German Edition: DOI: 10.1002/ange.201607003 Mass Spectrometry International Edition: DOI: 10.1002/anie.201607003 Multidimensional Mass Spectrometry of Synthetic Polymers and Advanced Materials** Chrys Wesdemiotis* ion mobility · LC-MS · mass spectrometry · polymers · tandem MS 1. Introduction Mass spectrometry (MS) has become an essential ana- lytical tool in polymer and materials science, in which it is increasingly used to verify or ascertain the microstructure of a wide range of synthetic polymers. [1–5] More widespread applications, similar to those in the -omics areas of biology and medicine, [6–8] are however hampered by the following limitations: 1) The sample must be capable of forming stable gas-phase ions, which precludes the analysis of saturated and very large or cross-linked polymers; 2) MS does not reveal specific information about the func- tional groups present in a polymeric material or about its primary and higher-order structure; and 3) mix- tures and blends may not be charac- terized properly due to differences in ionization and detection efficiencies of their constituents. This Minireview discusses new developments that help to resolve these problems and broaden the utility of MS in polymer and materials science. Chemical analysis by MS involves the conversion of the analyte molecules to gas-phase ions and the subsequent separation and detection of these ions according to their mass-to-charge ratio (m/z). The most widely used ionization methods for synthetic polymers are matrix-assisted laser desorption ionization (MALDI), [9, 10] electrospray ionization (ESI), [11] and atmospheric-pressure chemical ionization (AP- CI), [12] which ionize macromolecules by ion attachment (usually H + , Na + , or Ag + ) or ion removal (usually H + from acidic analytes). The m/z values of the resulting [M + X] + and [MH]  quasimolecular ions reveal the corresponding mac- romolecular compositions. Because the ions are separated before detection, MS affords fractionation by mass, a partic- ularly useful feature for synthetic polymers, which generally exhibit a distribution of molecular weights. This unique property permits characterization of individual oligomers (n- Multidimensional mass spectrometry interfaces a suitable ionization technique and mass analysis (MS) with fragmentation by tandem mass spectrometry (MS 2 ) and an orthogonal online separation method. Separation choices include liquid chromatography (LC) and ion- mobility spectrometry (IMS), in which separation takes place pre- ionization in the solution state or post-ionization in the gas phase, respectively. The MS step provides elemental composition informa- tion, while MS 2 exploits differences in the bond stabilities of a polymer, yielding connectivity and sequence information. LC conditions can be tuned to separate by polarity, end-group functionality, or hydro- dynamic volume, whereas IMS adds selectivity by macromolecular shape and architecture. This Minireview discusses how selected combinations of the MS, MS 2 , LC, and IMS dimensions can be applied, together with the appropriate ionization method, to determine the constituents, structures, end groups, sequences, and architectures of a wide variety of homo- and copolymeric materials, including multi- component blends, supramolecular assemblies, novel hybrid materials, and large cross-linked or nonionizable polymers. [*] Prof. Dr. C. Wesdemiotis Department of Chemistry, The University of Akron Akron, OH 44325 (USA) E-mail: wesdemiotis@uakron.edu [**] A list of the abbreviations used is supplied in Section 6. A ngewandte Chemie Minireviews 1452  2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Angew. Chem. Int. Ed. 2017, 56, 1452 – 1464