Biomarker Mapping on Skin Tape Strips Using MALDI Mass Spectrometry Imaging

  • Guillaume HochartEmail author
  • David Bonnel
  • Jonathan Stauber
  • Georgios N. Stamatas
Research Article


Keratinocyte organization and biochemistry are important in forming the skin’s protective barrier. Intrinsic and extrinsic factors can affect skin barrier function at the cellular and molecular levels. Matrix-assisted laser desorption/ionization (MALDI) mass spectrometric imaging, a technique which combines both molecular aspects and histological details, has proven to be a valuable method in various disciplines including pharmacology, dermatology and cosmetology. It typically requires ex vivo samples, prepared following frozen tissue sectioning. This paper demonstrates the feasibility of performing MALDI analysis on tape strips collected non-invasively on skin. The aim is to obtain molecular imaging of corneocytes on tapes towards novel biological insights. Tapes were collected from two skin sites (volar forearm and cheek) of human volunteers. Ten molecules relating to skin barrier function were detected with a single mode of acquisition at high spatial resolution with a 7 T MALDI-Fourier transform ion cyclotron resonance (FTICR) instrument. The method sensitivity was adequate to create molecular maps which could be overlaid on transmission microscopy images of the same area of the tape. Analysis of the molecular distributions from tapes at the two skin sites was consistent with the known skin properties of the two sites, confirming the validity of the observations. Hierarchical clustering analysis was used to differentiate corneocyte populations based on their molecular profiles. Furthermore, morphological analysis provided a new way of considering statistical populations of corneocytes on the same tape, rather than measuring a single averaged value, providing additional useful information relating to their structure-function relationship.


Molecular mapping Corneocytes MALDI-FTICR mass spectrometry imaging Skin barrier 







α-Cyano-4-hydroxycinnamic acid




Desorption electrospray ionization


Dihydroxybenzoic acid


Fourier transform ion cyclotron resonance


High definition




Liquid chromatography/mass spectrometry tandem


Matrix-assisted laser desorption/ionization


Mass spectrometry


Mass spectrometry Imaging


Natural moisturization factor


Pyrrolidine carboxylic acid


Root mean square


Region of interest


Trifluoroacetic acid


Time-of-flight secondary ion mass spectrometry


Urocanic acid



The authors would like to thank Gaël Picard de Müller and Fabien Pamelard for their contribution to the morphologic and statistical approaches.

Compliance with Ethical Standards

Conflict of Interest

GNS is employee of Johnson & Johnson Santé Beauté France, a manufacturer of skin care products. GH, DB, and JS are employees of ImaBiotech, SAS a provider of analytical services including MALDI-MSI. The authors of the manuscript declare no competing commercial/financial interests.

Supplementary material

13361_2019_2277_MOESM1_ESM.tif (8.4 mb)
ESM 1 Skin tape strip analysis workflow. a) Collection of the skin tape strips; b) Mounting of the tapes for digital HD scan; c) Mounting for MSI and matrix deposit; d) MALDI-imaging. (PNG 1273 kb) (JPG 337 kb)


