Real-Time Label-Free Monitoring of Nanoparticle-Cell Interactions in Single Tetrahymena thermophila by Mass Cytometry

Yaquan Liu; Zhen Liu; Junjie Ma; Liu Zhang; Qi Wu; Xinyue Yang; Ziniu Wang; Gang Tang; Haijiang Tian; Yun Ding; Guangxuan Wang; Runzeng Liu; Jonathan Woon Chung Wong; Li Zeng; Jie Gao; Guangbo Qu; Guibin Jiang

doi:10.1021/acs.analchem.6c02489

Real-Time Label-Free Monitoring of Nanoparticle-Cell Interactions in Single Tetrahymena thermophila by Mass Cytometry

Anal Chem. 2026 Jun 9;98(22):16694-16703. doi: 10.1021/acs.analchem.6c02489. Epub 2026 May 28.

Authors

Yaquan Liu^{1

2}, Zhen Liu³, Junjie Ma^{1

4}, Liu Zhang^{1

4}, Qi Wu¹, Xinyue Yang^{1

2}, Ziniu Wang^{1

2}, Gang Tang^{1

2}, Haijiang Tian¹, Yun Ding¹, Guangxuan Wang^{1

2}, Runzeng Liu⁵, Jonathan Woon Chung Wong⁶, Li Zeng⁶, Jie Gao¹, Guangbo Qu^{1

2

7}, Guibin Jiang^{1

4

2

7}

Affiliations

¹ State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
² College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China.
³ Department of Chemistry and the MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005, China.
⁴ College of Sciences, Northeastern University, Shenyang 110004, China.
⁵ Shandong Key Laboratory of Environmental Processes and Health, School of Environmental Science and Engineering, Shandong University, Qingdao 266237, China.
⁶ Research Center for Eco-Environmental Engineering, Dongguan University of Technology, Dongguan, Guangdong 523808, China.
⁷ Institute of Environment and Health, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310000, China.

PMID: 42206429
DOI: 10.1021/acs.analchem.6c02489

Abstract

Quantitative characterization of nanoparticle (NP)-cell interactions by aquatic organisms remains analytically challenging due to the rapid, heterogeneous, and dynamic nature of NP-cell processes. In this study, we presented a label-free, real-time analytical methodology that facilitated high-temporal-resolution analysis of NP-cell interactions in Tetrahymena thermophila by mass cytometry (CyTOF). By utilizing ⁸⁸Sr as a cellular fingerprint marker of T. thermophila, we achieved subsecond detection resolution of NP-cell interaction signals under continuous monitoring conditions. The interaction kinetics of NPs, evaluated using I₀/T_1/2 were significantly dependent on temporal resolution, with values obtained at high temporal resolution being approximately 2-fold higher than those derived from low-resolution sampling. This strategy reduced information loss by 39% compared to long-interval sampling. Furthermore, a distinct subpopulation exhibiting high NPs-associated signals was identified, with its proportion increasing from 1.4 ± 0.3 to 9.3 ± 0.5% over 10 h, which provided a quantitative basis for targeted characterization of functionally distinct cellular states at the single-cell level. Overall, this method achieved continuous, high-resolution, and high-throughput quantification of NP-cell interaction dynamics, providing an analytical framework for investigating time-dependent NP behavior at the single-cell level.