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

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Abstract

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.

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

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References

  1. Whitesides GM (2006) Nature 442:368–273

    Article  CAS  Google Scholar 

  2. Arora A, Simone G, Salieb-Beugelaar GB, Kim JT, Manz A (2010) Anal Chem 82:4830–4847

    Article  CAS  Google Scholar 

  3. Theberge AB, Courtois F, Schaerli Y, Fischlechner M, Abell C, Hollfelder F, Huck WTS (2010) Angew Chem 122:5982–6005

    Article  Google Scholar 

  4. Pompano RR, Liu W, Du W, Ismagilov RF (2011) Annu Rev Anal Chem 4:59–81

    Article  CAS  Google Scholar 

  5. Dittrich PS, Manz A (2006) Nat Rev Drug Disc 5:210–218

    Article  CAS  Google Scholar 

  6. Mark D, Haeberle S, Roth G, von Stetten F, Zengerle R (2010) Chem Soc Rev 39:1153–1182

    Article  CAS  Google Scholar 

  7. Hardt S, Hahn T (2012) Lab Chip 12:434–442

    Article  CAS  Google Scholar 

  8. Joensson HN, Svahn HA (2012) Angew Chem Int Ed 51:12176–12192

    Article  CAS  Google Scholar 

  9. de Mello AJ (2006) Nature 442:394–402

    Article  Google Scholar 

  10. Wegner J, Ceylan S, Kirschning A (2012) Adv Synth Catal 354:17–57

    Article  CAS  Google Scholar 

  11. Baxendale IR (2013) J Chem Technol Biotechnol 88:519–552

    Article  CAS  Google Scholar 

  12. Hartman RL, McMullen JP, Jensen KF (2011) Angew Chem Int Ed 50:7502–7519

    Article  CAS  Google Scholar 

  13. Oelgemöller M (2012) Chem Eng Technol 35:1144–1152

    Article  Google Scholar 

  14. Wiles C, Watts P (2011) Chem Commun 47:6512–6535

    Article  CAS  Google Scholar 

  15. Abou-Hassan A, Sandre O, Cabuil V (2010) Angew Chem Int Ed 49:6268–6286

    Article  CAS  Google Scholar 

  16. Popp A, Schneider JJ (2008) Angew Chem Int Ed 47:8958–8960

    Article  CAS  Google Scholar 

  17. Gutmann B, Roduit JP, Roberge D, Kappe CO (2010) Angew Chem Int Ed 49:7101–7105

    Article  CAS  Google Scholar 

  18. Moore JS, Jensen KF (2014) Angew Chem Int Ed 53:470–473

    Article  CAS  Google Scholar 

  19. März A, Henkel T, Cialla D, Schmitt M, Popp J (2011) Lab Chip 11:3584–3592

    Article  Google Scholar 

  20. Nagl S, Schulze P, Ohla S, Beyreiss R, Gitlin L, Belder D (2011) Anal Chem 83:3232–3238

    Article  CAS  Google Scholar 

  21. Küster SK, Fagerer SR, Verboket PE, Eyer K, Jefimovs K, Zenobi R, Dittrich PS (2013) Anal Chem 85:1285–1289

    Article  Google Scholar 

  22. Ehlert S, Tallarek U (2007) Anal Bioanal Chem 388:517–520

    Article  CAS  Google Scholar 

  23. Kutter JP (2012) J Chromatogr A 1221:72–82

    Article  CAS  Google Scholar 

  24. Yue J, Schouten JC, Nijhuis TA (2012) Ind Eng Chem Res 51:14583–14609

    Article  CAS  Google Scholar 

  25. Jáč P, Scriba GKE (2013) J Sep Sci 36:52–74

    Article  Google Scholar 

  26. Ohla S, Belder D (2012) Curr Opin Chem Biol 16:453–459

    Article  CAS  Google Scholar 

  27. Dittrich PS, Jahnz M, Schwille P (2005) ChemBioChem 6:811–814

    Article  CAS  Google Scholar 

  28. Belder D (2009) Angew Chem Int Ed 48:3736–3737

