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Phase Change Microvalve for Integrated Devices Rohit Pal,†,‡ Ming Yang,†,‡ Brian N. Johnson,† David T. Burke,§ and Mark A. Burns*,†,|
Department of Chemical Engineering, Department of Electrical Engineering, Department of Human Genetics, and Department of Biomedical Engineering, The University of Michigan, Ann Arbor, Michigan 48109-2136
An active microvalve that uses a meltable piston in place of a conventional solid material to obstruct fluid flow in a microfluidic channel has been developed. This phase change valve is simple to operate and requires no additional fabrication steps. The valve is inherently latched, reusable, and leak-proof (to at least 250 psi) and can be electronically addressed using resistive heaters. The valve has been characterized for a range of operational parameters that will serve as a design guide. For the designs tested, piston displacements of 5 mm or more in 1 s have been achieved. Valves 1.4 mm in length in a 50 µm × 200 µm channel have been integrated on a biochemical reaction device, and successful DNA amplification using PCR has been achieved. The phase change valve can be easily implemented in an array format that can be used to realize complex microfluidic circuits. Microfabricated systems not only offer significant scaling advantages in cost and data throughput by miniaturizing existing laboratory procedures but they also provide a platform for novel technologies that can be realized only at the micro/nanolength scales.1,2 Systems such as lab-on-a-chip are being adapted for genomic, proteomic, and cellular assays.3 Applications of such devices include drug screening, drug delivery, in situ monitoring, and portable diagnostics. Microfluidics holds the key to the on-chip system-level integration of sample preparation, mixing, reaction, and separation in such microfabricated systems.4,5 One of the main microfluidic components for realizing such fluidic integration is a microvalve. Microvalves have been used for directing fluids along required paths, sealing sections on the chip, providing check valves for micropumps, and metering of reagent volumes.6 In general, microvalves can be divided into passive valves (no actuator) and active valves.7 Passive valves can be created by * To whom correspondence should be addressed. Phone: (734) 764 4315. Fax: (734) 763 0459. E-mail:
[email protected]. † Department of Chemical Engineering. ‡ Department of Electrical Engineering. § Department of Human Genetics. | Department of Biomedical Engineering. (1) Feynman, R. P. J. Microelectromech. Syst. 1992, 1 (1), 60-66. (2) Jensen, K. F. Chem. Eng. Sci. 2001, 56 (2), 293-303. (3) Auroux, P. A.; Iossifidis, D.; Reyes, D. R.; Manz, A. Anal. Chem. 2002, 74 (12), 2637-2652. (4) Verpoorte, E.; De Prooij, N. F. Proc. IEEE 2003, 91 (6), 930-953. (5) Selvaganapathy, R. S.; Carlen E. T.; Mastrangelo, C. H. Proc. IEEE 2003, 91 (6), 954-975. (6) Reyes, D. R.; Iossifidis, D.; Auroux, P. A.; Manz, A. Anal. Chem. 2002, 74 (12), 2623-2636.
