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An auxiliary matrix for routine analysis of small molecules and biological macromolecules using matrix-assisted laser desorption ionization mass spectrometry

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Abstract

The great hurdles related with matrix-assisted laser desorption/ionization (MALDI) analysis are inhomogeneous crystallization, poor reproducibility, and low sensitivity. To effectively improve the performance of MALDI mass spectrometry (MS), graphene oxide (GO) was first utilized as an auxiliary matrix of the conventional matrices, including 2,5-dihydroxybenzoic acid (DHB), α-cyano-4-hydoxycyanocinnamic acid (CHCA), 2,4,6-trihydroxyacetophenone (THAP), and 3,5-dimethoxy-4-hydroxycinnamic acid (SA), for the analysis of small molecules and biological macromolecules on different MALDI MS systems. The results revealed that the DHB-GO composite matrix could provide much superior crystal homogenization, better reproducibility, higher sensitivity, and more excellent linearity for the statins’ tissue imaging on iMScope than the single-use DHB matrix. Moreover, the DHB-GO dramatically improved the spot-to-spot and shot-to-shot reproducibility, crystal homogenization, sensitivity, and linearity of MALDI-TOF MS for statins’ analysis in dried droplet. The capability of THAP on the analysis of lipids, similarly, could be greatly enhanced by the combined use of GO. THAP-GO composite matrix was expected to be widely used in the MALDI MS-based liposome studies. It was also found that CHCA-GO could provide superior analytical performance for peptides. The sensitivity and reproducibility of intact proteins could be greatly improved by SA-GO composite matrix. More importantly, the better reproducibility produced by the composite matrices sufficiently indicated that low concentration (0.1 mg mL−1) of GO almost did not cause contamination to MALDI MS system. Thus, GO was proved to be a versatile auxiliary matrix for the MALDI MS-based routine analysis of small molecules and biological macromolecules.

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References

  1. Wang J, Liu Q, Liang Y, Jiang G. Recent progress in application of carbon nanomaterials in laser desorption/ionization mass spectrometry. Anal Bioanal Chem. 2016;408:2861–73.

    Article  CAS  PubMed  Google Scholar 

  2. Karas M, Hillenkamp F. Laser desorption ionisation of proteins with molecular masses exceeding 10,000 Da. Anal Chem. 1988;60:2299–301.

    Article  CAS  PubMed  Google Scholar 

  3. Lacroix C, Gicquel A, Sendid B, Meyer J, Accoceberry I, François N, et al. Evaluation of two matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) systems for the identification of Candida species. Clin Microbiol Infect. 2014;20:153–8.

    Article  CAS  PubMed  Google Scholar 

  4. Köhler M, Neff C, Perez C, Brunner C, Pardon E, Steyaert J, et al. Binding specificities of nanobody membrane protein complexes obtained from chemical cross-linking and high-mass MALDI mass spectrometry. Anal Chem. 2018;90:5308–13.

    Article  CAS  Google Scholar 

  5. Zhang J, Zheng X, Ni Y. Selective enrichment and MALDI-TOF MS analysis of small molecule compounds with vicinal diols by boric acid-functionalized graphene oxide. J Am Soc Mass Spectrom. 2015;26:1291–8.

    Article  CAS  PubMed  Google Scholar 

  6. O’Rourke MB, Djordjevic SP, Padula MP. The quest for improved reproducibility in MALDI mass spectrometry. Mass Spectrom Rev. 2016;37:217–28.

    Article  CAS  PubMed  Google Scholar 

  7. Shi C, Meng J, Deng C. Enrichment and detection of small molecules using magnetic graphene as an adsorbent and a novel matrix of MALDI-TOF-MS. Chem Commun. 2012;48:2418–120.

    Article  CAS  Google Scholar 

  8. Toh-Boyo GM, Wulff SS, Basile F. Comparison of sample preparation methods and evaluation of intra- and intersample reproducibility in bacteria MALDI-MS profiling. Anal Chem. 2012;84:9971–80.

    Article  CAS  PubMed  Google Scholar 

  9. Šedo O, I S, Z Z. Sample preparation methods for MALDI-MS profiling of bacteria. Mass Spectrom Rev. 2011;30:417–34.

    Article  CAS  PubMed  Google Scholar 

  10. Zhao X, Barbersingh J, Shippy SA. MALDI-TOF MS detection of dilute, volume-limited peptide samples with physiological salt levels. Analyst. 2004;129:817–22.

    Article  CAS  PubMed  Google Scholar 

  11. Acland M, Mittal P, Lokman NA, Klinglerhoffmann M, Oehler MK, Hoffmann P. Mass spectrometry analyses of multicellular tumour spheroids. Proteomics Clin Appl. 2018;12:e1700124.

    Article  CAS  PubMed  Google Scholar 

  12. Gerald Stübiger A, Belgacem‡ O. Analysis of lipids using 2,4,6-trihydroxyacetophenone as a matrix for MALDI mass spectrometry. Anal Chem. 2007;79:3206–13.

