Microfluidic dual loops reactor for conducting a multistep reaction

  • Si Hyung Jin
  • Jae-Hoon Jung
  • Seong-Geun Jeong
  • Jongmin Kim
  • Tae Jung Park
  • Chang-Soo Lee
Research Article


Precise control of each individual reaction that constitutes a multistep reaction must be performed to obtain the desired reaction product efficiently. In this work, we present a microfluidic dual loops reactor that enables multistep reaction by integrating two identical loop reactors. Specifically, reactants A and B are synthesized in the first loop reactor and transferred to the second loop reactor to synthesize with reactant C to form the final product. These individual reactions have nano-liter volumes and are carried out in a stepwise manner in each reactor without any cross-contamination issue. To precisely control the mixing efficiency in each loop reactor, we investigate the operating pressure and the operating frequency on the mixing valves for rotary mixing. This microfluidic dual loops reactor is integrated with several valves to realize the fully automated unit operation of a multistep reaction, such as metering the reactants, rotary mixing, transportation, and collecting the product. For proof of concept, CdSeZn nanoparticles are successfully synthesized in a microfluidic dual loops reactor through a fully automated multistep reaction. Taking all of these features together, this microfluidic dual loops reactor is a general microfluidic screening platform that can synthesize various materials through a multistep reaction.


microfluidics multistep reaction rotary mixing nanoparticle 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.



This research was supported by Global Research Laboratory(GRL) Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Science and ICT(2015K1A1A 2033054).

Supplementary material

11705_2017_1680_MOESM1_ESM.pdf (251 kb)
Microfluidic dual loops reactor for conducting a multistep reaction


  1. 1.
    Webb D, Jamison T F. Continuous flow multi-step organic synthesis. Chemical Science (Cambridge), 2010, 1(6): 675–680CrossRefGoogle Scholar
  2. 2.
    Shukla C A, Kulkarni A A. Automating multistep flow synthesis: Approach and challenges in integrating chemistry, machines and logic. Beilstein Journal of Organic Chemistry, 2017, 13: 960–987CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Porta R, Benaglia M, Puglisi A. Flow chemistry: Recent developments in the synthesis of pharmaceutical products. Organic Process Research & Development, 2016, 20(1): 2–25CrossRefGoogle Scholar
  4. 4.
    Bannock J H, Krishnadasan S H, Nightingale A M, Yau C P, Khaw K, Burkitt D, Halls J J M, Heeney M, de Mello J C. Continuous synthesis of device-grade semiconducting polymers in dropletbased microreactors. Advanced Functional Materials, 2013, 23(17): 2123–2129CrossRefGoogle Scholar
  5. 5.
    Duraiswamy S, Khan S A. Droplet-dased microfluidic synthesis of anisotropic metal nanocrystals. Small, 2009, 5(24): 2828–2834CrossRefPubMedGoogle Scholar
  6. 6.
    Duraiswamy S, Khan S A. Plasmonic nanoshell synthesis in microfluidic composite foams. Nano Letters, 2010, 10(9): 3757–3763CrossRefPubMedGoogle Scholar
  7. 7.
    Nightingale A M, Bannock J H, Krishnadasan S H, O’Mahony F T F, Haque S A, Sloan J, Drury C, McIntyre R, deMello J C. Largescale synthesis of nanocrystals in a multichannel droplet reactor. Journal of Materials Chemistry. A, Materials for Energy and Sustainability, 2013, 1(12): 4067–4076CrossRefGoogle Scholar
  8. 8.
    McQuade D T, Seeberger P H. Applying flow chemistry: Methods, materials, and multistep synthesis. Journal of Organic Chemistry, 2013, 78(13): 6384–6389CrossRefPubMedGoogle Scholar
  9. 9.
    Asadi-Saghandi H, Karimi-Sabet J. Performance evaluation of a novel reactor configuration for oxidative dehydrogenation of ethane to ethylene. Korean Journal of Chemical Engineering, 2017, 34(7): 1905–1913CrossRefGoogle Scholar
  10. 10.
    Pennemann H, Watts P, Haswell S J, Hessel V, Lowe H. Benchmarking of microreactor applications. Organic Process Research & Development, 2004, 8(3): 422–439CrossRefGoogle Scholar
  11. 11.
    Jahnisch K, Hessel V, Lowe H, Baerns M. Chemistry in microstructured reactors. Angewandte Chemie International Edition, 2004, 43(4): 406–446CrossRefPubMedGoogle Scholar
  12. 12.
    Sahoo H R, Kralj J G, Jensen K F. Multistep continuous-flow microchemical synthesis involving multiple reactions and separations. Angewandte Chemie International Edition, 2007, 46(30): 5704–5708CrossRefPubMedGoogle Scholar
  13. 13.
    Singh R, Lee H J, Singh A K, Kim D P. Recent advances for serial processes of hazardous chemicals in fully integrated microfluidic systems. Korean Journal of Chemical Engineering, 2016, 33(8): 2253–2267CrossRefGoogle Scholar
  14. 14.
    Su M. Synthesis of highly monodisperse silica nanoparticles in the microreactor system. Korean Journal of Chemical Engineering, 2017, 34(2): 484–494CrossRefGoogle Scholar
  15. 15.
    Lee C C, Sui G D, Elizarov A, Shu C Y J, Shin Y S, Dooley A N, Huang J, Daridon A, Wyatt P, Stout D, et al. Multistep synthesis of a radiolabeled imaging probe using integrated microfluidics. Science, 2005, 310(5755): 1793–1796CrossRefPubMedGoogle Scholar
  16. 16.
    Chen S P, Javed MR, Kim H K, Lei J, Lazari M, Shah G J, van Dam R M, Keng P Y, Kim C J. Radiolabelling diverse positron emission tomography (PET) tracers using a single digital microfluidic reactor chip. Lab on a Chip, 2014, 14(5): 902–910CrossRefPubMedGoogle Scholar
  17. 17.
    Kobayashi J, Mori Y, Okamoto K, Akiyama R, Ueno M, Kitamori T, Kobayashi S. A microfluidic device for conducting gas-liquidsolid hydrogenation reactions. Science, 2004, 304(5675): 1305–1308CrossRefPubMedGoogle Scholar
  18. 18.
    Phillips T W, Lignos I G, Maceiczyk R M, de Mello A J, de Mello J C. Nanocrystal synthesis in microfluidic reactors: Where next? Lab on a Chip, 2014, 14(17): 3172–3180CrossRefPubMedGoogle Scholar
