Hyperpolarization of biological water using nanodiamonds by resonance matching

The National Institute of General Medical Sciences awarded Northwestern University $153,560 on February 1, 2027, under the Biomedical Research and Research Training program (CFDA 93.859) to develop hyperpolarization of biological water using nanodiamonds by resonance matching.

The project aims to enhance nuclear magnetic resonance and magnetic resonance imaging sensitivity by using nitrogen vacancy centers in nanodiamonds to achieve 10- to 100-fold hyperpolarization of surrounding water and tissue under biological conditions. The approach transfers polarization from optically polarizable electron spins within the nanodiamond lattice to nuclear spins, closing the sensitivity gap that currently limits single-cell and compartment-level NMR experiments. Nanodiamonds are biocompatible and already established in drug delivery, fluorescence imaging, and MRI contrast applications, but have not been deployed as a source of biological nuclear hyperpolarization. The research seeks to make water structure and dynamics at the cellular level accessible as a diagnostic and therapeutic design tool.

Performance occurs at Northwestern University's Evanston, Illinois campus through August 31, 2029.

Abstract

Biological water contains a huge amount of information on cellular health and function with enormous potential as a tool for diagnostics or therapeutic design. Accessing the information stored in water structure and dynamics in a non-invasive manner is a challenging problem, but one that nuclear magnetic resonance (NMR) is uniquely suited to solve. Magnetic resonance imaging (MRI) is a widely used medical technique that relies on the DIF- ferential relaxation rates of water protons to provide high-resolution internal maps of the body, but the limitation of MRI is still low signal-to-noise and insufficient contrast. The low sensitivity of NMR is also the reason why information on water structure, exchange, and dynamics at the single cell level is not readily accessible. RO- bust and replenishable hyperpolarization would enable single cell or compartment-level NMR experiments that promise to revolutionize our understanding of biological water and its potential as a reporter on cellular health. We propose an approach utilizing the network of coupled electrons spins within nanodiamonds - including the optically polarizable nitrogen vacancy center (NV-) - to achieve hyperpolarization of the surrounding water and tissue under biological conditions by 10 to 100 fold to close the sensitivity GAP. Considering that NV- centers in diamond are optically hyperpolarizable to a levels several orders of magnitude beyond protons, even a small polarization transfer from electron to nuclear spins will result in the target enhancement. Nanodiamonds are biocompatible and are already used in functionalized forms for targeted drug delivery, fluorescence imaging, and as MRI contrast agents, but have not been used as a source of biological nuclear hyperpolarization. While NV- centers are widely studied for quantum sensing, there has so far been limited success in transferring the enormous optically induced spin polarization of NV- centers to external nuclear spins of analytes. My proposal addresses a recognized need to bridge the knowledge from the fields of quantum sensing and magnetic reso- nance. Building from previous work on nanodiamonds and NV- hyperpolarization, we hypothesize that coupling the electron spin network within the diamond to external spin labels that satisfy resonance matching with external nuclear spins will lead to efficient hyperpolarization of the nuclear spin bulk. We will test this hypothesis with an exploration of fundamental spin physics of NV- centers and the complex network of coupled spins within diamond and in surface-functionalized paramagnetic groups. This understanding will guide our study of DNP mechanisms utilizing concepts in resonance matching for highly efficient polarization transfer, primarily at 0.35 t (x-band) but also extending to higher fields such as 7 t (200 GHZ). We will focus on frozen samples, with applications in monitoring cryopreservation processes, and gelled solutions designed to mimic in-cell conditions. The success- FUL demonstration of 1H DNP of water in vitrified and/or gelled solutions would present a significant advance in the pursuit of high sensitivity mris and single cell magnetic resonance, potentially enhance nanodiamond-based quantum sensing schemes, and deepen our fundamental understanding of diamond spin physics.