Skip to main content
Log in

Tag-femtosecond laser-induced breakdown spectroscopy for the sensitive detection of cancer antigen 125 in blood plasma

  • Research Paper
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

Successful treatment of cancers requires detecting early signs of the disease. One promising way to approach this is to develop minimally invasive tests for the sensitive and specific detection of biomarkers in blood. Irrespective of the detection approach one uses, this remains a challenging task because biomarkers are typically present in low concentrations and there are signals that interfere strongly with prevailing compounds of human fluids. In this paper, we show that elemental encoded particle assay coupled with femtosecond laser-induced breakdown spectroscopy for simultaneous multi-elemental analysis can significantly improve biomarker detectability. An estimated near single molecule per particle efficiency of this method leads to sensitive detection of ovarian cancer biomarker CA125 in human blood plasma. This work opens new ways for earlier detection of cancers and for multiplex assay developments in various analytical applications from proteomics, genomics, and neurology fields.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics. CA Cancer J Clin 60:277–300

    Article  Google Scholar 

  2. American Cancer Society (2012). Cancer facts & figures 2012. American Cancer Society, Atlanta

  3. Sturgeon CM, Duffy MJ, Stenman UH, Lilja H, Brünner N, Chan DW, Babaian R, Bast RC Jr, Dowell B, Esteva FJ, Haglund C, Harbeck N, Hayes DF, Holten-Andersen M, Klee GG, Lamerz R, Looijenga LH, Molina R, Nielsen HJ, Rittenhouse H, Semjonow A, Shih IM, Sibley P, Sölétormos G, Stephan C, Sokoll L, Hoffman BR, Diamandis EP (2008) National academy of clinical biochemistry laboratory medicine practice guidelines for use of tumor markers in testicular prostate, colorectal breast ovarian cancers. Clin Chem 55:e11–e79

    Article  Google Scholar 

  4. McGuire V, Whittemore AS, Norris R, Oakley-Girvan I (2000) Survival in epithelial ovarian cancer patients with prior breast cancer. Am J Epidemiol 152:528–532

    Article  CAS  Google Scholar 

  5. Lutz AM, Willmann JK, Drescher CW, Ray P, Cochran FV, Urban N et al (2011) Continuing medical education: early diagnosis of ovarian carcinoma: is a solution in sight? Radiology 259:329–345

    Article  Google Scholar 

  6. Yurkovetsky Z, Skates S, Lomakin A, Nolen B, Pulsipher T, Modugno F, Marks J, Godwin A, Gorelik E, Jacobs I, Menon U, Lu K, Badgwell D, Bast RC Jr, Lokshin AE (2010) Development of a multimarker assay for early detection of ovarian cancer. J Clin Oncol 28:2159–2166

    Article  Google Scholar 

  7. Davies C (2013) Principles of competitive and immunometric assays (including ELISA). In: Wild D, Kodak E, Squibb BM (eds) The immunoassay handbook: theory and applications of ligand binding, ELISA and related techniques, 4th edn. Elsevier, Oxford

    Google Scholar 

  8. Smith AM, Dave S, Nie S, True L, Gao X (2006) Multicolor quantum dots for molecular diagnostics of cancer. Expert Rev Mol Diagn 6:231–244

    Article  CAS  Google Scholar 

  9. Freeman RG, Raju PA, Norton SM, Walton ID, Smith PC, He L, Natan MJ, Sha MY, Penn SG (2005) Use of nanobarcodes particles in bioassays. In: Rosenthal SJ, Wright DW (eds) Methods in molecular biology. Humana Press Inc, Totowa

    Google Scholar 

  10. Fulton RJ, McDade RL, Smith PL, Kienker LJ, Kettman JR (1997) Advanced multiplexed analysis with the FlowMetrix system. Clin Chem 43:1749–1756

    CAS  Google Scholar 

  11. Ahrends R, Pieper S, Kühn A, Weisshoff H, Hamester M, Lindemann T, Scheler C, Lehmann K, Taubner K, Linscheid MW (2007) A metal-coded affinity tag approach to quantitative proteomics. Mol Cell Proteomics 6:1907–1916

    Article  CAS  Google Scholar 

  12. Koivunen ME, Krogsrud RL (2006) Principles of immunochemical techniques used in clinical laboratories. Lab Med 37:490–497

    Article  Google Scholar 

  13. Markushin Y, Melikechi N (2012) Sensitive detection of epithelial ovarian cancer biomarkers using tag-laser induced breakdown spectroscopy. In: Farghaly SA (ed) Ovarian cancer—basic science perspective. InTech, Croatia

    Google Scholar 

  14. Markushin Y, Melikechi N, Marcano A, Rock S, Henderson E, Connolly D (2009) LIBS-based multi-element coded assay for ovarian cancer application. Proc SPIE 7190:719015

    Article  Google Scholar 

  15. Boumans PWJM (1987) Inductively coupled plasma emission spectroscopy. Part II: applications and fundamentals. Volume 2. Wiley, New York

    Google Scholar 

  16. Miziolek AW, Palleschi V, Schechter I (2006) Laser-induced breakdown spectroscopy: fundamentals and applications. Cambridge University Press, Cambridge

    Book  Google Scholar 

  17. Gurevich EL, Hergenroeder R (2007) Femtosecond laser-induced breakdown spectroscopy: physics, applications, and perspectives. Appl Spectrosc 61:233A–242A

    Article  CAS  Google Scholar 

  18. Eland KL, Stratis DN, Gold DM, Goode SR, Angel SM (2001) Energy dependence of emission intensity and temperature in a LIBS plasma using femtosecond excitation. Appl Spectrosc 55:286–291

