Applied Physics B

, Volume 111, Issue 3, pp 359–365 | Cite as

Quantum cascade laser-based sensor for detection of exhaled and biogenic nitric oxide

  • D. Marchenko
  • J. Mandon
  • S. M. Cristescu
  • P. J. F. M. Merkus
  • F. J. M. Harren


A sensor based on a continuous wave quantum cascade laser, operating near 5.2 μm, in combination with integrated cavity output spectroscopy has been developed for simultaneous measurement of nitric oxide (NO) and carbon dioxide (CO2) traces in exhaled air. A detection limit of 0.7 parts-per-billion by volume of NO (acquisition time: 1 s) is achieved. Comparison is made with the standard chemiluminescence NO analyzer and commercial CO2 breath sampler. The QCL-based sensor is tested on healthy subjects at various exhalation flow rates (15, 50, 100 and 300 ml/s) for both online and offline sampling procedures as well as on asthmatic children (offline sampling). Possibilities for measurements of biogenic NO in vivo, i.e., NO coming from human skin tissue, are also demonstrated.


Nitric Oxide Asthmatic Child Skin Tissue Quantum Cascade Laser Integrate Cavity Output Spectroscopy 
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.



This work was supported by the GO-EFRO Ultragas, project no. 2009-010034 of province of Gelderland (The Netherlands) and EU, EU-Marie Curie fellowships EU-people-2010-IEF, project no. 275584, QCLaser Nose, the Asthma Fund grant AF 2011, project no., and IOP-Photonics, project no. IPD100025.


