Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Mass spectrometry as a tool to advance polymer science

Abstract

In contrast to natural polymers, which have existed for billions of years, the first well-understood synthetic polymers date back to just over one century ago. Nevertheless, this relatively short period has seen vast progress in synthetic polymer chemistry, which can now afford diverse macromolecules with varying structural complexities. To keep pace with this synthetic progress, there have been commensurate developments in analytical chemistry, where mass spectrometry has emerged as the pre-eminent technique for polymer analysis. This Perspective describes present challenges associated with the mass-spectrometric analysis of synthetic polymers, in particular the desorption, ionization and structural interrogation of high-molar-mass macromolecules, as well as strategies to lower spectral complexity. We critically evaluate recent advances in technology in the context of these challenges and suggest how to push the field beyond its current limitations. In this context, the increasingly important role of high-resolution mass spectrometry is emphasized because of its unrivalled ability to describe unique species within polymer ensembles, rather than to report the average properties of the ensemble.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: Influence of different pre-separations on the spectral complexity of a hypothetical mixture of polymers.
Fig. 2: Principles behind the three most widespread ionization techniques in polymer MS.
Fig. 3: The required resolving power and the optimum choice of mass analyser are highly sample dependent.
Fig. 4: Tandem mass spectrometry can be used to sequence polymers.
Fig. 5: Ion-mobility spectrometry exploits the m/z, size and shape dependence of ion diffusion to separate analytes.

References

  1. 1.

    Webster, J. & Oxley, D. in Chemical Genomics and Proteomics: Reviews and Protocols (ed. Zanders, E. D.) 227–240 (Springer, 2012).

  2. 2.

    Yamashita, M. & Fenn, J. B. Electrospray ion source. Another variation on the free-jet theme. J. Phys. Chem. 88, 4451–4459 (1984).

    CAS  Article  Google Scholar 

  3. 3.

    Fenn, J. B. Electrospray wings for molecular elephants (Nobel lecture). Angew. Chem. Int. Ed. 42, 3871–3894 (2003).

    CAS  Article  Google Scholar 

  4. 4.

    Fenn, J. B., Mann, M., Meng, C. K., Wong, S. F. & Whitehouse, C. M. Electrospray ionization for mass spectrometry of large biomolecules. Science 246, 64–71 (1989).

    CAS  PubMed  Article  Google Scholar 

  5. 5.

    Tanaka, K. et al. Protein and polymer analyses up to m/z 100 000 by laser ionization time-of-flight mass spectrometry. Rapid Commun. Mass Spectrom. 2, 151–153 (1988).

    CAS  Article  Google Scholar 

  6. 6.

    Karas, M. & Hillenkamp, F. Laser desorption ionization of proteins with molecular masses exceeding 10,000 daltons. Anal. Chem. 60, 2299–2301 (1988).

    CAS  PubMed  Article  Google Scholar 

  7. 7.

    Gruendling, T., Weidner, S., Falkenhagen, J. & Barner-Kowollik, C. Mass spectrometry in polymer chemistry: a state-of-the-art up-date. Polym. Chem. 1, 599–617 (2010).

    CAS  Article  Google Scholar 

  8. 8.

    Li, X., Guo, L., Casiano-Maldonado, M., Zhang, D. & Wesdemiotis, C. Top-down multidimensional mass spectrometry methods for synthetic polymer analysis. Macromolecules 44, 4555–4564 (2011).

    CAS  Article  Google Scholar 

  9. 9.

    Crotty, S., Gerişlioğlu, S., Endres, K. J., Wesdemiotis, C. & Schubert, U. S. Polymer architectures via mass spectrometry and hyphenated techniques: a review. Anal. Chim. Acta 932, 1–21 (2016).

    CAS  PubMed  Article  Google Scholar 

  10. 10.

    Uliyanchenko, E. Applications of hyphenated liquid chromatography techniques for polymer analysis. Chromatographia 80, 731–750 (2017).

    CAS  Article  Google Scholar 

  11. 11.

    Steckel, A. & Schlosser, G. An organic chemist’s guide to electrospray mass spectrometric structure elucidation. Molecules 24, 611 (2019).

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  12. 12.

    Raffaelli, A. & Saba, A. Atmospheric pressure photoionization mass spectrometry. Mass Spectrom. Rev. 22, 318–331 (2003).

    CAS  PubMed  Article  Google Scholar 

  13. 13.

    Awad, H., Khamis, M. M. & El-Aneed, A. Mass spectrometry, review of the basics: ionization. Appl. Spectrosc. Rev. 50, 158–175 (2015).

    CAS  Article  Google Scholar 

  14. 14.

    Crecelius, A. C., Vitz, J. & Schubert, U. S. Mass spectrometric imaging of synthetic polymers. Anal. Chim. Acta 808, 10–17 (2014).

    CAS  PubMed  Article  Google Scholar 

  15. 15.

    Harrisson, S. The downside of dispersity: why the standard deviation is a better measure of dispersion in precision polymerization. Polym. Chem. 9, 1366–1370 (2018).

    CAS  Article  Google Scholar 

  16. 16.

    Crecelius, A. C. & Schubert, U. S. in Mass Spectrometry in Polymer Chemistry (eds Barner-Kowollik, C., Gruendling, T., Falkenhagen, J. & Weidner, S.) 281–318 (Wiley-VCH, 2012).

  17. 17.

    De Bruycker, K., Krappitz, T. & Barner-Kowollik, C. High performance quantification of complex high resolution polymer mass spectra. ACS Macro Lett. 7, 1443–1447 (2018).

  18. 18.

    Jovic, K. et al. Hyphenation of size-exclusion chromatography to mass spectrometry for precision polymer analysis — a tutorial review. Polym. Chem. 10, 3241–3256 (2019).

    CAS  Article  Google Scholar 

  19. 19.

    Anastasaki, A., Willenbacher, J., Fleischmann, C., Gutekunst, W. R. & Hawker, C. J. End group modification of poly(acrylates) obtained via ATRP: a user guide. Polym. Chem. 8, 689–697 (2017).

    CAS  Article  Google Scholar 

  20. 20.

    Liarou, E. et al. Ultra-low volume oxygen tolerant photoinduced Cu-RDRP. Polym. Chem. 10, 963–971 (2019).

    CAS  Article  Google Scholar 

  21. 21.

    Blasco, E., Sims, M. B., Goldmann, A. S., Sumerlin, B. S. & Barner-Kowollik, C. 50th anniversary perspective: polymer functionalization. Macromolecules 50, 5215–5252 (2017).

    CAS  Article  Google Scholar 

  22. 22.

    Espeel, P. & Du Prez, F. E. “Click”-inspired chemistry in macromolecular science: matching recent progress and user expectations. Macromolecules 48, 2–14 (2015).

    CAS  Article  Google Scholar 

  23. 23.

    Das, A. & Theato, P. Activated ester containing polymers: opportunities and challenges for the design of functional macromolecules. Chem. Rev. 116, 1434–1495 (2016).

    CAS  PubMed  Article  Google Scholar 

  24. 24.

    Kubo, T., Figg, C. A., Swartz, J. L., Brooks, W. L. A. & Sumerlin, B. S. Multifunctional homopolymers: postpolymerization modification via sequential nucleophilic aromatic substitution. Macromolecules 49, 2077–2084 (2016).

    CAS  Article  Google Scholar 

  25. 25.

    Malik, M. I. & Pasch, H. Novel developments in the multidimensional characterization of segmented copolymers. Prog. Polym. Sci. 39, 87–123 (2014).

    CAS  Article  Google Scholar 

  26. 26.

    Lang, C., Barner, L., Blinco, J. P., Barner-Kowollik, C. & Fairfull-Smith, K. E. Direct access to biocompatible nitroxide containing polymers. Polym. Chem. 9, 1348–1355 (2018).

    CAS  Article  Google Scholar 

  27. 27.

    Winkler, M., Montero de Espinosa, L., Barner-Kowollik, C. & Meier, M. A. R. A new approach for modular polymer–polymer conjugations via Heck coupling. Chem. Sci. 3, 2607–2615 (2012).

    CAS  Article  Google Scholar 

  28. 28.

    Hurrle, S. et al. Two-in-one: λ-orthogonal photochemistry on a radical photoinitiating system. Macromol. Rapid Commun. 38, 1600598 (2017).

    Article  CAS  Google Scholar 

  29. 29.

    Oehlenschlaeger, K. K. et al. Light-induced modular ligation of conventional raft polymers. Angew. Chem. Int. Ed. 52, 762–766 (2013).

    CAS  Article  Google Scholar 

  30. 30.

    Gruendling, T., Dietrich, M. & Barner-Kowollik, C. A novel one-pot procedure for the fast and efficient conversion of raft polymers into hydroxy-functional polymers. Aust. J. Chem. 62, 806–812 (2009).

    CAS  Article  Google Scholar 

  31. 31.

    Tischer, T. et al. Modular ligation of thioamide functional peptides onto solid cellulose substrates. Adv. Funct. Mater. 22, 3853–3864 (2012).

    CAS  Article  Google Scholar 

  32. 32.

    Jovic, K. J., Richter, T., Lang, C., Blinco, J. P. & Barner-Kowollik, C. Correlating in-depth mechanistic understanding with mechanical properties of high-temperature resistant cyclic imide copolymers. Macromolecules 51, 8712–8720 (2018).

    CAS  Article  Google Scholar 

  33. 33.

    Steinkoenig, J., Nitsche, T., Tuten, B. T. & Barner-Kowollik, C. Radical-induced single-chain collapse of Passerini sequence-regulated polymers assessed by high-resolution mass spectrometry. Macromolecules 51, 3967–3974 (2018).

    CAS  Article  Google Scholar 

  34. 34.

    Steinkoenig, J., Rothfuss, H., Lauer, A., Tuten, B. T. & Barner-Kowollik, C. Imaging single-chain nanoparticle folding via high-resolution mass spectrometry. J. Am. Chem. Soc. 139, 51–54 (2017).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  35. 35.

    Bennet, F. et al. Transfer reactions in phenyl carbamate ethyl acrylate polymerizations. Macromol. Chem. Phys. 214, 236–245 (2013).

    CAS  Article  Google Scholar 

  36. 36.

    Gruendling, T., Voll, D., Guilhaus, M. & Barner-Kowollik, C. A perfect couple: PLP/SEC/ESI-MS for the accurate determination of propagation rate coefficients in free radical polymerization. Macromol. Chem. Phys. 211, 80–90 (2010).

    CAS  Article  Google Scholar 

  37. 37.

    Frick, E. et al. Toward a quantitative description of radical photoinitiator structure–reactivity correlations. Macromolecules 49, 80–89 (2016).

    CAS  Article  Google Scholar 

  38. 38.

    Voll, D., Junkers, T. & Barner-Kowollik, C. Quantitative comparison of the mesitoyl vs the benzoyl fragment in photoinitiation: a question of origin. Macromolecules 44, 2542–2551 (2011).

    CAS  Article  Google Scholar 

  39. 39.

    Fast, D. E. et al. Wavelength-dependent photochemistry of oxime ester photoinitiators. Macromolecules 50, 1815–1823 (2017).

    CAS  Article  Google Scholar 

  40. 40.

    Lauer, A. et al. Wavelength-dependent photochemical stability of photoinitiator-derived macromolecular chain termini. ACS Macro Lett. 6, 952–958 (2017).

    CAS  Article  Google Scholar 

  41. 41.

    Nitsche, T. et al. Mapping the compaction of discrete polymer chains by size exclusion chromatography coupled to high-resolution mass spectrometry. Macromolecules 52, 2597–2606 (2019).

    CAS  Article  Google Scholar 

  42. 42.

    Aaserud, D. J., Prokai, L. & Simonsick, W. J. Gel permeation chromatography coupled to Fourier transform mass spectrometry for polymer characterization. Anal. Chem. 71, 4793–4799 (1999).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  43. 43.

    Gruendling, T., Guilhaus, M. & Barner-Kowollik, C. Quantitative LC–MS of polymers: determining accurate molecular weight distributions by combined size exclusion chromatography and electrospray mass spectrometry with maximum entropy data processing. Anal. Chem. 80, 6915–6927 (2008).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  44. 44.

    Gruendling, T., Guilhaus, M. & Barner-Kowollik, C. Fast and accurate determination of absolute individual molecular weight distributions from mixtures of polymers via size exclusion chromatography–electrospray ionization mass spectrometry. Macromolecules 42, 6366–6374 (2009).

    CAS  Article  Google Scholar 

  45. 45.

    Viodé, A. et al. Coupling of size-exclusion chromatography with electrospray ionization charge-detection mass spectrometry for the characterization of synthetic polymers of ultra-high molar mass. Rapid Commun. Mass Spectrom. 30, 132–136 (2016).

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  46. 46.

    Falkenhagen, J. & Weidner, S. Determination of critical conditions of adsorption for chromatography of polymers. Anal. Chem. 81, 282–287 (2009).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  47. 47.

    Peters, R. et al. Quantitation of functionality of poly(methyl methacrylate) by liquid chromatography under critical conditions followed by evaporative light-scattering detection: comparison with NMR and titration. J. Chromatogr. A 949, 327–335 (2002).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  48. 48.

    van Leeuwen, S. M., Tan, B., Grijpma, D. W., Feijen, J. & Karst, U. Characterization of the chemical composition of a block copolymer by liquid chromatography/mass spectrometry using atmospheric pressure chemical ionization and electrospray ionization. Rapid Commun. Mass Spectrom. 21, 2629–2637 (2007).