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surface patterning regions on the chip or by tailoring channel resistances. A hydrophobic region on a chip, for example, has been used as a stop valve for capillary motion.8 Also, the channel geometry has been designed to realize structural valves that have been used for sequential injection of samples.9 Though these passive valves have been incorporated in integrated devices,10,11 they generally cannot be used for sealing or active microfluidic control. An exception to this are the active microfluidic control elements based on reversible surface modifications.12 Active valves traditionally have been based on deflecting diaphragms or cantilevers, a concept borrowed from the macroscale analogue. The deflection of the membrane or the cantilever can be obtained by a piezoelectric, electrostatic, electromagnetic, thermopneumatic, or bimetallic actuation mechanism.7 Though these valves sometimes have complicated fabrication steps, they are very versatile and have been used for a number of applications. Soft lithography has been used to develop active microvalves and microvalve arrays that require limited additional fabrication procedures.13 These valves have been used to multiplex hundreds of fluidic chambers on a single chip to realize fluidic circuits analogous to electronic comparator arrays and memory devices.14 Another approach for novel active microvalves involves valves in which valve plug and deflection mechanism are coupled into one unit. Examples of these valves are hydrogel valves15 and in situ polymerization valves.16,17 We describe a phase change valve based on the solid-liquid phase transition that can be easily adapted to a variety of lab-on(7) Shoji, S.; Esashi, M. J. Micromech. Microeng. 1994, 4, 157-171. (8) Handique, K.; Burke, D. T.; Mastrangelo, C. H.; Burns, M. A. Anal. Chem. 2000, 72 (17), 4100-4109. (9) Pe´rez-Castillejos, R.; Esteve, J.; Acero, M. C.; Plaza, J. A. Micro Total Anal. Syst. 2001 2001, 492-494. (10) Burns, M. A.; Johnson, B. N.; Brahmasandra, S. N.; Handique, K.; Webster, J. R.; Krishnan, M.; Sammarco, T. S.; Man, P. N.; Jones, D.; Heldsinger, D.; Mastrangelo, C. H.; Burke, D. T. Science 1998, 282 (5388), 484-487. (11) Puntambekar, A.; Hong, C.; Gao, C.; Zhu, X.; Trichur, R.; Han, J., Lee, S. H.; Kai, J.; Do, J.; Rong, R.; Chilukuru, S.; Dutta, M.; Ramasamy, L.; Murugesan, S.; Cole, R.; Nevin, J.; Beaucage, G.; Lee, J. B.; Lee, J. Y.; Bissell, M.; Choi J. W.; Ahn, C. H. Micro Total Anal. Syst. 2003 2003, 1, 12911294. (12) Lahann, J.; Mitragotri, S.; Tran, T.; Kaido, H.; Sundaran, J.; Hoffer, S.; Somorjai, G. A.; Langer, R. Science 2003, 299 (5605), 371-374. (13) Xia, Y. N.; Whitesides, G. M. Annu. Rev. Mater. Sci. 1998, 28, 153-184. (14) Thorsen, T.; Maerkl, S. J.; Quake, S. R. Science 2002, 298 (5593), 580584. (15) Yu, Q.; Bauer, J. M.; Moore, J. S.; Beebe, D. J. Appl. Phys. Lett. 2001, 78 (17), 2589-2591. (16) Hasselbrink, E. F.; Shepodd, T. J.; Rehm, J. E. Anal. Chem. 2002, 74 (19), 4913-4918. (17) Koh, C. G.; Tan, W.; Zhao, M.; Ricco, A. J.; Fan, Z. H. Anal. Chem. 2003, 75 (17), 4591-4598. 10.1021/ac0352934 CCC: $27.50
© 2004 American Chemical Society Published on Web 05/08/2004
Figure 1. Fabrication process flow for the glass and the silicon sides.
a-chip devices. A phase change material can be used either as a meltable plug18 or as a propellant for a membrane19,20 to realize a microvalve. We use thermal actuation of a meltable piston to perform the valve operation without any membrane. The construction and operation of the valve is simple and adds no new steps to most existing fabrication procedures. The valve is electronically addressable and effectively leak-proof, making it amenable for large-scale integration. Moreover, the valve can be latched, minimizing the energy required and enabling easy fluidic control. In this work, the operation principle and experimental characterization of the valve are presented. An example use of these valves, sealing reaction chambers for polymerase chain reaction on an integrated device, is also shown. MATERIALS AND METHODS Heater Side Fabrication. Silicon wafers (〈100〉, 500 µm thick, 10 cm diameter) were wet oxidized to grow a 2000 Å thick oxide layer (Figure 1). Positive photoresist (Microposit SC 1827; Shipley Co., Marlborough, MA) was spin-coated on the wafer at 3000 rpm and soft-baked on a hot plate at 90 °C for 5 min. A mask aligner (Cannon PLA 501FA) was then used to expose the heater pattern on the wafer. The wafer was developed in MF 319 solution (Shipley Co.) for 2.5 min to complete the lithography. A 300-Å titanium thin film was evaporated on the wafer as an adhesion layer followed by a 1000 Å film of platinum. A liftoff was performed by leaving the wafers in acetone (CMOS grade; J.T. Baker, Phillipsburg, NJ) for 5 h. The wafer was rinsed in DI water and dried. Channel Fabrication. Borofloat glass wafer (500 µm thick, 10 cm diameter) used for channel fabrication, was first thermally annealed at 560 °C for 1 h. Thin films of chromium (600 Å) and gold (4000 Å) were then evaporated on the glass surface (Figure 1). The lithography steps for patterning the glass wafer were the same as for the silicon wafer. After developing in MF 319 the wafer was hard baked on a hot plate at 100 °C for 45 min. The metal (18) Liu, R. H.; Bonanno, J.; Grodzinski, P. Micro Total Anal. Syst. 2002 2002, 1, 163-165. (19) Rich, C. A.; Wise, K. D. J. Microelectromech. Syst. 2003, 12 (2), 201-208. (20) Carlen, E. T.; Mastrangelo C. H. J. Microelectromech. Syst. 2002, 11 (5), 408-420.