  1. 1.
    L.E. Gustafsson, Eur. Respir. J. 11, 49s (1998)Google Scholar
  2. 2.
    A.P. Pietropaoli, I.B. Perillo, A. Torres, P.T. Perkins, L.M. Frasier, M.J. Utell, M.W. Frampton, R.W. Hyde, J. Appl. Physiol. 87(4), 1532 (1999)Google Scholar
  3. 3.
    M. Hogman, N. Drca, C. Ehrstedt, P. Merilainen, Respir. Med. 94(10), 985 (2000)CrossRefGoogle Scholar
  4. 4.
    A. Sandrini, D.R. Taylor, P.S. Thomas, D.H. Yates, Respirology 15(1), 57 (2010)CrossRefGoogle Scholar
  5. 5.
    P.E. Silkoff, P.A. McClean, A.S. Slutsky, H.G. Furlott, E. Hoffstein, S. Wakita, K.R. Chapman, J.P. Szalai, N. Zamel, Am. J. Respir. Crit. Care Med. 155(1), 260 (1997)CrossRefGoogle Scholar
  6. 6.
    J.H. Shorter, D.D. Nelson, J.B. McManus, M.S. Zahniser, S.R. Sama, D.K. Milton, J. Breath Res. 5(3) (2011)Google Scholar
  7. 7.
    Z. Borrill, D. Clough, N. Truman, J. Morris, S. Langley, D. Singh, Respir. Med. 100(8), 1392 (2006)CrossRefGoogle Scholar
  8. 8.
    K. Namjou, C.B. Roller, T.E. Reich, J.D. Jeffers, G.L. McMillen, P.J. McCann, M.A. Camp, Appl. Phys. B: Lasers Opt. 85(2–3), 427 (2006)ADSCrossRefGoogle Scholar
  9. 9.
    T.H. Risby, F.K. Tittel, Opt Eng 49(11) (2010)Google Scholar
  10. 10.
    F.K. Tittel, D. Richter, A. Fried, Solid-State Mid-Infrared Laser Sources 89, 445 (2003)CrossRefGoogle Scholar
  11. 11.
    R.F. Curl, F. Capasso, C. Gmachl, A.A. Kosterev, B. McManus, R. Lewicki, M. Pusharsky, G. Wysocki, F.K. Tittel, Chem. Phys. Lett. 487(1–3), 1 (2010)ADSCrossRefGoogle Scholar
  12. 12.
    S.M. Cristescu, S.T. Persijn, S.T.L. Hekkert, F.J.M. Harren, Appl. Phys. B: Lasers Opt. 92(3), 343 (2008)ADSCrossRefGoogle Scholar
  13. 13.
    L. Menzel, A.A. Kosterev, R.F. Curl, F.K. Tittel, C. Gmachl, F. Capasso, D.L. Sivco, J.N. Baillargeon, A.L. Hutchinson, A.Y. Cho, W. Urban, Appl. Phys. B: Lasers Opt. 72(7), 859 (2001)ADSCrossRefGoogle Scholar
  14. 14.
    J.B. McManus, J.H. Shorter, D.D. Nelson, M.S. Zahniser, D.E. Glenn, R.M. Mcgovern, Appl. Phys. B: Lasers Opt. 92(3), 387 (2008)ADSCrossRefGoogle Scholar
  15. 15.
    H. Ganser, W. Urban, A.M. Brown, Mol. Phys. 101(4–5), 545 (2003)ADSCrossRefGoogle Scholar
  16. 16.
    R. Lewicki, J.H. Doty, R.F. Curl, F.K. Tittel, G. Wysocki, Proc. Natl. Acad. Sci. USA. 106(31), 12587 (2009)ADSCrossRefGoogle Scholar
  17. 17.
    V. Spagnolo, A.A. Kosterev, L. Dong, R. Lewicki, F.K. Tittel, Appl. Phys. B: Lasers Opt. 100(1), 125 (2010)ADSCrossRefGoogle Scholar
  18. 18.
    L. Dong, V. Spagnolo, R. Lewicki, F.K. Tittel, Opt. Express 19(24), 24037 (2011)ADSCrossRefGoogle Scholar
  19. 19.
    D.S. Baer, J.B. Paul, J.B. Gupta, A. O’Keefe, Appl. Phys. B: Lasers Opt. 75(2–3), 261 (2002)ADSCrossRefGoogle Scholar
  20. 20.
    M.L. Silva, D.M. Sonnenfroh, D.I. Rosen, M.G. Allen, A. O’Keefe, Appl. Phys. B: Lasers Opt. 81(5), 705 (2005)ADSCrossRefGoogle Scholar
  21. 21.
    M.R. McCurdy, Y. Bakhirkin, G. Wysocki, F.K. Tittel, J. Biomed. Opt. 12(3) (2007)Google Scholar
  22. 22.
    B.A. Paldus, C.C. Harb, T.G. Spence, R.N. Zare, C. Gmachl, F. Capasso, D.L. Sivco, J.N. Baillargeon, A.L. Hutchinson, A.Y. Cho, Opt. Lett. 25(9), 666 (2000)ADSCrossRefGoogle Scholar
  23. 23.
    A.A. Kosterev, A.L. Malinovsky, F.K. Tittel, C. Gmachl, F. Capasso, D.L. Sivco, J.N. Baillargeon, A.L. Hutchinson, A.Y. Cho, Appl. Opt. 40(30), 5522 (2001)ADSCrossRefGoogle Scholar
  24. 24.
