Analytical and Bioanalytical Chemistry

, Volume 407, Issue 2, pp 387–396 | Cite as

An integrated microfluidic chip enabling control and spatially resolved monitoring of temperature in micro flow reactors

  • Christian Hoera
  • Stefan Ohla
  • Zhe Shu
  • Erik Beckert
  • Stefan Nagl
  • Detlev BelderEmail author
Research Paper


A strength of microfluidic chip laboratories is the rapid heat transfer that, in principle, enables a very homogeneous temperature distribution in chemical processes. In order to exploit this potential, we present an integrated chip system where the temperature is precisely controlled and monitored at the microfluidic channel level. This is realized by integration of a luminescent temperature sensor layer into the fluidic structure together with inkjet-printed micro heating elements. This allows steering of the temperature at the microchannel level and monitoring of the reaction progress simultaneously. A fabrication procedure is presented that allows for straightforward integration of thin polymer layers with optical sensing functionality in microchannels of glass–polydimethylsiloxane (PDMS) chips of only 150 μm width and 29 μm height. Sensor layers consisting of polyacrylonitrile and a temperature-sensitive ruthenium tris-phenanthroline probe with film thicknesses of about 0.5 to 6 μm were generated by combining blade coating and abrasion techniques. Optimal coating procedures were developed and evaluated. The chip-integrated sensor layers were calibrated and investigated with respect to stability, reproducibility, and response times. These microchips allowed observation of temperature in a wide range with a signal change of around 1.6 % per K and a maximum resolution of around 0.07 K. The device is employed to study temperature-controlled continuous micro flow reactions. This is demonstrated exemplarily for the tryptic cleavage of coumarin-modified peptides via fluorescence detection.

Graphical abstract

Left exploded view of the reactor chip; right schematic of the enzymatic conversion yielding the fluorescent product coumarin 120 and false-colored fluorescence micrographs (normalized to the highest intensity image) of the reactor near the outlet of the temperature and coumarin channel; background fluorescence micrograph of the integrated temperature sensor layer


Micro flow reactor Microscopic temperature control Luminescent temperature sensor Microheater Enzymatic reaction 



Surface profilometry measurements were performed at the Institut für Experimentelle Physik, Universität Leipzig. We thank Gabrielle Ramm for assistance. Financial support by the Bundesministerium für Bildung und Forschung (BMBF) for the joint research project “Komplexer Optofluidchip” (FKZ 03IPT609A) and Deutsche Forschungsgemeinschaft (DFG, NA947/1-2) is gratefully acknowledged.


