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Microfluidics Technology for Systems Biology Research

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Systems Biology

Part of the book series: Methods in Molecular Biology ((MIMB,volume 500))

Summary

Systems biology is a discipline seeking to understand the emergent behavior of a biological system by integrative modeling of the interactions of the molecular elements. The success of the approach relies on the quality of the biological data. In this chapter, we discuss how a systems biology laboratory can apply microfluidics technology to acquire comprehensive, systematic, and quantitative data for their modeling needs.

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References

  1. Hood, L., Heath, J. R., Phelps, M. E., and Lin, B. (2004) Systems biology and new technologies enable predictive and preventative medicine. Science 306, 640–643.

    Article  PubMed  CAS  Google Scholar 

  2. Kitano, H. (2002) Systems biology: a brief overview. Science 295, 1662–1664.

    Article  PubMed  CAS  Google Scholar 

  3. Ideker, T., Galitski, T., and Hood, L. (2001) A new approach to decoding life: systems biology. Annu. Rev. Genomics Hum. Genet. 2, 343–372.

    Article  PubMed  CAS  Google Scholar 

  4. Irish, J., Hovland, R., Krutzik, P. O., Perez, O. D., Bruserud, Ø., Gjertsen, B. T., and Nolan, G. P. (2004) Single cell profiling of potentiated phospho-protein networks in cancer cells. Cell 118, 217–228.

    Article  PubMed  CAS  Google Scholar 

  5. Levchenko, A. (2003) Dynamical and integrative cell signaling: challenges for the new biology. Biotechnol. Bioeng. 84, 773–782.

    Article  PubMed  CAS  Google Scholar 

  6. ZSzallasi, (2006) Biological data acquisition for system level modeling — an exercise in the art of compromise, in System Modeling in Cellular Biology: From Concepts to Nuts and Bolts (Szallasi, Z., Stelling, J. R., and Periwal, V., eds.), MIT Press, Cambridge, MA, pp. 201– 220.

    Google Scholar 

  7. Melin, J. and Quake, S. R. (2007) rofluidic large-scale integration: the evolution of design rules for biological automation. Annu. Rev. Biophys. Biomol. Struct. 36, 213–231.

    Article  PubMed  Google Scholar 

  8. Melin, J. and Quake, S. R. (2007) rofluidic large-scale integration: the evolution of design rules for biological automation. Annu. Rev. Biophys. Biomol. Struct. 36, 213–231.

    Article  PubMed  CAS  Google Scholar 

  9. Breslauer, D., Lee, P., and Lee, L. Mic Microfluidics-based systems biology. Mol. Syst. Biol. 2, 97–112.

    Google Scholar 

  10. Kholodenko, B. (2006) Cell-signalling dynamics in time and space. Nat. Rev. Mol. Cell Biol. 7, 165–176.

    Article  PubMed  CAS  Google Scholar 

  11. Ferrell, J. J. and Machleder, E. (1998) The biochemical basis of an all-or-none cell fate switch in Xenopus oocytes. Science 280, 895–898.

    Article  PubMed  CAS  Google Scholar 

  12. Paliwal, S., Iglesias, P., Campbell, K., Hilioti, Z., Groisman, A., and Levchenko, A. (2007) MAPK-mediated bimodal gene expression and adaptive gradient sensing in yeast. Nature 446, 46–51.

    Article  PubMed  CAS  Google Scholar 

  13. Nelson, C., Vanduijn, M. M., Inman, J. L., Fletcher, D. A., and Bissell, M. J. (2006) Tissue geometry determines sites of mammary branching morphogenesis in organotypic cultures. Science 314, 298–300.

    Article  PubMed  CAS  Google Scholar 

  14. Desai, T. (2000) Micro- and nanoscale structures for tissue engineering constructs. Med. Eng. Phys. 22, 595–606.

    Article  PubMed  CAS  Google Scholar 

  15. Bhatia, S. and Chen, C. (1999) Tissue engineering at the micro-scale. Biomed. Microdevices 2, 131–144.

    Article  Google Scholar 

  16. Andrec, M., Kholodenko, B., Levy, R., and Sontag, E. (2004) Inference of signaling and gene regulatory networks by steady-state perturbation experiments: structure and accuracy. J. Theor. Biol. 232, 427–441.

