PRACTICAL VALVES AND PUMPS FOR LARGE-SCALE INTEGRATION INTO MICROFLUIDIC ANALYSIS DEVICES William H. Grover, Alison M. Skelley, Chung N. Liu,1 Eric T. Lagally,2 and Richard A. Mathies 2
1 Departments of Chemistry and Chemical Engineering, UC Berkeley / UC San Francisco Joint Bioengineering Graduate Group, University of California, Berkeley, CA 94720
Y. Baba et al. (eds.), Micro Total Analysis Systems 2002, Nov. 3-7, Nara, Japan, Volume 1, Dordrecht, The Netherlands: Kluwer Academic Publishers, 136-138.
Abstract Pneumatically-actuated elastomer membrane valves and pumps for practical large-scale integration into glass µTAS devices are fabricated and characterized. The valves and pumps reliably manipulate nanoliterscale volumes of fluid, introduce low dead volumes into the microfluidic system, and are compatible with a wide range of device chemistries. The integrated pneumatic manifold and practical microfabrication process facilitate the production and use of high-density arrays of the valves and pumps. Keywords: PDMS membrane microvalve, micropump, integrated devices 1. Introduction An essential component of any point-of-analysis lab-on-a-chip device is an integrated mechanism for fluidic transport and reaction. For practical use in a µTAS device, microfabricated valves and pumps should be able to reproducibly manipulate nanoliter-scale volumes of fluid, be constructed of materials that are compatible with the assay chemistry, and be amenable to reliable large-scale high-density integration. The utility of microliter-scale pneumatically-driven membrane flex valves[l] encouraged us to develop a nanoliterscale version of this valve which was successfully incorporated into a device for the performance of nanoliter PCR coupled to capillary electrophoresis analysis on a chip. While these devices have worked well, the fabrication of these valves is neither practical nor reliable in high-density devices. To address these challenges, we have developed and characterized monolithic membrane valves and pumps suitable for large-scale integration into glass microfluidic analysis devices. 2. Experimental The monolithic membrane valves utilize a commercially-available PDMS (polydimethylsiloxane) membrane sandwiched between etched glass fluidic and manifold wafers, as shown in Figure 1. Channels are wet etched into the glass wafers using standard photolithographic techniques described elsewhere . Channels on the manifold wafer distribute vacuum or pressure to displacement chambers located below each valve. Two or more valves that require simultaneous actuation can be connected to the same manifold channel, thereby minimizing the number of pneumatic connections to the device. Applying a vacuum to a channel on the manifold layer deflects the PDMS membrane into the displacement chamber, allowing fluid to flow across the gaps in the fluidic channel and opening the valve. The three-layer design shown in Figure 1A utilizes hybrid glass-PDMS fluidic channels; it requires no thermal bonding and introduces very low (~ 10 nL) dead volumes to the fluidic system. The four-layer design shown in Figure 1B includes a thermallybonded 210 µm thick glass via wafer with pairs of 254 µm diameter drilled via holes positioned to correspond to the locations of valves on the fluidic wafer. The design features traditional all-glass fluidic channels for compatibility with many microfluidic analysis chemistries. We have also fabricated microfluidic diaphragm pumps consisting of three monolithic membrane valves placed in series, as shown in Figure 2. Darkfield images of the pump in operation are presented in Figure 3. Since the volume pumped per actuation cycle is determined in step 3 by the diaphragm valve displacement chamber volume, pumps for metering specific nanoliter- or microliter-scale volumes of fluids may be designed and fabricated. References 1. Anderson, R.C.; Su; X. Bogdan, G.J.; Fenton, J. Nucleic Acids Research 2000, 28, e60. 2. Lagally, E.T.; Simpson, P.C.; Mathies, R.A. Sensors and Actuators B 2000, 63, 138-146. 3. Lagally, E.T.; Medintz, I.; Mathies, R.A. Analytical Chemistry 2001, 73, 565-570. 4. Lagally, E.T.; Emrich, C.A.; Mathies, R.A. Lab-on-a-Chip 2001, 1, 102-107.
A) 3-layer topology
B) 4-layer topology Glass fluidic wafer
Glass fluidic wafer
Via PDMS membrane
PDMS membrane Glass manifold wafer
Glass manifold wafer
Displacement chamber Valve open
nt me ce ber a l p am Dis ch
1 Diaphragm valve
nt me ce ber a l p am Dis ch
Fig. 1. Cross-sectional, top, and oblique views of valves fabricated using 3-layer (A) and 4layer (B) topologies. Typical dimensions: d fluidic = 20 µm, dmanifold = 70 µm, wfluidic = 60 µm, wmanifold = 160 µm, Dvia = 254 µm, Dchamber = 1.28 to 6.28 mm.
Fig. 2. Oblique view of a diaphragm pump showing fluidic wafer (top), PDMS membrane, and manifold wafer (bottom).
Output valve 1 mm
Fig. 3. Darkfield images showing the five steps in the pumping cycle: (1) open input valve and close output valve, (2) open diaphragm valve, (3) close input valve, thereby defining the volume pumped p e r c yc l e , ( 4 ) o p e n o u t p u t va l ve , ( 5 ) c l o s e diaphragm valve.