Experiments in Fluids

, Volume 53, Issue 3, pp 777–782 | Cite as

Imaging diffusion in a microfluidic device by third harmonic microscopy

  • Uwe PetzoldEmail author
  • Andreas Büchel
  • Steffen Hardt
  • Thomas Halfmann
Research Article


We monitor and characterize near-surface diffusion of miscible, transparent liquids in a microfluidic device by third harmonic microscopy. The technique enables observations even of transparent or index-matched media without perturbation of the sample. In particular, we image concentrations of ethanol diffusing in water and estimate the diffusion coefficient from the third harmonic images. We obtain a diffusion coefficient D = (460 ± 30) μm2/s, which is consistent with theoretical predictions. The investigations clearly demonstrate the potential of harmonic microscopy also under the challenging conditions of transparent fluids.


Microfluidic Device Second Harmonic Generation Laser Focus Third Harmonic Generation Tunable Laser Source 
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.


  1. Abou-Hassan A, Sandre O, Cabuil V (2010) Microfluidics in inorganic chemistry. Angew Chem Int Ed 49:6268–6286. doi: 10.1002/anie.200904285 CrossRefGoogle Scholar
  2. Antes J, Boskovic D, Krause H et al (2003) Analysis and improvement of strong exothermic nitrations in microreactors. Chem Eng Res Des 81:760–765. doi: 10.1205/026387603322302931 CrossRefGoogle Scholar
  3. Aptel F, Olivier N, Deniset-Besseau A et al (2010) Multimodal nonlinear imaging of the human cornea. Invest Ophthalmol Vis Sci 51:2459–2465. doi: 10.1167/iovs.09-4586 CrossRefGoogle Scholar
  4. Barad Y, Eisenberg H, Horowitz M, Silberberg Y (1997) Nonlinear scanning laser microscopy by third harmonic generation. Appl Phys Lett 70:922–924CrossRefGoogle Scholar
  5. Boyd R (2008) Nonlinear optics, 3rd edn. Academic Press, AmsterdamGoogle Scholar
  6. Carriles R, Schafer D, Sheetz K et al (2009) Invited review article: imaging techniques for harmonic and multiphoton absorption fluorescence microscopy. Rev Sci Instrum 80:081101. doi: 10.1063/1.3184828 CrossRefGoogle Scholar
  7. Chan KLA, Gulati S, Edel JB et al (2009) Chemical imaging of microfluidic flows using ATR-FTIR spectroscopy. Lab Chip 9:2909–2913. doi: 10.1039/b909573j CrossRefGoogle Scholar
  8. Cheng J-X, Xie XS (2004) Coherent Anti-Stokes Raman scattering microscopy: instrumentation, theory, and applications. J Phys Chem B 108:827–840CrossRefGoogle Scholar
  9. Cleland AN (2003) Foundation of nanomechanics. Springer, HeidelbergGoogle Scholar
  10. Dittrich PS, Manz A (2006) Lab-on-a-chip: microfluidics in drug discovery. Nat Rev Drug Discov 5:210–218. doi: 10.1038/nrd1985 CrossRefGoogle Scholar
  11. Duncan MD, Reintjes J, Manuccia TJ (1982) Scanning coherent anti-Stokes Raman microscope. Opt Lett 7:350–352CrossRefGoogle Scholar
  12. Hellwarth R, Christensen P (1975) Nonlinear optical microscope using second harmonic generation. Appl Opt 14:247–248CrossRefGoogle Scholar
  13. Hessel V, Löwe H, Schönfeld F (2005) Micromixers: a review on passive and active mixing principles. Chem Eng Sci 60:2479–2501. doi: 10.1016/j.ces.2004.11.033 CrossRefGoogle Scholar
  14. Hessel V, Renken A, Schonten JC, Yoshida J-I (2008) Micro process engineering. Wiley-VCH, WeinheimGoogle Scholar
  15. Hinsmann P, Frank J, Svasek P et al (2001) Design, simulation and application of a new micro mixing device for time resolved infrared spectroscopy of chemical reactions in solution. Lab Chip 1:16–21. doi: 10.1039/b104391a CrossRefGoogle Scholar
  16. Hoffmann M, Schluter M, Rabiger N (2006) Experimental investigation of liquid–liquid mixing in T-shaped micro-mixers using μμ-LIF and μμ-PIV. Chem Eng Sci 61:2968–2976. doi: 10.1016/j.ces.2005.11.029 CrossRefGoogle Scholar
