spun stably at the magic angle. Spherical rotors conserve valuable space in the probe head and simplify sample exchange and microwave coupling for dynamic nuclear polarization. In this current implementation of spherical rotors, a single gas stream provides bearing gas to reduce friction, drive propulsion to generate and maintain angular momentum, and variable temperature control for thermostating. Grooves are machined directly into zirconia spheres, thereby converting the rotor body into a robust turbine with high torque. We demonstrate that 9.5–mm–outside diameter spherical rotors can be spun at frequencies up to 4.6 kHz with N2(g) and 10.6 kHz with He(g). Angular stability of the spinning axis is demonstrated by observation of 79Br rotational echoes out to 10 ms from KBr packed within spherical rotors. Spinning frequency stability of ±1 Hz is achieved with resistive heating feedback control. A sample size of 36 ul can be accommodated in 9.5-mm-diameter spheres with a cylindrical hole machined along the spinning axis. We further show that spheres can be more extensively hollowed out to accommodate 161 ul of the sample, which provides superior signal-to-noise ratio compared to traditional 3.2-mm-diameter cylindrical rotors.

Monday, November 19, 2018

Using hyperpolarised NMR and DFT to rationalise the unexpected hydrogenation of quinazoline to 3,4-dihydroquinazoline

Richards, Josh E., Alexander J. J. Hooper, Oliver W. Bayfield, Martin C. R. Cockett, Gordon J. Dear, A. Jonathon Holmes, Richard O. John, et al. “Using Hyperpolarised NMR and DFT to Rationalise the Unexpected Hydrogenation of Quinazoline to 3,4-Dihydroquinazoline.” Chemical Communications 54, no. 73 (2018): 10375–78.

PHIP and SABRE hyperpolarized NMR methods are used to follow the unexpected metal-catalysed hydrogenation of quinazoline (Qu) to 3,4-dihydroquinazoline as the sole product. A solution of [IrCl(IMes)(COD)] in dichloromethane reacts with H2 and Qu to form [IrCl(H)2(IMes)(Qu)2] (2). The addition of methanol then results in its conversion to [Ir(H)2(IMes)(Qu)3]Cl (3) which catalyses the hydrogenation reaction. Density functional theory calculations are used to rationalise a proposed outer sphere mechanism in which (3) converts to [IrCl(H)2(H2)(IMes)(Qu)2]Cl (4) and neutral [Ir(H)3(IMes)(Qu)2](6), both of which are involved in the formation of 3,4-dihydroquinazoline via the stepwise transfer of H+ and H, withH2 identified as the reductant. Successive ligand exchange in 3 results in the production of thermodynamically stable [Ir(H)2(IMes)(3,4-dihydroquinazoline)3]Cl (5).

Friday, November 16, 2018

Perspective on the Hyperpolarisation Technique Signal Amplification by Reversible Exchange (SABRE) in NMR Spectroscopy and MR Imaging

Robertson, Thomas B.R., and Ryan E. Mewis. “Perspective on the Hyperpolarisation Technique Signal Amplification by Reversible Exchange (SABRE) in NMR Spectroscopy and MR Imaging.” In Annual Reports on NMR Spectroscopy, 93:145–212. Elsevier, 2018.

Signal amplification by reversible exchange (SABRE) is a para-hydrogen-based technique that utilises a metal complex, normally centred on iridium, to propagate polarisation from para-hydrogen-derived hydride ligands to spin-½ nuclei located in a bound substrate. To date, substrates possessing 1H, 13C, 15N, 19F, 31P, 29Si, and 119Sn nuclei have been polarised by this technique. The exact positioning of these nuclei has a direct bearing on the enhancement observed and so substrates must be chosen or synthesised with care in order to maximise polarisation transfer, and hence the resulting enhancement. The chemical composition of the metal complex must be similarly appraised, as the exchange rate of substrates and para-hydrogen is implicated heavily in efficient polarisation transfer. The nature of the polarisation transfer, whether homogenous or heterogeneous, is another important facet to consider here, as is conducting SABRE in water-based systems. This review discusses the physical and theoretical aspects of the SABRE experiment, as well as the applications of the SABRE technique, namely, the detection of analytes at concentrations far below what would be possible with conventional NMR techniques and the collection of hyperpolarised magnetic resonance images. Advances relating to utilising singlet states for SABRE, pulse sequence design and the nature of the polarisation transfer mechanism are also discussed, and the implications for future SABRE-based discoveries highlighted.

Wednesday, November 14, 2018

Resolving the Core and the Surface of CdSe Quantum Dots and Nanoplatelets Using Dynamic Nuclear Polarization Enhanced PASS–PIETA NMR Spectroscopy #DNPNMR

Piveteau, Laura, Ta-Chung Ong, Brennan J. Walder, Dmitry N. Dirin, Daniele Moscheni, Barbara Schneider, Janine Bär, et al. “Resolving the Core and the Surface of CdSe Quantum Dots and Nanoplatelets Using Dynamic Nuclear Polarization Enhanced PASS–PIETA NMR Spectroscopy.” ACS Central Science 4, no. 9 (September 26, 2018): 1113–25.

