OSA's Digital Library

Biomedical Optics Express

Biomedical Optics Express

  • Editor: Joseph A. Izatt
  • Vol. 4, Iss. 11 — Nov. 1, 2013
  • pp: 2673–2682

A simple and rapid detection of tissue adhesive-induced biochemical changes in cells and DNA using Raman spectroscopy

Gyeong Bok Jung, Young Ju Lee, Gihyun Lee, and Hun-Kuk Park  »View Author Affiliations

Biomedical Optics Express, Vol. 4, Issue 11, pp. 2673-2682 (2013)

View Full Text Article

Enhanced HTML    Acrobat PDF (1287 KB)

Browse Journals / Lookup Meetings

Browse by Journal and Year


Lookup Conference Papers

Close Browse Journals / Lookup Meetings

Article Tools



We demonstrate a cytotoxicity evaluation of tissue adhesive using Raman spectroscopy. This method allows for quantitative, label-free, non-invasive and rapid monitoring of the biochemical changes of cells following tissue adhesive treatment. Here, we show the biochemical property changes in mouse fibroblast L929 cells and cellular DNA following tissue adhesive (Dermabond) treatment using Raman spectroscopy. The Raman band intensities were significantly decreased when the cells were treated with Dermabond as compared to control cells. These results suggest denaturation and conformational changes in proteins and degradation of DNA related to cell death. To support these conclusions, conventional cytotoxicity assays such as WST, LIVE/DEAD, and TUNEL were carried out, and the results were in agreement with the Raman results. Thus, Raman spectroscopy analysis not only distinguishes between viable and damaged cells, but can also be used for identification and quantification of a cytotoxicity of tissue adhesive, which based on the cellular biochemical and structural changes at a molecular level. Therefore, we suggest that this method could be used for cytotoxic evaluation of tissue adhesives by rapid and sensitive detection of cellular changes.

© 2013 Optical Society of America

OCIS Codes
(170.0170) Medical optics and biotechnology : Medical optics and biotechnology
(170.1530) Medical optics and biotechnology : Cell analysis
(170.5660) Medical optics and biotechnology : Raman spectroscopy
(300.6450) Spectroscopy : Spectroscopy, Raman

ToC Category:
Spectroscopic Diagnostics

Original Manuscript: July 18, 2013
Revised Manuscript: September 27, 2013
Manuscript Accepted: September 27, 2013
Published: October 29, 2013

Gyeong Bok Jung, Young Ju Lee, Gihyun Lee, and Hun-Kuk Park, "A simple and rapid detection of tissue adhesive-induced biochemical changes in cells and DNA using Raman spectroscopy," Biomed. Opt. Express 4, 2673-2682 (2013)

Sort:  Author  |  Year  |  Journal  |  Reset  


  1. J. S. Applebaum, T. Zalut, D. Applebaum, “The use of tissue adhesion for traumatic laceration repair in the emergency department,” Ann. Emerg. Med. 22(7), 1190–1192 (1993). [CrossRef] [PubMed]
  2. A. B. Leahey, J. D. Gottsch, W. J. Stark, “Clinical experience with N-butyl cyanoacrylate (Nexacryl) tissue adhesive,” Ophthalmology 100(2), 173–180 (1993). [PubMed]
  3. L. P. Blanco, “Lip suture with isobutyl cyanoacrylate,” Endod. Dent. Traumatol. 10(1), 15–18 (1994). [CrossRef] [PubMed]
  4. P. A. Leggat, D. R. Smith, U. Kedjarune, “Surgical applications of cyanoacrylate adhesives: a review of toxicity,” ANZ J. Surg. 77(4), 209–213 (2007). [CrossRef] [PubMed]
  5. B. J. Vote, M. J. Elder, “Cyanoacrylate glue for corneal perforations: a description of a surgical technique and a review of the literature,” Clin. Experiment. Ophthalmol. 28(6), 437–442 (2000). [CrossRef] [PubMed]
  6. J. Lin, R. Chen, S. Feng, J. Pan, B. Li, G. Chen, S. Lin, C. Li, L. Sun, Z. Huang, H. Zeng, “Surface-enhanced Raman scattering spectroscopy for potential noninvasive nasopharyngeal cancer detection,” J. Raman Spectrosc. 43(4), 497–502 (2012). [CrossRef]
  7. S. Dochow, C. Krafft, U. Neugebauer, T. Bocklitz, T. Henkel, G. Mayer, J. Albert, J. Popp, “Tumour cell identification by means of Raman spectroscopy in combination with optical traps and microfluidic environments,” Lab Chip 11(8), 1484–1490 (2011). [CrossRef] [PubMed]
  8. J. Schenk, L. Tröbs, F. Emmerling, J. Kneipp, U. Panne, M. Albrecht, “Simultaneous UV/Vis spectroscopy and surface enhanced Raman scattering of nanoparticle formation and aggregation in levitated droplets,” Anal. Methods 4(5), 1252–1258 (2012). [CrossRef]
  9. W. A. El-Said, T. H. Kim, H. C. Kim, J. W. Choi, “Analysis of intracellular state based on controlled 3D nanostructures mediated surface enhanced Raman scattering,” PLoS ONE 6(2), e15836 (2011). [CrossRef] [PubMed]
  10. M. M. Mariani, P. J. Day, V. Deckert, “Applications of modern micro-Raman spectroscopy for cell analyses,” Integr Biol (Camb) 2(2-3), 94–101 (2010). [CrossRef] [PubMed]
  11. J. Lin, R. Chen, S. Feng, Y. Li, Z. Huang, S. Xie, Y. Yu, M. Cheng, H. Zeng, “Rapid delivery of silver nanoparticles into living cells by electroporation for surface-enhanced Raman spectroscopy,” Biosens. Bioelectron. 25(2), 388–394 (2009). [CrossRef] [PubMed]
  12. L. Chen, X. X. Han, Z. Guo, X. Wang, W. Ruan, W. Song, B. Zhao, Y. Ozaki, “Biomagnetic glass beads for protein separation and detection based on surface-enhanced Raman scattering,” Anal. Methods 4(6), 1643–1647 (2012). [CrossRef]
  13. S. Feng, R. Chen, J. Lin, J. Pan, Y. Wu, Y. Li, J. Chen, H. Zeng, “Gastric cancer detection based on blood plasma surface-enhanced Raman spectroscopy excited by polarized laser light,” Biosens. Bioelectron. 26(7), 3167–3174 (2011). [CrossRef] [PubMed]
  14. J. Lin, R. Chen, S. Feng, J. Pan, Y. Li, G. Chen, M. Cheng, Z. Huang, Y. Yu, H. Zeng, “A novel blood plasma analysis technique combining membrane electrophoresis with silver nanoparticle-based SERS spectroscopy for potential applications in noninvasive cancer detection,” Nanomedicine 7(5), 655–663 (2011). [CrossRef] [PubMed]
  15. I. Notingher, J. Selvakumaran, L. L. Hench, “New detection system for toxic agents based on continuous spectroscopic monitoring of living cells,” Biosens. Bioelectron. 20(4), 780–789 (2004). [CrossRef] [PubMed]
  16. A. D. Ghanate, S. Kothiwale, S. P. Singh, D. Bertrand, C. M. Krishna, “Comparative evaluation of spectroscopic models using different multivariate statistical tools in a multicancer scenario,” J. Biomed. Opt. 16(2), 025003 (2011). [CrossRef] [PubMed]
  17. A. J. Makowski, C. A. Patil, A. Mahadevan-Jansen, J. S. Nyman, “Polarization control of Raman spectroscopy optimizes the assessment of bone tissue,” J. Biomed. Opt. 18(5), 055005 (2013). [CrossRef] [PubMed]
  18. J. W. Kang, N. Lue, C. R. Kong, I. Barman, N. C. Dingari, S. J. Goldfless, J. C. Niles, R. R. Dasari, M. S. Feld, “Combined confocal Raman and quantitative phase microscopy system for biomedical diagnosis,” Biomed. Opt. Express 2(9), 2484–2492 (2011). [CrossRef] [PubMed]
  19. I. Barman, N. C. Dingari, A. Saha, S. McGee, L. H. Galindo, W. Liu, D. Plecha, N. Klein, R. R. Dasari, M. Fitzmaurice, “Application of Raman spectroscopy to identify microcalcifications and underlying breast lesions at stereotactic core needle biopsy,” Cancer Res. 73(11), 3206–3215 (2013). [CrossRef] [PubMed]
