Abstract
During the last decade, the development of nuclear spin polarization enhanced (hyperpolarized) molecular probes has opened up new opportunities for studying the inner workings of living cells in real time. The hyperpolarized probes are produced ex situ, introduced into biological systems and detected with high sensitivity and contrast against background signals using high resolution NMR spectroscopy. A variety of natural, derivatized and designed hyperpolarized probes has emerged for diverse biological studies including assays of intracellular reaction progression, pathway kinetics, probe uptake and export, pH, redox state, reactive oxygen species, ion concentrations, drug efficacy or oncogenic signaling. These probes are readily used directly under natural conditions in biofluids and are often directly developed and optimized for cellular assays, thus leaving little doubt about their specificity and utility under biologically relevant conditions. Hyperpolarized molecular probes for biological NMR spectroscopy enable the unbiased detection of complex processes by virtue of the high spectral resolution, structural specificity and quantifiability of NMR signals. Here, we provide a survey of strategies used for the selection, design and use of hyperpolarized NMR probes in biological assays, and describe current limitations and developments.
Highlights
Technological and methodological improvements allow for the study of increasingly complex processes and systems, not least for studying the inner workings of living cells [1,2]
nuclear magnetic resonance (NMR) spectroscopy is understood from first principles and the interaction between magnetic moments can be used to enhance otherwise weak signals in a controlled manner by transfer of polarization from spins with high magnetic moments to nuclear spins with lower magnetic moments (e.g., 13C and 15N)
This review consecutively covers nuclear spin hyperpolarization, assay designs for hyperpolarized NMR probing, emerging strategies and applications using designed and natural probes, current technological developments and future hopes for NMR assays based on hyperpolarized probes and labels
Summary
Technological and methodological improvements allow for the study of increasingly complex processes and systems, not least for studying the inner workings of living cells [1,2]. The choice of appropriate methods requires consideration of the ease of use, commercial availability, sensitivity, biocompatibility, selectivity, spatiotemporal resolution, general applicability, non-invasiveness and quantifiability [1]. NMR spectroscopy is a robust, generally applicable and noninvasive method yielding quantifiable and high-resolution spectroscopic data that can distinguish analytes by resolving individual atomic sites. Isotope enrichment of NMR active atoms with low natural abundance, in particular 13C and 15N, has been a means to use NMR active probes that are selectively enhanced over background signals by a factor given by their isotope enrichment. A new generation of nuclear magnetic resonance probes has become popular that affords signal improvements relative to spectral noise and biological backgrounds of at least 3–4 orders of magnitude. Several excellent reviews have recently described the development of hyperpolarized contrast agents for functional magnetic resonance imaging [6,7,8,9], an application area that is not discussed
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