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  49. 49.

    Barner-Kowollik, C., Gruendling, T., Falkenhagen, J. & Weidner, S. (eds) Mass Spectrometry in Polymer Chemistry (Wiley-VCH, 2012).

  50. 50.

    Wesdemiotis, C. Multidimensional mass spectrometry of synthetic polymers and advanced materials. Angew. Chem. Int. Ed. 56, 1452–1464 (2017).

    CAS  Article  Google Scholar 

  51. 51.

    Hoteling, A. J. & Papagelis, P. T. Structural characterization of silicone polymers using compositional ultra-high performance liquid chromatography separation, electrospray ionization, and high resolution/accurate mass. Anal. Chim. Acta 808, 231–239 (2014).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  52. 52.

    Yin, C., Fu, J. & Lu, X. Characterization of polyethermethylsiloxanes using ultra-high performance liquid chromatography-electrospray ionization and time-of-flight mass spectrometry. Anal. Chim. Acta 1082, 194–201 (2019).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  53. 53.

    Weidner, S., Falkenhagen, J., Krueger, R.-P. & Just, U. Principle of two-dimensional characterization of copolymers. Anal. Chem. 79, 4814–4819 (2007).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  54. 54.

    Radke, W. & Falkenhagen, J. in Liquid Chromatography: Applications (eds Fanali, S., Haddad, P. R., Poole, C. F., Schoenmakers, P. & Lloyd, D.) 93–129 (Elsevier, 2013).

  55. 55.

    Girod, M., Phan, T. N. T. & Charles, L. Tuning block copolymer structural information by adjusting salt concentration in liquid chromatography at critical conditions coupled with electrospray tandem mass spectrometry. Rapid Commun. Mass Spectrom. 23, 1476–1482 (2009).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  56. 56.

    Fandrich, N. et al. Characterization of new amphiphilic block copolymers of N-vinylpyrrolidone and vinyl acetate, 2 - chromatographic separation and analysis by MALDI-TOF and FT-IR coupling. Macromol. Chem. Phys. 211, 1678–1688 (2010).

    CAS  Article  Google Scholar 

  57. 57.

    Malke, M., Barqawi, H. & Binder, W. H. Synthesis of an amphiphilic β-turn mimetic polymer conjugate. ACS Macro Lett. 3, 393–397 (2014).

    CAS  Article  Google Scholar 

  58. 58.

    Lee, S., Lee, H., Chang, T. & Hirao, A. Synthesis and characterization of an exact polystyrene-graft-polyisoprene: a failure of size exclusion chromatography analysis. Macromolecules 50, 2768–2776 (2017).

    CAS  Article  Google Scholar 

  59. 59.

    Vandewalle, S., Billiet, S., Driessen, F. & Du Prez, F. E. Macromolecular coupling in seconds of triazolinedione end-functionalized polymers prepared by RAFT polymerization. ACS Macro Lett. 5, 766–771 (2016).

    CAS  Article  Google Scholar 

  60. 60.

    Julka, S. et al. Quantitative characterization of solid epoxy resins using comprehensive two dimensional liquid chromatography coupled with electrospray ionization-time of flight mass spectrometry. Anal. Chem. 81, 4271–4279 (2009).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  61. 61.

    Petton, L. et al. High molar mass segmented macromolecular architectures by nitroxide mediated polymerisation. Polym. Chem. 4, 4697–4709 (2013).

    CAS  Article  Google Scholar 

  62. 62.

    Viktor, Z. et al. Comprehensive two-dimensional liquid chromatography for the characterization of acrylate-modified hyaluronic acid. Anal. Bioanal. Chem. 411, 3321–3330 (2019).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  63. 63.

    Maiko, K., Hehn, M., Hiller, W. & Pasch, H. Comprehensive two-dimensional liquid chromatography of stereoregular poly(methyl methacrylates) for tacticity and molar mass analysis. Anal. Chem. 85, 9793–9798 (2013).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  64. 64.

    Lee, S., Choi, H., Chang, T. & Staal, B. Two-dimensional liquid chromatography analysis of polystyrene/polybutadiene block copolymers. Anal. Chem. 90, 6259–6266 (2018).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  65. 65.

    Pirok, B. W. J., Stoll, D. R. & Schoenmakers, P. J. Recent developments in two-dimensional liquid chromatography: fundamental improvements for practical applications. Anal. Chem. 91, 240–263 (2019).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  66. 66.

    Barqawi, H., Ostas, E., Liu, B., Carpentier, J.-F. & Binder, W. H. Multidimensional characterization of α,ω-telechelic poly(ε-caprolactone)s via online coupling of 2D chromatographic methods (LC/SEC) and ESI-TOF/MALDI-TOF-MS. Macromolecules 45, 9779–9790 (2012).

    CAS  Article  Google Scholar 

  67. 67.

    Barqawi, H., Schulz, M., Olubummo, A., Saurland, V. & Binder, W. H. 2D-LC/SEC-(MALDI-TOF)-MS characterization of symmetric and nonsymmetric biocompatible PEOm–PIB–PEOn block copolymers. Macromolecules 46, 7638–7649 (2013).

    CAS  Article  Google Scholar 

  68. 68.

    Pretorius, N. O., Rhode, K., Simpson, J. M. & Pasch, H. Characterization of complex phthalic acid/propylene glycol based polyesters by the combination of 2D chromatography and MALDI-TOF mass spectrometry. Anal. Bioanal. Chem. 407, 217–230 (2015).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  69. 69.

    Malik, M. I., Trathnigg, B. & Saf, R. Characterization of ethylene oxide–propylene oxide block copolymers by combination of different chromatographic techniques and matrix-assisted laser desorption ionization time-of-flight mass spectroscopy. J. Chromatogr. A 1216, 6627–6635 (2009).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  70. 70.

    Ozeki, Y., Omae, M., Kitagawa, S. & Ohtani, H. Electrospray ionization-ion mobility spectrometry–high resolution tandem mass spectrometry with collision-induced charge stripping for the analysis of highly multiply charged intact polymers. Analyst 144, 3428–3435 (2019).

    CAS  PubMed  Article  Google Scholar 

  71. 71.

    Crescentini, T. M., May, J. C., McLean, J. A. & Hercules, D. M. Alkali metal cation adduct effect on polybutylene adipate oligomers: ion mobility-mass spectrometry. Polymer 173, 58–65 (2019).

    CAS  PubMed  Article  Google Scholar 

  72. 72.

    Gerislioglu, S., Adams, S. R. & Wesdemiotis, C. Characterization of singly and multiply pegylated insulin isomers by reversed-phase ultra-performance liquid chromatography interfaced with ion mobility mass spectrometry. Anal. Chim. Acta 1004, 58–66 (2018).