    Article  CAS  Google Scholar 

  19. Baudelet M, Guyon L, Yu J, Wolf JP, Amodeo T, Fréjafon E, Laloi P (2006) Femtosecond time-resolved laser-induced breakdown spectroscopy for detection and identification of bacteria: a comparison to the nanosecond regime. J Appl Phys 99:084701

    Article  Google Scholar 

  20. Gunaratne T, Kangas M, Singh S, Gross A, Dantus M (2006) Influence of bandwidth and phase shaping on laser induced breakdown spectroscopy with ultrashort laser pulses. Chem Phys Lett 423:197–201

    Article  CAS  Google Scholar 

  21. Rohwetter P, Stelmaszczyk K, Wöste L, Ackermann R, Méjean G, Salmon E et al (2005) Filament-induced remote surface ablation for long range laser-induced breakdown spectroscopy operation. Spectrochim Acta Part B Atom Spectrosc 60:1025–1033

    Article  Google Scholar 

  22. Niloff JM, Bast RC, Schaetzl EM, Knapp RC (1985) Predictive value of CA 125 antigen levels in second-look procedures for ovarian cancer. Am J Obstet Gynecol 151:981–986

    Article  CAS  Google Scholar 

  23. Thomas CM, Massuger LF, Segers MF, Schijf CP, Doesburg WH, Wobbes T (1995) Analytical and clinical performance of improved Abbott IMx CA 125 assay: comparison with Abbott CA 125 RIA. Clin Chem 41:221–216

    Google Scholar 

  24. Yin BWT, Lloyd KO (2001) Molecular cloning of the CA125 ovarian cancer antigen. J Biol Chem 276:27371–27375

    Article  CAS  Google Scholar 

  25. Drapkin R, Clauss A, Skates S (2008) Urokinase-type plasminogen activator receptor: a beacon of malignancy? Clin Cancer Res 14:5643–5645

    Article  CAS  Google Scholar 

  26. Sivakumar P, Taleh L, Markushin Y, Melikechi N, Lasue J (2013) An experimental observation of the different behavior of ionic and neutral lines of iron as a function of number density in a binary carbon–iron mixture. Spectrochim Acta Part B 82:76–82

    Article  CAS  Google Scholar 

  27. Wisbrun R, Schechter I, Niessner R, Schröeder H, Kompa KL (1994) Detector for trace elemental analysis of solid environmental samples by laser plasma spectroscopy. Anal Chem 66:2964–2975

    Article  CAS  Google Scholar 

  28. Saarelainen SK, Peltonen N, Lehtimaki T, Perheentupa A, Vuento MH, Maenpaa JU (2013) Predictive value of serum HE4 and CA125 concentrations in endometrial carcinoma. Am J Obstet Gynecol 209:142e1–142e6

    Article  Google Scholar 

  29. Bulatov V, Schechter I (2006) Plasma morphology. In: Vincenzo P, Israel S, Andrzej WM (eds) Laser-induced breakdown spectroscopy fundamental application. Cambridge University Press, Cambridge

    Google Scholar 

  30. Cremers DA, Radziemski LJ (2006) History and fundamentals of LIBS. In: Vincenzo P, Israel S, Andrzej WM (eds) Laser-induced breakdown spectroscopy fundamental application. Cambridge University Press, Cambridge

    Chapter  Google Scholar 

  31. Wiklund M, Nord O, Gothall R, Chernyshev AV, Nygren PA, Hertz HM (2005) Fluorescence-microscopy-based image analysis for analyte-dependent particle doublet detection in a single-step immunoagglutination assay. Anal Biochem 338:90–101

    Article  CAS  Google Scholar 

  32. Chunara R, Godin M, Knudsen SM, Manalisa SR (2007) Mass-based readout for agglutination assays. Appl Phys Lett 91:193902

    Article  Google Scholar 

  33. Butch AW (2000) Dilution protocols for detection of hook effects/prozone phenomenon. Clin Chem 46:1719–1721

    CAS  Google Scholar 

  34. Schelp C, Pauly HE (2001) Detection methods. US20100311185 A1

  35. Gubbels JAA, Belisle J, Onda M, Rancourt C, Migneault M, Ho M et al (2006) Mesothelin-MUC16 binding is a high affinity, N-glycan dependent interaction that facilitates peritoneal metastasis of ovarian tumors. Mol Cancer 5:50

    Article  Google Scholar 

  36. UniProtKB/Swiss-Prot protein data base (2014) http://www.uniprot.org/uniprot/Q8WXI7. Accessed 5 Sept 2014

  37. Lutz AM, Willmann JK, Cochran FV, Ray P, Gambhir SS (2008) Cancer screening: a mathematical model relating secreted blood biomarker levels to tumor sizes. PLoS Med 5:e170

    Article  Google Scholar 

  38. Mongia SK, Rawlins ML, Owen WE, Roberts WL (2006) Performance characteristics of seven automated CA 125 assays. Am J Clin Pathol 125:921–927

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This research was supported by grants from the National Science Foundation Centers of Research Excellence in Science and Technology (0630388) and National Aeronautics and Space Administration (NX09AU90A). We thank the Blood Bank of Delmarva for providing human blood plasma for the research.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Noureddine Melikechi.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Markushin, Y., Sivakumar, P., Connolly, D. et al. Tag-femtosecond laser-induced breakdown spectroscopy for the sensitive detection of cancer antigen 125 in blood plasma. Anal Bioanal Chem 407, 1849–1855 (2015). https://doi.org/10.1007/s00216-014-8433-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-014-8433-0

Keywords

Navigation