    Article  CAS  PubMed  Google Scholar 

  13. Sun N, Wu Y, Nanba K, Sbiera S, Kircher S, Kunzke T, et al. High-resolution tissue mass spectrometry imaging reveals a refined functional anatomy of the human adult adrenal gland. Endocrinology. 2018;159:1511–24.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Rodrigo MA, Zitka O, Krizkova S, Moulick A, Adam V, Kizek R. MALDI-TOF MS as evolving cancer diagnostic tool: a review. J Pharm Biomed Anal. 2014;95:245–55.

    Article  CAS  PubMed  Google Scholar 

  15. Chughtai K, Heeren RM. Mass spectrometric imaging for biomedical tissue analysis. Chem Rev. 2010;110:3237–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Shimma S, Kumada HO, Taniguchi H, Konno A, Yao I, Furuta K, et al. Microscopic visualization of testosterone in mouse testis by use of imaging mass spectrometry. Anal Bioanal Chem. 2016;408:7607–15.

    Article  CAS  PubMed  Google Scholar 

  17. Harada T, Yubakubo A, Sugiura Y, Zaima N, Hayasaka T, Gotoinoue N, et al. Visualization of volatile substances in different organelles with an atmospheric-pressure mass microscope. Anal Chem. 2009;81:9153–7.

    Article  CAS  PubMed  Google Scholar 

  18. Kurabe N, Igarashi H, Ohnishi I, Tajima S, Inoue Y, Takahashi Y, et al. Visualization of sphingolipids and phospholipids in the fundic gland mucosa of human stomach using imaging mass spectrometry. World J Gastrointes Pathophysiol. 2016;7:235–41.

    Article  Google Scholar 

  19. Fukuyama Y. MALDI matrix research for biopolymers. Mass Spectrometry. 2015;4:A0037.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Li F, Wang X, Liu Y, Liu H, Li Z. Dephosphorylation of intact glycoprotein to greatly improve digestion efficiency coupled with matrix-assisted laser desorption/ionization-Fourier transform ion cyclotron resonance mass spectrometric analysis. Anal Chim Acta. 2013;787:140–7.

    Article  CAS  PubMed  Google Scholar 

  21. Largy E, Cantais F, Van VG, Beck A, Delobel A. Orthogonal liquid chromatography-mass spectrometry methods for the comprehensive characterization of therapeutic glycoproteins, from released glycans to intact protein level. J Chromatogr A. 2017;1498:128–46.

    Article  CAS  PubMed  Google Scholar 

  22. Wei Y, Zhang Y, Lin Y, Li L, Liu J, Wang Z, et al. A uniform 2,5-dihydroxybenzoic acid layer as a matrix for MALDI-FTICR MS-based lipidomics. Analyst. 2015;140:1298–305.

    Article  CAS  PubMed  Google Scholar 

  23. Malys BJ, Owens KG. Improving the analyte ion signal in matrix assisted laser desorption ionization imaging mass spectrometry via electrospray deposition by enhancing incorporation of the analyte in the matrix. Rapid Commun Mass Spectrom. 2017;31:804–12.

    Article  CAS  PubMed  Google Scholar 

  24. Doktycz SJ, Savickas PJ, Krueger DA. Matrix/sample interactions in ultraviolet laser-desorption of proteins. Rapid Commun Mass Spectrom. 1991;5:145–8.

    Article  CAS  Google Scholar 

  25. Chan TWD, Colburn AW, Derrick PJ, Gardiner DJ, Bowden M. Suppression of matrix ions in ultraviolet laser desorption: scanning electron microscopy and Raman spectroscopy of the solid samples. J Mass Spectrom. 1992;27:188–94.

    CAS  Google Scholar 

  26. Cai YH, Wang YS. Impact of uneven sample morphology on mass resolving power in linear MALDI-TOF mass spectrometry: a comprehensive theoretical investigation. J Mass Spectrom. 2018;53:361–8.

    Article  CAS  PubMed  Google Scholar 

  27. Strupat K, Karas M, Hillenkamp F. 2,5-Dihydroxybenzoic acid: a new matrix for laser desorption—ionization mass spectrometry. Int J Mass Spectrom. 1991;111:89–102.

    Article  CAS  Google Scholar 

  28. Liu Q, Shi J, Jiang G. Application of graphene in analytical sample preparation. Trends Analyt Chem. 2012;37:1–11.

    Article  CAS  Google Scholar 

  29. Liang X, Liu S, Wang S, Guo Y, Jiang S. Carbon-based sorbents: carbon nanotubes. J Chromatogr A. 2014;1357:53–67.

    Article  CAS  PubMed  Google Scholar 

  30. Zhang BT, Zheng X, Li HF, Lin JM. Application of carbon-based nanomaterials in sample preparation: a review. Anal Chim Acta. 2013;784:1–17.

