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State-of-the-art NMR spectrometers using superconducting magnets have enabled, with their ultrafine spectral resolution, the determination of the structure of large molecules such as proteins, which is one of the most profound applications of modern NMR spectroscopy. Many chemical and biotechnological applications, however, involve only small-to-medium size molecules, for which the ultrafine resolution of the bulky, expensive, and high-maintenance NMR spectrometers is not required. For these applications, there is a critical need for portable, affordable, and low-maintenance NMR spectrometers to enable in-field, on-demand, or online applications (e.g., quality control, chemical reaction monitoring) and co-use of NMR with other analytical methods (e.g., chromatography, electrophoresis). As a critical step toward NMR spectrometer miniaturization, small permanent magnets with high field homogeneity have been developed. In contrast, NMR spectrometer electronics capable of modern multidimensional spectroscopy have thus far remained bulky. Complementing the magnet miniaturization, here we integrate the NMR spectrometer electronics into 4-mm 2 silicon chips. Furthermore, we perform various multidimensional NMR spectroscopies by operating these spectrometer electronics chips together with a compact permanent magnet. This combination of the spectrometer-electronics-on-a-chip with a permanent magnet represents a useful step toward miniaturization of the overall NMR spectrometer into a portable platform. N MR spectroscopy has been celebrated for its ability to probe molecular structures and dynamics with the atomic resolution (1-9). State-of-the-art NMR spectrometers use large superconducting magnets, whose high and uniform magnetic fields lead to the fine spectral resolution necessary for interrogating large molecules such as proteins. In fact, the structural study of large molecules is one of the most profound applications of modern NMR spectroscopy.However, the spectral resolution of the bulky, expensive, and high-maintenance NMR spectrometers is not necessary for a broad array of studies involving small-to-medium size molecules in chemistry, chemical engineering, and biotechnology (10, 11). In this case, portable, affordable, and low-maintenance NMR spectrometers built with a permanent magnet can make the benefits of NMR spectroscopy more broadly available and enable new applications. Bulky superconducting systems have to be permanently placed in dedicated laboratories, but portable systems can enable in-field, on-demand, or online applications such as quality control and chemical reaction monitoring (4), and can greatly facilitate co-use of NMR spectroscopy with other analytical methods such as liquid chromatography (12) and capillary electrophoresis (13). Thus, much effort has been devoted to miniaturizing NMR spectrometers, leading to the critical development of small permanent magnets with high field homogeneity (10,14,15).Complementing this advance in magnet miniaturization, here we integrate the spectrometer elec...

Portable NMR combining a permanent magnet and a complementary metal-oxide-semiconductor (CMOS) integrated circuit has recently emerged to offer the long desired online, on-demand, or in situ NMR analysis of small molecules for chemistry and biology. Here we take this cutting-edge technology to the next level by introducing parallelism to a state-of-the-art portable NMR platform to accelerate its experimental throughput, where NMR is notorious for inherently low throughput. With multiple (N) samples inside a single magnet, we perform simultaneous NMR analyses using a single silicon electronic chip, going beyond the traditional single-sample-per-magnet paradigm. We execute the parallel analyses via either time-interleaving or magnetic resonance imaging (MRI). In the time-interleaving method, the N samples occupy N separate NMR coils: we connect these N NMR coils to the single silicon chip one after another and repeat these sequential NMR scans. This time-interleaving is an effective parallelization, given a long recovery time of a single NMR scan. To demonstrate this time-interleaved parallelism, we use N = 2 for high-resolution multidimensional spectroscopy such as J-coupling resolved free induction decay spectroscopy and correlation spectroscopy (COSY) with the field homogeneity carefully optimized (<0.16 ppm) and N = 4 for multidimensional relaxometry such as diffusion-edited T 2 mapping and T 1-T 2 correlation mapping, expediting the throughput by 2–4 times. In the MRI technique, the N samples (N = 18 in our demonstration) share 1 NMR coil connected to the single silicon chip and are imaged all at once multiple times, which reveals the relaxation time of all N samples simultaneously. This imaging-based approach accelerates the relaxation time measurement by 4.5 times, and it could be by 18 times if the signal-to-noise were not limited. Overall, this work demonstrates the first portable high-resolution multidimensional NMR with throughput-accelerating parallelism.

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