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Addressing of Concentration Spaces for Bioscreenings by Micro Segmented Flow with Microphotometric and Microfluorimetric Detection

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Optical Nano- and Microsystems for Bioanalytics

Part of the book series: Springer Series on Chemical Sensors and Biosensors ((SSSENSORS,volume 10))

Abstract

Microfluid segments allow the efficient realization and application of well-separated test volumes for high-resolved and multidimensional investigations. With typical volumes in the nanoliter and lower microliter range, screening runs with several hundred up to several thousand single volumes can be realized with a total consumption of less than 1 mL test solution. The fluid segments act as confinements for the determination of the dose-related cell response on different effectors which can be applied in a precision better than 1% in concentration. One, two, or higher dimensional concentration spaces are addressed by PC-controlled low-pulsation syringe pumps. Micro flow-through photometric measurements allow the characterization of the quality of segment sequences and the determination of up to four optical channels with typical measurement frequencies between 500 and 5,000 Hz. The generation and characterization of microfluid segment sequences for screening purposes, the realization of different concentration spaces for the determination of effects of single substances and combinatorial effects, and the cultivation of different organisms are reported. The investigations have shown the applicability of micro segmented flow for fast microtoxicological screenings with prokaryotic and eukaryotic microorganisms like E. Coli, Chlorella vulgaris, and Saccharomyces cerevisiae and for multicellular systems like embryos of Danio rerio.

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References

  1. Csaki A, Kaplanek P, Möller R, Fritzsche W (2003) The optical detection of individual DNA-conjugated gold nanoparticles labels after metal enhancement. Nanotechnology 14:1262–1268, DOI:dx.doi.org

    Article  CAS  Google Scholar 

  2. Stehr J, Hrelescu C, Sperling RA et al (2008) Gold nano-stoves for microsecond DNA melting analysis. Nano Lett 8:619–623

    Article  CAS  Google Scholar 

  3. Li Y, Schluesener HJ, Xu S (2010) Gold nanoparticle-based biosensors. Gold Bull 43:29–41

    Article  Google Scholar 

  4. Hardt S, Schönfeld F (eds) (2007) Microfluidic technologies for miniaturized analysis systems. Springer, New York

    Google Scholar 

  5. Fent K (1998) Ökotoxikologie. Thieme, Stuttgart

    Google Scholar 

  6. Alloway BJ, Ayres DC (1996) Schadstoffe in der Umwelt. Spektrum, Berlin

    Google Scholar 

  7. Zakrzewski SF (1997) Principles of environmental toxicology. ACS, Washington, DC

    Google Scholar 

  8. Wang RGM (1994) Water contamination and health. Marcel Dekker, New York

    Google Scholar 

  9. Grimme LH, Faust M, Boedecker W, Altenburger R (1996) Hum Ecol Risk Assess 2:426–433

    Article  CAS  Google Scholar 

  10. Berenbaum MC (1985) Environ Res 38:310–318

    Article  CAS  Google Scholar 

  11. Berenbaum MC (1989) Pharmacol Rev 41:93–141

    CAS  Google Scholar 

  12. Therberge AB, Courtois F, Schaerli Y et al (2010) Microdroplets in microfluidics: an evolving platform for discoveries in chemistry and biology. Angew Chem Int Ed Engl 49:5846–5868

    Google Scholar 

  13. Köhler JM, Henkel T, Grodrian A, Kirner T, Roth M, Martin K, Metze J (2004) Digital reaction technology by micro segmented flow – components, concepts and applications. Chem Engn J 101:201–216, DOI:dx.doi.org

    Article  Google Scholar 

  14. Song H, Chen DL, Ismagilov RF (2006) Reactions in droplets in microfluidic channels. Angew Chem Int Ed Engl 45:7336–7356

    Article  CAS  Google Scholar 

  15. Malsch D, Gleichmann N, Kielpinski M et al (2009) Dynamics of droplet formation at T-shaped nozzles with elastic feed lines. Microfluid Nanofluid 10:479–507

    Google Scholar 

  16. Köhler JM, Kirner T (2005) Nanoliter segment formation in micro fluid devices for chemical and biological micro serial flow processes in dependence on flow rate and viscosity. Sens Actuators A 119:19–27

    Article  Google Scholar 

  17. Vanapalli SA, Banpurkar AG, Vanden Ende D, Duits MHG, Mugele F (2009) Hydrodynamic resistance of single confined moving droplets in rectangular microchannels. Lab Chip 9:982–990

    Article  CAS  Google Scholar 

  18. Baroud CN, Willaime H (2004) Multiphase flows in microfluidics. CR Phys 5:547–555

    Article  CAS  Google Scholar 

  19. Baroud CN, Gallaire F, Dangla R (2010) Critical review: dynamics of microfluidic droplets. Lab Chip 10:2032–2045

    Article  CAS  Google Scholar 

  20. Adzima BJ, Velankar SS (2006) Pressure drops for droplet flows in microfluidic channels. J Micromech Microeng 16:1504–1510

    Article  Google Scholar 

  21. Gross GA, Thyagarajan V, Kielpinski M, Henkel T, Köhler JM (2008) Viscosity-dependent enhancement of fluid resistance in water/glycerol micro fluid segments. Microfluid Nanofluidics 5:281–287

    Article  CAS  Google Scholar 

  22. Malsch D, Gleichmann N, Kielpinski M, Mayer G, Henkel T (2008) Proc. ICNM 2008, No 62328

    Google Scholar 

  23. Mazutis L, Baret JCh, Griffith AD (2009) A fast and efficient microfluidic system for highly selective one-to-one droplet fusion. Lab Chip 9:2665–2672

    Article  CAS  Google Scholar 

  24. Wang W, Yang Ch, Li ChM (2009) On-demand microfluidic droplet trapping and fusion for on-chip static droplet ass ays. Lab Chip 9:1504–1506

    Article  CAS  Google Scholar 

  25. Hsieh YS, Crouch SR (1995) Air-segmented flow injection: a hybrid technique for automated, low dispersion determinations. Anal Chim Acta 303:231–239

    Article  CAS  Google Scholar 

  26. Nisisako T, Okushima S, Torii T (2005) Controlled formulation of monodisperse double emulsions in a multiple-phase microfluidic system. Soft Matter 1:23–27

    Article  CAS  Google Scholar 

  27. Chae S-K, Lee ChL, Lee SH, Kim T-S, Kang JY (2009) Oil droplet generation in PDMS microchannel using an amphiphilic continuous phase. Lab Chip 9:1957–1961

    Article  CAS  Google Scholar 

  28. Zhu J, Hayward RC (2008) Hierarchically structured microparticles formed by interfacial instabilities of emulsion droplets containing amphiphilic block copolymers. Angew Chem Int Ed Engl 47:2113–2116

    Article  CAS  Google Scholar 

  29. Ismagilov RF (2003) Integrierte mikrofluidsysteme. Angew Chem Int Ed Engl 115:4262–4264

    Article  Google Scholar 

  30. Günther PM, Möller F, Henkel T, Köhler JM, Gross GA (2005) Formation of monomieric and novolak azo dayes in nanofluid segments by use of a double injector chip reactor. Chem Eng Technol 28:520–527

    Article  Google Scholar 

  31. Donnet M, Jongen N, Lemaitre J, Bowen P (2000) New morphology of calcium oxalate trihydrate precipitated in a segmented flow tubular reactor. J Mater Sci 19:749–750

    CAS  Google Scholar 

  32. Jongen N, Donnet M, Bowen P et al (2003) Development of a continuous segmented flow tubular reactor and the scale-out concept – in search of perfect powders. Chem Eng Technol 26:303–305

    Article  CAS  Google Scholar 

  33. Yen BKH, Stott NE, Jensen KF, Bawendi MG (2003) A continuous-flow microcapillary reactor for the preparation of a size series of CdSe nanocrystals. Adv Mater 15:1858–1862

    Article  CAS  Google Scholar 

  34. Shestopalov I, Tice JD, Ismagilov RF (2004) Multi-step chemical reactions performed on millisecond time scale in a microfluidic droplet-based system. Lab Chip 4:316–321

    Article  CAS  Google Scholar 

  35. Chan EM, Alivisatos PA, Mathies RA (2005) High-temperature microfluidic synthesis of cdse nanocrystals in nanoliter droplets. J Am Chem Soc 127:13854–13861

    Article  CAS  Google Scholar 

  36. Li S, Günther PM, Köhler JM (2009) Micro segmented-flow technique for continuous synthesis of different kinds of ZnO nanoparticles in aqueous and DMSO solution. J Chem Eng Jpn 42:338–345

    Article  CAS  Google Scholar 

  37. Bu W-B, Sung M, Gu S-Q, Zhu Y, Fang Q (2010) Automated microfluidic screening assay platform based on DropLab. Anal Chem 82:9941–9947

    Article  Google Scholar 

  38. Köhler JM, Henkel T (2005) Chip devices for miniaturized biotechnology. Appl Microbiol Biotechnol 69:113–125

    Article  Google Scholar 

  39. Boedicker JQ, Li L, Kline TR, Ismagilov RF (2008) Detecting bacteria and determining their susceptibility to antibiotics by stochastic confinement in nanoliter droplets using plug-based microfluidics. Lab Chip 8:1265–1272

    Article  CAS  Google Scholar 

  40. Clausell-Tornos J, Lieber D, Baret J-Ch et al (2008) Droplet-based microfluidic platforms for the encapsulation and screening of mammalian cells and multicellular organisms. Chem Biol 15:427–437

    Article  Google Scholar 

  41. Hufnagel H, Huebner A, Gülch C, Güse K, Abel Ch, Hollfelder F (2009) An integrated cell culture lab on a chip: modular microdevices for cultivation of mammalian cells and delivery into microfluidic microdroplets. Lab Chip 9:1576–1582

