Low-Cost Purpose-Built Ultra-Low-Field NMR Spectrometer

Abstract

Low-field NMR has emerged as a new analytical technique for the investigation of molecular structure and dynamics. Here, we introduce a highly integrated ultralow-frequency NMR spectrometer designed for the purpose of ultralow-field NMR polarimetry of hyperpolarized contrast media. The device measures 10 cm × 10 cm × 2.0 cm and weighs only 370 g. The spectrometer's aluminum enclosure contains all components, including an RF amplifier. The device has four ports for connecting to a high-impedance RF transmit-receive coil, a trigger input, a USB port for connectivity to a PC computer, and an auxiliary RS-485/24VDC port for system integration with other devices. The NMR spectrometer is configured for a pulse-wait-acquire-recover pulse sequence, and key sequence parameters are readily controlled by a graphical user interface (GUI) of a Windows-based PC computer. The GUI also displays the time-domain and Fourier-transformed NMR signal and allows autosaving of NMR data as a CSV file. Alternatively, the RS485 communication line allows for operating the device with sequence parameter control and data processing directly on the spectrometer board in a fully automated and integrated manner. The NMR spectrometer, equipped with a 250 ksamples/s 17-bit analog-to-digital signal converter, can perform acquisition in the 1-125 kHz frequency range. The utility of the device is demonstrated for NMR polarimetry of hyperpolarized ¹²⁹Xe gas and [1-¹³C]pyruvate contrast media (which was compared to the ¹³C polarimetry using a more established technology of benchtop ¹³C NMR spectroscopy, and yielded similar results), allowing reproducible quantification of polarization values and relaxation dynamics. The cost of the device components is only ∼$200, offering a low-cost integrated NMR spectrometer that can be deployed as a plug-and-play device for a wide range of applications in hyperpolarized contrast media production─and beyond.

Figure 1.

a) 3D rendering of ULF spectrometer; b) photograph of the device with the top cover removed; c) 3D rendering of the printed circuit board (PCB) of the ULF spectrometer (see Figures S2 and S3 for additional close-up views); d) photograph of the device with the protective cover on (overall dimensions of 10 cm × 10 cm × 2.0 cm); e) overall block diagram of the ULF spectrometer (see Figure S1 for complete details).

Figure 2.

a) graphical user interface (GUI) of the NMR spectrometer showing an NMR signal acquired during the SEOP of ¹²⁹Xe; b) corresponding example of acquired reflected power frequency response of the [1-¹³C]pyruvate polarimetry RF coil, operating at 42 kHz. In displays a and b, (left) control menu, (top right) FID, and (bottom right) FT spectrum; c) RF pulse waveform of the NMR spectrometer transmitter at 40 kHz (recorded using digital oscilloscope); d) RF transmitter voltage (Volts peak-to-peak) as a function of RF pulse transmitter power setting (%); e) RF transmitter power (milliwatts) as a function of RF pulse transmitter power setting (%).

Figure 3.

a) Annotated photographs of second-generation (GEN-2) hyperpolarizer device’s open upper chassis with B₀ magnet to show important components required for the SEOP process e.g., SEOP cell, laser (with beam expander), in situ NMR coil, heating jacket, etc. b) Schematic diagram of the HP ¹²⁹Xe detection process using the XeUS spectrometer. A representative GUI-enabled acquired NMR signal during the in situ NMR polarimetry of HP ¹²⁹Xe using the ULF NMR spectrometer is shown on the laptop window. c) A photograph of the ULF spectrometer with annotated dimensions and weight. The spectrometer is connected to the RF coil interfacing the SEOP cell jacket via a SMA connection; the spectrometer is also connected to a PC computer via a USB C-type interface that provides power and GUI-enabled features. d) An annotated photograph of the SEOP cell oven. e) NMR spectrum of 190,000-scan water ¹H NMR signal detected at 40.8 kHz resonance frequency. f) Single-shot HP ¹²⁹Xe NMR spectrum detected at 40.8 kHz resonance frequency. g) ¹²⁹Xe polarization buildup (at 65 °C) and h) T₁ relaxation at room temperature (25 °C) plotted using NMR acquisition every 4 minutes.

Figure 4.

Quantitative ¹³C NMR polarimetry of HP [1-¹³C]pyruvate in CD₃OD using XeUS spectrometer. a) Schematic of SABRE-SHEATH hyperpolarization process. b) Overall schematic of experimental setup of ¹³C hyperpolarization followed by sample transfer to 15 MHz NMR spectrometer or 42-kHz electromagnet-based setups for polarimetry. c) ¹H NMR of thermally polarized signal-reference water sample (20,000 scans, 110 M) and d) ¹³C NMR signal of HP [1-¹³C]pyruvate (1 scan, 30 mM) using the ULF spectrometer at 42 kHz (note 12,000 corresponds to approximately 500 Hz). e) ¹³C NMR signal from HP [1-¹³C]pyruvate (1 scan, 30 mM) and f) ¹³C NMR signal from signal-reference thermally polarized [1-¹³C]acetic acid (1 scan, 17.5 M) obtained using 15 MHz benchtop ¹³C NMR SpinSolve NMR spectrometer. g) ¹³C %P_13C build-up of HP [1-¹³C]pyruvate at 0.42 μT detected at 42 kHz. h) ¹³C %P_13C T₁ decay of HP [1-¹³C]pyruvate at 0.42 μT detected at 42 kHz. i) %P_13C build-up of HP [1-¹³C]pyruvate at 0.42 μT detected at 15 MHz. j) %P_13C T₁ decay of HP [1-¹³C]pyruvate at 0.42 μT detected at 15 MHz. k) ¹³C RF pulse duration sweep at 42 kHz using the sample of HP [1-¹³C]pyruvate. l) Frequency response of the RF coil at 42 kHz using pre-acquisition time of 1 ms, showing the reflected power maximum at a resonance frequency (one scan). m) ¹³C NMR signal intensity of HP [1-¹³C]pyruvate as a function of B₀ magnetic field current. n) The comparison between average %P_13C values obtained from five repeat experiments using 15 MHz (blue: 10.0±0.2%) and 42 kHz (green: 8.4±0.5%) experimental setups, respectively.