ARTICLES Multipurpose microfluidic probe DAVID JUNCKER* † , HEINZ SCHMID AND EMMANUEL DELAMARCHE Z¨ urich Research Laboratory, IBM Research GmbH, 8803 R ¨ uschlikon, Switzerland *Present address: Micro and Nanosystems, ETH Z ¨ urich, 8092 Z ¨ urich, Switzerland † e-mail: djuncker@yahoo.com Published online: 24 July 2005; doi:10.1038/nmat1435 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. M icrofluidic systems are extraordinary in reducing sample consumption, speeding up reaction rates and improving efficiency while allowing for parallelization 1–8 . Microconduits form the heart of microfluidic systems in providing the microfluidic space where mass transport is enhanced because of reduced diffusion distances and where laminar flow prevails 6–10 . However, high flow resistances, the difficulty of introducing the samples into microconduits and the clogging of the microfluidic systems with samples or impurities limit their practical use. For example, if large surfaces need to be processed, microfluidics become unpractical because for centimetre-long channels the flow resistance is excessively large and does not allow one to flush sufficient quantities of liquids or to exchange solutions within the microchannels. Moreover, large objects, for example, tissue slices, cannot be enclosed within a microchannel and up to now could not be processed with microfluidics. Here, we present an approach where the microfluidic flow is locally created on the sample surface and confined by liquid boundaries in the gap formed between an MFP—described in detail below—and the surface. This approach circumvents the need for inserting the sample into a closed microchannel by replacing solid walls with liquid boundaries that are formed by hydrodynamic forces. Thus, a microfluidic flow can be created locally on any object or surface in a geometrically open space and moved to a random location or scanned along an arbitrary path by moving the MFP. Let us consider a mesa immersed in a fluid that has a microscopic aspiration aperture at its middle. The aspiration of fluid into the aperture will generate a hemispherical flow field around the aperture. Positioning the mesa parallel to a surface defines a gap in which the aspiration of the immersion fluid generates a radial flow field between the two surfaces. If the gap is sufficiently small, it forms a microfluidic space where turbulences are suppressed and the flow field is laminar 9 . On adding a second aperture in the mesa, a fluid can be injected into the flow field of the immersion fluid. We define as an MFP a chip with a mesa that has both an aspiration and an injection aperture. A processing solution injected into the gap and aspirated downstream into the aspiration aperture can now be confined entirely if the geometrical parameters as well as the flow rates of both the injected solution and of the aspirated surrounding liquid are properly adjusted. That is, if the injection flow rate (Q I ) is nature materials ADVANCE ONLINE PUBLICATION www.nature.com/naturematerials 1 © 2005 Nature Publishing Group