    Article  CAS  Google Scholar 

  29. Trapp O, Weber SK, Bauch S, Hofstadt W (2007) Angew Chem Int Ed 46:7307–7310

    Article  CAS  Google Scholar 

  30. Janasek D, Franzke J, Manz A (2006) Nature 442:374

    Article  CAS  Google Scholar 

  31. Hessel V (2009) Chem Eng Technol 32:1655–1681

    Article  CAS  Google Scholar 

  32. Grumann M, Geipel A, Riegger L, Zengerle R, Ducrée J (2005) Lab Chip 5:560–565

    Article  CAS  Google Scholar 

  33. Brivio M, Verboom W, Reinhoudt DN (2006) Lab Chip 6:329–344

    Article  CAS  Google Scholar 

  34. Geyer K, Codée JDC, Seeberger PH (2006) Chem Eur J 12:8434–8442

    Article  CAS  Google Scholar 

  35. McMullen JP, Jensen KF (2010) Annu Rev Anal Chem 3:19–42

    Article  CAS  Google Scholar 

  36. McQuade DT, Seeberger PH (2013) J Org Chem 78:6384–6389

    Article  CAS  Google Scholar 

  37. Yoshida J, Kim H, Nagaki A (2011) ChemSusChem 4:331–340

    Article  CAS  Google Scholar 

  38. Rasheed M, Wirth T (2011) Angew Chem Int Ed 50:357–358

    Article  CAS  Google Scholar 

  39. Fritzsche S, Ohla S, Glaser P, Giera DS, Sickert M, Schneider C, Belder D (2011) Angew Chem Int Ed 50:9467–9470

    Article  CAS  Google Scholar 

  40. Wiles C, Watts P (2012) Green Chem 14:38–5

    Article  CAS  Google Scholar 

  41. Wegner J, Ceylan S, Kirschning A (2011) Chem Commun 47:4583–4592

    Article  CAS  Google Scholar 

  42. Xu BB, Zhang YL, Wei S, Ding H, Sun HB (2013) ChemCatChem 5:2091–2099

    Article  CAS  Google Scholar 

  43. Belder D, Ludwig M, Wang LW, Reetz MT (2006) Angew Chem Int Ed 45:2463–2466

    Article  CAS  Google Scholar 

  44. Ohla S, Beyreiss R, Fritzsche S, Glaser P, Nagl S, Stockhausen K, Schneider C, Belder D (2012) Chem Eur J 18:1240–1246

    Article  CAS  Google Scholar 

  45. Valera FE, Quaranta M, Moran A, Blacker J, Armstrong A, Cabral JT, Blackmond DG (2010) Angew Chem Int Ed 49:2478–2485

    Article  CAS  Google Scholar 

  46. Elvira KS, Casadevall i Solvas X, Wootton RCR, de Mello AJ (2013) Nat Chem 5:905–915

    Article  CAS  Google Scholar 

  47. Mao HB, Yang TL, Cremer PS (2002) J Am Chem Soc 124:4432–4435

    Article  CAS  Google Scholar 

  48. Hessel V, Cortese B, de Croon MHJM (2011) Chem Eng Sci 66:1426–1448

    Article  CAS  Google Scholar 

  49. Jähnisch K, Hessel V, Löwe H, Baerns M (2004) Angew Chem Int Ed 43:406–446

    Article  Google Scholar 

  50. Miralles V, Huerre A, Malloggi F, Jullien MC (2013) Diagnostics 3:33–67

    Article  Google Scholar 

  51. Khandurina J, McKnight TE, Jacobson SC, Waters LC, Foote RS, Ramsey JM (2000) Anal Chem 72:2995–3000

    Article  CAS  Google Scholar 

  52. Kopp MU, de Mello AJ, Manz A (1998) Science 280:1046–1048

    Article  CAS  Google Scholar 

  53. Ko HS, Gau C (2011) Microfluid Nanofluid 4:793–807

    Article  Google Scholar 

  54. Yan W, Li H, Kuang Y, Du L, Guo J (2008) J Alloys Compd 1–2:210–213

    Article  Google Scholar 

  55. Nam SK, Kim JK, Cho SC, Lee SK (2010) Sensors 10:6594–6611

    Article  CAS  Google Scholar 

  56. Kuvshinov D, Bown MR, MacInnes JM, Allen RWK, Ge R, Aldous L, Hardacre C, Doy N, Newton MI, McHale G (2011) Microfluid Nanofluid 10:123–132

