arXiv subjects

Stephan Knecht

Publications and source records attributed to Stephan Knecht.

10 recordsLinked to original sources

arXiv2026

Robust nuclear hyperpolarization of small molecules through intermolecular transfer of parahydrogen-derived polarization

The recent advent of hyperpolarization techniques, which can enhance NMR signals by several orders of magnitude relative to thermally polarized samples, has enabled applications traditionally out of reach due to the inherently low sensitivity of NMR techniques. However, a high barrier to entry remains, as most hyperpolarization approaches either require complex instrumentation or are applicable only to a relatively small set of molecules. Here we introduce PHIPNOE, a platform that directly addresses both limitations. PHIPNOE is based on parahydrogen-induced polarization (PHIP), which is well-established as a scalable route to hyperpolarization requiring minimal instrumentation, but has been mostly restricted to molecules that undergo specific chemical reactions. We overcome this barrier by tailoring PHIP to create highly polarized, highly concentrated solutions of one specific molecule, which acts as an intermediate source of polarization. This 'source molecule' then distributes polarization to a broad range of target molecules mixed into the solution, via the spin polarization-induced nuclear Overhauser effect (SPINOE). We investigate chemical influences on PHIPNOE, and develop a predictive model to estimate enhancement based on molecular mass and T1 relaxation times. A complete run from PHIP hyperpolarization to PHIPNOE polarization transfer and signal detection takes less than one minute, the approach does not require any modifications to the NMR spectrometer, and enhancements are repeatable across molecular classes. PHIPNOE thus enables applications including single-shot multidimensional NMR, real-time monitoring of dynamic processes, and, with 300-fold signal amplification demonstrated on a benchtop spectrometer, practical low-field NMR, where we show enhanced sensitivity in detecting per- and polyfluoroalkyl substances (PFAS).

physics.chem-ph↗

arXiv2026

Improved SABRE hyperpolarisation using pulse sequences to reduce effective coupling

Hyperpolarisation using Signal Amplification By Reversible Exchange (SABRE) is a convenient method for high repeatability studies. The core of this technique is polarisation transfer to the target substrate during an on-going chemical exchange process. Typically, polarisation transfer is achieved as fast as possible. In this study we employ NMR sequences that on contrary slow down the polarisation transfer and yet demonstrate improved performance. Simulations confirm that such methods can lead to high polarisation yield in SABRE system that exhibit higher magnetic inequivalence and lower chemical exchange rate.

physics.chem-ph↗

arXiv2025

Hierarchical Maximum Likelihood Estimation for Time-Resolved NMR Data

Metabolic monitoring and reaction rate estimation using hyperpolarized NMR technology requires accurate quantitative analysis of multidimensional data scenarios. Currently, this analysis is often performed in a two-stage procedure, which is prone to errors in uncertainty propagation and estimation. We propose an approach derived from a Bayesian hierarchical model that intrinsically propagates uncertainties and operates on the full data to maximize the precision at minimal uncertainty. In an analytic treatment, we reduce the estimation procedure to a least-squares optimization problem which can be understood as an extension of the Variable Projection (VarPro) approach for data scenarios with two predictors. We investigate the method's efficacy in two experiments with hyperpolarized metabolites recorded with conventional high-field NMR devices and a micronscale NMR setup using Nitrogen-Vacancy centers in diamond for detection, respectively. In both examples, the new approach improves estimates compared to Fourier methods and proves operational advantages over a two-stage procedure employing VarPro. While the approach presented is motivated by NMR analysis, it is straightforwardly applicable to further estimation scenarios with similar data structure, such as time-resolved photospectroscopy.

