NUCLEAR magnetic resonance (NMR) spectrometry is known for its ability to rapidly identify chemicals. Because this technique does not compromise the sample, the sample’s properties remain intact for additional testing. A typical NMR spectrometer, however, weighs a ton and occupies an entire laboratory. A research team from Livermore’s Physical and Life Sciences Directorate has revamped the technology so that it weighs a mere 9 kilograms (20 pounds) and fits inside a briefcase. The new device can be transported into the field for on-the-spot analysis of potential chemical warfare agents or other hazardous chemicals.
NMR spectrometry measures how nuclei move in a magnetic field. Electromagnetic pulses generated by the spectrometer move through a sample, and the material’s nuclei are “excited,” absorbing energy from the pulse and subsequently radiating energy back out. Changes in the resonant frequency of each nucleus due to the surrounding electrons provide a fingerprint that distinguishes different molecular structures, making NMR spectrometry a powerful tool that is used extensively for chemical, material, biological, and medical applications. Separation techniques such as liquid chromatography and capillary electrophoresis are routinely coupled with an NMR analysis to supply additional information about a sample. Together, these tools can separate, unambiguously identify, and provide structural information about samples in small volumes.
When Time Is of the Essence
A typical NMR spectrometer requires huge superconducting magnets that are cooled with liquid nitrogen. Livermore’s briefcase-size device operates on the same principles as the laboratory-scale machine, but it has a small permanent magnet that does not require cooling.
In the portable NMR briefcase, samples are introduced to the system through tiny capillaries. Three-dimensional lithographic and laser-cutting techniques combine to etch micrometer-scale coils on the capillary wall. “Other research groups are developing small NMR instruments,” says Herberg, “but the coils on those machines are typically hand-wound, which limits the coil size, configuration, and reproducibility.” In contrast, a Livermore-designed technique called LaserLathe can be programmed to repeatedly produce the miniature helical radio-frequency coils that are at the heart of any magnetic resonance system. The LaserLathe can fabricate radio-frequency coils with adjustable widths and line spacings on tiny capillary tubes ranging from 0.1 to 1.3 millimeters in diameter. A lithography-on-cylinder technology, LaserLathe is also used to produce heating wires around hohlraums for fusion experiments at the National Ignition Facility and coils for guide catheters in magnetic resonance imaging procedures.
With the microcoil, the smaller device is as accurate as the laboratory-scale spectrometer with its huge superconducting magnet and can analyze concentrated samples in volumes as small as a microliter or even a nanoliter (10–6 or 10–9 liters). To improve the portable device even more, the Livermore team is coupling it with capillary electrophoresis to provide concentrated samples that are separated for analysis. In the combined technique, the miniscule sample is added to a 360-micrometer capillary filled with a buffer solution. The capillary ends are placed in the buffer, and a voltage is applied. Electrophoresis then separates the chemical species based on the different molecules’ size and charge.
“We use a capillary within a capillary,” says Herberg. “This setup allows a responder in the field to easily replace the inner capillary should it clog or break. The design also provides continuous current across the capillary for good electrophoresis separations.”
Conundrums to Solve
Another issue is balancing NMR sensitivity and electrophoresis resolution. For optimal NMR, the higher the sample concentration is, the higher the spectrometer’s sensitivity will be. But capillary electrophoresis requires very small samples and lower concentrations, in the parts-per-million range. Using a capillary with a large inner diameter allows more sample into the coil volume, which will increase NMR sensitivity but can result in less homogeneity from the magnetic field and the coil itself. A capillary with a smaller internal diameter combined with high voltage and small sample size results in the best electrophoresis resolution but decreases the NMR detection limit.
Yet another challenge is that the field strength of the device’s permanent magnet fluctuates with temperature. “If samples are of low concentration, we want to scan for a long time to increase the nuclear resonance signal-to-noise ratio,” says Herberg. But in an environment with changing temperature, scans extended over a long period will produce smeared images that are difficult to interpret. “We are evaluating materials that are more temperature stable for our portable magnets,” says Herberg. In addition, the team is applying a predictive model to increase detection capabilities by taking shorter scans, limiting temperature shifts, and combining scanned images to reveal spectra that were not clear before.
Even with these challenges remaining, the team has made considerable progress. And the briefcase-size NMR device offers many advantages. “Our portable system is inexpensive and robust,” says Herberg, “important factors that will make it available to more users and improve its reliability in the field.”
Key Words: chemical warfare agent, electrophoresis, LaserLathe, nuclear magnetic resonance (NMR) spectrometry.
For further information contact Julie Herberg (925) 422-5900 (firstname.lastname@example.org).
Lawrence Livermore National Laboratory
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