    CAS  PubMed  Article  Google Scholar 

  73. 73.

    Shi, C., Gerişlioğlu, S. & Wesdemiotis, C. Ultrahigh performance liquid chromatography interfaced with mass spectrometry and orthogonal ion mobility separation for the microstructure characterization of amphiphilic block copolymers. Chromatographia 79, 961–969 (2016).

    CAS  Article  Google Scholar 

  74. 74.

    Foley, C. D., Zhang, B., Alb, A. M., Trimpin, S. & Grayson, S. M. Use of ion mobility spectrometry–mass spectrometry to elucidate architectural dispersity within star polymers. ACS Macro Lett. 4, 778–782 (2015).

    CAS  Article  Google Scholar 

  75. 75.

    Duez, Q. et al. One step further in the characterization of synthetic polymers by ion mobility mass spectrometry: evaluating the contribution of end-groups. Polymers 11, 688 (2019).

    CAS  PubMed Central  Article  PubMed  Google Scholar 

  76. 76.

    Duez, Q. et al. Correlation between the shape of the ion mobility signals and the stepwise folding process of polylactide ions. J. Mass Spectrom. 52, 133–138 (2017).

    CAS  PubMed  Article  Google Scholar 

  77. 77.

    Haler, J. R. N. et al. Fundamental studies on poly(2-oxazoline) side chain isomers using tandem mass spectrometry and ion mobility-mass spectrometry. J. Am. Soc. Mass Spectrom. 30, 1220–1228 (2019).

    CAS  PubMed  Article  Google Scholar 

  78. 78.

    Haler, J. R. N. et al. Predicting ion mobility-mass spectrometry trends of polymers using the concept of apparent densities. Methods 144, 125–133 (2018).

    CAS  PubMed  Article  Google Scholar 

  79. 79.

    Benninghoven, A., Hagenhoff, B. & Niehuis, E. Surface MS: probing real-world samples. Anal. Chem. 65, 630A–640A (1993).

    CAS  Article  Google Scholar 

  80. 80.

    Manicke, N. E., Dill, A. L., Ifa, D. R. & Cooks, R. G. High-resolution tissue imaging on an orbitrap mass spectrometer by desorption electrospray ionization mass spectrometry. J. Mass Spectrom. 45, 223–226 (2010).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  81. 81.

    Gross, J. H. Direct analysis in real time — a critical review on DART-MS. Anal. Bioanal. Chem. 406, 63–80 (2014).

    CAS  PubMed  Article  Google Scholar 

  82. 82.

    Rondeau, D. in Direct Analysis in Real Time Mass Spectrometry (ed. Dong, Y.) 43–80 (Wiley-VCH, 2017).

  83. 83.

    Liigand, P. et al. Think negative: finding the best electrospray ionization/MS mode for your analyte. Anal. Chem. 89, 5665–5668 (2017).

    CAS  PubMed  Article  Google Scholar 

  84. 84.

    Liigand, P. et al. The evolution of electrospray generated droplets is not affected by ionization mode. J. Am. Soc. Mass Spectrom. 28, 2124–2131 (2017).

    CAS  PubMed  Article  Google Scholar 

  85. 85.

    Kebarle, P. & Peschke, M. On the mechanisms by which the charged droplets produced by electrospray lead to gas phase ions. Anal. Chim. Acta 406, 11–35 (2000).

    CAS  Article  Google Scholar 

  86. 86.

    Crotti, S., Seraglia, R. & Traldi, P. Some thoughts on electrospray ionization mechanisms. Eur. J. Mass Spectrom. 17, 85–99 (2011).

    CAS  Article  Google Scholar 

  87. 87.

    Pasch, H. & Schrepp, W. MALDI-TOF Mass Spectrometry of Synthetic Polymers (Springer, 2003).

  88. 88.

    Swanson, K. D., Spencer, S. E. & Glish, G. L. Metal cationization extractive electrospray ionization mass spectrometry of compounds containing multiple oxygens. J. Am. Soc. Mass Spectrom. 28, 1030–1035 (2017).

    CAS  PubMed  Article  Google Scholar 

  89. 89.

    Chen, R. & Li, L. Lithium and transition metal ions enable low energy collision-induced dissociation of polyglycols in electrospray ionization mass spectrometry. J. Am. Soc. Mass Spectrom. 12, 832–839 (2001).

    CAS  PubMed  Article  Google Scholar 

  90. 90.

    Steinkoenig, J., Cecchini, M. M., Reale, S., Goldmann, A. S. & Barner-Kowollik, C. Supercharging synthetic polymers: mass spectrometric access to nonpolar synthetic polymers. Macromolecules 50, 8033–8041 (2017).

    CAS  Article  Google Scholar 

  91. 91.

    Li, L. et al. Comprehensive comparison of ambient mass spectrometry with desorption electrospray ionization and direct analysis in real time for direct sample analysis. Talanta 203, 140–146 (2019).

    CAS  PubMed  Article  Google Scholar 

  92. 92.

    Ifa, D. R., Wu, C. P., Ouyang, Z. & Cooks, R. G. Desorption electrospray ionization and other ambient ionization methods: current progress and preview. Analyst 135, 669–681 (2010).

    CAS  PubMed  Article  Google Scholar 

  93. 93.

    Harris, G. A., Galhena, A. S. & Fernández, F. M. Ambient sampling/ionization mass spectrometry: applications and current trends. Anal. Chem. 83, 4508–4538 (2011).

    CAS  PubMed  Article  Google Scholar 

  94. 94.

    Friia, M., Legros, V., Tortajada, J. & Buchmann, W. Desorption electrospray ionization-orbitrap mass spectrometry of synthetic polymers and copolymers. J. Mass Spectrom. 47, 1023–1033 (2012).

    CAS  PubMed  Article  Google Scholar 

  95. 95.

    Soeriyadi, A. H., Whittaker, M. R., Boyer, C. & Davis, T. P. Soft ionization mass spectroscopy: insights into the polymerization mechanism. J. Polym. Sci. A Polym. Chem. 51, 1475–1505 (2013).

    CAS  Article  Google Scholar 

  96. 96.

    Paine, M. R. L., Barker, P. J. & Blanksby, S. J. Ambient ionisation mass spectrometry for the characterisation of polymers and polymer additives: a review. Anal. Chim. Acta 808, 70–82 (2014).

    CAS  PubMed  Article  Google Scholar 

  97. 97.

    Bonnaire, N., Dannoux, A., Pernelle, C., Amekraz, B. & Moulin, C. On the use of electrospray ionization and desorption electrospray ionization mass spectrometry for bulk and surface polymer analysis. Appl. Spectrosc. 64, 810–818 (2010).

