Scalable NMR Spectroscopy with Semiconductor Chips
Contributors: Ham, Donhee; Loncar, Marko; Song, Yi-Qiao; Westervelt, Robert
Published: 2014
Language: eng
Description: Conventional nuclear magnetic resonance (NMR) spectrometers—the electronic brain that orchestrates and monitors nuclear spin motions—are bulky, expensive, thus, not scalable. In this thesis, we report on scalable 4-mm2 silicon spectrometer chips that perform a broad range of two-dimensional NMR spectroscopy—e.g., correlation spectroscopy, J-resolved spectroscopy, and heteronuclear quantum coherence spectroscopy—as well as one-dimensional spectroscopy and relaxometry. In this way, they examine a wealth of nuclear spin behaviors and interactions in biological, organic, and pharmaceutical compound molecules, elucidating their structures and dynamics. This semiconductor-based NMR spectroscopy opens up new exciting vistas with two prime advantages. First, with size/cost economy and scalability, the spectrometer chips can be parallelized sharing the same bore of a magnet—whether a large superconducting or small permanent magnet—to greatly simplify multi-channel spectroscopy and vastly increase the spectroscopy throughput, overcoming the intrinsic slowness of NMR spectroscopy; such parallelism may enable the much-desired high-throughput NMR paradigm for drug discovery, metabolomics/metabonomics, and structural biology. We demonstrate the concept of this parallelism by 2-channel heteronuclear quantum coherence NMR experiments, where 2 chips run synchronously in an ultra-compact configuration. Second, the chip spectrometers can complement the recent advance in magnet miniaturization to realize bona fide portable NMR spectroscopy systems. To demonstrate this miniaturization benefit (in addition to the orthogonal benefit of parallelism), we perform all our spectroscopy experiments in a platform combining the spectrometer chips with a compact permanent NdFeB magnet. These demonstrations suggest new dimensions to the technology and applications of NMR spectroscopy enabled by the integrated spectrometers.
Notes: Keywords: Integrated circuits, NMR spectroscopy, Portable NMR spectroscopy, Scalable NMR spectroscopy, Semiconductor.

Thesis Ph.D. Harvard University 2014