Diamond NMR spectrometer for microfluidic metabolite profiling - Project Summary. Nuclear magnetic resonance (NMR) is among the most powerful analytical
techniques ever invented, as recognized by 6 Nobel Prizes for methods development alone.
Nonetheless, NMR is notoriously plagued by poor sensitivity. State-of-the-art NMR
spectrometers feature detection thresholds of ~1 nanomole for µL sample volumes (~100
nanograms). This places NMR sensitivity many orders of magnitude behind other analytical
chemistry techniques such as mass spectrometry, Raman spectroscopy, and fluorescence
labeling. Improvements in NMR often focus on using larger magnets, but progress has
plateaued; over the last 25 years, the fundamental signal strength has only increased ~2-fold.
We seek to fundamentally change the NMR hardware by using diamond films doped with
Nitrogen-Vacancy centers to detect nuclear magnetization non-inductively via pulsed optically
detected magnetic resonance methods. The form factor of our NMR detector is easily integrated
with hyphenation techniques so that samples can be separated into sub-components before
analysis. Recently, we built a tabletop microfluidic diamond NMR apparatus with 40 pL detection
volume and used it in proof-of-principle analytical chemistry applications including the first 2D
NMR spectra acquired by a diamond NMR sensor. In Phase I, we will optimize sensor spectral
resolution and sensitivity and validate its operation using metabolite mixtures. This work will
place us in the position to deliver our devices to end-users in industry (Merck) and academia
(UW) and incorporate feedback to scale up to market.
If successful, our prototype could have a profound impact on analytic biochemistry research, by
combining mass-spectrometry-level sensitivity with NMR-level accuracy. Specifically, we
improve upon existing analytical methods by offering:
1. Greater performance. We offer 1000-fold better sensitivity (pmol instead of nmol) than
current NMR spectrometers. This sensitivity approaches that of mass spectrometry but retains
benefits of NMR such as non-destructive, absolute quantitation and structural identification.
2. Compatibility with hyphenated separation techniques. Our spectrometer is compact and
easily integrated into microfluidic chips for online chromatography-based assays (HPLC) for
sample-limited analyses (metabolomics, pharmacodynamics, natural products).
3. Lower cost. The small sample volume in our spectrometer leads to reduced engineering
costs, leading to greater affordability compared to current NMR spectrometers.
