Filaggrin pp 93-101 | Cite as

Noninvasive Detection of Filaggrin Molecules by Raman Spectroscopy



The Raman effect consists of a shift in photon energy due to inelastic collisions of photons with molecules. These wavelength shifts are unique for each molecule, and they provide a fingerprint of the molecular structure of the sample that can be used to identify the material that is being analyzed, providing a noninvasive method to detect substances with clinical relevance. In the particular case of detecting filaggrin, Raman spectroscopy has been used successfully to characterize this molecule, and measurements have been successfully correlated to filaggrin-related diseases. In this chapter, the basic theory behind Raman spectroscopy is presented along with the instrumentation needed to perform Raman spectroscopy in a clinical setting and some of the recent work on using Raman spectroscopy to detect filaggrin-related skin conditions.


Raman Spectrum Raman Spectroscopy Atopic Dermatitis Stratum Corneum Reference Spectrum 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The author would like to acknowledge the work of Dr. Benjamín Moncada and the Dermatology Department at the “Dr. Ignacio Morones Prieto” Central Hospital (San Luis Potosi, Mexico), where most of the clinical work was performed. Also, the author would like to acknowledge the valuable collaboration of Dr. Victor Saavedra-Alanís, who performed the filaggrin genotyping; Dr. Javier Alda from the University Complutense of Madrid and Dr. Miguel G. Ramírez-Elías, who performed most of the principal component analysis; and Dr. Edgar Briones, who made the figures for this chapter.