films were etched in commercial gold etchant (Gold Etchant TFA, Transene Co.) and chromium etchant (CR-14, Cyantek Corp., Fremont, CA) for 2 min each, in the channel area exposed by lithography. The glass was then etched in hydrofluoric acid (49% HF, CMOS grade; J.T. Baker). The rate of etching was 7.0 µm/ min and the etch depth was measured using a stylus surface profilometer. After etching to the desired depth, the metal layers were stripped using the corresponding etchants. The wafer was rinsed in DI water and dried. Device Assembly. After individual devices on the substrate wafers were diced, holes (∼300 µm diameter) were drilled in the glass substrate using an electrochemical spark discharge apparatus. The silicon dies were mounted on a printed circuit board using a steel weld epoxy (ITW Performance Polymers, Riviera Beach, FL). The area of the circuit board under the silicon die was routed out before mounting (if active cooling was needed). Heater pads were wire-bonded to the leads on the printed circuit board by 2‰ gold wire bonds (Kulicke Soffa 4124 ball bonder). The wire bonds were encapsulated using an electrical grade epoxy (EP939, Thermoset, Indianapolis, IN). The glass channel was then bonded to the silicon substrate using a UV-cured optical adhesive (SK-9 Lens Bond, Summers Laboratories, Fort Washington, PA). The bond was cured under a UV light source (365 nm) for 6 h. Air pressure connections to the holes were made using either stainless steel hypodermic tubing or plastic pipet tips that were epoxyed to the air-line hole using a fast-setting epoxy. For highpressure testing, a stainless steel union was used. Teflon tubing was used to connect the needle, pipet tip, or union to an air pressure source through a pressure regulator. On-Chip Heater Control. On-chip resistance temperature detectors (RTDs) were calibrated by heating the chip in an oven and recording the temperature-resistance data for the RTDs. This calibration curve was recorded by a Labview (National Instruments) VI, using a MIO-PCI6031E board. The slope-intercept data was read into another Labview VI that used a PI module to control temperature using an AO32-PCI6704 board. Energy pulses given to the on-chip heaters were also regulated using Labview ER-16 relay boards interfaced to the computer through a DIO96 board. Analytical Chemistry, Vol. 76, No. 13, July 1, 2004
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Figure 2. Schematic of the phase change valve operation. (i) Loading wax by actuating inlet port heater. (ii) Closing valve by actuating the inlet port and stem channel heaters with pressure at inlet port. (iii) Opening valve by actuating the stem channel and intersection heaters with vacuum at the inlet port.
Figure 3. Results for off-chip Snrpn mouse DNA PCR carried out in the presence of different waxes to test for biocompatibility. The PCR volume was 20 µl.
