AI 中文总结
研究基于自由扩散纳米颗粒散射信号重建照明轮廓以实现精确纳米颗粒尺寸测量的问题，提出自归一化方法，通过在空间重叠区域归一化单粒子轨迹消除偏差，验证该方法可降低信号变异性并兼容现有平台。
AI 中文摘要
基于干涉或暗场成像的无标记全光学纳米尺寸测量方法，通过单粒子散射信号推断尺寸、成分或形状，但这些信号与成像系统空间不均匀照明轮廓紧密耦合。现有归一化策略需直接测量照明场，在无背景几何结构（如光片型照明）中该方法失效。本文介绍一种自归一化方法，直接从许多自由扩散纳米颗粒的散射信号重建照明轮廓，无需额外硬件、校准样本或直接场测量。通过在空间重叠区域相互归一化单粒子轨迹，消除了粒子异质性偏差。在二维和三维几何结构中对不同尺寸金纳米颗粒验证了该方法，包括传统方法无法检测照明场的90°侧照配置，重建轮廓与真实测量值紧密匹配，大幅降低信号变异性，并可立即与现有平台兼容并扩展到其他模态。
英文摘要
Label-free all-optical nanosizing approaches based on interferometric or darkfield-imaging infer size, composition, or shape from single-particle scattering signals, but these signals are inseparably coupled to the spatially non-uniform illumination profile of the imaging system. Existing normalisation strategies require directly measuring this illumination field, an approach that fails for background-free geometries, such as lightsheet-type illumination, where the field cannot be detected. Here we introduce a self-normalisation method that reconstructs the illumination profile directly from the scattering signals of many freely diffusing nanoparticles, requiring no additional hardware, calibration samples, or direct field measurement. Critically, our approach eliminates the particle-heterogeneity bias that otherwise corrupts such reconstructions, by normalising single-particle trajectories against each other in regions of spatial overlap, where distinct particles necessarily sample identical illumination and detection conditions. We validate this method for gold nanoparticles of various size in two- and three-dimensional geometries, including a 90° side-illumination configuration in which the illumination field is entirely undetectable by conventional means, and show that reconstructed profiles closely match ground-truth measurements, thus drastically reducing signal variability. Relying solely on the scattering signal already acquired for sizing, our approach is immediately compatible with existing interferometric and darkfield nanoscopy platforms and broadly extendable to other scattering or fluorescent modalities, including light-sheet microscopy.
