TRENDS Trends in single-cell analysis by use of ICP-MS Larissa Mueller & Heike Traub & Norbert Jakubowski & Daniela Drescher & Vladimir I. Baranov & Janina Kneipp Received: 5 June 2014 /Revised: 14 August 2014 /Accepted: 28 August 2014 /Published online: 1 October 2014 # Springer-Verlag Berlin Heidelberg 2014 Abstract The analysis of single cells is a growing research field in many disciplines such as toxicology, medical diagno- sis, drug and cancer research or metallomics, and different methods based on microscopic, mass spectrometric, and spec- troscopic techniques are under investigation. This review focuses on the most recent trends in which inductively coupled plasma mass spectrometry (ICP-MS) and ICP optical emission spectrometry (ICP-OES) are applied for single-cell analysis using metal atoms being intrinsically present in cells, taken up by cells (e.g., nanoparticles), or which are artificially bound to a cell. For the latter, especially element tagged antibodies are of high interest and are discussed in the review. The application of different sample introduction systems for liquid analysis (pneumatic nebulization, droplet generation) and elemental imaging by laser ablation ICP-MS (LA-ICP- MS) of single cells are highlighted. Because of the high complexity of biological systems and for a better understand- ing of processes and dynamics of biologically or medically relevant cells, the authors discuss the idea of “multimodal spectroscopies.” Keywords Bioanalytical methods . Cell systems/single cell analysis . Mass spectrometry/ICP-MS Introduction In recent years, a growing interest in single-cell analysis can be recognized and numerous analytical methods have been developed or improved to allow the analysis of individual cells and their cellular compartments. The aim of most of these studies is related to identification and quantification of all or at least many components in cellular systems with spatial and/or temporal resolution. Reams of new develop- ments of different methods have been applied so far, such as fluorescence microscopy, mass spectrometry, mass spectrom- etry imaging, electrochemistry imaging, and lab-on-chip de- vices. An overview of these methods and more is presented in different review articles [1–6]. The reason for this research interest is that the common lysate-based assays provide only integrated information, but not all cells respond alike. If we want to understand the “whole story” of rare cell populations, the biology of individual cells needs to be studied. This article is focused on highlighting the most recent trends and applications in which ICP-MS (partly ICP optical emission spectrometry ICP-OES) is applied for single-cell analysis using metal atoms that are intrinsically present in cells, taken up by cells (for instance uptake of engineered metallic nanoparticles by cells), or which are bound to a cell or cell component. Using inductively coupled plasma mass spectrometry (ICP-MS) for single-cell analysis is a very new and fast growing research field, and the applications are not well established and still far from being routine. ICP-MS is a mass spectrometric multi-element method based on counting the number of atoms in a sample. It pro- vides easy sample preparation, multi-elemental detection combined with high sensitivity (ng L –1 range), and large dynamic range (up to nine orders of magnitude), and can often be calibrated by simple standards, thus offering the advantage of providing quantitative information. Additionally, isotope ratio measurements are accessible and isotope-labeled Published in the topical collection Single Cell Analysis with guest editors Petra Dittrich and Norbert Jakubowski. L. Mueller (*) : H. Traub : N. Jakubowski : D. Drescher : J. Kneipp BAM Federal Institute for Materials Research and Testing, 12200 Berlin, Germany e-mail: larissa.mueller@bam.de D. Drescher : J. Kneipp Department of Chemistry, Humboldt-Universität zu Berlin, Brook-Taylor-Str. 2, 12489 Berlin, Germany V. I. Baranov DVS Sciences Inc., Markham, ON L3R 6E7, Canada Anal Bioanal Chem (2014) 406:6963–6977 DOI 10.1007/s00216-014-8143-7