  20. M. S. Bergholt, W. Zheng, K. Y. Ho, M. Teh, K. G. Yeoh, J. B. Y. So, A. Shabbir, Z. Huang, “Fiber-optic Raman spectroscopy probes gastric carcinogenesis in vivo at endoscopy,” J Biophotonics 6(1), 49–59 (2013). [CrossRef] [PubMed]
  21. A. D. Meade, C. Clarke, F. Draux, G. D. Sockalingum, M. Manfait, F. M. Lyng, H. J. Byrne, “Studies of chemical fixation effects in human cell lines using Raman microspectroscopy,” Anal. Bioanal. Chem. 396(5), 1781–1791 (2010). [CrossRef] [PubMed]
  22. J. Lin, Y. Yu, B. Li, H. Huang, S. Lin, C. Li, Y. Su, S. Feng, G. Chen, Y. Li, Z. Huang, H. Zeng, R. Chen, “Electrical pulse – mediated enhanced delivery of silver nanoparticles into living suspension cells for surface enhanced Raman spectroscopy,” Laser Phys. Lett. 9(3), 240–246 (2012). [CrossRef]
  23. Y. Yu, J. Lin, Y. Wu, S. Feng, Y. Li, Z. Huang, R. Chen, H. Zeng, “Optimizing electroporation assisted silver nanoparticle delivery into living C666 cells for surface-enhanced Raman spectroscopy,” Spectroscopy 25(1), 13–21 (2011). [CrossRef]
  24. H. N. Yehia, R. K. Draper, C. Mikoryak, E. K. Walker, P. Bajaj, I. H. Musselman, M. C. Daigrepont, G. R. Dieckmann, P. Pantano, “Single-walled carbon nanotube interactions with HeLa cells,” J. Nanobiotechnology 5(1), 8 (2007). [CrossRef] [PubMed]
  25. T. J. Moritz, D. S. Taylor, D. M. Krol, J. Fritch, J. W. Chan, “Detection of doxorubicin-induced apoptosis of leukemic T-lymphocytes by laser tweezers Raman spectroscopy,” Biomed. Opt. Express 1(4), 1138–1147 (2010). [CrossRef] [PubMed]
  26. H. Huang, H. Shi, S. Feng, W. Chen, Y. Yu, D. Lin, R. Chen, “Confocal Raman spectroscopic analysis of the cytotoxic response to cisplatin in nasopharyngeal carcinoma cells,” Anal. Methods 5(1), 260–266 (2012). [CrossRef]
  27. P. Candeloro Luca Tirinato, N. Malara, A. Fregola, E. Casals, V. Puntes, G. Perozziello, F. Gentile, M. L. Coluccio, G. Das, C. Liberale, F. De Angelisand, E. Di Fabrizio, “Nanoparticle microinjection and Raman spectroscopy as tools for nanotoxicology studies,” Analyst (Lond.) 136(21), 4402–4408 (2011).
  28. Q. Matthews, A. Jirasek, J. Lum, X. Duan, A. G. Brolo, “Variability in Raman spectra of single human tumor cells cultured in vitro: correlation with cell cycle and culture confluency,” Appl. Spectrosc. 64(8), 871–887 (2010). [CrossRef] [PubMed]
  29. J. W. Chan, D. S. Taylor, T. Zwerdling, S. M. Lane, K. Ihara, T. Huser, “Micro-Raman spectroscopy detects individual neoplastic and normal hematopoietic cells,” Biophys. J. 90(2), 648–656 (2006). [CrossRef] [PubMed]
  30. J. De Gelder, K. De Gussem, P. Vandenabeele, L. Moens, “Reference database of Raman spectra of biological molecules,” J. Raman Spectrosc. 38(9), 1133–1147 (2007). [CrossRef]
  31. C. A. Owen, J. Selvakumaran, I. Notingher, G. Jell, L. L. Hench, M. M. Stevens, “In vitro toxicology evaluation of pharmaceuticals using Raman micro-spectroscopy,” J. Cell. Biochem. 99(1), 178–186 (2006). [CrossRef] [PubMed]
  32. I. Notingher, C. Green, C. Dyer, E. Perkins, N. Hopkins, C. Lindsay, L. L. Hench, “Discrimination between ricin and sulphur mustard toxicity in vitro using Raman spectroscopy,” J. R. Soc. Interface 1(1), 79–90 (2004). [CrossRef] [PubMed]
  33. J. Weyermann, D. Lochmann, A. Zimmer, “A practical note on the use of cytotoxicity assays,” Int. J. Pharm. 288(2), 369–376 (2005). [CrossRef] [PubMed]
  34. G. Fotakis, J. A. Timbrell, “In vitro cytotoxicity assays: comparison of LDH, neutral red, MTT and protein assay in hepatoma cell lines following exposure to cadmium chloride,” Toxicol. Lett. 160(2), 171–177 (2006). [CrossRef] [PubMed]
  35. S. K. Bhatia, A. B. Yetter, “Correlation of visual in vitro cytotoxicity ratings of biomaterials with quantitative in vitro cell viability measurements,” Cell Biol. Toxicol. 24(4), 315–319 (2008). [CrossRef] [PubMed]

Cited By

Alert me when this paper is cited

OSA is able to provide readers links to articles that cite this paper by participating in CrossRef's Cited-By Linking service. CrossRef includes content from more than 3000 publishers and societies. In addition to listing OSA journal articles that cite this paper, citing articles from other participating publishers will also be listed.

« Previous Article  |  Next Article »

OSA is a member of CrossRef.

CrossCheck Deposited