A Portable Chip-Based Overhauser DNP Platform for Biomedical Liquid Sample Analysis

Abstract

Low-field nuclear magnetic resonance (NMR) instruments are an indispensable tool in industrial research and quality control. However, the intrinsically low spin polarization at low magnetic fields severely limits their detection sensitivity and measurement throughput, preventing their widespread use in biomedical analysis. Overhauser dynamic nuclear polarization (ODNP) effectively addresses this problem by transferring the spin polarization from free electrons to protons, significantly enhancing sensitivity. In this paper, we explore the potential of using ODNP for signal enhancement in a custom-designed portable chip-based DNP-enhanced NMR platform, which is centered around a miniaturized microwave (MW) transmitter, a custom-designed NMR-on-a-chip transceiver, and two application-specific ODNP probes. The MW transmitter provides frequency synthesis, signal modulation, and power amplification, providing sufficient output power for efficient polarization transfer. The NMR-on-a-chip transceiver combines a radio frequency (RF) transmitter with a fully differential quadrature receiver, providing pulsed excitation and NMR signal down-conversion and amplification. Two custom-designed ODNP probes are used for proof-of-concept DNP-enhanced NMR relaxometry and spectroscopy measurements. The presented chip-based ODNP platform achieves a maximum MW output power of $34 \textrm{dBm}$, resulting in a signal enhancement of $-162$ using the relaxometry ODNP probe with $1.4 \mu\textrm{L}$ of $10 \textrm{mM}$ non-degassed TEMPOL solution, and an enhancement of $-63$ with the spectroscopy ODNP probe using $50 \textrm{nL}$ of the same solution. The proton polarization was increased from $0.5\times 10^{-6}$ to $81\times 10^{-6}$ at a low field of $0.16 \textrm{T}$. Proof-of-concept measurements on radical-doped tattoo inks and acetic acid verify the potential of our chip-based ODNP platform for the analysis of biologically and medically relevant parameters such as relaxation times, chemical shifts, and hyperfine interactions.