    Article  CAS  Google Scholar 

  42. Chronis N (2010) Worm chips: microtools for C. elegans biology. Lab Chip 10:432–437

    Article  CAS  Google Scholar 

  43. Crane MM, Chung K, Stirman J, Lu H (2010) Microfluidics-enabled phenotyping, imaging and screening of multicellular organism. Lab Chip 10:1509–1517

    Article  CAS  Google Scholar 

  44. Martin K, Henkel T, Baier V et al (2003) Generation of large numbers of separated microbial populations by cultivation in segmented-flow microdevices. Lab Chip 3:202–207

    Article  CAS  Google Scholar 

  45. Kopp MU, DeMello AJ, Manz A (1998) Chemical amplification: continuous-flow PCR on a chip. Science 280:1046–1948

    Article  CAS  Google Scholar 

  46. Auroux P-A, Koc Y, DeMello A, Manz A, Day PJR (2004) Lab Chip 4:534–546

    Article  CAS  Google Scholar 

  47. Hartung R, Brösing A, Sczcepankiewisz G et al (2009) Application of an asymmetric helical tube reactor for fast identification of gene transcripts of pathogenic viruses by micro flow-through PCR. Biomed Microdevices 11:685–692

    Article  CAS  Google Scholar 

  48. Williams R, Peisajovich SG, Miller OJ, Magdassi S, Tawfik DS, Griffith AD (2006) Amplification of complex gene libraries by emulsion PCR. Nat Methods 3:545–550

    Article  CAS  Google Scholar 

  49. Schemberg J, Grodrian A, Römer R, Cahill BP, Gastrock G, Lemke K (2010) Application of segmented flow for quality control of food using microfluidic tools. Physica Status Solidi 207:904–912

    Article  CAS  Google Scholar 

  50. Funfak A, Hartung R, Cao J, Martin K, Wiesmüller K-H, Wolfbeis OS, Köhler JM (2009) Highly resolved dose–response functionsfor drug-modulated bacteria cultivation obtained by fluorometric and photometric flow-through sensing in microsegmented flow. Sens Actuators B 142:66–72

    Article  Google Scholar 

  51. Funfak A, Cao J, Wolfbeis OS, Martin K, Köhler JM (2009) Monitoring cell cultivation in microfluid segments by optical pH sensing with a micro flow-through fluorometer using dye-doped polymer particles. Microchim Acta 164:279–286

    Article  CAS  Google Scholar 

  52. Funfak A, Brösing A, Brand M, Köhler JM (2007) Micro fluid segment technique for screening and development studies on Danio rerio embryos. Lab Chip 7:1132–1138

    Article  CAS  Google Scholar 

  53. Günther PM, Funfak A, Cao J, Schneider S, Möller F, Köhler JM (2010) Realization of two- and three-dimensional concentration spaces by micro segmented flow for microtoxicological screenings. Proc μ-TAS 14:1565–1567

    Google Scholar 

  54. Funfak A, Cao J, Knauer A, Martin K, Köhler JM (2011) Synergistic effects of metal nanoparticles and a phenolic uncoupler using microdroplet-based two-dimensional approach. J Environ Monit 13:410–415

    Article  CAS  Google Scholar 

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Acknowledgment

The research on micro segmented flow, on multidimensional concentration spaces, and segment switching was supported by the BMBF (VDI/VDE-IT, Kz. 16SV3701 and 16SV5065). The investigations on microreaction technology and microtoxicology have been financed by the German Environmental Foundation (DBU).

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Authors and Affiliations

  1. Institute of Micro- und Nanotechnologies, Technical University Ilmenau, 10 05 65, 98684, Ilmenau, Germany

    J. Michael Köhler, Anette Funfak, Jialan Cao, Dana Kürsten, Steffen Schneider & P. Mike Günther

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  1. J. Michael Köhler
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  2. Anette Funfak
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  3. Jialan Cao
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  4. Dana Kürsten
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  5. Steffen Schneider
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  6. P. Mike Günther
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Corresponding author

Correspondence to J. Michael Köhler .

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Editors and Affiliations

  1. , Department of Nano Biophotonics, Institute of Photonic Technology (IPHT), Albert-Einstein-Str. 9, Jena, 07745, Germany

    Wolfgang Fritzsche

  2. , Inst. für Physikalische Chemie, Universität Jena, Helmholtzweg 4, Jena, 07743, Germany

    Jürgen Popp

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Köhler, J.M., Funfak, A., Cao, J., Kürsten, D., Schneider, S., Günther, P.M. (2012). Addressing of Concentration Spaces for Bioscreenings by Micro Segmented Flow with Microphotometric and Microfluorimetric Detection. In: Fritzsche, W., Popp, J. (eds) Optical Nano- and Microsystems for Bioanalytics. Springer Series on Chemical Sensors and Biosensors, vol 10. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-25498-7_2

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