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

电子自旋共振（ESR）是现代化学中最强大的技术之一，因为它利用电子自旋作为其环境的纳米探针，具有极好的选择性和信号强度。与其近亲核磁共振（NMR）光谱学不同，基于esr的技术针对具有净电子自旋的物质，如自由基，为许多生理过程和生物医学反应提供了独特的见解，这些生理过程和生物医学反应本身就严重依赖于这些自由基。尽管ESR具有强大的分析能力，但直到最近，它的使用还仅限于一小部分专家。这主要是由于实验的复杂性、高成本和ESR设备固有的局限性。为了改变这种情况，AdvICE （Advanced In-cell ESR）项目建立在先进的IC和类似mems的制造技术基础上，结合一种基于压控振荡器（VCO）的新型检测方法，将ESR转变为一种可扩展且易于使用的方法，并提高了灵敏度。针对生物ESR的两大应用，即直接检测自然细胞环境中的自由基（细胞内ESR）和基于ESR的生化反应在线监测，AdvICE项目的研究旨在原型化一个先进的、小型化的、独立的ESR检测平台，该平台包括在小生物样品上进行ESR实验所需的所有组件。原理验证实验将展示先进的系统功能，包括脉冲ESR实验的无死区检测，以及改进的q波段（34 GHz）灵敏度，可以在室温下检测分析物的生理浓度。

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.