Single-chip in-cell ESR and online reaction monitoring using VCO-based detectors

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Electron spin resonance (ESR) is among the most powerful techniques in modern chemistry, because it utilizes the electron spin as a nanoscopic probe of its environment with superb selectivity and signal strength. Unlike its close relative, nuclear magnetic resonance (NMR) spectroscopy, ESR-based techniques target species that possess a net electron spin, such as free radicals, providing unique insights into many physiological processes and biomedical reactions in general, which themselves critically depend upon these radicals. Despite its great analytical power, until very recently, the use of ESR has been restricted to a small group of experts. This is mainly due to the experimental complexity, high cost, and existing limitations inherent in ESR equipment. To change this situation, the AdvICE (Advanced In-cell ESR) project builds upon advanced IC and MEMS-like manufacturing techniques, combined with a novel detection approach based on a voltage controlled oscillator (VCO), to transform ESR into a scalable and easy-to-use method with improved sensitivity. Targeting two major applications of biological ESR, i.e., the direct detection of free radicals inside their natural cellular environment (in-cell ESR), and ESR-based online monitoring of biochemical reactions, research in the AdvICE project aims at prototyping an advanced, miniaturized, and standalone ESR detection platform that includes all required components to perform ESR experiments on small biological samples. Proof-of-principle experiments will demonstrate advanced system features, including dead-time-free detection of pulsed ESR experiments, and an improved Q-band (34 GHz) sensitivity that will allow for the room-temperature detection of physiological concentrations of analytes.