  17. Kang L, Chung BG, Langer R, Khademhosseini A (2008) Microfluidics for drug discovery and development: from target selection to product lifecycle management. Drug Discov Today 13:1–13. doi: 10.1016/j.drudis.2007.10.003 CrossRefGoogle Scholar
  18. Kihm KD (2011) Near-field characterization of micro/nano-scaled fluid flows. Annu Rev Fluid. doi: 10.1017/S0022112064210970 Google Scholar
  19. Neethirajan S, Kobayashi I, Nakajima M et al (2011) Microfluidics for food, agriculture and biosystems industries. Lab Chip 11:1574–1586. doi: 10.1039/c0lc00230e CrossRefGoogle Scholar
  20. Nguyen N-T, Wu Z (2005) Micromixers: a review. J Micromech Microeng 15:R1–R16. doi: 10.1088/0960-1317/15/2/R01 CrossRefGoogle Scholar
  21. Ohno K-I, Tachikawa K, Manz A (2008) Microfluidics: applications for analytical purposes in chemistry and biochemistry. Electrophoresis 29:4443–4453. doi: 10.1002/elps CrossRefGoogle Scholar
  22. Petzold U, Büchel A, Halfmann T (2012) Effects of laser polarization and interface orientation in harmonic generation microscopy. Opt Express 20:967–971CrossRefGoogle Scholar
  23. Ray S, Mehta G, Srivastava S (2010) Label-free detection techniques for protein microarrays: prospects, merits and challenges. Proteomics 10:731–748. doi: 10.1002/pmic.200900458 CrossRefGoogle Scholar
  24. Rinke G, Ewinger A, Kerschbaum S, Rinke M (2010) In situ Raman spectroscopy to monitor the hydrolysis of acetal in microreactors. Microfluid Nanofluid 10:145–153. doi: 10.1007/s10404-010-0654-8 CrossRefGoogle Scholar
  25. Schafer D, Müller M, Bonn M et al (2009) Coherent anti-Stokes Raman scattering microscopy for quantitative characterization of mixing and flow in microfluidics. Opt Lett 34:211–213CrossRefGoogle Scholar
  26. Shcheslavskiy V, Petrov GI, Saltiel S, Yakovlev VV (2004) Quantitative characterization of aqueous solutions probed by the third-harmonic generation microscopy. J Sruct Biol 147:42–49. doi: 10.1016/j.jsb.2003.10.015 CrossRefGoogle Scholar
  27. Squier J, Müller M, Brakenhoff GJ, Wilson KR (1998) Third harmonic generation microscopy. Opt Express 3:315–324CrossRefGoogle Scholar
  28. Squires T, Quake S (2005) Microfluidics: fluid physics at the nanoliter scale. Rev Mod Phys 77:977–1026. doi: 10.1103/RevModPhys.77.977 CrossRefGoogle Scholar
  29. Strehle KR, Cialla D, Rösch P et al (2007) A reproducible surface-enhanced Raman spectroscopy approach. Online SERS measurements in a segmented microfluidic system. Anal Chem 79:1542–1547. doi: 10.1021/ac0615246 CrossRefGoogle Scholar
  30. Tyn MT, Calus WF (1975) Temperature and concentration dependence of mutual diffusion coefficients of some binary liquid systems. J Chem Eng Data 20:310–316. doi: 10.1021/je60066a009 CrossRefGoogle Scholar
  31. Tzeng Y–Y, Zhuo Z-Y, Lee M-Y et al (2011) Observation of spontaneous polarization misalignments in periodically poled crystals using second-harmonic generation microscopy. Opt Express 19:11106–11113CrossRefGoogle Scholar
  32. Wu Z, Nguyen N-T, Huang X (2004) Nonlinear diffusive mixing in microchannels: theory and experiments. J Micromech Microeng 14:604–611. doi: 10.1088/0960-1317/14/4/022 Google Scholar
  33. Zhang L, Wang Q, Liu Y-C, Zhang L-Z (2006) On the mutual diffusion properties of ethanol-water mixtures. J Chem Phys 125:104502. doi: 10.1063/1.2244547 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Uwe Petzold
    • 1
    Email author
  • Andreas Büchel
    • 1
  • Steffen Hardt
    • 2
  • Thomas Halfmann
    • 1
  1. 1.Institut für Angewandte PhysikTechnische Universität DarmstadtDarmstadtGermany
  2. 2.Center of Smart InterfacesTechnische Universität DarmstadtDarmstadtGermany

Personalised recommendations