Heteronuclear micro-helmholtz coil facilitates μm-range spatial and sub-Hz spectral resolution NMR of nL-volume samples on customisable microfluidic chips

We present a completely revised generation of a modular micro-NMR detector, featuring an active sample volume of ∗ 100 nL, and an improvement of 87% in probe efficiency. The detector is capable of rapidly screening different samples using exchangeable, applicationspecific, MEMS-fabricated, microfluidic sample containers. In contrast to our previous design, the sample holder chips can be simply sealed with adhesive tape, with excellent adhesion due to the smooth surfaces surrounding the fluidic ports, and so withstand pressures of ∗2.5 bar, while simultaneously enabling high spectral resolution up to 0.62 Hz for H2 O, due to its optimised geometry. We have additionally reworked the coil design and fabrication processes, replacing liquid photoresists by dry film stock, whose final thickness does not depend on accurate volume dispensing or precise levelling during curing. We further introduced mechanical alignment structures to avoid time-intensive optical alignment of the chip stacks during assembly, while we exchanged the laser-cut, PMMA spacers by diced glass spacers, which are not susceptible to melting during cutting. Doing so led to an overall simplification of the entire fabrication chain, while simultaneously increasing the yield, due to an improved uniformity of thickness of the individual layers, and in addition, due to more accurate vertical positioning of the wirebonded coils, now delimited by a post base plateau. We demonstrate the capability of the design by acquiring a1 H spectrum of ∗ \11 nmol sucrose dissolved in D2 O, where we achieved a linewidth of 1.25 Hz for the TSP reference peak. Chemical shift imaging experiments were further recorded from voxel volumes of only ∗ 1.5nL, which corresponded to amounts of just 1.5 nmol per voxel for a 1 M concentration. To extend the micro-detector to other nuclei of interest, we have implemented a trap circuit, enabling heteronuclear spectroscopy, demonstrated by two 1H/13 C 2D HSQC experiments. © 2016 Spengler et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited