Nuclear magnetic resonance (NMR) spectroscopy is among the most important analytical techniques in the chemical sciences — with applications ranging from chemical structure elucidation to precision measurement of dynamics in proteins and nucleic acids — and the imaging modality (MRI) is an invaluable diagnostic tool for non-invasive medical imaging. My research is focused on the development of new NMR methods in order to redefine what is possible with NMR, with the ultimate goal of revolutionizing chemical and material analysis.
My research program covers three cutting-edge techniques:
(1) Zero- to ultralow-field (ZULF) NMR, which enables high-resolution NMR spectra even in
messy heterogeneous or conductive environments;
(2) NMR signal enhancement using the entangled spin order in the para nuclear spin
isomer of H2; and
(3) Nano- to micro-scale NMR spectroscopy and imaging using quantum sensors.
Zero- to Ultralow-Field Nuclear Magnetic Resonance and Imaging
Conventional (high-field) NMR is well established as a powerful, noninvasive spectroscopic tool and is regularly employed for molecular structural elucidation and chemical reaction monitoring. There are, however, fundamental limitations that prevent acquisition of high-resolution spectra from heterogeneous samples or those encased in metal.
I have spent the past decade developing ZULF NMR into a technique for precision measurement and chemical analysis, and I am now working to apply these methods to the study of practically important systems like electrochemical devices (for example, Li-ion batteries). The ability to measure NMR with or without an applied magnetic field allows one to cut out complexities related to magnetic susceptibility and obtain detailed chemical information from measurements of spin-spin couplings and relaxation. This opens the door to high-precision spatially resolved operando spectroscopy in important, but notoriously challenging systems.
Nuclear Spin Hyperpolarization for the Study of Catalysis and Metabolism
The relatively weak coupling of nuclear spins to the environment is both a blessing and a curse for NMR — long coherence times enable high-resolution spectroscopy, but thermal spin polarization is correspondingly small, limiting sensitivity. To solve this problem, hyperpolarization techniques, which generate non-equilibrium spin states in order to achieve dramatic signal enhancements, have been a major focus of magnetic-resonance research.
One important application area is fundamental catalysis research, where NMR is one of the key analytical techniques, but few studies have been performed involving actual heterogeneous catalytic processes, largely due to limited sensitivity. I plan to apply hyperpolarization methods, particularly those related to parahydrogen-induced polarization (PHIP), in order to extend the reach of NMR in the study of catalysis. Hydrogenation reactions are particularly important for both the petrochemical and fine chemical industries, and the fact that signal enhancement relies on pairwise hydrogenation provides insight into reaction mechanisms, aiding in the optimization of heterogeneous catalysts, for which single-site hydrogenation with better-defined and structured active centers is a general goal.
Another exciting application is hyperpolarized metabolic MRI, which has been shown to be particularly useful for metabolic profiling of potentially cancerous tissues, with exciting applications in neuroscience and materials chemistry.
Microscopic NMR Spectroscopy and Imaging with Quantum Sensors
Even with hyperpolarization, NMR is limited to fairly large samples, typically at least μL. This is because appropriate detectors can only be made so small — any pickup coil smaller than a few hundred microns stops behaving much like a coil, and atomic vapor cells are dominated by wall relaxation below about 1 mm. In order to be able to analyze smaller samples, we need a smaller sensor. So now we turn to quantum sensing.
Individually addressable and controllable electron spins have a variety of applications in quantum information processing and quantum sensing. One particular electronic spin that can be optically initialized, coherently manipulated with microwaves, and individually read out is the negatively charged nitrogen-vacancy (NV) center in diamond, with spin coherence times that can exceed a millisecond.
Quantum sensors based on NV centers in diamond have recently been shown to be capable of performing NMR spectroscopy on previously inaccessible length scales. Major application directions include nanoscale NMR of solid interfaces and NMR spectroscopic imaging of chemical/biological reactions on a microfluidic platform.
Fundamental Physics with Magnetic Resonance
Ultralight Bosonic Dark Matter
The nature of dark matter, the invisible substance that makes up over 80% of the matter in the universe, is one of the most intriguing mysteries of modern physics. Elucidating the nature of dark matter will profoundly impact our understanding of cosmology, astrophysics, and particle physics, providing insights into the evolution of the Universe and potentially uncovering new physical laws and fundamental forces beyond the Standard Model.
To date, experimental efforts to directly detect dark matter have largely focused on Weakly Interacting Massive Particles (WIMPs). The absence of evidence for WIMPs has reinvigorated efforts to search for ultralight bosonic fields, another class of theoretically well-motivated dark matter candidates, composed of bosons with masses smaller than a few eV.
CASPEr, the Cosmic Axion Spin Precession Experiment
The Cosmic Axion Spin Precession Experiment (CASPEr) is a multi-faceted research program using NMR techniques to search for dark-matter-driven spin precession. The essence of CASPEr is straightforward: under appropriate experimental conditions, axions/ALPs induce spin precession when interacting with nuclear spins. One can treat the ALP–nuclear-spin coupling as a pseudo-magnetic field, BALP(t), with amplitude proportional to the coupling strength and oscillation frequency determined by the boson mass.
It is thus possible to search for ultralight bosonic dark matter using what is essentially a field-swept CW-NMR experiment where the RF driving field B1 is replaced with BALP. When the nuclear Larmor frequency is equal to the dark matter frequency, BALP drives nuclear spin precession into the transverse plane, such that the oscillating magnetization can be measured with a sensitive magnetometer. Nuclear spin polarization is typically on the order of 10−5 at room temperature in a 1 T magnet, so production of enhanced, non-equilibrium spin polarization is a critical experimental task — Phase I of CASPEr-Wind implemented liquid 129Xe polarized via spin-exchange optical pumping.
Next-Generation Nuclear Spin Haloscopes
Under the NuSHIELD (Nuclear Spin Haloscopes for Interactions with Extremely Light Dark Matter) program, I have been developing new, targeted experiments to focus on high-impact boson mass ranges that are not as effectively investigated by the existing CASPEr apparatus. NuSHIELD’s efforts to investigate new detection and spin-polarization methods in order to extend the reach of CASPEr into unexplored regions of parameter space can be thought of as CASPEr’s research-and-development branch.
This includes developing methods to hyperpolarize a range of alternative samples featuring a variety of nuclear spins, including 1H, 13C, 15N, and 31P. These “axion-scattering targets” can be implemented both in ZULF experiments and in high-field narrow-band searches which serve (1) to focus on theoretically motivated mass ranges — such as those predicted by the SMASH model or other Grand Unified Theories — and (2) to develop the techniques required for future broad-band phases of CASPEr.
Molecular Parity Violation and Antisymmetric Spin-Spin Couplings
Parity nonconservation (PNC) has been observed in nuclear decays and in atomic spectroscopy, but its effects in molecules have not yet been observed. One possible avenue for measurement of molecular parity nonconservation is the measurement of parity-violating components of nuclear spin interactions. We have demonstrated a proof-of-principle experiment based on high-field NMR that may have the potential to achieve the required sensitivity in the future.
Another potentially appealing option would be to measure parity-nonconserving components of the rank-1 antisymmetric nuclear spin-spin coupling (a nuclear-spin analog of the Dzyaloshinskii–Moriya interaction), but as this interaction has no first-order contribution to high-field NMR spectra, it has never been measured directly. ZULF NMR, however, is particularly well-suited to the measurement of interactions that do not commute with the high-field Zeeman Hamiltonian, such as the antisymmetric nuclear spin-spin coupling. This coupling is fundamentally related to chirality, and theoretical work has suggested that such measurements could enable direct observation of molecular chirality by NMR.