  19. 19.
    Chan E M, Mathies R A, Alivisatos A P. Size-controlled growth of CdSe nanocrystals in microfluidic reactors. Nano Letters, 2003, 3 (2): 199–201CrossRefGoogle Scholar
  20. 20.
    Wang J, Bunimovich Y L, Sui G D, Savvas S, Wang J Y, Guo Y Y, Heath J R, Tseng H R. Electrochemical fabrication of conducting polymer nanowires in an integrated microfluidic system. Chemical Communications, 2006, 29: 3075–3077CrossRefGoogle Scholar
  21. 21.
    Hou S, Wang S, Yu Z T F, Zhu N Q M, Liu K, Sun J, Lin WY, Shen C K F, Fang X, Tseng H R. A hydrodynamically focused stream as a dynamic template for site-specific electrochemical micropatterning of conducting polymers. Angewandte Chemie International Edition, 2008, 47(6): 1072–1075CrossRefPubMedGoogle Scholar
  22. 22.
    Li W, Pharn H H, Nie Z, MacDonald B, Guenther A, Kumacheva E. Multi-step microfluidic polymerization reactions conducted in droplets: The internal trigger approach. Journal of the American Chemical Society, 2008, 130(30): 9935–9941CrossRefPubMedGoogle Scholar
  23. 23.
    Hartman R L, Naber J R, Buchwald S L, Jensen K F. Multistep microchemical synthesis enabled by microfluidic distillation. Angewandte Chemie International Edition, 2010, 49(5): 899–903CrossRefPubMedGoogle Scholar
  24. 24.
    Noel T, Kuhn S, Musacchio A J, Jensen K F, Buchwald S L. Suzuki-Miyaura cross-coupling reactions in flow: Multistep synthesis enabled by a microfluidic extraction. Angewandte Chemie International Edition, 2011, 50(26): 5943–5946CrossRefPubMedGoogle Scholar
  25. 25.
    Lee C C, Snyder T M, Quake S R. A microfluidic oligonucleotide synthesizer. Nucleic Acids Research, 2010, 38(8): 2514–2521CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Zhou X C, Cai S Y, Hong A L, You Q M, Yu P L, Sheng N J, Srivannavit O, Muranjan S, Rouillard J M, Xia Y M, et al. Microfluidic Picoarray synthesis of oligodeoxynucleotides and simultaneous assembling of multiple DNA sequences. Nucleic Acids Research, 2004, 32(18): 5409–5417CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Kim E B, Seo J M, Kim G W, Lee S Y, Park T J. In vivo synthesis of europium selenide nanoparticles and related cytotoxicity evaluation of human cells. Enzyme and Microbial Technology, 2016, 95: 201–208CrossRefPubMedGoogle Scholar
  28. 28.
    Jeong H H, Jin S H, Lee B J, Kim T, Lee C S. Microfluidic static droplet array for analyzing microbial communication on a population gradient. Lab on a Chip, 2015, 15(3): 889–899CrossRefPubMedGoogle Scholar
  29. 29.
    Jin S H, Jeong H H, Lee B, Lee S S, Lee C S. A programmable microfluidic static droplet array for droplet generation, transportation, fusion, storage, and retrieval. Lab on a Chip, 2015, 15(18): 3677–3686CrossRefPubMedGoogle Scholar
  30. 30.
    Jeong H H, Lee B, Jin S H, Jeong S G, Lee C S. A highly addressable static droplet array enabling digital control of a single droplet at pico-volume resolution. Lab on a Chip, 2016, 16(9): 1698–1707CrossRefPubMedGoogle Scholar
  31. 31.
    Jang S, Lee B, Jeong H H, Jin S H, Jang S, Kim S G, Jung G Y, Lee C S. On-chip analysis, indexing and screening for chemical producing bacteria in a microfluidic static droplet array. Lab on a Chip, 2016, 16(10): 1909–1916CrossRefPubMedGoogle Scholar
  32. 32.
    Chou H P, Unger M A, Quake S R. A microfabricated rotary pump. Biomedical Microdevices, 2001, 3(4): 323–330CrossRefGoogle Scholar
  33. 33.
    Hong J W, Studer V, Hang G, Anderson W F, Quake S R. A nanoliter-scale nucleic acid processor with parallel architecture. Nature Biotechnology, 2004, 22(4): 435–439CrossRefPubMedGoogle Scholar
  34. 34.