    L.S. Rothman, I.E. Gordon, A. Barbe, D.C. Benner, P.E. Bernath, M. Birk, V. Boudon, L.R. Brown, A. Campargue, J.P. Champion, K. Chance, L.H. Coudert, V. Dana, V.M. Devi, S. Fally, J.M. Flaud, R.R. Gamache, A. Goldman, D. Jacquemart, I. Kleiner, N. Lacome, W.J. Lafferty, J.Y. Mandin, S.T. Massie, S.N. Mikhailenko, C.E. Miller, N. Moazzen-Ahmadi, O.V. Naumenko, A.V. Nikitin, J. Orphal, V.I. Perevalov, A. Perrin, A. Predoi-Cross, C.P. Rinsland, M. Rotger, M. Simeckova, M.A.H. Smith, K. Sung, S.A. Tashkun, J. Tennyson, R.A. Toth, A.C. Vandaele, J. Vander Auwera, J. Quant. Spectrosc. Radiat. Transfer 110(9–10), 533 (2009)ADSCrossRefGoogle Scholar
  25. 25.
    E. Eissfeller, W.K.R. Barnikol, Funkt Biol Med 2(1), 64 (1983)Google Scholar
  26. 26.
    A.H. Kars, J.M. Bogaard, T. Stijnen, J. de Vries, A.F.M. Verbraak, C. Hilvering, Eur. Respir. J. 10(8), 1829 (1997)CrossRefGoogle Scholar
  27. 27.
    J.T. Rose, M.J. Banner, Crit. Care Med. 28(12), A85 (2000)Google Scholar
  28. 28.
    American Thoracic Society, European Respiratory Society, Am. J. Respir. Crit. Care. Med. 171(8), 912 (2005)Google Scholar
  29. 29.
    P.H. Fischer, P.A. Steerenberg, J.D. Snelder, H. van Loveren, J.G.C. van Amsterdam, Int. Arch. Occup. Environ. Health 75(5), 348 (2002)CrossRefGoogle Scholar
  30. 30.
    J. Mandon, M. Hogman, J.F.M. Merkus, J. van Amsterdam, F.J.M. Harren, S.M. Cristescu, J. Biomed. Opt. 17(1) (2012)Google Scholar
  31. 31.
    R. Weller, S. Pattullo, L. Smith, M. Golden, A. Ormerod, N. Benjamin, J. Investig. Dermatol. 107(3), 327 (1996)CrossRefGoogle Scholar
  32. 32.
    D. Bruch-Gerharz, T. Ruzicka, V. Kolb-Bachofen, J. Investig. Dermatol. 110(1), 1 (1998)CrossRefGoogle Scholar
  33. 33.
    M.M. Cals-Grierson, A.D. Ormerod, Nitric Oxide-Biol Ch 10(4), 179 (2004)CrossRefGoogle Scholar
  34. 34.
    G.F. Clough, A.R. Bennett, M.K. Church, J. Vasc. Res. 35(5), 378 (1998)Google Scholar
  35. 35.
    H. Ganser, M. Horstjann, C.V. Suschek, P. Hering, M. Murtz, Appl. Phys. B: Lasers Opt. 78(3–4), 513 (2004)ADSCrossRefGoogle Scholar
  36. 36.
    J.M. Bland, D.G. Altman, Int. J. Nurs. Stud. 47(8), 931 (2010)CrossRefGoogle Scholar
  37. 37.
    R.W. Schafer, IEEE Signal Proc Mag 28(4), 111 (2011)ADSCrossRefGoogle Scholar
  38. 38.
    S.C. George, M. Hogman, S. Permutt, P.E. Silkoff, J. Appl. Physiol. 96(3), 831 (2004)CrossRefGoogle Scholar
  39. 39.
    N.M. Tsoukias, S.C. George, J. Appl. Physiol. 85(2), 653 (1998)Google Scholar
  40. 40.
    M.R. McCurdy, A. Sharafkhaneh, H. Abdel-Monem, J. Rojo, F.K. Tittel, J. Breath Res. 5(1) (2011)Google Scholar
  41. 41.
    H.A. Bull, J. Hothersall, N. Chowdhury, J. Cohen, P.M. Dowd, J. Investig. Dermatol. 106(4), 655 (1996)CrossRefGoogle Scholar
  42. 42.
    M. Sakai, Y. Shimizu, I. Nagatsu, H. Ueda, Arch. Dermatol. Res. 288(10), 625 (1996)CrossRefGoogle Scholar
  43. 43.
    G. Deliconstantinos, V. Villiotou, J.C. Stravrides, Br. J. Pharmacol. 114(6), 1257 (1995)CrossRefGoogle Scholar
  44. 44.
    P.C. Goldsmith, T.A. Leslie, N.A. Hayes, N.J. Levell, P.M. Dowd, J.C. Foreman, J. Investig. Dermatol. 106(1), 113 (1996)CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • D. Marchenko
    • 1
  • J. Mandon
    • 1
  • S. M. Cristescu
    • 1
  • P. J. F. M. Merkus
    • 2
  • F. J. M. Harren
    • 1
  1. 1.Life Science Trace Gas Facility, Molecular and Laser PhysicsInstitute for Molecules and Materials, Radboud UniversityNijmegenThe Netherlands
  2. 2.Department of Pediatric PulmonologyRadboud University Nijmegen Medical CentreNijmegenThe Netherlands

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