Reaction Product Analysis. The product from the reactions was analyzed on a polyacrylamide gel. For the off-chip controls, a slab gel configuration for the gel was used. The sample was loaded onto the separation media along with the loading dye. A constant electric field of 120 V was applied across the gel for ∼60 min. A Polaroid snapshot of the gel illuminated by UV light was taken at the end of the run. The on-chip reaction product was analyzed on a commercial sequencer (ALF Express; Amersham Pharmacia Biotech). A polyacrylamide gel was used for separation at a temperature of 55 °C and an electric field of ∼30 V/cm. RESULTS AND DISCUSSION The active phase change microvalve is fabricated on a siliconglass hybrid device; microfluidic channels are etched in the glass substrate and heating elements are deposited on the silicon substrate. Though glass or polymers can be used for either substrate, silicon has been used to allow integration of on-chip circuit elements such as photodiodes. The generic model of the valve has an inlet port and a stem channel that is connected to the main fluidic channel (Figure 2). A piston of meltable material in the stem channel is used to seal the main channel. Heaters used to melt the piston are strategically placed at the inlet port, the stem channel, and the intersection. 3742
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The operation of the valve involves loading the meltable piston, closing the valve, and opening the valve. For loading, molten phase change material is imbibed into the stem channel by capillary forces. The valve is closed by changing the phase of the piston to liquid and moving the molten piston pneumatically to the intersection thereby sealing the main channel. Opening the valve involves moving the piston in the molten state away from the intersection by applying vacuum at the inlet port. Once positioned in either the closed or the open state, the phase of the piston is changed to solid. The phase change valve can be electronically addressed and inherently latched. Electronic addressability of the valve is provided by the electronic signal sent to the heaters that induces a phase change in materials such as waxes (solid at ambient). Other materials such as thermoreversible polymers,21 electrorheological fluids,22 and paramagnetic fluids9 can also be used for an electronically addressable valve. However, phase change valves are latched, requiring energy only to switch the valve state and not to maintain it. Note that the valves can easily be assembled into an array with a single pressure/vacuum line; only those valves that are heated will close or open. (21) Buchholz, B. A.; Doherty, E. A. S.; Albarghouthi, M. N.; Bogdan, F. M.; Zahn, J. M.; Barron, A. E. Anal. Chem. 2001, 73 (2), 157-164.
Figure 4. Rheological properties of different waxes and blends of waxes as a function of temperature as measured on a constant stress rheometer. (a) Viscosity of pure wax samples. (b) Viscosity, G′, and G′′ values of the combination wax (25% Lycojet and 75% M1595 wax).
Phase Change Material. The main considerations for choosing a phase change material to act as a valve piston are its process compatibility, phase transition temperature, and molten phase rheology. For successful integration of the valve into an integrated device, the wax must be compatible with the processes occurring on the device. For biological systems, particularly those involving DNA, compatibility with the polymerase chain reaction (PCR) is important. Figure 3 shows the slab gel electrophoresis plot of a 20 µL macroscale Snrpn mouse DNA PCR performed in the presence of different waxes. The PCR reaction was not affected by paraffin wax, M1595 synthetic wax, and C105 synthetic wax. It should be noted that this is a sufficient and not a necessary test. In the actual valve, the reaction mixture will typically contact the wax for a short time and not the entire duration of the reaction as with these macroscopic tests. Though the biocompatibility tests establish the feasibility of using wax as the valve piston, the actual valve operation is related to the phase transition temperature and molten phase rheology. Figure 4a shows the phase transition temperature of different waxes, as seen from the sharp decrease in the sample viscosity. The paraffin wax has a phase transition temperature of ∼50 °C, the Logitech wax melts at ∼75 °C, and the M1595 synthetic wax (22) Yoshida, K.; Kikuchi, M.; Park, J. H.; Yokota, S. Sens. Actuators, A 2002, 95 (2-3), 227-233.
Figure 5. Isothermal mode of actuation. (a) The position of the front interface of the piston interface as a function of the pulsed pressure duration for isothermal operation. The channel temperature was 75 °C and the pulse pressure was 8 psi. (b) The velocity of the molten piston as a function of the pressure for isothermal operation for three different temperatures (2, 70 °C; 9, 75 °C; ×, 80 °C). The dashed lines correspond to theoretical velocities at the different temperatures (- - -, 70 °C; ‚‚‚, 75 °C; - ‚ -, 80 °C). The straight channel device used for these experiments had a width of 700 µm and a depth of 50 µm.
melts at ∼85 °C. For a phase change valve to have a stable latched state, the temperature of the area surrounding the valve should not exceed the phase transition temperature of the piston. However, a wax sample with a melting point lower than the maximum device temperature can be used if the chip is appropriately designed. While the phase transition temperature ensures reliable latching of the valve, switching of the valve between the closed and open states is a function of the piston’s molten phase rheology. The two rheological properties that characterize molten piston motion are viscosity and elasticity. The velocity of the molten piston in the stem channel is related to the applied pressure difference by the following equation.23
v ) (d2/SµL)∆P
(1)
where v is the average drop velocity, d is the channel depth, S is the geometric shape factor, µ is the bulk viscosity, L is the piston (23) Sammarco, T. S.; Burns M. A. AIChE J. 1999, 45, 5 (2), 350-366.
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Figure 6. Operation of the phase change valve. (a) Device picture showing the heater locations. (b) Loading of the combination wax. (c) Closing the phase change valve. (d) Opening the phase change valve.
length, and ∆P is the internal liquid phase pressure difference between the drop ends. The low viscosity of most waxes in the molten state such as the M1595 wax (∼10-2 Pa‚s) give velocities of ∼70 mm/s for a 1 mm piston and a nominal pressure difference of 1 psi (ignores contact angle hysteresis). The piston displacement distance for valve operation is less than 1 mm, corresponding to an actuation time of a few tens of milliseconds. In addition to a change in viscosity, some elasticity in the molten piston is advantageous both to prevent residue adhesion on the channel walls and to aid in opening the valve. This elasticity can be achieved by the addition of resin to the wax sample. The Lycojet wax is a mixture of paraffin and resin with a phase transition temperature of ∼50 °C (Figure 4a). While this wax was advantageous from the standpoint of elasticity, the melting temperature is too low and the molten viscosity too high for some applications (e.g., valves for a PCR chamber). To increase the transition temperature and lower the viscosity, a mixture of 25% Lycojet and 75% M1595 was used for most of the studies here. The elasticity of a linear viscoelastic sample is characterized by the relative values of the storage modulus (G′) and the loss modulus (G′′).24 As seen from Figure 4b, the measured value of G′ for the Lycojet/M1595 wax mixture is more than the measured value of G′′ in the molten state. While this suggests that the melt is a solidlike viscoelastic material, a more complete study of the viscoelastic behavior is needed to predict the exact nature and magnitude of the elasticity. Thermal Actuation Modes. Thermal actuation of the piston is achieved using either capillary or air pressure and an isothermal, spatial, or temporal heating profile. As the names suggest, in the isothermal mode, the entire stem channel is heated to one temperature; in the spatial mode only, a section of the stem (24) Larson, R. G. The structure and rheology of complex fluids; Oxford University Press: New York, 1999; Chapter 1.
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channel is actively heated; and in the temporal mode, a sharp energy pulse heats the entire channel for a short period of time. The thermal modes differ in ease, control, and complexity of operation. The advantages and disadvantages of the different thermal modes were characterized using a straight channel device. Isothermal Actuation. For isothermal actuation, the stem channel is heated uniformly and the molten piston is propelled by discrete air pulses. A solenoid valve, actuated by Labview controlled relays and connected to a regulated 30 psi pressure source, generates these pressure pulses. Multiple pulses of varying duration can be generated by a periodic electronic waveform from Labview; this pulsed pressure scheme can also be used to pump a variety of other fluids in microchannels.25 We have used highpressure and low-duration pulses because by using higher pressures contact angle hysteresis is eliminated. Figure 5a shows the distance moved by the combination wax piston in response to a single pressure pulse of 8 psig, as a function of the pulse duration, when the channel is heated to 75 °C. As seen from the figure, the motion of the piston varies approximately linearly from ∼0.025 mm for a 0.3 s duration pulse to ∼0.12 mm for a 1.2 s duration pulse. The velocity of the molten piston also varies with the pressure applied across the piston and the temperature of the stem channel. Velocities of different wax samples were measured using a 30 µmdeep straight channel device. Velocities of 1.2 mm/s for the M1595 wax and 0.0075 mm/s for the Lycojet wax (0.5 psi, 90 °C) were measured for a molten piston of ∼3.5 mm long. Theoretical velocities (computed by eq 1) are slightly higher than the experimental velocities, 2.2 mm/s for the M1595 wax and 0.013 mm/s for the Lycojet wax (viscosity of 10.2 Pa‚s at 90 °C). The slightly lower experimental values are due to the large volume of (25) Unpublished work. University of Michigan, 2003.