  1. 1.
    Raman CV. The colour of the sea. Nature. 1921;108(2716):367.CrossRefGoogle Scholar
  2. 2.
    Ferraro JR, Nakamoto K, Brown C. Introductory Raman spectroscopy. 2nd ed. San Diego: Academic; 2003.Google Scholar
  3. 3.
    Zhao J, Lui H, McLean DI, Zheng H. Real-time Raman spectroscopy for noninvasive in vivo skin analysis and diagnosis. In: Campolo R, editor. Recent advances in biomedical engineering. Vienna: IN-TECH; 2010. p. 455–74.Google Scholar
  4. 4.
    Ramírez-Elías MG, Alda J, González FJ. Noise and artifact characterization of in-vivo Raman spectroscopy skin measurements. Appl Spectrosc. 2012;66(6):650–5.PubMedCrossRefGoogle Scholar
  5. 5.
    Shreve P, Cherepy NJ, Mathies RA. Effective rejection of fluorescence interference in Raman spectroscopy using a shifted excitation difference technique. Appl Spectrosc. 1992;46(4):707–11.CrossRefGoogle Scholar
  6. 6.
    Baraga JJ, Feld MS, Rava RP. Rapid near-infrared Raman spectroscopy of human tissue with a spectrograph and CCD detector. Appl Spectrosc. 1992;46(2):187–90.CrossRefGoogle Scholar
  7. 7.
    Knorr F, Smith ZJ, Wachsmann-Hogiu S. Development of a time-gated system for Raman spectroscopy of biological samples. Opt Exp. 2010;18(19):20049–58.CrossRefGoogle Scholar
  8. 8.
    Zhao J, Lui H, McLean D, Zeng H. Automated autofluorescence background subtraction algorithm for biomedical Raman spectroscopy. Appl Spectrosc. 2007;61(11):1225–32.PubMedCrossRefGoogle Scholar
  9. 9.
    Schulze G, Jirasek A, Yu ML, Lim A, Turner RFB, Blades MW. Investigation of selected baseline removal techniques as candidates for automated implementation. Appl Spectrosc. 2005;59(5):545–74.PubMedCrossRefGoogle Scholar
  10. 10.
    Villanueva-Luna AE, Castro-Ramos J, Vazquez-Montiel S, Flores-Gil A, Delgado-Atencio JA, Vázquez-Villa A. Raman spectra and optical coherence tomography images skin. Proc SPIE. 2010;7883:788310.CrossRefGoogle Scholar
  11. 11.
    Ehrentreich F, Summchen L. Spike removal and denoising of Raman spectra by wavelet transform methods. Anal Chem. 2001;73(1):4364–73.PubMedCrossRefGoogle Scholar
  12. 12.
    Huang Z, Chen X, Chen Y, Chen J, Dou M, Feng S, et al. Raman spectroscopic characterization and differentiation of seminal plasma. J Biomed Opt. 2011;16:110501.PubMedCrossRefGoogle Scholar
  13. 13.
    Wang HH, Huang N, Zhao J, Lui H, Korbelik M, Zeng H. Depth-resolved in vivo micro Raman spectroscopy of a murine skin tumor model reveals cancer-specific spectral biomarkers. J Raman Spectrosc. 2011;42(2):160–1660.CrossRefGoogle Scholar
  14. 14.
    Ramos PM, Ruisánchez I. Noise and background removal in Raman spectra of ancient pigments using wavelet transform. J Raman Spectrosc. 2005;36(9):848–56.CrossRefGoogle Scholar
  15. 15.
    Zhang DM, Ben-Amotz D. Enhanced chemical classification of Raman images in the presence of strong fluorescence interference. Appl Spectrosc. 2000;54(9):1379–83.CrossRefGoogle Scholar
  16. 16.
    O’Grady A, Dennis AC, Denvir D, McGarvey JJ, Bell SEJ. Quantitative Raman spectroscopy of highly fluorescent samples using pseudosecond derivatives and multivariate analysis. Anal Chem. 2001;73(9):2058–65.PubMedCrossRefGoogle Scholar
  17. 17.
    Mahadevan-Jansen A, Richards-Kortum R. Raman spectroscopy for the detection of cancers and precancers. J Biomed Opt. 1996;1:31.PubMedCrossRefGoogle Scholar
  18. 18.
    Garfin DE. Gel electrophoresis of proteins. In: Davey J, Lord M, editors. Essential cell biology, Cell structure, a practical approach, vol. 1. Oxford: Oxford University Press; 2003. p. 197–268.Google Scholar
  19. 19.
    Mlitz V, Latreille J, Gardinier S, Jdid R, Drouault Y, Hufnagl P, et al. Impact of filaggrin mutations on Raman spectra and biophysical properties of the stratum corneum in mild to moderate atopic dermatitis. J Eur Acad Dermatol Venereol. 2012;26(8):983–90.PubMedCrossRefGoogle Scholar
  20. 20.
    Kezic S, O’Regan GM, Lutter R, Jakasa I, Koster ES, Saunders S, Caspers P, et al. Filaggrin loss-of-function mutations are associated with enhanced expression of IL-1 cytokines in the stratum corneum of patients with atopic dermatitis and in a murine model of filaggrin deficiency. J Allergy Clin Immunol. 2012;129(4):1031–9.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    O’Regan GM, Kemperman PM, Sandilands A, Chen H, Campbell LE, Kroboth K, et al. Raman profiles of the stratum corneum define 3 filaggrin genotype-determined atopic dermatitis endophenotypes. J Allergy Clin Immunol. 2010;126(3):574–80.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Kezic S, O’Regan GM, Yau N, Sandilands A, Chen H, Campbell LE, et al. Levels of filaggrin degradation products are influenced by both filaggrin genotype and atopic dermatitis severity. Allergy. 2011;66:934–40.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    López-Alonso JM, Alda J, Bernabeu E. Principal component characterization of noise for infrared images. Appl Opt. 2002;41:320–31.PubMedCrossRefGoogle Scholar
  24. 24.
    López-Alonso JM, Alda J. Operational parametrization of the 1/f noise of a sequence of frames by means of the principal component analysis in focal plane arrays. Opt Eng. 2004;42:1915–22.CrossRefGoogle Scholar
  25. 25.
    González FJ, Alda J, Moreno-Cruz B, Martínez-Escanamé M, Ramírez-Elías MG, Torres-Álvarez B, et al. Use of Raman spectroscopy in the early detection of filaggrin-related atopic dermatitis. Skin Res Technol. 2011;17(1):45–50.PubMedCrossRefGoogle Scholar
  26. 26.
    Hannifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Derm Venereol. 1980;92:44–7.Google Scholar
  27. 27.
    Williams HC, Jburney PG, Hay RJ, Archer CB, Shipley MJ, Hunter JJ, et al. The U.K. Working Party’s diagnostic criteria for atopic dermatitis. I. Derivation of a minimum set of discriminators for atopic dermatitis. Br J Dermatol. 1994;131:383–96.PubMedCrossRefGoogle Scholar
  28. 28.
    González FJ, Valdes-Rodríguez R, Ramírez-Elías MG, Castillo-Martínez C, Saavedra-Alanis VM, Moncada B. Noninvasive detection of filaggrin gene mutations using Raman spectroscopy. Biomed Opt Express. 2011;2(12):3363–6.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Smith FJD, Irvine AD, Terron-Kwiatkowski A, Sandilands A, Campbell LE, Zhao Y, et al. Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis vulgaris. Nat Genet. 2006;38(3):337–42.PubMedCrossRefGoogle Scholar
  30. 30.
    Novak N, Simon D. Atopic dermatitis – from new pathophysiologic insights to individualized therapy. Allergy. 2011;66(7):830–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Center for the Investigation and Application of Science and TechnologyAutonomous University of San Luis PotosiSan Luis PotosiMexico

Personalised recommendations