    CAS  PubMed  Article  Google Scholar 

  98. 98.

    Drzeżdżon, J., Jacewicz, D., Sielicka, A. & Chmurzyński, L. MALDI-MS for polymer characterization — recent developments and future prospects. TrAC Trends Anal. Chem. 115, 121–128 (2019).

    Article  CAS  Google Scholar 

  99. 99.

    National Institute of Standards and Technology. NIST synthetic polymer MALDI recipes database. NIST https://maldi.nist.gov/ (2014).

  100. 100.

    Pasch, H. & Ghahary, R. Analysis of complex polymers by MALDI-TOF mass spectrometry. Macromol. Symp. 152, 267–278 (2000).

    CAS  Article  Google Scholar 

  101. 101.

    Navarrete, P., Pizzi, A., Pasch, H. & Delmotte, L. Study on lignin–glyoxal reaction by MALDI-TOF and CP-MAS 13C-NMR. J. Adhes. Sci. Technol. 26, 1069–1082 (2012).

    CAS  Article  Google Scholar 

  102. 102.

    Hoong, Y. B., Pizzi, A., Tahir, P. M. & Pasch, H. Characterization of Acacia mangium polyflavonoid tannins by MALDI-TOF mass spectrometry and CP-MAS 13C NMR. Eur. Polym. J. 46, 1268–1277 (2010).

    CAS  Article  Google Scholar 

  103. 103.

    Liu, C., Fei, Y.-y., Zhang, H.-l., Pan, C.-y. & Hong, C.-y. Effective construction of hyperbranched multicyclic polymer by combination of ATRP, UV-induced cyclization, and self-accelerating click reaction. Macromolecules 52, 176–184 (2019).

    CAS  Article  Google Scholar 

  104. 104.

    Nakamura, S., Fouquet, T. & Sato, H. Molecular characterization of high molecular weight polyesters by matrix-assisted laser desorption/ionization high-resolution time-of-flight mass spectrometry combined with on-plate alkaline degradation and mass defect analysis. J. Am. Soc. Mass Spectrom. 30, 355–367 (2019).

    CAS  PubMed  Article  Google Scholar 

  105. 105.

    Endres, K. J., Hill, J. A., Lu, K., Foster, M. D. & Wesdemiotis, C. Surface layer matrix-assisted laser desorption ionization mass spectrometry imaging: a surface imaging technique for the molecular-level analysis of synthetic material surfaces. Anal. Chem. 90, 13427–13433 (2018).

    CAS  PubMed  Article  Google Scholar 

  106. 106.

    Zhou, D. et al. High-quality conjugated polymers via one-pot Suzuki–Miyaura homopolymerization. RSC Adv. 7, 27762–27769 (2017).

    CAS  Article  Google Scholar 

  107. 107.

    Payne, M. E. & Grayson, S. M. Characterization of synthetic polymers via matrix assisted laser desorption ionization time of flight (MALDI-TOF) mass spectrometry. J. Vis. Exp. 136, e57174 (2018).

    Google Scholar 

  108. 108.

    Crescentini, T. M., May, J. C., McLean, J. A. & Hercules, D. M. Mass spectrometry of polyurethanes. Polymer 181, 121624 (2019).

    Article  CAS  Google Scholar 

  109. 109.

    Montaudo, G., Samperi, F. & Montaudo, M. S. Characterization of synthetic polymers by MALDI-MS. Prog. Polym. Sci. 31, 277–357 (2006).

    CAS  Article  Google Scholar 

  110. 110.

    Laskin, J., Laskin, A. & Nizkorodov, S. A. New mass spectrometry techniques for studying physical chemistry of atmospheric heterogeneous processes. Int. Rev. Phys. Chem. 32, 128–170 (2013).

    CAS  Article  Google Scholar 

  111. 111.

    Huang, D. et al. Secondary ion mass spectrometry: the application in the analysis of atmospheric particulate matter. Anal. Chim. Acta 989, 1–14 (2017).

    CAS  PubMed  Article  Google Scholar 

  112. 112.

    Arlinghaus, H. F. in Surface and Thin Film Analysis: A Compendium of Principles, Instrumentation, and Applications 2nd edn (eds Friedbacher, G. & Bubert, H.) 179–189 (Wiley-VCH, 2011).

  113. 113.

    Henkel, T. & Gilmour, J. in Treatise on Geochemistry 2nd edn Vol. 15 (eds Holland, H. D. & Turekian, K. K.) 411–424 (Elsevier, 2013).

  114. 114.

    Kopnarski, M. & Jenett, H. in Surface and Thin Film Analysis: A Compendium of Principles, Instrumentation, and Applications 2nd edn (eds Friedbacher, G. & Bubert, H.) 161–177 (Wiley-VCH, 2011).

  115. 115.

    Oechsner, H. in Encyclopedia of analytical science 2nd edn (eds Worsfold, P., Townshend, P., Poole, A. & Amsterdam, C.) 514–526 (Elsevier, 2004).

  116. 116.

    Bhardwaj, C. & Hanley, L. Ion sources for mass spectrometric identification and imaging of molecular species. Nat. Prod. Rep. 31, 756–767 (2014).

    CAS  PubMed  Article  Google Scholar 

  117. 117.

    Getty, S. A., Brinckerhoff, W. B., Cornish, T., Ecelberger, S. & Floyd, M. Compact two-step laser time-of-flight mass spectrometer for in situ analyses of aromatic organics on planetary missions. Rapid Commun. Mass Spectrom. 26, 2786–2790 (2012).

    CAS  PubMed  Article  Google Scholar 

  118. 118.

    Barré, F. P. Y. et al. Enhanced sensitivity using MALDI imaging coupled with laser postionization (MALDI-2) for pharmaceutical research. Anal. Chem. 91, 10840–10848 (2019).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  119. 119.

    Touboul, D., Kollmer, F., Niehuis, E., Brunelle, A. & Laprévote, O. Improvement of biological time-of-flight-secondary ion mass spectrometry imaging with a bismuth cluster ion source. J. Am. Soc. Mass Spectrom. 16, 1608–1618 (2005).

    CAS  PubMed  Article  Google Scholar 

  120. 120.

    Shard, A. G. et al. Argon cluster ion beams for organic depth profiling: results from a VAMAS interlaboratory study. Anal. Chem. 84, 7865–7873 (2012).

    CAS  PubMed  Article  Google Scholar 

  121. 121.

    Niehuis, E., Möllers, R., Rading, D., Cramer, H.-G. & Kersting, R. Analysis of organic multilayers and 3D structures using Ar cluster ions. Surf. Interface Anal. 45, 158–162 (2013).

    CAS  Article  Google Scholar 

  122. 122.

    Passarelli, M. K. et al. The 3D orbisims — label-free metabolic imaging with subcellular lateral resolution and high mass-resolving power. Nat. Methods 14, 1175–1183 (2017).

    CAS  PubMed  Article  Google Scholar 

  123. 123.

    Kotowska, A. M. et al. In situ protein identification and mapping using secondary ion mass spectrometry. Preprint at bioRxiv https://doi.org/10.1101/803940 (2019).

    Article  Google Scholar 

  124. 124.

    Lub, J., van Vroonhoven, F. C. B. M., van Leyen, D. & Benninghoven, A. Static secondary ion mass spectrometry analysis of polycarbonate surfaces. Effect of structure and of surface modification on the spectra. Polymer 29, 998–1003 (1988).

    CAS  Article  Google Scholar 

  125. 125.

    Gardella Jr, J. A. & Pireaux, J.-J. Analysis of polymer surfaces using electron and ion beams. Anal. Chem. 62, 645A–661A (1990).

    Article  Google Scholar 

  126. 126.

    Garrison, B. J., Delcorte, A. & Krantzman, K. D. Molecule liftoff from surfaces. Acc. Chem. Res. 33, 69–77 (2000).

    CAS  PubMed  Article  Google Scholar 

  127. 127.

    Wojciechowski, I., Delcorte, A., Gonze, X. & Bertrand, P. Mechanism of metal cationization in organic SIMS. Chem. Phys. Lett. 346, 1–8 (2001).

    CAS  Article  Google Scholar 

  128. 128.

    Bertrand, P., Delcorte, A. & Garrison, B. J. Molecular SIMS for organic layers: new insights. Appl. Surf. Sci. 203–204, 160–165 (2003).

    Article  Google Scholar 

  129. 129.

    Delcorte, A., Bour, J., Aubriet, F., Muller, J.-F. & Bertrand, P. Sample metallization for performance improvement in desorption/ionization of kilodalton molecules: quantitative evaluation, imaging secondary ion MS, and laser ablation. Anal. Chem. 75, 6875–6885 (2003).

    CAS  PubMed  Article  Google Scholar 

  130. 130.

    Wehbe, N., Heile, A., Arlinghaus, H. F., Bertrand, P. & Delcorte, A. Effects of metal nanoparticles on the secondary ion yields of a model alkane molecule upon atomic and polyatomic projectiles in secondary ion mass spectrometry. Anal. Chem. 80, 6235–6244 (2008).

    CAS  PubMed  Article  Google Scholar 

  131. 131.

    Bletsos, I. V., Hercules, D. M., VanLeyen, D. & Benninghoven, A. Time-of-flight secondary ion mass spectrometry of polymers in the mass range 500–10000. Macromolecules 20, 407–413 (1987).

    CAS  Article  Google Scholar 

  132. 132.

    Mezger, S. T. P., Mingels, A. M. A., Bekers, O., Cillero-Pastor, B. & Heeren, R. M. A. Trends in mass spectrometry imaging for cardiovascular diseases. Anal. Bioanal. Chem. 411, 3709–3720 (2019).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  133. 133.

    He, J. M. et al. A sensitive and wide coverage ambient mass spectrometry imaging method for functional metabolites based molecular histology. Adv. Sci. 5, 1802201 (2018).

    Google Scholar 

  134. 134.

    Zandanel, C. et al. Biodistribution of polycyanoacrylate nanoparticles encapsulating doxorubicin by matrix-assisted laser desorption ionization (MALDI) mass spectrometry imaging (MSI). J. Drug Delivery Sci. Technol. 47, 55–61 (2018).

    CAS  Article  Google Scholar 

  135. 135.

    Buck, A. et al. Round robin study of formalin-fixed paraffin-embedded tissues in mass spectrometry imaging. Anal. Bioanal. Chem. 410, 5969–5980 (2018).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  136. 136.

    Rivas, D. et al. Using MALDI-TOF MS imaging and LC-HRMS for the investigation of the degradation of polycaprolactone diol exposed to different wastewater treatments. Anal. Bioanal. Chem. 409, 5401–5411 (2017).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  137. 137.

    Crecelius, A. C., Schubert, U. S. & von Eggeling, F. MALDI mass spectrometric imaging meets “omics”: Recent advances in the fruitful marriage. Analyst 140, 5806–5820 (2015).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  138. 138.

    Trindade, G. F., Abel, M.-L., Lowe, C., Tshulu, R. & Watts, J. F. A time-of-flight secondary ion mass spectrometry/multivariate analysis (TOF-SIMS/MVA) approach to identify phase segregation in blends of incompatible but extremely similar resins. Anal. Chem. 90, 3936–3941 (2018).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  139. 139.

    Taylor, M. J. et al. Time of flight secondary ion mass spectrometry — a method to evaluate plasma-modified three-dimensional scaffold chemistry. Biointerphases 13, 03B415 (2018).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  140. 140.

    Hook, A. L., Williams, P. M., Alexander, M. R. & Scurr, D. J. Multivariate TOF-SIMS image analysis of polymer microarrays and protein adsorption. Biointerphases 10, 019005 (2015).

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  141. 141.

    Bailey, J. et al. 3D TOF-SIMS imaging of polymer multi layer films using argon cluster sputter depth profiling. ACS Appl. Mater. Interfaces 7, 2654–2659 (2015).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  142. 142.

    Kollmer, F., Paul, W., Krehl, M. & Niehuis, E. Ultra high spatial resolution SIMS with cluster ions — approaching the physical limits. Surf. Interface Anal. 45, 312–314 (2013).

    CAS  Article  Google Scholar 

  143. 143.

    Dubey, M. et al. Surface analysis of photolithographic patterns using ToF-SIMS and PAC. Surf. Interface Anal. 41, 645–652 (2009).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  144. 144.

    Wood, A. R., Smith, P. A. & Watts, J. F. The forensic study of single fibre pull-out specimens using TOF-SIMS. Compos. Interfaces 14, 387–402 (2007).

    CAS  Article  Google Scholar 

  145. 145.

    Lee, C.-Y., Harbers, G. M., Grainger, D. W., Gamble, L. J. & Castner, D. G. Fluorescence, XPS, and TOF-SIMS surface chemical state image analysis of DNA microarrays. J. Am. Chem. Soc. 129, 9429–9438 (2007).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  146. 146.

    Kubicek, M. et al. A novel TOF-SIMS operation mode for sub 100 nm lateral resolution: application and performance. Appl. Surf. Sci. 289, 407–416 (2014).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  147. 147.

    Bernard, L. et al. Plasma polymer film designs through the eyes of TOF-SIMS. Biointerphases 13, 03B417 (2018).

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  148. 148.

    Muir, B. W. et al. Effects of oxygen plasma treatment on the surface of bisphenol a polycarbonate: a study using SIMS, principal component analysis, ellipsometry, XPS and AFM nanoindentation. Surf. Interface Anal. 38, 1186–1197 (2006).

