Biological interactions, toxicity, and environmental fate of engineered nanoparticles are affected by colloidal stability and aggregation. To assess nanoparticle aggregation, analytical methods are needed that allow quantification of individual nanoparticle aggregates. However, most techniques used for nanoparticle aggregation analysis are limited to ensemble measurements or require harsh sample preparation that may introduce artifacts. An ideal method would analyze aggregate size in situ with single-nanoparticle resolution. Here, we established and validated single-particle inductively coupled plasma mass spectrometry (SP-ICP-MS) as an unbiased high-throughput analytical technique to quantify nanoparticle size distributions and aggregation in situ. We induced nanoparticle aggregation by exposure to physiologically relevant saline conditions and applied SP-ICP-MS to quantify aggregate size and aggregation kinetics at the individual aggregate level. In situ SP-ICP-MS analysis revealed rational surface engineering principles for the preparation of colloidally stable nanoparticles. Our quantitative SP-ICP-MS technique is a platform technology to evaluate aggregation characteristics of various types of surface-engineered nanoparticles under physiologically relevant conditions. Potential widespread applications of this method may include the study of nanoparticle aggregation in environmental samples and the preparation of colloidally stable nanoparticle formulations for bioanalytical assays and nanomedicine.

Graphical abstract

工程纳米颗粒的生物相互作用，毒性和环境命运受胶体稳定性和聚集的影响。为了评估纳米颗粒的聚集，需要允许对单个纳米颗粒聚集体进行定量的分析方法。但是，用于纳米颗粒聚集分析的大多数技术仅限于整体测量或需要进行苛刻的样品前处理，否则可能会引入伪影。理想的方法是使用单纳米颗粒分辨率原位分析聚集体尺寸。在这里，我们建立并验证了单颗粒电感耦合等离子体质谱（SP-ICP-MS），这是一种无偏的高通量分析技术，用于量化纳米颗粒的尺寸分布和原位聚集。我们通过暴露于生理相关的生理盐水条件下诱导纳米颗粒聚集，并应用SP-ICP-MS在单个聚集体水平上量化聚集体尺寸和聚集动力学。SP-ICP-MS的原位分析揭示了制备胶体稳定纳米粒子的合理表面工程原理。我们的定量SP-ICP-MS技术是一种平台技术，可在生理相关条件下评估各种类型的表面工程纳米粒子的聚集特性。该方法的潜在广泛应用可能包括研究环境样品中的纳米颗粒聚集以及制备用于生物分析和纳米医学的胶体稳定的纳米颗粒制剂。

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