  1. 1.
    Whitesides GM (2006) Nature 442:368–273CrossRefGoogle Scholar
  2. 2.
    Arora A, Simone G, Salieb-Beugelaar GB, Kim JT, Manz A (2010) Anal Chem 82:4830–4847CrossRefGoogle Scholar
  3. 3.
    Theberge AB, Courtois F, Schaerli Y, Fischlechner M, Abell C, Hollfelder F, Huck WTS (2010) Angew Chem 122:5982–6005CrossRefGoogle Scholar
  4. 4.
    Pompano RR, Liu W, Du W, Ismagilov RF (2011) Annu Rev Anal Chem 4:59–81CrossRefGoogle Scholar
  5. 5.
    Dittrich PS, Manz A (2006) Nat Rev Drug Disc 5:210–218CrossRefGoogle Scholar
  6. 6.
    Mark D, Haeberle S, Roth G, von Stetten F, Zengerle R (2010) Chem Soc Rev 39:1153–1182CrossRefGoogle Scholar
  7. 7.
    Hardt S, Hahn T (2012) Lab Chip 12:434–442CrossRefGoogle Scholar
  8. 8.
    Joensson HN, Svahn HA (2012) Angew Chem Int Ed 51:12176–12192CrossRefGoogle Scholar
  9. 9.
    de Mello AJ (2006) Nature 442:394–402CrossRefGoogle Scholar
  10. 10.
    Wegner J, Ceylan S, Kirschning A (2012) Adv Synth Catal 354:17–57CrossRefGoogle Scholar
  11. 11.
    Baxendale IR (2013) J Chem Technol Biotechnol 88:519–552CrossRefGoogle Scholar
  12. 12.
    Hartman RL, McMullen JP, Jensen KF (2011) Angew Chem Int Ed 50:7502–7519CrossRefGoogle Scholar
  13. 13.
    Oelgemöller M (2012) Chem Eng Technol 35:1144–1152CrossRefGoogle Scholar
  14. 14.
    Wiles C, Watts P (2011) Chem Commun 47:6512–6535CrossRefGoogle Scholar
  15. 15.
    Abou-Hassan A, Sandre O, Cabuil V (2010) Angew Chem Int Ed 49:6268–6286CrossRefGoogle Scholar
  16. 16.
    Popp A, Schneider JJ (2008) Angew Chem Int Ed 47:8958–8960CrossRefGoogle Scholar
  17. 17.
    Gutmann B, Roduit JP, Roberge D, Kappe CO (2010) Angew Chem Int Ed 49:7101–7105CrossRefGoogle Scholar
  18. 18.
    Moore JS, Jensen KF (2014) Angew Chem Int Ed 53:470–473CrossRefGoogle Scholar
  19. 19.
    März A, Henkel T, Cialla D, Schmitt M, Popp J (2011) Lab Chip 11:3584–3592CrossRefGoogle Scholar
  20. 20.
    Nagl S, Schulze P, Ohla S, Beyreiss R, Gitlin L, Belder D (2011) Anal Chem 83:3232–3238CrossRefGoogle Scholar
  21. 21.
    Küster SK, Fagerer SR, Verboket PE, Eyer K, Jefimovs K, Zenobi R, Dittrich PS (2013) Anal Chem 85:1285–1289CrossRefGoogle Scholar
  22. 22.
    Ehlert S, Tallarek U (2007) Anal Bioanal Chem 388:517–520CrossRefGoogle Scholar
  23. 23.
    Kutter JP (2012) J Chromatogr A 1221:72–82CrossRefGoogle Scholar
  24. 24.
    Yue J, Schouten JC, Nijhuis TA (2012) Ind Eng Chem Res 51:14583–14609CrossRefGoogle Scholar
  25. 25.
    Jáč P, Scriba GKE (2013) J Sep Sci 36:52–74CrossRefGoogle Scholar
  26. 26.
    Ohla S, Belder D (2012) Curr Opin Chem Biol 16:453–459CrossRefGoogle Scholar
  27. 27.
    Dittrich PS, Jahnz M, Schwille P (2005) ChemBioChem 6:811–814CrossRefGoogle Scholar
  28. 28.
    Belder D (2009) Angew Chem Int Ed 48:3736–3737CrossRefGoogle Scholar
  29. 29.
    Trapp O, Weber SK, Bauch S, Hofstadt W (2007) Angew Chem Int Ed 46:7307–7310CrossRefGoogle Scholar
  30. 30.
