DOI: 10.1002/adma.200501129 Microfluidics for Processing Surfaces and Miniaturizing Biological Assays** By Emmanuel Delamarche ,* David Juncker, and Heinz Schmid 1. Introduction to Microfluidic Systems Microfluidics refers to the handling of liquids or gases at a scale generally below 1 mm, where a number of phenomena that are not present or not predominant at larger scales can be exploited for numerous purposes. [1] The field of microflui- dics is in essence multidisciplinary as it combines microfabri- cation techniques with chemistry and biology. [2,3] Within mi- crofluidics, the currencies are nanoliters for reaction volumes, [4] micrometers for dimensions, [5] and milliseconds for diffusion and reaction times. [6,7] The accurate sampling, posi- tioning, and transport of nanoliter volumes of liquids using microfluidics mirror the high dimensional control with which microfluidic devices are made. In this review, we describe a technology based on microfluidic networks (MFNs) and mi- crofluidic probes (MFPs) that is useful to localize chemical and biochemical reactions on a surface, where the possibility of reversibly placing a microfluidic element in contact with or close to a surface constitutes an essential feature for attaining patterning resolutions on the submicrometer scale. [5,8] REVIEW Adv. Mater. 2005, 17, 2911–2933 © 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim 2911 This review is an account of our efforts to develop a versatile and flexible microfluidic technology for surface-processing applications and miniatur- izing biological assays. The review is presented in the context of current trends in microfluidic technology and addresses some of the major chal- lenges for confining chemical and biochemical processes on surfaces: the sealing of a microchannel with a surface, the world-to-chip interface, the displacement of liquids in small conduits, the sequential delivery of multiple solutions, the accurate patterning of surfaces, the coincident detection of various analytes, and the detection of analytes in a small and dilute sample. Our solutions to these problems include the use of reversible sealing, capillary phenomena for powering and controlling liquid transport, and non-contact microfluidics for spotting and drawing (on surfaces) with flow conditions. These solutions offer many advantages over conventional tech- niques for handling minute amounts of liquids and may find applications in lithography, biopat- terning (e.g., the patterning of biomolecules), diagnostics, drug discovery, and also cellular assays. – [*] Dr. E. Delamarche,Dr. D. Juncker, [+] H. Schmid IBM Research GmbH, Zürich Research Laboratory Säumerstrasse 4, 8803 Rüschlikon (Switzerland) E-mail: emd@zurich.ibm.com [+] Present address: Dept. of Biomedical Engineering, McGill University, 3775 University Street, Montreal, Quebec H3A 2B4, Canada. [**] We are very grateful to Bruno Michel, Paul F. Seidler, and Walter Riess for their continuous support of this work. We also would like to thank André Bernard, Hans Biebuyck, Sandro Cesaro-Tadic, Isabelle Caelen, Alexander Papra, Alexander Bietsch, Heiko Wolf, Matthias Geissler, Jean-Philippe Renault, Marc Wolf, Martin Zim- mermann, Patrick Hunziker, Steven Bentley, Jennifer Foley, Gregor Dernick, Christof Fattinger, Gerrit Buurman, and Harald Krops- hofer for their valuable help with many aspects of our work. We also thank Ute Drechsler, Richard Stutz, and Michel Despont for their expertise in and support with the microfabrication of Si chips, and Govindarajan Natarajan and James Humenik for the development and fabrication of ceramic microfluidic chips and for making Figures 4D,E available to us. We thank Erich Ruetsche, Scott Partington, Matthew Denesuk, Albert Young, Nils Omland, Laurent Malaquin, and Tobias Kraus for helpful discussions, and Charlotte Bolliger for her help with the manu- script.