q-bio.QM↗

arXiv2024

Robust Parahydrogen-Induced Polarization at High Concentrations

Parahydrogen-Induced Polarization (PHIP) is a potent technique for generating target molecules with high nuclear spin polarization. The PHIP process involves a chemical reaction between parahydrogen and a target molecule, followed by the transformation of nuclear singlet spin order into magnetization of a designated nucleus through magnetic field manipulations. Although the singlet-to-magnetization polarization transfer process works effectively at moderate concentrations, it is observed to become much less efficient at high molar polarization, defined as the product of polarization and concentration. This strong dependence on the molar polarization is attributed to interference from the field produced by the sample's magnetization during polarization transfer, which leads to complex dynamics and can severely impact the scalability of the technique. We address this challenge with a pulse sequence that negates the influence of the distant dipolar field, while simultaneously achieving singlet-to-magnetization polarization transfer to the desired target spins, free from restrictions on the molar polarization.

physics.chem-ph↗

arXiv2023

Towards a unified picture of polarization transfer -- pulsed DNP and chemically equivalent PHIP

Nuclear spin hyperpolarization techniques, such as dynamic nuclear polarization (DNP) and parahydrogen-induced polarization (PHIP), have revolutionized nuclear magnetic resonance and magnetic resonance imaging. In these methods, a readily available source of high spin order, either electron spins in DNP or singlet states in hydrogen for PHIP, is brought into close proximity with nuclear spin targets, enabling efficient transfer of spin order under external quantum control. Despite vast disparities in energy scales and interaction mechanisms between electron spins in DNP and nuclear singlet states in PHIP, a pseudo-spin formalism allows us to establish an intriguing equivalence. As a result, the important low-field polarization transfer regime of PHIP can be mapped onto an analogous system equivalent to pulsed-DNP. This establishes a correspondence between key polarization transfer sequences in PHIP and DNP, facilitating the transfer of sequence development concepts. This promises fresh insights and significant cross-pollination between DNP and PHIP polarization sequence developers.

quant-ph↗

arXiv2022

Radio-Frequency Sweeps at {\mu}T Fields for Parahydrogen-Induced Polarization of Biomolecules

Magnetic resonance imaging of $^{13}$C-labeled metabolites enhanced by parahydrogen-induced polarization (PHIP) can enable real-time monitoring of processes within the body. We introduce a robust, easily implementable technique for transferring parahydrogen-derived singlet order into 13C magnetization using adiabatic radio-frequency sweeps at $\mu$T fields. We experimentally demonstrate the applicability of this technique to several molecules, including some molecules relevant for metabolic imaging, where we show significant improvements in the achievable polarization, in some cases reaching above 60%. Furthermore, we introduce a site-selective deuteration scheme, where deuterium is included in the coupling network of a pyruvate ester to enhance the efficiency of the polarization transfer. These improvements are enabled by the fact that the transfer protocol avoids relaxation induced by strongly coupled quadrupolar nuclei.

physics.chem-ph↗

arXiv2021

Hyperpolarized solution-state NMR spectroscopy with optically polarized crystals

Nuclear spin hyperpolarization provides a promising route to overcome the challenges imposed by the limited sensitivity of nuclear magnetic resonance. Here we demonstrate that dissolution of spin-polarized pentacene-doped naphthalene crystals enables transfer of polarization to target molecules via intermolecular cross relaxation at room temperature and moderate magnetic fields (1.45$\,$T). This makes it possible to exploit the high spin polarization of optically polarized crystals while mitigating the challenges of its transfer to external nuclei, particularly of the large distances and prohibitively weak coupling between source and target nuclei across solid-solid or solid-liquid interfaces. With this method, here we inject the highly polarized mixture into a benchtop NMR spectrometer and observe the polarization dynamics for target $^1$H nuclei. Although the spectra are radiation damped due to the high naphthalene magnetization, we describe a procedure to process the data in order to obtain more conventional NMR spectra, and extract the target nuclei polarization. With the entire process occurring on a timescale of one minute, we observe NMR signals enhanced by factors between -200 and -1730 at 1.45$\,$T for a range of small molecules.

