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Multipurpose microfluidic probe


Microfluidic systems allow (bio)chemical processes to be miniaturized with the benefit of shorter time-to-result, parallelism, reduced sample consumption, laminar flow, and increased control and efficiency. However, such miniaturization inherently limits the size of the solid objects that can be processed and entails new challenges such as the interfacing of macroscopic samples with microscopic conduits. Here, we report a microfluidic probe (MFP) that overcomes these problems by combining the concepts of ‘microfluidics’ and of ‘scanning probes’. Here, liquid boundaries formed by hydrodynamic forces underneath the MFP confine a flow of processing solution and replace the solid walls of closed microchannels. The MFP is therefore mobile and can be used to process large surfaces and objects by scanning across them. We illustrate the versatility of this concept with several examples including protein microarraying, complex gradient-formation, multiphase laminar-flow patterning, erasing, localized staining of cells and the contact-free detachment of a single cell. Many constraints imposed by the monolithic construction of microfluidic channels can now be circumvented using an MFP, opening up new avenues for microfluidic processing.

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Figure 1: MFP and HFC.
Figure 2: Fluorescence micrographs of patterns of fluorescently labelled proteins deposited on glass using an MFP.
Figure 3: Manipulation of an MFP using a slender clamping rod.
Figure 4: Fluorescence micrograph of a protein array that was patterned using an MFP.
Figure 5: Advanced surface processes enabled by using an MFP.
Figure 6: Contact-free processing of selected adherent cells performed using an MFP under immersion conditions.
Figure 7: Selective detachment and collection of a single living cell from a surface.

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  1. Nguyen, N. -T. & Wereley, S. T. Fundamentals and Applications of Microfluidics (Artech House MEMS Series, Artech House, Boston, 2002).

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

    Article  CAS  Google Scholar 

  4. Hansen, C. & Quake, S. R. Microfluidics in structural biology: smaller, faster … better. Curr. Opin. Struct. Biol. 13, 538–544 (2003).

    Article  CAS  Google Scholar 

  5. Kopp, M. U., de Mello, A. J. & Manz, A. Chemical amplification: continuous-flow PCR on a chip. Science 280, 1046–1048 (1998).

    Article  CAS  Google Scholar 

  6. Hatch, A. et al. A rapid diffusion immunoassay in a T-sensor. Nature Biotechnol. 19, 461–465 (2001).

    Article  CAS  Google Scholar 

  7. Knight, J. B., Vishwanath, A., Brody, J. P. & Austin, R. H. Hydrodynamic focusing on a silicon chip: mixing nanoliters in microseconds. Phys. Rev. Lett. 80, 3863–3866 (1998).

    Article  CAS  Google Scholar 

  8. Juncker, D. et al. Autonomous microfluidic capillary system. Anal. Chem. 74, 6139–6144 (2002).

    Article  CAS  Google Scholar 

  9. Brody, J. P., Yager, P., Goldstein, R. E. & Austin, R. H. Biotechnology at low Reynolds numbers. Biophys. J. 6, 3430–3441 (1996).

    Article  Google Scholar 

  10. Delamarche, E. et al. Microfluidic networks for chemical patterning of substrates: design and application to bioassays. J. Am. Chem. Soc. 120, 500–508 (1998).

    Article  CAS  Google Scholar 

  11. Streeter, V. L., Wylie, E. B. & Bedford, K. Fluid Mechanics 9th edn 260–262 (McGraw-Hill, Singapore, 1998).

    Google Scholar 

  12. Stroock, A. D. et al. Chaotic mixer for microchannels. Science 295, 647–651 (2002).

    Article  CAS  Google Scholar 

  13. Myers, R. D. An improved push-pull cannula system for perfusing an isolated region of the brain. Physiol. Behav. 5, 243–246 (1970).

    Article  CAS  Google Scholar 

  14. Kottegada, S., Imtiazuddin, S. & Shippy, S. A. Demonstration of low flow push-pull perfusion. J. Neurosci. Methods 121, 93–101 (2002).

    Article  Google Scholar 

  15. Feinerman, O. & Moses, E. A picoliter ‘fountain-pen’ using co-axial dual pipettes. J. Neurosci. Methods 127, 75–84 (2003). Erratum. ibid 128, 197 (2003).

    Article  Google Scholar 

  16. Meyer, E., Hug, H. J. & Bennewitz, R. Scanning Probe Microscopy: The Lab on a Tip (Springer, Berlin, 2004).

    Book  Google Scholar 

  17. Bard, A. J. & Mirkin, M. V. Scanning Electrochemical Microscopy (Marcel Dekker, New York, 2001).

    Book  Google Scholar 

  18. Ginger, D. S., Zhang, H. & Mirkin, C. A. The evolution of dip-pen nanolithography. Angew. Chem. Int. Edn Engl. 43, 30–45 (2003).

    Article  CAS  Google Scholar 

  19. Bruckbauer, A. et al. Multicomponent submicron features of biomolecules created by voltage controlled deposition from a nanopipet. J. Am. Chem. Soc. 125, 9834–9839 (2003).

    Article  CAS  Google Scholar 

  20. Kundu, P. K. & Cohen, I. M. Fluid Mechanics 2nd edn 274–277 (Academic, San Diego, California, 2002).

    Google Scholar 

  21. Rose, D. in Microarray Biochip Technologies (ed. Schena, M.) 19–38 (Eaton Publishing, Natick, Massachusetts, USA, 2000).

    Google Scholar 

  22. McQuain, M. K., Seale, K., Peek, J., Levy, S. & Haselton, F. R. Effects of relative humidity and buffer additives on the contact printing of microarrays by quill pins. Anal. Biochem. 320, 281–287 (2003).

    Article  CAS  Google Scholar 

  23. Wolf, M., Juncker, D., Michel, B., Hunziker, P. & Delamarche, E. Simultaneous detection of C-reactive protein and other cardiac markers in human plasma using micromosaic immunoassays and self-regulating microfluidic networks. Biosen. Bioelectron. 19, 1193–1202 (2004).

    Article  CAS  Google Scholar 

  24. Caelen, I. et al. Formation of gradients of proteins on surfaces with microfluidic networks. Langmuir 16, 9125–9130 (2000).

    Article  CAS  Google Scholar 

  25. Fosser, K. A. & Nuzzo, R. G. Fabrication of patterned multicomponent protein gradients and gradient arrays using microfluidic depletion. Anal. Chem. 75, 5775–5782 (2003).

    Article  CAS  Google Scholar 

  26. Smith, J. T. et al. Measurement of cell migration on surface-bound fibronectin gradients. Langmuir 20, 8279–8286 (2004).

    Article  CAS  Google Scholar 

  27. Jeon, N. L. et al. Neutrophil chemotaxis in linear and complex gradients of interleukin-8 formed in a microfabricated device. Nature Biotechnol. 20, 826–830 (2002).

    Article  CAS  Google Scholar 

  28. Chung, B. G. et al. Human neural stem cell growth and differentiation in a gradient-generating microfluidic device. Lab on a Chip 5, 401–406 (2005).

    Article  CAS  Google Scholar 

  29. Kenis, P. J. A., Ismagilov, R. F. & Whitesides, G. M. Microfabrication inside capillaries using multiphase laminar flow patterning. Science 285, 83–85 (1999).

    Article  CAS  Google Scholar 

  30. Sirringhaus, H. et al. High-resolution inkjet printing of all-polymer transistor circuits. Science 290, 2123–2126 (2000).

    Article  CAS  Google Scholar 

  31. Takayama, S. et al. Selective chemical treatment of cellular microdomains using multiple laminar streams. Chem. Biol. 10, 123–130 (2003).

    Article  CAS  Google Scholar 

  32. Oberti, S., Stemmer, A., Juncker, D., Dürig, U. & Schmid, H. Microsqueeze force sensor useful as contact-free profilometer and viscometer. Appl. Phys. Lett. 86, 063508 (2005).

    Article  Google Scholar 

  33. Shimoda, T., Morii, K., Seki, S. & Kiguchi, H. Inkjet printing of light-emitting polymer displays. Mater. Res. Soc. Bull. 28, 821–828 (2003).

    Article  CAS  Google Scholar 

  34. Juncker, D. et al. Soft and rigid two-level microfluidic networks for patterning surfaces. J. Micromech. Microeng. 11, 532–541 (2001).

    Article  CAS  Google Scholar 

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We thank U. Drechsler and R. Stutz for technical assistance, W. Riess, B. Michel and M. Despont for discussions, T. Hocker for performing finite-element-model simulations, G. Csúcs for providing the cells and P. F. Seidler for support.

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Correspondence to David Juncker.

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Juncker, D., Schmid, H. & Delamarche, E. Multipurpose microfluidic probe. Nature Mater 4, 622–628 (2005).

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