    CAS  Article  Google Scholar 

  149. 149.

    Trindade, G. F., Williams, D. F., Abel, M. L. & Watts, J. F. Analysis of atmospheric plasma-treated polypropylene by large area ToF-SIMS imaging and NMF. Surf. Interface Anal. 50, 1180–1186 (2018).

    CAS  Article  Google Scholar 

  150. 150.

    Ravati, S., Poulin, S., Piyakis, K. & Favis, B. D. Phase identification and interfacial transitions in ternary polymer blends by TOF-SIMS. Polymer 55, 6110–6123 (2014).

    CAS  Article  Google Scholar 

  151. 151.

    Gardella, Jr, J. A. & Mahoney, C. M. Determination of oligomeric chain length distributions at surfaces using ToF-SIMS: segregation effects and polymer properties. Appl. Surf. Sci. 231–232, 283–288 (2004).

    Article  CAS  Google Scholar 

  152. 152.

    Hook, A. L. & Scurr, D. J. ToF-SIMS analysis of a polymer microarray composed of poly(meth)acrylates with C6 derivative pendant groups. Surf. Interface Anal. 48, 226–236 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  153. 153.

    Brison, J., Muramoto, S. & Castner, D. G. ToF-SIMS depth profiling of organic films: a comparison between single-beam and dual-beam analysis. J. Phys. Chem. C 114, 5565–5573 (2010).

    CAS  Article  Google Scholar 

  154. 154.

    Graham, D. J., Wilson, J. T., Lai, J. J., Stayton, P. S. & Castner, D. G. Three-dimensional localization of polymer nanoparticles in cells using ToF-SIMS. Biointerphases 11, 02A304 (2016).

    Article  CAS  Google Scholar 

  155. 155.

    Xian, F., Hendrickson, C. L. & Marshall, A. G. High resolution mass spectrometry. Anal. Chem. 84, 708–719 (2012).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  156. 156.

    Lössl, P., Snijder, J. & Heck, A. J. R. Boundaries of mass resolution in native mass spectrometry. J. Am. Soc. Mass Spectrom. 25, 906–917 (2014).

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  157. 157.

    Satoh, T., Tsuno, H., Iwanaga, M. & Kammei, Y. The design and characteristic features of a new time-of-flight mass spectrometer with a spiral ion trajectory. J. Am. Soc. Mass Spectrom. 16, 1969–1975 (2005).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  158. 158.

    Makarov, A., Denisov, E. & Lange, O. Performance evaluation of a high-field orbitrap mass analyzer. J. Am. Soc. Mass Spectrom. 20, 1391–1396 (2009).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  159. 159.

    Murray, K. K. et al. Definitions of terms relating to mass spectrometry (IUPAC Recommendations 2013). Pure Appl. Chem. 85, 1515–1609 (2013).

    CAS  Article  Google Scholar 

  160. 160.

    Snijder, J., Rose, R. J., Veesler, D., Johnson, J. E. & Heck, A. J. R. Studying 18MDa virus assemblies with native mass spectrometry. Angew. Chem. Int. Ed. 52, 4020–4023 (2013).

    CAS  Article  Google Scholar 

  161. 161.

    Zenaidee, M. A., Leeming, M. G., Zhang, F., Funston, T. T. & Donald, W. A. Highly charged protein ions: the strongest organic acids to date. Angew. Chem. Int. Ed. 56, 8522–8526 (2017).

    CAS  Article  Google Scholar 

  162. 162.

    Stutzman, J. R., Crowe, M. C., Alexander, IV, J. N., Bell, B. M. & Dunkle, M. N. Coupling charge reduction mass spectrometry to liquid chromatography for complex mixture analysis. Anal. Chem. 88, 4130–4139 (2016).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  163. 163.

    Stutzman, J. R. et al. Microdroplet fusion chemistry for charge state reduction of synthetic polymers via bipolar dual spray with anionic reagents. J. Am. Soc. Mass Spectrom. 30, 1742–1749 (2019).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  164. 164.

    Mehmood, S., Allison, T. M. & Robinson, C. V. Mass spectrometry of protein complexes: from origins to applications. Annu. Rev. Phys. Chem. 66, 453–474 (2015).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  165. 165.

    McLuckey, S. A. & Goeringer, D. E. Slow heating methods in tandem mass spectrometry. J. Mass Spectrom. 32, 461–474 (1997).

    CAS  Article  Google Scholar 

  166. 166.

    Dongré, A. R., Jones, J. L., Somogyi, Á. & Wysocki, V. H. Influence of peptide composition, gas-phase basicity, and chemical modification on fragmentation efficiency:  evidence for the mobile proton model. J. Am. Chem. Soc. 118, 8365–8374 (1996).

    Article  Google Scholar 

  167. 167.

    Nilsson, T. et al. Mass spectrometry in high-throughput proteomics: ready for the big time. Nat. Methods 7, 681–685 (2010).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  168. 168.

    Tuten, B. T. et al. Polyselenoureas via multicomponent polymerizations using elemental selenium as monomer. ACS Macro Lett. 7, 898–903 (2018).

    CAS  Article  Google Scholar 

  169. 169.

    Roy, R. K. et al. Design and synthesis of digitally encoded polymers that can be decoded and erased. Nat. Commun. 6, 7237 (2015).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  170. 170.

    Martens, S. et al. Multifunctional sequence-defined macromolecules for chemical data storage. Nat. Commun. 9, 4451 (2018).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  171. 171.

    Amalian, J.-A., Trinh, T. T., Lutz, J.-F. & Charles, L. MS/MS digital readout: analysis of binary information encoded in the monomer sequences of poly(triazole amide)s. Anal. Chem. 88, 3715–3722 (2016).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  172. 172.

    Fisher, G. L. et al. A new method and mass spectrometer design for TOF-SIMS parallel imaging MS/MS. Anal. Chem. 88, 6433–6440 (2016).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  173. 173.

    Hoskins, J. N., Trimpin, S. & Grayson, S. M. Architectural differentiation of linear and cyclic polymeric isomers by ion mobility spectrometry-mass spectrometry. Macromolecules 44, 6915–6918 (2011).

    CAS  Article  Google Scholar 

  174. 174.

    Frisch, H., Mundsinger, K., Poad, B. L. J., Blanksby, S. J. & Barner-Kowollik, C. Wavelength-gated photoreversible polymerization and topology control. Chem. Sci. https://doi.org/10.1039/C9SC05381F (2020).

  175. 175.

    Giles, K. et al. A cyclic ion mobility-mass spectrometry system. Anal. Chem. 91, 8564–8573 (2019).

    CAS  PubMed  Article  Google Scholar 

  176. 176.

