Microfluidic Overhauser DNP chip for signal-enhanced compact NMR

Abstract

Nuclear magnetic resonance at low field strength is an insensitive spectroscopic technique, precluding portable applications with small sample volumes, such as needed for biomarker detection in body fluids. Here we report a compact double resonant chip stack system that implements in situ dynamic nuclear polarisation of a 130 nL sample volume, achieving signal enhancements of up to - 60 w.r.t. the thermal equilibrium level at a microwave power level of 0.5 W. This work overcomes instrumental barriers to the use of NMR detection for point-of-care applications.

Figure 1

Computer aided design (CAD) views of the ODNP probe inside a palm-sized permanent magnet. The microfluidic chip features a sample reservoir and a MW resonator. A stacked figure-8 type RF transceive coil accepts the sample container and is sandwiched between a set of bi-planar electrical shim coils. A $B_0$-field modulation coil is part of phase sensitive EPR detection. Figure used with permission.

Figure 2

(a) Comparison between a thermal (160 averages, 10× scaled) and the ODNP enhanced ${}^1\mathrm{H}$ spectrum (130 nL of 15 mM TEMPOL in DI water, $P_{\mathrm{MW}}\approx 50$ mW, 16 averages). (b) Measured ${}^1\mathrm{H}$ ODNP enhancements as a function of the applied MW input power. Three concentrations of TEMPOL in DI water are shown (sample volume always 130 nL). (c) ODNP build-up curve as a function of MW radiation time (see text for details). (d) Measured ${}^1\mathrm{H}$ ODNP enhancement profile. Shown are the NMR signal peak values plotted versus the available $\mathrm{\Delta }B$-field range of the $B_0$-field sweep coil (centre $B_0$-field strength was 4940 G).

Figure 3

RF coil geometry and 3D EM field simulations at self-resonance (ca. 48 MHz). (a) Exploded view model of the stacked figure-8 coil. The total height of the pressed PCB stack is approximately 1.1 mm. A $6\text{mm}\times 30\text{mm}$ sized slot is milled into the mid layer spacer (ca. 0.8 mm in height) to accept the fluidic insert featuring the MW resonator. (b) Zoomed-in details of the coil traces. The slot and sample region are indicated by dashed lines. (c) Density plot (top- and cross-sectional view) of the $B_{\mathrm{y}}$-field component, showing three distinct high magnetic field regions due to in-phase field superposition. (d) $B_{\mathrm{y}}$-field profiles along the y- ($x=z=0$) and z-direction ($x=y=0$) of the coil, as well as normalised data shown over the sample region (gray rectangles). Figure used with permission.

Figure 4

(a) Topview of the ODNP probe head model, shown with the MW resonator detached. (b) Overview of the MW fixture and the microfluidic chip. (c) Geometric details of the two designs of microstrip resonators (ground-plane not shown). (d) Electric and magnetic field profiles as extracted from the EM simulations for resonator type 1 and 2. Profiles are shown along the corresponding axes. As a guide to the eye, the lateral extent of the metallisation of the resonator (depicted in orange) and sample (grey) are indicated in the diagrams. Figure used with permission.

Figure 5

(a) The 0.5 T permanent magnet is suspended inside an RF-shielded box for environmental isolation. For precise positioning at the magnet’s most uniform spot, the probe was mounted on a motorised x/y linear stage. (b) Top and bottom of the fabricated PCB-based, five channel, bi-planar shim coils as well as the custom made shim current driver. (c) Schematic of the ODNP measurement setup. The reference arm (blue) as well as the one-port reflectometry setup (gray) are optional and were not permanently connected. The magnet + probe head panel includes, (1) $B_0$-field coil of permanent magnet, (2) RF coil, (3) MW resonator and (4) EPR modulation coil. Figure used with permission.

Figure 6

(a) Photograph of a bonded wafer stack featuring 30 individual microstrip resonators. The insets demonstrate the loading of aqueous sample (colored by blue pigments) via capillary forces. (b) Fabricated MW fixture, equipped with a resonator chip. (c) Fabricated ODNP probe head, shown with the MW microfluidic chip being inserted into the stacked figure-8 NMR transceive coil. Figure used with permission.