    Janasek D, Franzke J, Manz A (2006) Nature 442:374CrossRefGoogle Scholar
  31. 31.
    Hessel V (2009) Chem Eng Technol 32:1655–1681CrossRefGoogle Scholar
  32. 32.
    Grumann M, Geipel A, Riegger L, Zengerle R, Ducrée J (2005) Lab Chip 5:560–565CrossRefGoogle Scholar
  33. 33.
    Brivio M, Verboom W, Reinhoudt DN (2006) Lab Chip 6:329–344CrossRefGoogle Scholar
  34. 34.
    Geyer K, Codée JDC, Seeberger PH (2006) Chem Eur J 12:8434–8442CrossRefGoogle Scholar
  35. 35.
    McMullen JP, Jensen KF (2010) Annu Rev Anal Chem 3:19–42CrossRefGoogle Scholar
  36. 36.
    McQuade DT, Seeberger PH (2013) J Org Chem 78:6384–6389CrossRefGoogle Scholar
  37. 37.
    Yoshida J, Kim H, Nagaki A (2011) ChemSusChem 4:331–340CrossRefGoogle Scholar
  38. 38.
    Rasheed M, Wirth T (2011) Angew Chem Int Ed 50:357–358CrossRefGoogle Scholar
  39. 39.
    Fritzsche S, Ohla S, Glaser P, Giera DS, Sickert M, Schneider C, Belder D (2011) Angew Chem Int Ed 50:9467–9470CrossRefGoogle Scholar
  40. 40.
    Wiles C, Watts P (2012) Green Chem 14:38–5CrossRefGoogle Scholar
  41. 41.
    Wegner J, Ceylan S, Kirschning A (2011) Chem Commun 47:4583–4592CrossRefGoogle Scholar
  42. 42.
    Xu BB, Zhang YL, Wei S, Ding H, Sun HB (2013) ChemCatChem 5:2091–2099CrossRefGoogle Scholar
  43. 43.
    Belder D, Ludwig M, Wang LW, Reetz MT (2006) Angew Chem Int Ed 45:2463–2466CrossRefGoogle Scholar
  44. 44.
    Ohla S, Beyreiss R, Fritzsche S, Glaser P, Nagl S, Stockhausen K, Schneider C, Belder D (2012) Chem Eur J 18:1240–1246CrossRefGoogle Scholar
  45. 45.
    Valera FE, Quaranta M, Moran A, Blacker J, Armstrong A, Cabral JT, Blackmond DG (2010) Angew Chem Int Ed 49:2478–2485CrossRefGoogle Scholar
  46. 46.
    Elvira KS, Casadevall i Solvas X, Wootton RCR, de Mello AJ (2013) Nat Chem 5:905–915CrossRefGoogle Scholar
  47. 47.
    Mao HB, Yang TL, Cremer PS (2002) J Am Chem Soc 124:4432–4435CrossRefGoogle Scholar
  48. 48.
    Hessel V, Cortese B, de Croon MHJM (2011) Chem Eng Sci 66:1426–1448CrossRefGoogle Scholar
  49. 49.
    Jähnisch K, Hessel V, Löwe H, Baerns M (2004) Angew Chem Int Ed 43:406–446CrossRefGoogle Scholar
  50. 50.
    Miralles V, Huerre A, Malloggi F, Jullien MC (2013) Diagnostics 3:33–67CrossRefGoogle Scholar
  51. 51.
    Khandurina J, McKnight TE, Jacobson SC, Waters LC, Foote RS, Ramsey JM (2000) Anal Chem 72:2995–3000CrossRefGoogle Scholar
  52. 52.
    Kopp MU, de Mello AJ, Manz A (1998) Science 280:1046–1048CrossRefGoogle Scholar
  53. 53.
    Ko HS, Gau C (2011) Microfluid Nanofluid 4:793–807CrossRefGoogle Scholar
  54. 54.
    Yan W, Li H, Kuang Y, Du L, Guo J (2008) J Alloys Compd 1–2:210–213CrossRefGoogle Scholar
  55. 55.
    Nam SK, Kim JK, Cho SC, Lee SK (2010) Sensors 10:6594–6611CrossRefGoogle Scholar
  56. 56.
    Kuvshinov D, Bown MR, MacInnes JM, Allen RWK, Ge R, Aldous L, Hardacre C, Doy N, Newton MI, McHale G (2011) Microfluid Nanofluid 10:123–132CrossRefGoogle Scholar