    Yun J Y, Jambovane S, Kim S K, Cho S H, Duin E C, Hong J W. Log-scale dose response of inhibitors on a chip. Analytical Chemistry, 2011, 83(16): 6148–6153CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Wang Y J, Lin WY, Liu K, Lin R J, Selke M, Kolb H C, Zhang N G, Zhao X Z, Phelps M E, Shen C K F, Faull K F, Tseng H R. An integrated microfluidic device for large-scale in situ click chemistry screening. Lab on a Chip, 2009, 9(16): 2281–2285CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Unger M A, Chou H P, Thorsen T, Scherer A, Quake S R. Monolithic microfabricated valves and pumps by multilayer soft lithography. Science, 2000, 288(5463): 113–116CrossRefPubMedGoogle Scholar
  37. 37.
    Lin W Y, Wang Y, Wang S, Tseng H R. Integrated microfluidic reactors. Nano Today, 2009, 4(6): 470–481CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Tseng H Y, Wang C H, Lin W Y, Lee G B. Membrane-activated microfluidic rotary devices for pumping and mixing. Biomedical Microdevices, 2007, 9(4): 545–554CrossRefPubMedGoogle Scholar
  39. 39.
    Chang C C, Yang R J. Computational analysis of electrokinetically driven flow mixing in microchannels with patterned blocks. Journal of Micromechanics and Microengineering, 2004, 14(4): 550–558CrossRefGoogle Scholar
  40. 40.
    Wang C H, Lee G B. Automatic bio-sampling chips integrated with micro-pumps and micro-valves for disease detection. Biosensors & Bioelectronics, 2005, 21(3): 419–425CrossRefGoogle Scholar
  41. 41.
    Wang C H, Lee G B. Pneumatically driven peristaltic micropumps utilizing serpentine-shape channels. Journal of Micromechanics and Microengineering, 2006, 16(2): 341–348CrossRefGoogle Scholar
  42. 42.
    Kelly K L, Coronado E, Zhao L L, Schatz G C. The optical properties of metal nanoparticles: The influence of size, shape, and dielectric environment. Journal of Physical Chemistry B, 2003, 107 (3): 668–677CrossRefGoogle Scholar
  43. 43.
    Zaniewski A M, Schriver M, Lee J G, Crommie M F, Zettl A. Electronic and optical properties of metal-nanoparticle filled graphene sandwiches. Applied Physics Letters, 2013, 102(2): 023108CrossRefGoogle Scholar
  44. 44.
    Seo W S, Jo H H, Lee K, Kim B, Oh S J, Park J T. Size-dependent magnetic properties of colloidal Mn3O4 and MnO nanoparticles. Angewandte Chemie International Edition, 2004, 43(9): 1115–1117CrossRefPubMedGoogle Scholar
  45. 45.
    Bruchez M Jr, Moronne M, Gin P, Weiss S, Alivisatos A P. Semiconductor nanocrystals as fluorescent biological labels. Science, 1998, 281(5385): 2013–2016CrossRefPubMedGoogle Scholar
  46. 46.
    Coe S, Woo W K, Bawendi M, Bulovic V. Electroluminescence from single monolayers of nanocrystals in molecular organic devices. Nature, 2002, 420(6917): 800–803CrossRefPubMedGoogle Scholar
  47. 47.
    McDonald S A, Konstantatos G, Zhang S G, Cyr P W, Klem E J D, Levina L, Sargent E H. Solution-processed PbS quantum dot infrared photodetectors and photovoltaics. Nature Materials, 2005, 4 (2): 138–142CrossRefPubMedGoogle Scholar
  48. 48.
    Sun Y G, Xia Y N. Shape-controlled synthesis of gold and silver nanoparticles. Science, 2002, 298(5601): 2176–2179CrossRefPubMedGoogle Scholar
  49. 49.
    Song L M, Zhang S J. Hydrothermal synthesis and highly visible light-induced photocatalytic activity of zinc-doped cadmium selenide photocatalysts. Chemical Engineering Journal, 2011, 166 (2): 779–782CrossRefGoogle Scholar
  50. 50.
    Park T J, Lee S Y, Heo N S, Seo T S. In vivo synthesis of diverse metal nanoparticles by recombinant Escherichia coli. Angewandte Chemie International Edition, 2010, 49(39): 7019–7024CrossRefPubMedGoogle Scholar

Copyright information

© Higher Education Press and Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Si Hyung Jin
    • 1
  • Jae-Hoon Jung
    • 2
    • 3
  • Seong-Geun Jeong
    • 1
  • Jongmin Kim
    • 1
  • Tae Jung Park
    • 3
  • Chang-Soo Lee
    • 1
  1. 1.Department of Chemical EngineeringChungnam National UniversityDaejeonKorea
  2. 2.Lotte Chemical R&D CenterDaejeonKorea
  3. 3.Department of ChemistryChung-Ang UniversitySeoulKorea

Personalised recommendations