Understanding the surface of semiconductor nanocrystals (NCs) prepared using colloidal methods is a longstanding goal of paramount importance for all their potential optoelectronic applications, which remains unsolved largely because of the lack of site-specific physical techniques. Here, we show that multidimensional 113Cd dynamic nuclear polarization (DNP) enhanced NMR spectroscopy allows the resolution of signals originating from different atomic and magnetic surroundings in the NC cores and at the surfaces. This enables the determination of the structural perfection, and differentiation between the surface and core atoms in all major forms of size- and shape-engineered CdSe NCs: irregularly faceted quantum dots (QDs) and atomically flat nanoplatelets, including both dominant polymorphs (zinc-blende and wurtzite) and their epitaxial nanoheterostructures (CdSe/CdS core/shell quantum dots and CdSe/CdS core/crown nanoplatelets), as well as magic-sized CdSe clusters. Assignments of the NMR signals to specific crystal facets of oleate-terminated ZB structured CdSe NCs are proposed. Significantly, we discover far greater atomistic complexity of the surface structure and the species distribution in wurtzite as compared to zinc-blende CdSe QDs, despite an apparently identical optical quality of both QD polymorphs.

Monday, November 12, 2018

NMR Spectroscopy Unchained: Attaining the Highest Signal Enhancements in Dissolution Dynamic Nuclear Polarization #DNPNMR

Niedbalski, Peter, Andhika Kiswandhi, Christopher Parish, Qing Wang, Fatemeh Khashami, and Lloyd Lumata. “NMR Spectroscopy Unchained: Attaining the Highest Signal Enhancements in Dissolution Dynamic Nuclear Polarization.” The Journal of Physical Chemistry Letters 9, no. 18 (September 20, 2018): 5481–89.

Dynamic nuclear polarization (DNP) via the dissolution method is one of the most successful methods for alleviating the inherently low Boltzmann-dictated sensitivity in nuclear magnetic resonance (NMR) spectroscopy. This emerging technology has already begun to positively impact chemical and metabolic research by providing the much-needed enhancement of the liquid-state NMR signals of insensitive nuclei such as 13C by several thousand-fold. In this Perspective, we present our viewpoints regarding the key elements needed to maximize the NMR signal enhancements in dissolution DNP, from the very core of the DNP process at cryogenic temperatures, DNP instrumental conditions, and chemical tuning in sample preparation to current developments in minimizing hyperpolarization losses during the dissolution transfer process. The optimization steps discussed herein could potentially provide important experimental and theoretical considerations in harnessing the best possible sensitivity gains in NMR spectroscopy as afforded by optimized dissolution DNP technology.

Friday, November 9, 2018

Computationally Assisted Design of Polarizing Agents for Dynamic Nuclear Polarization Enhanced NMR: The AsymPol Family #DNPNMR

Mentink-Vigier, Frédéric, Ildefonso Marin-Montesinos, Anil P. Jagtap, Thomas Halbritter, Johan van Tol, Sabine Hediger, Daniel Lee, Snorri Th. Sigurdsson, and Gaël De Paëpe. “Computationally Assisted Design of Polarizing Agents for Dynamic Nuclear Polarization Enhanced NMR: The AsymPol Family.” Journal of the American Chemical Society 140, no. 35 (September 5, 2018): 11013–19.

We introduce a new family of highly efficient polarizing agents for dynamic nuclear polarization (DNP)-enhanced nuclear magnetic resonance (NMR) applications, composed of asymmetric bis-nitroxides, in which a piperidine-based radical and a pyrrolinoxyl or a proxyl radical are linked together. The design of the AsymPol family was guided by the use of advanced simulations that allow computation of the impact of the radical structure on DNP efficiency. These simulations suggested the use of a relatively short linker with the intention to generate a sizable intramolecular electron dipolar coupling/J-exchange interaction, while avoiding parallel nitroxide orientations. The characteristics of AsymPol were further tuned, for instance with the addition of a conjugated carbon−carbon double bond in the 5-membered ring to improve the rigidity and provide a favorable relative orientation, the replacement of methyls by spirocyclohexanolyl groups to slow the electron spin relaxation, and the introduction of phosphate groups to yield highly water-soluble dopants. An in-depth experimental and theoretical study for two members of the family, AsymPol and AsymPolPOK, is presented here. We report substantial sensitivity gains at both 9.4 and 18.8 T. The robust efficiency of this new family is further demonstrated through high-resolution surface characterization of an important industrial catalyst using fast sample spinning at 18.8 T. This work highlights a new direction for polarizing agent design and the critical importance of computations in this process.

Wednesday, November 7, 2018

Photogenerated Radical in Phenylglyoxylic Acid for in Vivo Hyperpolarized 13C MR with Photosensitive Metabolic Substrates #DNPNMR

Marco-Rius, Irene, Tian Cheng, Adam P. Gaunt, Saket Patel, Felix Kreis, Andrea Capozzi, Alan J. Wright, Kevin M. Brindle, Olivier Ouari, and Arnaud Comment. “Photogenerated Radical in Phenylglyoxylic Acid for in Vivo Hyperpolarized 13 C MR with Photosensitive Metabolic Substrates.” Journal of the American Chemical Society 140, no. 43 (October 31, 2018): 14455–63.

Whether for 13C magnetic resonance studies in chemistry, biochemistry or biomedicine, hyperpolarization methods based on dynamic nuclear polarization (DNP) have become ubiquitous. DNP requires a source of unpaired electrons, which are commonly added to the sample to be hyperpolarized in the form of stable free radicals. Once polarized, the presence of these radicals is unwanted. These radicals can be replaced by nonpersistent radicals created by photo-irradiation of pyruvic acid (PA), which are annihilated upon dissolution or thermalization in the solid state. However, since PA is readily metabolized by most cells, its presence may be undesirable for some metabolic studies. In addition, some 13C substrates are photo-sensitive and, therefore, may degrade during photo-generation of PA radical, which requires ultraviolet (UV) light. We show here that photoirradiation of phenylglyoxylic acid (PhGA) using visible light produces a non-persistent radical that, in principle, can be used to hyperpolarize any molecule. We compare radical yields in samples containing PA and PhGA upon photo-irradiation with broadband and narrowband UV-visible light sources. To demonstrate the suitability of PhGA as a radical precursor for DNP, we polarized the gluconeogenic probe 13C-dihydroxyacetone, which is UV-sensitive, using a commercial 3.35 T DNP polarizer and then injected this into a mouse and followed its metabolism in vivo.

Monday, November 5, 2018

Adiabatic-NOVEL for Nano-Scale Magnetic Resonance Imaging #DNPNMR

Annabestani, Razieh, Maryam Mirkamali, and Raffi Budakian. “Adiabatic-NOVEL for Nano-Scale Magnetic Resonance Imaging.” ArXiv:1712.09128 [Quant-Ph], December 25, 2017.

We propose a highly efficient dynamic nuclear polarization technique that is robust against field in-homogeneity. This technique is designed to enhance the detection sensitivity in nano-MRI, where large Rabi field gradients are required. The proposed technique consists of an adiabatic half passage pulse followed by an adiabatic linear sweep of the electron Rabi frequency and can be considered as an adiabatic version of nuclear orientation via electron spin locking (adiabatic-NOVEL). We analyze the spin dynamics of an electron-nuclear system that is under microwave irradiation at high static magnetic field and at cryogenic temperature. The result shows that an amplitude modulation of the microwave field makes adiabatic-NOVEL highly efficient and robust against both the static and microwave field in-homogeneity.

Friday, November 2, 2018

Determination of binding affinities using hyperpolarized NMR with simultaneous 4-channel detection

Kim, Yaewon, Mengxiao Liu, and Christian Hilty. “Determination of Binding Affinities Using Hyperpolarized NMR with Simultaneous 4-Channel Detection.” Journal of Magnetic Resonance 295 (October 2018): 80–86.

Dissolution dynamic nuclear polarization (D-DNP) is a powerful technique to improve NMR sensitivity by a factor of thousands. Combining D-DNP with NMR-based screening enables to mitigate solubility or availability problems of ligands and target proteins in drug discovery as it can lower the concentration requirements into the sub-micromolar range. One of the challenges that D-DNP assisted NMR screening methods face for broad application, however, is a reduced throughput due to additional procedures and time required to create hyperpolarization. These requirements result in a delay of several tens of minutes in-between each NMR measurement. To solve this problem, we have developed a simultaneous 4-channel detection method for hyperpolarized 19F NMR, which can increase throughput four-fold utilizing a purpose-built multiplexed NMR spectrometer and probe. With this system, the concentration-dependent binding interactions were observed for benzamidine and benzylamine with the serine protease trypsin. A T2 relaxation measurement of a hyperpolarized reporter ligand (TFBC; CF3C6H4CNHNH2), which competes for the same binding site on the trypsin with the other ligands, was used. The hyperpolarized TFBC was mixed with trypsin and the ligand of interest, and injected into four flow cells inside the NMR probe. Across the set of four channels, a concentration gradient was created. From the simultaneously acquired relaxation datasets, it was possible to determine the dissociation constant (KD) of benzamidine or benzylamine without the requirement for individually optimizing experimental conditions for different affinities. A simulation showed that this 4-channel detection method applied to D-DNP NMR extends the screenable KD range to up to three orders of magnitude in a single experiment.