    Google Scholar 

  17. Sontag, E., Kiyatkin, A., and Kholodenko, B. (2004) Inferring dynamic architecture of cellular networks using time series of gene expression, protein and metabolite data. Bioinformatics 20, 1877–1886.

    Article  PubMed  CAS  Google Scholar 

  18. Whitesides, G. M. (2006) The origins and the future of microfluidics. Nature 442, 368–373.

    Article  PubMed  CAS  Google Scholar 

  19. Beebe, D. J., Mensing, G. A., and Walker, G. M. (2002) Physics and applicaitons of microfluidics in biology. Annu. Rev. Biomed. Eng. 4, 261–286.

    Article  PubMed  CAS  Google Scholar 

  20. El-Ali, J., Sorger, P. K., and Jensen, K. F. (2006) Cells on chips. Nature 442, 403–411.

    Article  PubMed  CAS  Google Scholar 

  21. Haeberle, S. and Zengerle, R. (2007) Microfluidic platforms for lab-on-a-chip applications. Lab Chip 7, 1094–1110.

    Article  PubMed  CAS  Google Scholar 

  22. Helmke, B. P. and Minerick, A. R. (2006) Designing a nano-interface in a microfluidic chip to probe living cells: challenges and perspectives. Proc. Natl. Acad. Sci. USA 103, 6419–6424.

    Article  PubMed  CAS  Google Scholar 

  23. Xia, Y. and Whitesides, G. M. (1998) Soft lithography. Annu. Rev. Mater. Sci. 28, 153–184.

    Article  CAS  Google Scholar 

  24. Thorsen, T., Maerkl, S. J., and Quake, S. R. (2002) Microfluidic large-scale integration. Science 298, 580–584.

    Article  PubMed  CAS  Google Scholar 

  25. Unger, M. A., Chou, H.-P., Thorsen, T., Scherer, A., and Quake, S. R. (2000) Monolithic microfabricated valves and pumps by multilayer soft lithography. Science 288, 113–136.

    Article  PubMed  CAS  Google Scholar 

  26. Meyer, T. and Teruel, M. N. (2003) Fluorescence imaging of signaling networks. Trends Cell Biol. 13, 101–106.

    Article  PubMed  CAS  Google Scholar 

  27. Xie, X. S., Yu, J., and Yang, W. Y. (2006) Living cells as test tubes. Science 312, 228–230.

    Article  PubMed  CAS  Google Scholar 

  28. Goldman, R. D. and Spector, D. L. (eds.) (2004) Live Cell Imaging. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.

    Google Scholar 

  29. The Lee Company (http://www.theleeco.com)

  30. National Instrumentation (http://www.ni.com).

  31. Fluidigm Corporation, USA (http://www.fluidigm.com).

  32. Kartalov, E. P. and Quake, S. R. (2004) Microfluidic device reads up to four consecutive base pairs in DNA sequencing-by-synthesis. Nucleic Acids Res. 32, 2873–2879.

    Article  PubMed  CAS  Google Scholar 

  33. Haubert, K., Drier, T., and Beebe, D. (2006) PDMS bonding by means of a portable, low-cost corona system. Lab Chip 6, 1548–1549.

    Article  PubMed  CAS  Google Scholar 

  34. Vickers, J. A., Caulum, M. M., and Henry, C. S. (2006) Generation of hydrophilic poly(dimethylsiloxane) for high-performance microchip electrophoresis. Anal. Chem. 78, 7446–7452.

    Article  PubMed  CAS  Google Scholar 

  35. Jeon, N. L., Dertinger, S. K. W., Chiu, D. T., Choi, I. S., Stroock, A. D., and Whitesides, G. M. (2000) Generation of solution and surface gradients using microfluidic systems. Langmuir 16, 8311–8316.

    Article  CAS  Google Scholar 

  36. Jeon, N. L., Baskaran, H., Dertinger, S. K., Whitesides, G. M., Van de Water, L., and Toner, M. (2002) Neutrophil chemotaxis in linear and complex gradients of interleukin-8 formed in a microfabricated device. Nat. Biotechnol. 20, 826–830.

    CAS  Google Scholar 

  37. Dertinger, S. K., Jiang, X., Li, Z., Murthy, V. N., and Whitesides, G. M. (2002) Gradients of substrate-bound laminin orient axonal specification of neurons. Proc. Natl. Acad. Sci. USA 99, 12542–12547.

    Article  PubMed  CAS  Google Scholar 

  38. Wang, C. J., Li, X., Lin, B., Shim, S., Ming, G.-L., and Levchenko, A. (2008) A microfluidics-based turning assay reveals complex growth cone responses to integrated gradients of substrate-bound ECM molecules and diffusible guidance cues. Lab Chip 8, 227–237.

    Article  CAS  Google Scholar 

  39. Abhyankar, V. V., Lokuta, M. A., Huttenlocher, A., and Beebe, D. J. (2006) Characterization of a membrane-based gradient generator for use in cell-signaling studies. Lab Chip 6, 389–393.

    Article  PubMed  CAS  Google Scholar 

  40. Taylor, A. M., Blurton-Jones, M., Rhee, S. W., Cribbs, D. H., Cotman, C. W., and Jeon, N. L. (2005) A microfluidic culture platform for CNS axonal injury, regeneration and transport. Nat. Methods 2, 599–605.

    Article  PubMed  CAS  Google Scholar 

  41. Lucchetta, E. M., Lee, J. H., Fu, L. A., Patel, N. H., and Ismagilov, R. F. (2005) Dynamics of Drosophila embryonic patterning network perturbed in space and time using microfluidics. Nature 434, 1134–1138.

    Article  PubMed  CAS  Google Scholar 

  42. Sawano, A., Takayama, S., Matsuda, M., and Miyawaki, A. (2002) Lateral propagation of EGF signaling after local stimulation is dependent on receptor density. Dev. Cell 3, 245–257.

    Article  PubMed  CAS  Google Scholar 

  43. Bhalla, U. S., Ram, P. T., and Iyengar, R. (2002) MAP kinase phosphatase as a locus of flexibility in a mitogen-activated protein kinase signaling network. Science 297, 1018–1023.

    Article  PubMed  CAS  Google Scholar 

  44. Krishnan , J. and Iglesias , P. A .(2004) Uncovering directional sensing: where are we headed?Syst. Biol. 1 , 54–61 .

    Article  CAS  Google Scholar 

  45. King, K. R., Wang, S., Jayaraman, A., Yarmush, M. L., and Toner, M. (2008) Microfluidic flow-encoded switching for parallel control of dynamic cellular microenvironments. Lab Chip 8, 107–116.

    Article  PubMed  CAS  Google Scholar 

  46. Cheong, R., Wang, C. J., and Levchenko, A. (2008) High-throughput immunofluorescence analysis of single cell signaling dynamics using microfluidics. Submitted for publication .

    Google Scholar 

  47. Kaneda, A., Wang, C. J., Cheong, R., Timp, W., Onyango, P., Wen, B., Iacobuzio-Donahue, C. A., Ohlsson, R., Andraos, R., Pearson, M. A., Sharov, A. A., Longo, D. L., Ko, M. S., Levchenko, A., and Feinberg, A. P. (2007) Enhanced sensitivity to IGF-II signaling links loss of imprinting of IGF2 to increased cell proliferation and tumor risk. Proc. Natl. Acad. Sci. USA 104, 20926–20931.

    Article  PubMed  CAS  Google Scholar 

  48. Cho, H., Jönsson.H., Campbell, K., Melke, P., Williams, J. W., Jedynak, B., Stevens, A. M., Groisman, A., and Levchenko, A. (2007) Self-organization in high-density bacterial colonies: efficient crowd control. PLoS Biol. 5, e302.

    Article  PubMed  Google Scholar 

  49. Groisman, A., Lobo, C., Cho, H., Campbell, J. K., Dufour, Y. S., Stevens, A. M., and Levchenko, A. (2005) A microfluidic chemostat for experiments with bacterial and yeast cells. Nat. Methods 2, 685–689.

    Article  PubMed  CAS  Google Scholar 

  50. Higgins, J. M., Eddington, D. T., Bhatia, S. N., and Mahadevan, L. (2007) Sickle cell vasoocclusion and rescue in a microfluidic device. Proc. Natl. Acad. Sci. USA 104, 20496–20500.

    Article  PubMed  CAS  Google Scholar 

  51. Runyon, M. K., Johnson-Kerner, B. L., and Ismagilov, R. F. (2004) Minimal functional model of hemostasis in a biomimetic microfluidic system. Angew. Chem. Int. Ed. Engl. 43, 1531–1536.

    Article  PubMed  CAS  Google Scholar 

  52. Loscalzo , J. , Kohane , I. , and Barabasi , A.-L .(2007) Human disease classification in the postgenomic era: a complex systems approach to human pathobiology . Mol. Syst. Biol . 3–124 .

    Article  PubMed  Google Scholar 

  53. Ottesen, E. A., Hong, J. W., Quake, S. R., and Leadbetter, J. R. (2006) Microfluidic digital PCR enables multigene analysis of individual environmental bacteria. Science 314, 1464–1467.

    Article  PubMed  CAS  Google Scholar 

  54. Warren, L., Bryder, D., Weissman, I. L., and Quake, S. R. (2006) Transcription factor profiling in individual hematopoietic progenitors by digital RT-PCR. Proc. Natl. Acad. Sci. USA 103, 17807–17812.

    Article  PubMed  CAS  Google Scholar 

  55. Vogelstein, B. and Kinzler, K. W. (1999) Digital PCR. Proc. Natl. Acad. Sci. USA 96, 9236–9241.

    Article  PubMed  CAS  Google Scholar 

  56. Maerkl, S. J. and Quake, S. R. (2007) A systems approach to measuring the binding energy landscapes of transcription factors. Science 315, 233–237.

    Article  PubMed  CAS  Google Scholar 

  57. Fu, A. Y., Chou, H.-P., Spence, C., Arnold, F. H., and Quake, S. R. (2002) An integrated microfabricated cell sorter. Anal. Chem. 74, 2451–2457.

    Article  PubMed  CAS  Google Scholar 

  58. Takahashi, K., Hattori, A., Suzuki, I., Ichiki, T., and Yasuda, K. (2004) Non-destructive on-chip cell sorting system with real-time microscopic image processing. J. Nanobiotechnol. 2, 5.

    Article  Google Scholar 

  59. Wang, M. M., Tu, E., Raymond, D. E., Yang, J. M., Zhang, H., Hagen, N., Dees, B., Mercer, E. M., Forster, A. H., Kariv, I., Marchand, P. J., and Butler, W. F. (2005) Microfluidic sorting of mammalian cells by optical force switching. Nat. Biotechnol. 23, 83–87.

    Article  PubMed  CAS  Google Scholar 

  60. Marcy, Y., Ishoey, T., Lasken, R. S., Stockwell, T. B., Walenz, B. P., Halpern, A. L., Beeson, K. Y., Goldberg, S. M., and Quake, S. R. (2007) Nanoliter reactors improve multiple displacement amplification of genomes from single cells. PLoS Genet. 3, 1702–1708.

    Article  PubMed  CAS  Google Scholar 

  61. Hong, J. W., Studer, V., Hang, G., Anderson, W. F., and Quake, S. R. (2004) A nanoliter-scale nucleic acid processor with parallel architecture. Nat. Biotechnol. 22, 435–439.

    Article  PubMed  CAS  Google Scholar 

  62. Marcus, J. S., Anderson, W. F., and Quake, S. R. (2006) Microfluidic single-cell mRNA isolation and analysis. Anal. Chem. 78, 3084–3089.

    Article  PubMed  CAS  Google Scholar 

  63. Burg, T. P., Godin, M., Knudsen, S. M., Shen, W., Carlson, G., Foster, J. S., Babcock, K., and Manalis, S. R. (2007) Weighing of biomolecules, single cells and single nanoparticles in fluid. Nature 446, 1066–1069.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors would like to thank Benjamin Lin for reading the manuscript critically.

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Authors and Affiliations

  1. Whitaker Institute for Biomedical Engineering, Institute for Cell Engineering, Department of Biomedical Engineering, Johns Hopkins University, School of Medicine, 208C Clark Hall, 3400 North Charles Street, Baltimore, MD, 21218, USA

    Andre Levchenko

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  1. C. Joanne Wang
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  2. Andre Levchenko
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Correspondence to Andre Levchenko .

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    © 2009 Humana Press

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    Wang, C., Levchenko, A. (2009). Microfluidics Technology for Systems Biology Research. In: Maly, I. (eds) Systems Biology. Methods in Molecular Biology, vol 500. Humana Press. https://doi.org/10.1007/978-1-59745-525-1_7

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    • DOI: https://doi.org/10.1007/978-1-59745-525-1_7

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    • Publisher Name: Humana Press

    • Print ISBN: 978-1-934115-64-0

    • Online ISBN: 978-1-59745-525-1

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