Abstract
Nuclear Magnetic Resonance (NMR) is a non-contact, powerful structure-elucidation technique for biochemical analysis. NMR spectroscopy is used extensively in a variety of life science applications including drug discovery. However, existing NMR technology is limited in that it cannot run a large number of experiments simultaneously in one unit. Recent advances in micro-fabrication technologies have attracted the attention of researchers to overcome these limitations and significantly accelerate the drug discovery process by developing the next generation of high-throughput NMR spectrometers using Complementary Metal Oxide Semiconductor (CMOS). In this paper, we examine this paradigm shift and explore new design strategies for the development of the next generation of high-throughput NMR spectrometers using CMOS technology. A CMOS NMR system consists of an array of high sensitivity micro-coils integrated with interfacing radio-frequency circuits on the same chip. Herein, we first discuss the key challenges and recent advances in the field of CMOS NMR technology, and then a new design strategy is put forward for the design and implementation of highly sensitive and high-throughput CMOS NMR spectrometers. We thereafter discuss the functionality and applicability of the proposed techniques by demonstrating the results. For microelectronic researchers starting to work in the field of CMOS NMR technology, this paper serves as a tutorial with comprehensive review of state-of-the-art technologies and their performance levels. Based on these levels, the CMOS NMR approach offers unique advantages for high resolution, time-sensitive and high-throughput bimolecular analysis required in a variety of life science applications including drug discovery.
Highlights
Drug discovery is a costly and time consuming undertaking
For microelectronic researchers starting to work in the field of Complementary Metal Oxide Semiconductor (CMOS) Nuclear Magnetic Resonance (NMR) technology, this paper serves as a tutorial with comprehensive review of state-of-the-art technologies and their performance levels
The key challenge for high precision NMR spectroscopy is the development of larger magnets with higher B0
Summary
Drug discovery is a costly and time consuming undertaking It takes years for a few potential drugs to make it to the market. The most appropriate among these molecules are retained for the phases of the drug discovery process, typically consisting of validation, characterization of pharmacodynamics, and toxicology studies for selected drug candidates, which is followed by intensive clinical studies [1]. The conventional NMR systems can non-invasively and in a label-free manner identify chemical species present within a given sample. These systems suffer from an inherent lack of sensitivity required for many bio-molecular studies. Despite great advances in drug discovery using NMR technologies, the challenge of high throughput NMR spectroscopy for accelerating the drug discovery process remains unmet
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