  57. 57.
    Kim SH, Noh J, Jeon MK, Kim KW, Lee LP, Woo SI (2006) J Micromech Microeng 16:526–530CrossRefGoogle Scholar
  58. 58.
    Liu L, Peng S, Wen W, Sheng P (2007) Appl Phys Lett. doi: 10.1063/1.2776848 Google Scholar
  59. 59.
    Cheng JY, Hsieh CJ, Chuang YC, Hsieh JR (2005) Analyst 130:931–940CrossRefGoogle Scholar
  60. 60.
    Basson M, Pottebaum TS (2012) Exp Fluids 53:803–814CrossRefGoogle Scholar
  61. 61.
    Noh J, Sung SW, Jeon MK, Kim SH, Lee LP, Woo SI (2005) Sens Actuators A Phys 122:196–202CrossRefGoogle Scholar
  62. 62.
    Glawdel T, Almutairi Z, Wang S, Ren C (2009) Lab Chip 9:171–174CrossRefGoogle Scholar
  63. 63.
    Motosuke M, Akutsu D, Honami S (2009) J Mech Sci Technol 23:1821–1828CrossRefGoogle Scholar
  64. 64.
    Fu R, Xu B, Li D (2006) Int J Therm Sci 45:841–847CrossRefGoogle Scholar
  65. 65.
    Guijt RM, Dodge A, Dedem GWK, Rooija NF, Verpoorte E (2003) Lab Chip 3:1–4CrossRefGoogle Scholar
  66. 66.
    Ross D, Gaitan M, Locascio LE (2001) Anal Chem 73:4117–4123CrossRefGoogle Scholar
  67. 67.
    Natrajan VK, Christensen KT (2009) Meas Sci Technol. doi: 10.1088/0957-0233/20/1/015401 Google Scholar
  68. 68.
    Fogg D, David M, Goodson K (2009) Exp Fluids 46:725–736CrossRefGoogle Scholar
  69. 69.
    Koc Y, Hofmann O, Requejo-Isidro J, Neil MAA, French PMW, de Mello AJ (2006) Anal Chem 78:2272–2278CrossRefGoogle Scholar
  70. 70.
    Bennet MA, Richardson PR, Arlt J, McCarthy A, Bullerd GS, Jones AC (2011) Lab Chip 11:3821–3828CrossRefGoogle Scholar
  71. 71.
    Wang XD, Wolfbeis OS, Meier R (2013) J Chem Soc Rev 42:7834–7869CrossRefGoogle Scholar
  72. 72.
    Samy R, Glawdel T, Rem CL (2008) Anal Chem 80:369–375CrossRefGoogle Scholar
  73. 73.
    Gui L, Ren CL (2008) Appl Phys Lett. doi: 10.1063/1.2828717 Google Scholar
  74. 74.
    Nguyen NT, Wu Z (2005) Micromech Microeng 15:R1–R16CrossRefGoogle Scholar
  75. 75.
    Chen L, Wang G, Lim C, Seong GH, Choo J, Lee E, Kang SH, Song JM (2009) Microfluid Nanofluid 7:267–273CrossRefGoogle Scholar
  76. 76.
    Brandrup J, Immergut EH, Grulke EA (1999) Polymer handbook, 4th edn. Wiley-Interscience, HobokenGoogle Scholar
  77. 77.
    Gitlin L, Hoera C, Meier RJ, Nagl S, Belder D (2013) Lab Chip 13:4134–4141CrossRefGoogle Scholar
  78. 78.
    Baleizao C, Nagl S, Schaeferling M, Berberan-Santos MN, Wolfbeis OS (2008) Anal Chem 80:6449–6457CrossRefGoogle Scholar
  79. 79.
    Dinca MP, Gheorghe M, Aherne M, Galvin P (2009) J Micromech Microeng 19:065009CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Christian Hoera
    • 1
  • Stefan Ohla
    • 1
  • Zhe Shu
    • 2
  • Erik Beckert
    • 2
  • Stefan Nagl
    • 1
  • Detlev Belder
    • 1
    Email author
  1. 1.Institut für Analytische ChemieUniversität LeipzigLeipzigGermany
  2. 2.Fraunhofer-Institut für Angewandte Optik und Feinmechanik (IOF)JenaGermany

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