    Ridgeway, M. E., Lubeck, M., Jordens, J., Mann, M. & Park, M. A. Trapped ion mobility spectrometry: a short review. Int. J. Mass Spectrom. 425, 22–35 (2018).

    CAS  Article  Google Scholar 

  177. 177.

    Webb, I. K. et al. Experimental evaluation and optimization of structures for lossless ion manipulations for ion mobility spectrometry with time-of-flight mass spectrometry. Anal. Chem. 86, 9169–9176 (2014).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  178. 178.

    Haler, J. R. N. et al. Multiple gas-phase conformations of a synthetic linear poly(acrylamide) polymer observed using ion mobility-mass spectrometry. J. Am. Soc. Mass Spectrom. 28, 2492–2499 (2017).

    CAS  PubMed  Article  Google Scholar 

  179. 179.

    Inglese, P. et al. Deep learning and 3D-DESI imaging reveal the hidden metabolic heterogeneity of cancer. Chem. Sci. 8, 3500–3511 (2017).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  180. 180.

    Ràfols, P. et al. Signal preprocessing, multivariate analysis and software tools for MA(LDI)-TOF mass spectrometry imaging for biological applications. Mass Spectrom. Rev. 37, 281–306 (2018).

    PubMed  Article  CAS  Google Scholar 

  181. 181.

    Poté, N. et al. Identification of tissue microvascular invasion biomarkers in hepatocellular carcinomas by MALDI imaging mass spectrometry. Virchows Arch. 461, S9–S10 (2012).

    Google Scholar 

  182. 182.

    Lagarrigue, M. et al. New analysis workflow for MALDI imaging mass spectrometry: application to the discovery and identification of potential markers of childhood absence epilepsy. J. Proteome Res. 11, 5453–5463 (2012).

    CAS  PubMed  Article  Google Scholar 

  183. 183.

    Alexandrov, T. MALDI imaging mass spectrometry: statistical data analysis and current computational challenges. BMC Bioinformatics 13, S11 (2012).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  184. 184.

    Wagner, M. S., Graham, D. J. & Castner, D. G. Simplifying the interpretation of ToF-SIMS spectra and images using careful application of multivariate analysis. Appl. Surf. Sci. 252, 6575–6581 (2006).

    CAS  Article  Google Scholar 

  185. 185.

    Graham, D. J., Wagner, M. S. & Castner, D. G. Information from complexity: challenges of TOF-SIMS data interpretation. Appl. Surf. Sci. 252, 6860–6868 (2006).

    CAS  Article  Google Scholar 

  186. 186.

    Graham, D. J. & Castner, D. G. Multivariate analysis of ToF-SIMS data from multicomponent systems: the why, when, and how. Biointerphases 7, 49 (2012).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  187. 187.

    Trindade, G. F., Abel, M. L. & Watts, J. F. simsMVA: a tool for multivariate analysis of ToF-SIMS datasets. Chemometr. Intell. Lab. Syst. 182, 180–187 (2018).

    CAS  Article  Google Scholar 

  188. 188.

    Madiona, R. M. T., Winkler, D. A., Muir, B. W. & Pigram, P. J. Effect of mass segment size on polymer ToF-SIMS multivariate analysis using a universal data matrix. Appl. Surf. Sci. 478, 465–477 (2019).

    CAS  Article  Google Scholar 

  189. 189.

    Fischer, C. R., Ruebel, O. & Bowen, B. P. An accessible, scalable ecosystem for enabling and sharing diverse mass spectrometry imaging analyses. Arch. Biochem. Biophys. 589, 18–26 (2016).

    CAS  PubMed  Article  Google Scholar 

  190. 190.

    Ucal, Y., Coskun, A. & Ozpinar, A. Quality will determine the future of mass spectrometry imaging in clinical laboratories: the need for standardization. Expert Rev. Proteomics 16, 521–532 (2019).

    CAS  PubMed  Article  Google Scholar 

  191. 191.

    Kendrick, E. A mass scale based on CH2 = 14.0000 for high resolution mass spectrometry of organic compounds. Anal. Chem. 35, 2146–2154 (1963).

    CAS  Article  Google Scholar 

  192. 192.

    Hughey, C. A., Hendrickson, C. L., Rodgers, R. P., Marshall, A. G. & Qian, K. Kendrick mass defect spectrum:  a compact visual analysis for ultrahigh-resolution broadband mass spectra. Anal. Chem. 73, 4676–4681 (2001).

    CAS  PubMed  Article  Google Scholar 

  193. 193.

    Sato, H., Nakamura, S., Teramoto, K. & Sato, T. Structural characterization of polymers by MALDI spiral-TOF mass spectrometry combined with Kendrick mass defect analysis. J. Am. Soc. Mass Spectrom. 25, 1346–1355 (2014).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  194. 194.

    Gaiffe, G., Cole, R. B., Lacpatia, S. & Bridoux, M. C. Characterization of fluorinated polymers by atmospheric-solid-analysis-probe high-resolution mass spectrometry (ASAP/HRMS) combined with Kendrick-mass-defect analysis. Anal. Chem. 90, 6035–6042 (2018).

    CAS  PubMed  Article  Google Scholar 

  195. 195.

    Cody, R. B. & Fouquet, T. “Reverse Kendrick mass defect analysis”: rotating mass defect graphs to determine oligomer compositions for homopolymers. Anal. Chem. 90, 12854–12860 (2018).

    CAS  PubMed  Article  Google Scholar 

  196. 196.

    Kehr, S. & Luftmann, H. Polymer characterization by electrospray-mass-spectrometry — shifting the upper mass limit. e-Polymers 7, 10 (2007).

    Article  Google Scholar 

  197. 197.

    Łącki, M. K., Startek, M., Valkenborg, D. & Gambin, A. Isospec: hyperfast fine structure calculator. Anal. Chem. 89, 3272–3277 (2017).

    PubMed  Article  CAS  Google Scholar 

Download references

Acknowledgements

C.B.-K. acknowledges funding from the Australian Research Council (ARC) in the form of a Laureate Fellowship (FL170100014) enabling his photochemical research program, as well as key support from the Queensland University of Technology (QUT). The authors thank B. Poad and D. Marshall (Central Analytical Research Facility (CARF), QUT) for fruitful discussions.

Author information

Affiliations

Authors

Contributions

All authors researched data for the article and contributed to discussion of content and writing. K.D.B. made the figures and reviewed/edited the manuscript before submission.

Corresponding authors

Correspondence to Stephen J. Blanksby or Christopher Barner-Kowollik.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

De Bruycker, K., Welle, A., Hirth, S. et al. Mass spectrometry as a tool to advance polymer science. Nat Rev Chem 4, 257–268 (2020). https://doi.org/10.1038/s41570-020-0168-1

Download citation

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing