J.W.G. Janssen

High-resolution liquid- and solid-state nuclear magnetic resonance of nanoliter sample volumes using microcoil detectors

The predominant means to detect nuclear magnetic resonance (NMR) is to monitor the voltage induced in a radiofrequency coil by the precessing magnetization. To address the sensitivity of NMR for mass-limited samples it is worthwhile to miniaturize this detector coil. Although making smaller coils seems a trivial step, the challenges in the design of microcoil probeheads are to get the highest possible sensitivity while maintaining high resolution and keeping the versatility to apply all known NMR experiments. This means that the coils have to be optimized for a given sample geometry, circuit losses should be avoided, susceptibility broadening due to probe materials has to be minimized, and finally the B(1)-fields generated by the rf coils should be homogeneous over the sample volume. This contribution compares three designs that have been miniaturized for NMR detection: solenoid coils, flat helical coils, and the novel stripline and microslot designs. So far most emphasis in microcoil research was in liquid-state NMR. This contribution gives an overview of the state of the art of microcoil solid-state NMR by reviewing literature data and showing the latest results in the development of static and micro magic angle spinning (microMAS) solenoid-based probeheads. Besides their mass sensitivity, microcoils can also generate tremendously high rf fields which are very useful in various solid-state NMR experiments. The benefits of the stripline geometry for studying thin films are shown. This geometry also proves to be a superior solution for microfluidic NMR implementations in terms of sensitivity and resolution.

Optimization of stripline-based microfluidic chips for high-resolution NMR

We here report on the optimization, fabrication and experimental characterization of a stripline-based microfluidic NMR probe, realized in a silicon substrate. The stripline geometry was modelled in respect of rf-homogeneity, sensitivity and spectral resolution. Using these models, optimal dimensional ratios were found, which hold for every sample size. Based on the optimized parameters, a simple integrated stripline-based microfluidic chip was realized. The fabrication of this chip is described in detail. We achieved a sensitivity of 0.47 nmol/square root(Hz) and a resolution of 0.7 Hz. The rf-homogeneity (A(810 degrees)/A(90 degrees)) was 76% and was proved to be suitable for 2D-NMR analysis of glucose.

Towards nuclear magnetic resonance μ-spectroscopy and μ-imaging

The first successful experiments demonstrating Nuclear Magnetic Resonance (NMR) were a spin-off from the development of electromagnetic technology and its introduction into civilian life in the late forties. It was soon discovered that NMR spectra held chemically relevant information making it useful as an analytical tool. By introducing a new way of detection, moving away from continuous wave spectroscopy, Fourier Transform NMR helped to overcome sensitivity problems and subsequently opened the way for multi-dimensional spectroscopy. As a result NMR has developed into one of the most powerful analysis techniques with widespread applications. Still sensitivity is a limiting factor in the applicability of NMR. Therefore we witness a renaissance of technique development in magnetic resonance striving to improve its receptiveness. This tutorial review introduces the efforts currently made in miniaturizing inductive detection by designing optimal radio-frequency microcoils. A second approach is to introduce a new way of detecting magnetic resonance signals by means of very sensitive micromechanical force detectors. This shows that the detection limits in terms of absolute sensitivity or imaging resolution are still open to significant improvements.

Spatially resolved spectroscopy using tapered stripline NMR.

Magnetic field B0 gradients are essential in modern Nuclear Magnetic Resonance spectroscopy and imaging. Although RF/B1 gradients can be used to fulfill a similar role, this is not used in common practice because of practical limitations in the design of B1 gradient coils. Here we present a new method to create B1 gradients using stripline RF coils. The conductor-width of a stripline NMR chip and the strength of its radiofrequency field are correlated, so a stripline chip can be tapered to produce any arbitrary shaped B1 field gradient. Here we show the characterization of this tapered stripline configuration and demonstrate three applications: magnetic resonance imaging on samples with nL-μL volumes, reaction monitoring of fast chemical reactions (10(-2)-10(1)s) and the compensation of B0 field gradients to obtain high-resolution spectra in inhomogeneous magnetic fields.

Microfluidic high-resolution NMR chip for biological fluids

This contribution describes a silicon-based microfluidic chip with an integrated RF stripline for NMR detection, with high spectral resolution (ca. 1 Hz at 600 MHZ proton resonance) and high sensitivity (ca. 1.2 mM) for mass-limited (600 nL) biological samples, with a particular focus on human cerebrospinal fluid samples.