Figure 8. Temporal mode of actuation. (a) Temporal temperature gradients in response to a voltage pulse of 30 V given to all four heaters with pulse duration of 2 s. The heaters are located at 0, 2.2, 4.4, and 6.6 mm with reference to the inlet port, and the temperature response was measured by four RTDs located alongside the four heaters (o, sensor 1; x, sensor 2; -, sensor 3; +, sensor 4). (b) Position of the M1595 wax interface as a function of energy pulse duration for different pulse intensities. The voltage pulse was applied to heaters 1 and 2. A pressure of 0.5 psi was applied at the inlet port.
Figure 7. Spatial mode of actuation. (a) Spatial temperature gradients along the stem channel when heater 1 (located at the inlet port, distance 0 mm) was actuated to different temperatures. (b) Temperature vs amount of M1595 wax loaded in the stem channel when heater 1 was actuated. (c) Position of the M1595 wax interface as a function of temperature set point for sensor 4 (located ∼6.6 mm from the inlet port) controlled by actuating heaters 1 and 2 (located 2.2 mm from the inlet port).
the tubing and possible leaks in the inlet, both leading to a lower pressure at the back end of the drop relative to the source pressure. The experimental velocities for the combination wax, in contrast to the other wax samples, are significantly higher than that predicted by eq 1. An experimental velocity of 0.75 mm/s for a 3.9 mm molten piston was measured in a 30-µm-deep straight channel device at a pressure of 0.5 psi and a temperature of 90 °C. The theoretically predicted velocity is only 0.14 mm/s. This discrepancy is further accentuated in the 70-85 °C temperature
Figure 9. Schematic of microfluidic channel for measuring leak rate from a closed valve.
range where the wax shows a gradual phase transition. Figure 5b shows the velocity of the piston as a function of pressure when the channel is heated to different temperatures. Velocities vary from 0.01 mm/s at 70 °C and 5 psi to 5.25 mm/s at 80 °C and 9 psi. As seen from Figure 5b, these velocities are orders of magnitude higher than the predicted velocities. The higher velocities are most likely because the piston travels like an elastic solid and experiences slip at the wall. Thus, while the theory would Analytical Chemistry, Vol. 76, No. 13, July 1, 2004
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Figure 10. Reproducibility of valve operation. (a) Position of the front interface of the piston with respect to the valve intersection for repeated closing and opening of the valve. Average position of the front interface for closing was 0.18 mm (with a standard deviation of 55 µm) and for opening was -0.59 mm (with a standard deviation of 30 µm). (b) Size of the piston as a function of the number of valve operation cycle. Size is plotted as percentage of the average size over the 10 cycles. Standard deviation of the piston size was 1.22%.
indicate that the valve would be difficult to close quickly, the valve can be actuated in less than 1 s in the transition region for the combination wax. Figure 6 shows the operation of a phase change valve using the isothermal mode of operation. The valve has a stem channel length of 4.6 mm, a channel depth of 50 µm, and a channel width of 500 µm. Four heaters are placed along the stem channel at a distance 1.6 mm from each other (Figure 6a). Approximately 2 mm of combination wax was loaded into the stem channel (Figure 6b). For closing, the stem channel was heated to 78 °C using heaters 1, 2, and 4 and air pulses of 2-3 psi and 0.5 s were applied (Figure 6c). To open the valve, the stem channel was heated to 78 °C using the same heaters and vacuum pulses of 1-1.5 psi and 0.5 s were applied to the inlet port (Figure 6d). Once the desired state is obtained, all heaters are deactivated, the temperature rapidly (