  1. 1.
    Proksch, E., Brandner, J.M., Jensen, J.-M.: The skin: an indispensable barrier. Exp. Dermatol. 17, 1063–1072 (2008)CrossRefGoogle Scholar
  2. 2.
    Sakai, S., Sasai, S., Endo, Y., Matue, K., Tagami, H., Inoue, S.: Characterization of the physical properties of the stratum corneum by a new tactile sensor. Skin Res. Technol. 6, 128–134 (2000)CrossRefGoogle Scholar
  3. 3.
    Rawlings, A.V.: Recent advances in skin “barrier” research. J. Pharm. Pharmacol. 62, 671–677 (2010)CrossRefGoogle Scholar
  4. 4.
    Pierard, G.E.: EEMCO guidance for the assessment of dry skin (xerosis) and ichthyosis: evaluation by stratum corneum shippings. Skin Res. Technol. 2, 3–11 (1996)CrossRefGoogle Scholar
  5. 5.
    Hendrix, S.W., Miller, K.H., Youket, T.E., Adam, R., O’Connor, R.J., Morel, J.G., Tepper, B.E.: Optimization of the skin multiple analyte profile bioanalytical method for determination of skin biomarkers from D-Squame tape samples. Skin Res. Technol. 13, 330–342 (2007)CrossRefGoogle Scholar
  6. 6.
    Hirao, T., Denda, M., Takahashi, M.: Identification of immature cornified envelopes in the barrier-impaired epidermis by characterization of their hydrophobicity and antigenicities of the components. Exp. Dermatol. 10, 35–44 (2001)CrossRefGoogle Scholar
  7. 7.
    Kezutyte, T., Desbenoit, N., Brunelle, A., Briedis, V.: Studying the penetration of fatty acids into human skin by ex vivo TOF-SIMS imaging. Biointerphases. 8, 3 (2013)CrossRefGoogle Scholar
  8. 8.
    Cizinauskas, V., Elie, N., Brunelle, A., Briedis, V.: Fatty acids penetration into human skin ex vivo: a TOF-SIMS analysis approach. Biointerphases. 12, 11003 (2017)CrossRefGoogle Scholar
  9. 9.
    Sjovall, P., Greve, T.M., Clausen, S.K., Moller, K., Eirefelt, S., Johansson, B., Nielsen, K.T.: Imaging of distribution of topically applied drug molecules in mouse skin by combination of time-of-flight secondary ion mass spectrometry and scanning electron microscopy. Anal. Chem. 86, 3443–3452 (2014)CrossRefGoogle Scholar
  10. 10.
    Sjovall, P., Skedung, L., Gregoire, S., Biganska, O., Clement, F., Luengo, G.S.: Imaging the distribution of skin lipids and topically applied compounds in human skin using mass spectrometry. Sci. Rep. 8, 16683 (2018)CrossRefGoogle Scholar
  11. 11.
    Siekkeri Vandikas, M., Hellstrom, E., Malmberg, P., Osmancevic, A.: Imaging of vitamin D in psoriatic skin using time-of-flight secondary ion mass spectrometry (ToF-SIMS): a pilot case study. J. Steroid Biochem. Mol. Biol. 189, 154–160 (2019)CrossRefGoogle Scholar
  12. 12.
    D’Alvise, J., Mortensen, R., Hansen, S.H., Janfelt, C.: Detection of follicular transport of lidocaine and metabolism in adipose tissue in pig ear skin by DESI mass spectrometry imaging. Anal. Bioanal. Chem. 406, 3735–3742 (2014)CrossRefGoogle Scholar
  13. 13.
    Caldwell, R.L., Caprioli, R.M.: Tissue profiling by mass spectrometry: a review of methodology and applications. Mol. Cell. Proteomics. 4, 394–401 (2005)CrossRefGoogle Scholar
  14. 14.
    Cornett, D., Frappier, S., Caprioli, R.: MALDI-FTICR imaging mass spectrometry of drugs and metabolites in tissue. Anal. Chem. 80, 5648–5653 (2008)CrossRefGoogle Scholar
  15. 15.
    Bonnel, D., Legouffe, R., Eriksson, A.H., Mortensen, R.W., Pamelard, F., Stauber, J., Nielsen, K.T.: MALDI imaging facilitates new topical drug development process by determining quantitative skin distribution profiles. Anal. Bioanal. Chem. (2018).
  16. 16.
    Lewis, E.E.L., Barrett, M.R.T., Freeman-Parry, L., Bojar, R.A., Clench, M.R.: Examination of the skin barrier repair/wound healing process using a living skin equivalent model and matrix-assisted laser desorption-ionization-mass spectrometry imaging. Int. J. Cosmet. Sci. 40, 148–156 (2018)CrossRefGoogle Scholar
  17. 17.
    Russo, C., Brickelbank, N., Duckett, C., Mellor, S., Rumbelow, S., Clench, M.R.: Quantitative investigation of terbinafine hydrochloride absorption into a living skin equivalent model by MALDI-MSI. Anal. Chem. 90, 10031–10038 (2018)CrossRefGoogle Scholar
  18. 18.
    Sorensen, I.S., Janfelt, C., Nielsen, M.M.B., Mortensen, R.W., Knudsen, N.O., Eriksson, A.H., Pedersen, A.J., Nielsen, K.T.: Combination of MALDI-MSI and cassette dosing for evaluation of drug distribution in human skin explant. Anal. Bioanal. Chem. 409, 4993–5005 (2017)CrossRefGoogle Scholar
  19. 19.
    Nguyen, J., Lewis, H., Queja, A., Diep, A.N., Hochart, G., Ameri, M.: Pharmacokinetics and skin tolerability of intracutaneous zolmitriptan delivery in swine using adhesive dermally applied microarray. J. Pharm. Sci. 107, 2192–2197 (2018)CrossRefGoogle Scholar
  20. 20.
    Marrakchi, S., Maibach, H.I.: Biophysical parameters of skin: map of human face, regional, and age-related differences. Contact Dermatitis. 57, 28–34 (2007)CrossRefGoogle Scholar
  21. 21.
    Firooz, A., Sadr, B., Babakoohi, S., Sarraf-Yazdy, M., Fanian, F., Kazerouni-Timsar, A., Nassiri-Kashani, M., Naghizadeh, M.M., Dowlati, Y.: Variation of biophysical parameters of the skin with age, gender, and body region. ScientificWorldJournal. 2012, 386936 (2012)CrossRefGoogle Scholar
  22. 22.
    Hayashi, S., Matsue, K., Takiwaki, H.: Image analysis of the distribution of turnover rate in the stratum corneum. Skin Res. Technol. 4, 109–120 (1998)CrossRefGoogle Scholar
  23. 23.
    Kashibuchi, N., Hirai, Y., O’Goshi, K., Tagami, H.: Three-dimensional analyses of individual corneocytes with atomic force microscope: morphological changes related to age, location and to the pathologic skin conditions. Skin Res. Technol. 8, 203–211 (2002)CrossRefGoogle Scholar
  24. 24.
    Rawlings, A.V., Harding, C.R.: Moisturization and skin barrier function. Dermatol. Ther. 17(Suppl 1), 43–48 (2004)CrossRefGoogle Scholar
  25. 25.
    Wu, Z., Hansmann, B., Meyer-Hoffert, U., Gläser, R., Schröder, J.-M.: Molecular identification and expression analysis of filaggrin-2, a member of the S100 fused-type protein family. PLoS One. 4, e5227 (2009)CrossRefGoogle Scholar
  26. 26.
    Picard de Muller, G., Ait-Belkacem, R., Bonnel, D., Longuespee, R., Stauber, J.: Automated morphological and morphometric analysis of mass spectrometry imaging data: application to biomarker discovery. J. Am. Soc. Mass Spectrom. 28, 2635–2645 (2017)CrossRefGoogle Scholar

Copyright information

© American Society for Mass Spectrometry 2019

Authors and Affiliations

  • Guillaume Hochart
    • 1
    Email author
  • David Bonnel
    • 1
  • Jonathan Stauber
    • 2
  • Georgios N. Stamatas
    • 3
  1. 1.ImaBiotech SASLoosFrance
  2. 2.ImaBiotech CorpBillericaUSA
  3. 3.Johnson & Johnson Santé Beauté FranceIssy-les-MoulineauxFrance

Personalised recommendations