Electron paramagnetic resonance (EPR) is the gold standard for studying paramagnetic species. As an example, in structural biology, it allows to extract information about distance distributions on the nanometer scale via site-directed spin labeling. Conventional pulsed EPR of biological samples is currently limited to relatively large sample concentrations and cryogenic temperatures, mainly due to low sensitivity and the significant dead time associated with conventional resonator-based EPR setups, essentially precluding in-cell EPR under physiological conditions. This paper presents our latest progress toward single-cell pulsed EPR using VCO-based EPR-on-a-chip (EPRoC) sensors. Together with an analytical model for VCO-based pulsed EPR, we present an experimental scheme to perform dead-time-free pulsed EPR measurements using EPRoC detectors. The proposed scheme is validated using extensive numerical simulations and proof-of-concept experiments on the spin dynamics of an organic radical at room temperature using a custom-designed EPRoC detector operating in the Ka-band around 30.4 GHz. Additionally, we discuss methods to improve the excitation field homogeneity and sample handling through chip post-processing and custom-designed microfluidics. Finally, we present our progress towards compact, portable pulsed EPR spectrometers incorporating EPRoC detectors, microfluidics, and custom-designed permanent magnets. Such portable EPR spectrometers can pave the way toward new EPR applications, including point-of-care diagnostics.

中文翻译：

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使用基于 VCO 的片上 EPR 检测器实现单细胞脉冲 EPR

电子顺磁共振 (EPR) 是研究顺磁物种的黄金标准。例如，在结构生物学中，它允许通过定点自旋标记提取有关纳米尺度上距离分布的信息。生物样品的常规脉冲 EPR 目前仅限于相对较大的样品浓度和低温温度，这主要是由于与传统的基于谐振器的 EPR 设置相关的低灵敏度和显着的死区时间，基本上排除了生理条件下的细胞内 EPR。本文介绍了我们使用基于 VCO 的片上 EPR (EPRoC) 传感器在单细胞脉冲 EPR 方面的最新进展。连同基于 VCO 的脉冲 EPR 的分析模型，我们提出了一个实验方案，以使用 EPRoC 探测器执行无死区时间脉冲 EPR 测量。使用在 30.4 GHz 附近工作的定制设计的 EPRoC 检测器，使用在室温下有机自由基的自旋动力学的广泛数值模拟和概念验证实验验证了所提出的方案。此外，我们讨论了通过芯片后处理和定制设计的微流体来改善激发场均匀性和样品处理的方法。最后，我们展示了我们在紧凑型便携式脉冲 EPR 光谱仪方面取得的进展，该光谱仪结合了 EPRoC 探测器、微流体和定制设计的永磁体。这种便携式 EPR 光谱仪可以为新的 EPR 应用铺平道路，包括即时诊断。