    Article  CAS  Google Scholar 

  57. Kim SH, Noh J, Jeon MK, Kim KW, Lee LP, Woo SI (2006) J Micromech Microeng 16:526–530

    Article  CAS  Google Scholar 

  58. Liu L, Peng S, Wen W, Sheng P (2007) Appl Phys Lett. doi:10.1063/1.2776848

    Google Scholar 

  59. Cheng JY, Hsieh CJ, Chuang YC, Hsieh JR (2005) Analyst 130:931–940

    Article  CAS  Google Scholar 

  60. Basson M, Pottebaum TS (2012) Exp Fluids 53:803–814

    Article  CAS  Google Scholar 

  61. Noh J, Sung SW, Jeon MK, Kim SH, Lee LP, Woo SI (2005) Sens Actuators A Phys 122:196–202

    Article  CAS  Google Scholar 

  62. Glawdel T, Almutairi Z, Wang S, Ren C (2009) Lab Chip 9:171–174

    Article  CAS  Google Scholar 

  63. Motosuke M, Akutsu D, Honami S (2009) J Mech Sci Technol 23:1821–1828

    Article  Google Scholar 

  64. Fu R, Xu B, Li D (2006) Int J Therm Sci 45:841–847

    Article  CAS  Google Scholar 

  65. Guijt RM, Dodge A, Dedem GWK, Rooija NF, Verpoorte E (2003) Lab Chip 3:1–4

    Article  CAS  Google Scholar 

  66. Ross D, Gaitan M, Locascio LE (2001) Anal Chem 73:4117–4123

    Article  CAS  Google Scholar 

  67. Natrajan VK, Christensen KT (2009) Meas Sci Technol. doi:10.1088/0957-0233/20/1/015401

    Google Scholar 

  68. Fogg D, David M, Goodson K (2009) Exp Fluids 46:725–736

    Article  CAS  Google Scholar 

  69. Koc Y, Hofmann O, Requejo-Isidro J, Neil MAA, French PMW, de Mello AJ (2006) Anal Chem 78:2272–2278

    Article  Google Scholar 

  70. Bennet MA, Richardson PR, Arlt J, McCarthy A, Bullerd GS, Jones AC (2011) Lab Chip 11:3821–3828

    Article  CAS  Google Scholar 

  71. Wang XD, Wolfbeis OS, Meier R (2013) J Chem Soc Rev 42:7834–7869

    Article  CAS  Google Scholar 

  72. Samy R, Glawdel T, Rem CL (2008) Anal Chem 80:369–375

    Article  CAS  Google Scholar 

  73. Gui L, Ren CL (2008) Appl Phys Lett. doi:10.1063/1.2828717

    Google Scholar 

  74. Nguyen NT, Wu Z (2005) Micromech Microeng 15:R1–R16

    Article  Google Scholar 

  75. Chen L, Wang G, Lim C, Seong GH, Choo J, Lee E, Kang SH, Song JM (2009) Microfluid Nanofluid 7:267–273

    Article  CAS  Google Scholar 

  76. Brandrup J, Immergut EH, Grulke EA (1999) Polymer handbook, 4th edn. Wiley-Interscience, Hoboken

    Google Scholar 

  77. Gitlin L, Hoera C, Meier RJ, Nagl S, Belder D (2013) Lab Chip 13:4134–4141

    Article  CAS  Google Scholar 

  78. Baleizao C, Nagl S, Schaeferling M, Berberan-Santos MN, Wolfbeis OS (2008) Anal Chem 80:6449–6457

    Article  CAS  Google Scholar 

  79. Dinca MP, Gheorghe M, Aherne M, Galvin P (2009) J Micromech Microeng 19:065009

    Article  Google Scholar 

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Acknowledgments

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.

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Authors and Affiliations

  1. Institut für Analytische Chemie, Universität Leipzig, Linnéstr. 3, 04103, Leipzig, Germany

    Christian Hoera, Stefan Ohla, Stefan Nagl & Detlev Belder

  2. Fraunhofer-Institut für Angewandte Optik und Feinmechanik (IOF), Albert-Einstein-Str. 7, 07745, Jena, Germany

    Zhe Shu & Erik Beckert

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  1. Christian Hoera
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  2. Stefan Ohla
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  5. Stefan Nagl
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  6. Detlev Belder
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Correspondence to Detlev Belder.

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Hoera, C., Ohla, S., Shu, Z. et al. An integrated microfluidic chip enabling control and spatially resolved monitoring of temperature in micro flow reactors. Anal Bioanal Chem 407, 387–396 (2015). https://doi.org/10.1007/s00216-014-8297-3

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  • DOI: https://doi.org/10.1007/s00216-014-8297-3

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