    Article  CAS  PubMed  Google Scholar 

  31. Sunner J, Dratz E, Chen YC. Graphite surface-assisted laser desorption/ionization time-of-flight mass spectrometry of peptides and proteins from liquid solutions. Anal Chem. 1995;67:4335–42.

    Article  CAS  PubMed  Google Scholar 

  32. Chang C, Li X, Bai Y, Xu G, Feng B, Liao Y, et al. Graphene matrix for signal enhancement in ambient plasma assisted laser desorption ionization mass spectrometry. Talanta. 2013;114:54–9.

    Article  CAS  PubMed  Google Scholar 

  33. Dale MJ, Knochenmuss R, Zenobi R. Graphite/liquid mixed matrices for laser desorption/ionization mass spectrometry. Anal Chem. 1996;68:3321–9.

    Article  CAS  PubMed  Google Scholar 

  34. Wang Z, Cai Y, Wang Y, Zhou X, Zhang Y, Lu H. Improved MALDI imaging MS analysis of phospholipids using graphene oxide as new matrix. Sci Rep. 2017;7:44466.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Gorka J, Bahr U, Karas M. Graphite supported preparation (GSP) of α-cyano-4-hydroxycinnamic acid (CHCA) for matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) for peptides and proteins. J Am Soc for Mass Spectrom. 2012;23:1949–54.

    Article  CAS  Google Scholar 

  36. Li X, Rao T, Xu Y, Hu K, Zhu Z, Li H, et al. Pharmacokinetic and pharmacodynamic evidence for developing an oral formulation of octreotide against gastric mucosal injury. Acta Pharmacol Sin. 2018;39(8):1373–85.

  37. Rao T, Shao Y, Hamada N, Li Y, Ye H, Kang D, et al. Pharmacokinetic study based on a matrix-assisted laser desorption/ionization quadrupole ion trap time-of-flight imaging mass microscope combined with a novel relative exposure approach: a case of octreotide in mouse target tissues. Anal Chim Acta. 2017;952:71–80.

  38. Beavis RC, Chait BT, Fales HM. Cinnamic acid derivatives as matrices for ultraviolet laser desorption mass spectrometry of proteins. Rapid Commun Mass Spectrom. 1989;3(12):432–35.

  39. Kudina O, Eral B, Mugele F. e-MALDI: an electrowetting-enhanced drop drying method for MALDI mass spectrometry. Anal Chem. 2016;88(9):4669–75.

  40. Vorm O, Roepstorff P, Mann M. Improved resolution and very high sensitivity in MALDI TOF of matrix surfaces made by fast evaporation. Anal Chem. 2002;66(19):3281–87.

  41. Li X, Xu G, Zhang H, Liu S, Niu H, Peng J, et al. A homogeneous carbon nanosphere film-spot: for highly efficient laser desorption/ionization of small biomolecules. Carbon. 2017;121:343–52.

  42. Shi R, Dai X, Li W, Lu F, Liu Y, Qu H, et al. Hydroxyl-group-dominated graphite dots reshape laser desorption/ionization mass spectrometry for small biomolecular analysis and imaging. ACS Nano. 2017;11(9):9500–13.

Download references

Funding

This study was supported by the National Nature Science Foundation (81573559, 81530098), the Nature Science Foundation of Jiangsu Province (BK20171395), and the National Key Special Project of Science and Technology for Innovation Drugs of China (2017ZX09301013).

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Author notes

  1. Zhangpei Zhu, Jiajia Shen, and Dawei Wang contributed equally to this work.

Authors and Affiliations

  1. Key Lab of Drug Metabolism & Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Tongjiaxiang 24, Nanjing, 210009, China

    Zhangpei Zhu, Jiajia Shen, Chong Chen, Yangfan Xu, Huimin Guo, Dian Kang, Guangji Wang & Yan Liang

  2. Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Shizi Street 100, Nanjing, 210028, China

    Dawei Wang

  3. Shimadzu China Mass Spectrometry Center, No. 16 Chao Yang Men Wai Street, Chaoyang District, Beijing, 100020, China

    Naoki Hamada & Jing Dong

Authors
  1. Zhangpei Zhu
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  2. Jiajia Shen
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  3. Dawei Wang
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  4. Chong Chen
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  10. Guangji Wang
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  11. Yan Liang
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All authors have given approval to the final version of the manuscript.

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Correspondence to Guangji Wang or Yan Liang.

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All the animal experiments in the present study were approved by the Ethical Committee of Animal Experiments of China Pharmaceutical University.

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Zhu, Z., Shen, J., Wang, D. et al. An auxiliary matrix for routine analysis of small molecules and biological macromolecules using matrix-assisted laser desorption ionization mass spectrometry. Anal Bioanal Chem 411, 1041–1052 (2019). https://doi.org/10.1007/s00216-018-1532-6

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  • DOI: https://doi.org/10.1007/s00216-018-1532-6

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