Monolithic membrane valves and diaphragm pumps for practical large-scale integration into glass micro¯uidic devices William H. Grover a , Alison M. Skelley a , Chung N. Liu b , Eric T. Lagally c , Richard A. Mathies a,c,* a Department of Chemistry, University of California, Berkeley, CA 94720, USA b Department of Chemical Engineering, University of California, Berkeley, CA 94720, USA c UC Berkeley/UC San Francisco Joint Bioengineering Graduate Group, University of California, Berkeley, CA 94720, USA Accepted 11 December 2002 Abstract Monolithic elastomer membrane valves and diaphragm pumps suitable for large-scale integration into glass micro¯uidic analysis devices are fabricated and characterized. Valves and pumps are fabricated by sandwiching an elastomer membrane between etched glass ¯uidicchannelandmanifoldwafers.Athree-layervalveandpumpdesignfeaturessimplenon-thermaldevicebondingandahybridglass- PDMS ¯uidic channel; a four-layer structure includes a glass ¯uidic system with minimal ¯uid-elastomer contact for improved chemical and biochemical compatibility. The pneumatically actuated valves have <10nl dead volumes, can be fabricated in dense arrays, and can beaddressedinparallelviaanintegratedmanifold.Themembranevalvesprovide¯owratesupto380nl/sat30kPadrivingpressureand seal reliably against ¯uid pressures as high as 75kPa. The diaphragm pumps are self-priming, pump from a few nanoliters to a few microliters per cycle at overall rates from 1 to over 100nl/s, and can reliably pump against 42kPa pressure heads. These valves and pumps provide a facile and reliable integrated technology for ¯uid manipulation in complex glass micro¯uidic and electrophoretic analysis devices. # 2003 Elsevier Science B.V. All rights reserved. Keywords: PDMS membrane valves; Micropumps; Integrated devices 1. Introduction Micro¯uidic lab-on-a-chip analyzers have advanced rapidly from early single-channel devices [1] to current complex systems that can perform a wide variety of assays [2,3]. Successful micro¯uidic assays have included poly- morphism detection for breast cancer risk assessment [4], parallel combinatorial synthesis and analysis of chemical libraries [5], high-throughput genotyping [6] and DNA sequencing [7], chemical and biological antigen detection [8], and chiral resolution of amino acids for exobiological analysis [9]. However, the development of complete inte- grated systems for on-chip sample preparation and manip- ulationhasshownmoremodestgrowth.Thusfar,automated HIVgenotypinghasbeendemonstratedinapolymermicro- ¯uidic device that combines puri®cation, ampli®cation, and microarray hybridization steps [10],DNAampli®cationand integrated electrophoretic analysis in a glass micro¯uidic device has been demonstrated using individually addressed valves and vents to isolate ¯uids [11], automated protein sizing has been performed in a glass device using pressure- driven ¯ow and electrophoresis to route ¯uids [12], and automated pathogen detection has been demonstrated in a micromachined polymer device utilizing membrane valves and pumps [13]. Complex fabrication, chemical compat- ibility, and unreliable ¯uid manipulation, among other problems, have made existing ¯uidic manipulation technol- ogies disadvantageous for integration into large-scale, high- throughputlab-on-a-chipdevices.Ausefulon-chipmechan- ismfornl-to ml-scale¯uidmanipulationmustbecompatible with the assay chemistry, be able to accurately and reliably meter known volumes of ¯uid, and be amenable to facile large-scale integration. Avarietyofmicrofabricatedvalvesandpumpshavebeen developedforon-chip¯uidicmanipulationandcontrol.The earliest examples were fabricated using anodically bonded silicon and glass wafers and actuated piezoelectrically [14,15]. The electrical conductivity and chemical compat- ibility of silicon, which can complicate its use in analytical Sensors and Actuators B 89 (2003) 315±323 * Corresponding author. Tel.: 1-510-642-4192; fax: 1-510-642-3599. E-mail address: rich@zinc.cchem.berkeley.edu (R.A. Mathies). 0925-4005/03/$ ± see front matter # 2003 Elsevier Science B.V. All rights reserved. doi:10.1016/S0925-4005(02)00468-9