physics.chem-ph↗

arXiv2020

Theoretical Description of Hyperpolarization Formation in the SABRE-relay Method

SABRE (Signal Amplification By Reversible Exchange) has become a widely used method for hyper-polarizing nuclear spins, thereby enhancing their Nuclear Magnetic Resonance (NMR) signals by orders of magnitude. In SABRE experiments, non-equilibrium spin order is transferred from parahydrogen to a substrate in a transient organometallic complex. Applicability of SABRE is expanded by the methodology of SABRE-relay, in which polarization can be relayed to a second substrate either by direct chemical exchange of hyperpolarized nuclei or by polarization transfer between two substrates in a second organometallic complex. To understand the mechanism of the polarization transfer and study the transfer efficiency, we propose a theoretical approach to SABRE-relay, which can treat both spin dynamics and chemical kinetics as well as the interplay between them. The approach is based on a set of equations for the spin density matrices of the spin systems involved (i.e., SABRE substrates and complexes), which can be solved numerically. Using this method, we perform a detailed study of polarization formation and analyse in detail the dependence of attainable polarization level on various chemical kinetic and spin dynamic parameters. We foresee applications of the present approach for optimizing SABRE-relay experiments with the ultimate goal of achieving maximal NMR signal enhancements for substrates of interest.

physics.chem-ph↗

arXiv2018

Quantitative quantum mechanical approach to SABRE hyperpolarization at high magnetic fields

A theoretical approach is proposed for quantitative modeling of SABRE (Signal Amplification By Reversible Exchange) experiments performed at a high magnetic field of an NMR spectrometer. SABRE is a method, which exploits the spin order of parahydrogen (the H$_2$ molecule in its nuclear singlet state) for hyper-polarizing the spins of various substrates to enhance their NMR signals. An important feature of SABRE is that the substrate is not modified chemically: instead spin order transfer takes place in a transient complex with parahydrogen. In high-field SABRE experiments, such a transfer is achieved by using suitable NMR excitation schemes. The approach presented here can explicitly treat the spin dynamics in the SABRE complex as well as the kinetics of substrate exchange (between the free and bound form) and complex interplay of spin evolution and chemical processes. One more important effect included in the model is the alteration of the spin state of parahydrogen giving rise to the formation of anti-phase spin order from the initial singlet order. Such a treatment enables a detailed analysis of known high-field SABRE schemes, quantitative comparison with experiments and elucidation of the key factors that limit the resulting NMR signal enhancement.

physics.chem-ph↗

arXiv2018

Efficient conversion of anti-phase spin order of protons into 15N magnetization using SLIC-SABRE

SABRE (Signal Amplification By Reversible Exchange) is a technique for enhancement of NMR (Nuclear Magnetic Resonance) signals, which utilizes parahydrogen (pH2, the H2 molecule in its nuclear spin state) as a source of non-thermal spin order. In SABRE experiments, pH2 binds to an organometallic complex with a to-be-polarized substrate; subsequently, spin order transfer takes place and the substrate acquires non-thermal spin polarization resulting in strong NMR signal enhancement. In this work we argue that the spin order of H2 in SABRE experiments performed at high magnetic fields is not necessarily the singlet order but rather anti-phase polarization, $S_{1z}S_{2z}$. Although SABRE exploits pH2, i.e., the starting spin order of H2 is supposed to be the singlet order, in solution S-T0 conversion becomes efficient once pH2 binds to a complex. Such a variation of the spin order, which becomes $S_{1z}S_{2z}$, has an important consequence: NMR methods used for transferring SABRE polarization need to be modified. Here we demonstrate that methods proposed for the initial singlet order may not work for the S_1z S_2z order; however, a simple modification makes them efficient again. A theoretical treatment of the problem under consideration is proposed; these considerations are supported by high-field SABRE experiments. Hence, for efficient use of SABRE one should note that polarization formation is a complex multi-stage process: careful optimization of this process may not only deal with chemical aspects but also with the spin dynamics, including the spin dynamics of H2.

physics.chem-ph↗