Short communication Determination of quantum dots in single cells by inductively coupled plasma mass spectrometry Ling-Na Zheng a , Meng Wang a,n , Bing Wang a , Han-Qing Chen a , Hong Ouyang a , Yu-Liang Zhao a,b , Zhi-Fang Chai a , Wei-Yue Feng a a Key Laboratory of Nuclear Analytical Techniques and Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China b National Center for Nanoscience and Technology of China, Chinese Academy of Sciences, Beijing 100190, China article info Article history: Received 4 April 2013 Received in revised form 22 July 2013 Accepted 27 July 2013 Available online 7 August 2013 Keywords: ICP–MS Nanotoxicity Single cell analysis Quantum dots abstract In order to assess cytotoxicity of quantum dots (QDs), new reliable analytical techniques that can provide comparative information at a single-cell level are required. In this study, a single cell ICP–MS (SC-ICP–MS) method was established to determine intracellular QDs in single cells after exposure. Uptake kinetics of QDs into cells was studied using the established method. The results were compared and validated by flow cytometry and cell digestion methods. In contrast to other methods, SC-ICP–MS can directly detect QDs and their degradation products via elements, and thus is a promising complement to available methods for single cell analysis and is expected to be a critical tool in the future. & 2013 Elsevier B.V. All rights reserved. 1. Introduction Quantum dots (QDs) are semiconductor nanocrystals of a few nanometers in diameter with unique optical and electrical proper- ties, and thus have been widely applied in research and industry, such as in vivo biomedical imaging and electronics industries [1,2]. Meanwhile, research has raised potential risks of QDs to organisms and the environment under certain circumstances [3], because of their particulate nature and composition. Structurally, QDs are composed of a crystalline core and a shell that shields the core and gives QDs bioavailability. QD cores are typically made of chalco- genides of metals (such as CdSe). In order to improve water solubility and obtain a desired bioactivity, QDs usually need to be further coated by functional groups, such as peptides or proteins. Chemical composition of QD cores is considered as an important factor of QD cytotoxicity. Research shows that toxic elements (for example Cd) can be gradually released from the QDs after internalization in cells and produce many harmful effects including DNA and protein damage, cell functional impairment, and cell apoptosis [4]. In addition, the structure of the outer capping layer is also a key factor affecting QD cytotoxicity. For example, QDs with shells, e.g. CdSe/ZnS, are less toxic than “bare” QDs, e.g. CdTe [5]. In order to assess the QD cytotoxicity, it is prerequisite to quantitatively analyze intracellular QDs after exposure. Up to now, intracellular QDs have been successfully determined by many analytical methods [3,6]. Some methods, however, can only provide the ensemble average from thousands of cells [7]. It is well known that cell heterogeneity is a widespread phenomenon among an isogenic cell population. Therefore, the ensemble average from a large amount of cells obtained by traditional methods usually masks the stochastic diversity of individual cellular response. For example, Liu et al. have shown the average results of gene expression from 50 cells were not representative of any one individual cell [8]. Other methods, such as some fluorescence techniques, may not reflect the actual concentration of QDs in single cells, because intracellular QDs can be partly oxidized and induce fluorescence quenching [9]. Another challenge in analysis of QDs in cells is correlating dosage across different studies. Intracellular QD concentrations reported in the literature vary in their unit of measurement due to different analytical methods used. It is usually difficult to compare results from different laboratories [3]. Therefore, characterization and quantification of intracellular QDs in cells are still challenging and new reliable techniques that can provide easily comparative information at a single cell level are urgently required as a complement to available methods in studies of QD cytotoxicity. Inductively coupled plasma–mass spectrometry (ICP–MS), the most advanced and sensitive means for ultra-trace element analysis, has been widely used in many research fields, such as Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/talanta Talanta 0039-9140/$ - see front matter & 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.talanta.2013.07.075 n Corresponding author. Tel.: +86 1088236519. E-mail address: wangmeng@ihep.ac.cn (M. Wang). Talanta 116 (2013) 782–787