Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Integrated nanoliter systems


Microfluidic chip platforms for manipulating liquid volumes in the nanoliter range are slowly inching their way into mainstream genomic and proteomic research. The principal challenge faced by these technologies is the need for high-throughput processing of increasingly smaller volumes, with ever higher degrees of parallelization. Significant advances have been made over the past few years in addressing these needs through electrokinetic manipulation, vesicle encapsulation and mechanical valve approaches. These strategies allow levels of integration density and platform complexity that promise to make them into serious alternatives to current robotic systems.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type



Prices may be subject to local taxes which are calculated during checkout

Figure 1: Optical micrograph of a nanofluidic system that can be used for parallelized high-throughput screening of fluorescence-based single-cell assays.
Figure 2: Automated microfluidic single-cell analysis device.
Figure 3: Parallel processing with nanoliters.
Figure 4: The analog of Moore's Law for nanofluidic systems.


  1. Manz, A. et al. Planar chips technology for miniaturization and integration of separation techniques into monitoring systems: capillary electrophoresis on a chip. J. Chromatogr. 593, 253–258 (1992).

    Article  CAS  Google Scholar 

  2. Reyes, D.R., Iossifidis, D., Auroux, P.A. & Manz, A. Micro total analysis systems. 1. Introduction, theory, and technology. Anal. Chem. 74, 2623–2636 (2002).

    Article  CAS  Google Scholar 

  3. Auroux, P.A., Iossifidis, D., Reyes, D.R. & Manz, A. Micro total analysis systems. 2. Analytical standard operations and applications. Anal. Chem. 74, 2637–2652 (2002).

    Article  CAS  Google Scholar 

  4. Khandurina, J. & Guttman, A. Bioanalysis in microfluidic devices. J. Chromatogr. A 943, 159–183 (2002).

    Article  CAS  Google Scholar 

  5. Quake, S.R. & Scherer, A. From micro- to nanofabrication with soft materials. Science 290, 1536–1540 (2000).

    Article  CAS  Google Scholar 

  6. Hansen, C.L. & Quake, S.R. Microfluidics in structural biology: smaller, faster... better. Curr. Opin. Struct. Biol. in the press (2003).

  7. Madou, M.J. Fundamentals of Microfabrication: The Science of Miniaturization. edn 2 (CRC Press, Boca Raton, Florida, 2002).

  8. Yuen, P.K. et al. Microchip module for blood sample preparation and nucleic acid amplification reactions. Genome Res. 11, 405–412 (2001).

    Article  CAS  Google Scholar 

  9. Anderson, R.C., Su, X., Bogdan, G.J. & Fenton, J. A miniature integrated device for automated multistep genetic assays. Nucleic Acids Res. 28, E60 (2000).

    Article  CAS  Google Scholar 

  10. Moorthy, J. & Beebe, D. Organic and biomimetic designs for microfluidic systems. Anal. Chem. 75, 293A–301A (2003).

    Article  Google Scholar 

  11. Emrich, C.A., Tian, H., Medintz, I.L. & Mathies, R.A. Microfabricated 384-lane capillary array electrophoresis bioanalyzer for ultrahigh-throughput genetic analysis. Anal. Chem. 74, 5076–5083 (2002).

    Article  CAS  Google Scholar 

  12. Kuo, T.-C., Cannon, D.M. Jr., Shannon, M.A., Bohn, P.W. & Sweedler, J.V. Hybrid three-dimensional nanofluidic/microfluidic devices using molecular gates. Sens. Actuators A 102, 223–233 (2003).

    Article  CAS  Google Scholar 

  13. Burns, M.A. et al. An integrated nanoliter DNA analysis device. Science 282, 484–487 (1998).

    Article  CAS  Google Scholar 

  14. Thorsen, T., Roberts, R.W., Arnold, F.H. & Quake, S.R. Dynamic pattern formation in a vesicle-generating microfluidic device. Phys. Rev. Lett. 86, 4163–4166 (2001).

    Article  CAS  Google Scholar 

  15. Anna, S., Bontoux, N. & Stone, H. Formation of dispersions using “flow focusing” in microchannels. Appl. Phys Lett. 82, 364–366 (2003).

    Article  CAS  Google Scholar 

  16. Song, H., Tice, J.D. & Ismagilov, R.F. A microfluidic system for controlling reaction networks in time. Angew. Chem. Int. Ed. 42, 768–772 (2003).

    Article  CAS  Google Scholar 

  17. Karlsson, A. et al. Nanofluidic networks based on surfactant membrane technology. Anal. Chem. 75, 2529–2537 (2003).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  19. Jacobson, S.C. & Ramsey, J.M. Anal. Chem. 68, 720–723 (1996).

    Article  CAS  Google Scholar 

  20. Broyles, B.S., Jacobson, S.C. & Ramsey, J.M. Sample filtration, concentration, and separation integrated on microfluidic devices. Anal. Chem. 75, 2761–2767 (2003).

    Article  CAS  Google Scholar 

  21. Tang, T. et al. Integrated microfluidic electrophoresis system for analysis of genetic materials using signal amplification methods. Anal. Chem. 74, 725–733 (2002).

    Article  CAS  Google Scholar 

  22. Ramsey, J.M. et al. Anal. Chem. AC0346510, in the press (2003).

  23. Hansen, C.L., Skordalakes, E., Berger, J.M. & Quake, S.R. A robust and scalable microfluidic metering method that allows protein crystal growth by free interface diffusion. Proc. Natl. Acad. Sci. USA 99, 16531–16536 (2002).

    Article  CAS  Google Scholar 

  24. Liu, J., Hansen, C.L. & Quake, S.R. Solving the world-to-chip interface problem with a microfluidic matrix. Anal. Chem. in the press (2003).

  25. Jeon, N. et al. Neutrophil chemotaxis in linear and complex gradients of interleukin-8 formed in a microfabricated device. Nat. Biotechnol. 20, 826–836 (2002).

    Article  CAS  Google Scholar 

  26. Pollack, L. et al. Time-resolved collapse of a folding protein observed with small angle X-ray scattering. Phys. Rev. Lett. 86, 4962–4965 (2001).

    Article  CAS  Google Scholar 

Download references


The authors would like to thank the various members of the Quake group, past and present, for many stimulating discussions.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Stephen R Quake.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Hong, J., Quake, S. Integrated nanoliter systems. Nat Biotechnol 21, 1179–1183 (2003).

Download citation

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing