Anal. Chem. 2010, 82, 8039–8041
Letters to Analytical Chemistry Pneumatically Pumping Fluids Radially Inward On Centrifugal Microfluidic Platforms in Motion Matthew C. R. Kong and Eric D. Salin* Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, Quebec, Canada, H3A 2K6 This paper describes a pumping technique applicable to centrifugal microfluidic platforms, involving the use of a regulated stream of compressed gas to pump liquid radially inward and toward the center of the platform while spinning. This technique provides a noncontact method for pumping fluids and is highly efficient, requiring only approximately 60 s to reach completion. This pumping operation can be attained with an applied gas flow rate of 58.8 L min-1, while the platform is rotated at frequencies less than 180 rpm (3.0 Hz). An important focus in instrument design has revolved around the concept of micro total analytical systems (µTAS).1 These systems are expected to provide rapid results using small amounts of reagents and sample, thereby providing environmental waste, cost and size advantages as described by Mark et al.2 Microfluidic flow is a fundamental aspect of the design of µTAS platforms, with the flows often controlled by external pumps or electrically through electroosmotic pumping. The interface between micro devices and the macro world is sometimes called the “world-tochip” problem and has been the source of some study.3 Centrifugal microfluidic systems use centrifugal force to induce the flow of liquids in microfluidic platforms, often a spinning disk. This mode of operation has certain advantages, one of them being that there is no need for any type of connection to the microfluidic platform, thereby reducing the “world-to-chip” problem. Centrifugal systems are also well suited to portable and point-of-care applications due to the lack of connectors. Other advantages of centrifugal microfluidic systems are described in greater detail in a review by Ducre´e.4 Fluid flow control in centrifugal microfluidic systems is extremely important. Centrifugally induced fluid flow in a radially outward direction is most commonly controlled by using passive capillary valves, which allow fluid to flow (i.e., burst) above a certain threshold frequency of rotation. However, a fundamental limitation caused by this unidirectional flow of fluid * Corresponding author. Phone: +1-514-398-6236. Fax: +1-514-398-3797. E-mail:
[email protected]. (1) Andersson, P.; Jesson, G.; Kylberg, G.; Ekstrand, G.; Thorse´n, G. Anal. Chem. 2007, 79, 4022–4030. (2) Mark, D.; Haeberle, S.; Roth, G.; Von Stetten, F.; Zengerle, R. Chem. Soc. Rev. 2010, 39, 1153–1182. (3) Fang, Q.; Xu, G. M.; Fang, Z. L. Anal. Chem. 2002, 74, 1223–1231. (4) Ducre´e, J.; Haeberle, S.; Lutz, S.; Pausch, S.; Von Stetten, F.; Zengerle, R. J. Micromech. Microeng. 2007, 17, S103–S115. 10.1021/ac102071b 2010 American Chemical Society Published on Web 09/03/2010
is known as the “real estate” or “footprint” problem.5 This refers to there being limited space along the radius of the centrifugal microfluidic platform, allowing only a certain number of operations (e.g., reagent addition, mixing) to be implemented. To overcome this apparent fundamental limitation, there is a need to develop techniques that allow for controlled fluid flow back toward the center of the disk, permitting more operations to be carried out. Wang6 has described a pumping method based on electrophoresis and has demonstrated its usefulness for liquids suited for electroosmosis. Unfortunately, this method places certain constraints on the chemical properties of the solutions and materials used in the platform and will not be applicable to a wide variety of solvents or analytes. Gorkin5 describes a method using high rotational frequencies to generate compressed air on the disk, and subsequently priming a siphon using the pressure generated. The inward flow distance was quite limited. Haeberle7 has described a centrifugo-magnetic micropump integrated onto the disk; however, it requires relatively complex disk designs and fabrication. In a patent, Lee8 has described the pumping of fluids by the injection of air after stopping the disk. Although stopping the disk is effective, having a noncontact approach and pumping fluids while spinning is preferable as it allows for a constant centrifugal force to be acting on the fluids on the disk. This prevents undesirable fluid flow such as wicking caused by the loss of centrifugal force. To address these issues, we describe a noncontact, easily implemented technique which allows for the pumping of fluids from a radially outward position to a radially inward position. This technique provides a way to pump fluids while spinning, without the need for complex disk designs or fabrication processes. Also, as this pumping method can be applied at relatively low rotational frequencies, valving can still be done with the methods described above. This technique allows for many sequences of operations to be linked via a single pumping (5) Gorkin, R.; Clime, L.; Madou, M.; Kido, H. Microfluid. Nanofluid. 2010, 9, 541–549. (6) Wang, G.-j.; Hsu, W.-h.; Chang, Y.-z.; Yang, H. Biomed. Microdevices 2004, 6, 47–53. (7) Haeberle, S.; Schmitt, N.; Zengerle, R.; Ducre´e, J. Sens. Actuators, A: Phys. 2007, 135, 28–33. (8) Lee, H.-J.; Huh, N.; Lee, S.-S.; Jung, S.-O.; Choi, S.-H. Microfluidic Device Using Centrifugal Force And Pump To Control Fluid Movement, Microfluidic System Comprising The Same And Method Of Manufacturing The Microfluidic Device (Samsung Electronics Co., Ltd., S. Korea). U.S. Patent Application 0135101 A1, June 12, 2008.
Analytical Chemistry, Vol. 82, No. 19, October 1, 2010
8039
Figure 2. Schematic of experimental configuration: (a) cylinder containing compressed air, (b) rotameter used to measure flow rate, (c) centrifugal microfluidic platform, and (d) servo motor and spindle shaft. Figure 1. Schematic of disk design. Chambers A, B, and E have radii of 4 mm. Chamber D has a radius of 5 mm. Channel C and vents H and I have radii of 0.5 mm. Capillaries F and G have inner diameters of 322 and 150 µm, respectively.
operation, allowing a much longer sequence of operations, effectively diminishing the limit imposed upon centrifugal microfluidic platforms by their radii. EXPERIMENTAL SECTION Reagents. Blue commercial food coloring was mixed with distilled deionized water (DDW) to simulate an analytical sample that was clearly visible. Fabrication. A polycarbonate disk platform was fabricated using materials and techniques described in detail by LaCroixFralish.9 Fused silica capillaries (inner diameters 322 and 150 µm) (Polymicro Technologies, AZ) were used as burst valves to control fluid flow. The capillary construction methods have been described in more detail by LaCroix-Fralish.10 Data Acquisition. High-speed digital images were obtained using a motorized stage and strobe system developed by Duford11 supplemented with a color digital camera (GRAS-14S5C-C, Point Gray, BC, Canada). The motorized stage, strobe, and camera were controlled by a LabVIEW program (LabVIEW 8.6, Developer Version, National Instruments, QC, Canada). Design and Experimental Setup. The disk design with dimensions is illustrated in schematic form in Figure 1. The experimental configuration is illustrated in schematic form in Figure 2. All chambers are 1.4 mm deep, while channels and vents are 0.7 mm deep. In our demonstration, Chamber A was used to introduce the sample into the disk and would represent an earlier chamber in a sequence of operations on an actual experimental platform. Chamber B represents the most radially outward chamber in a sequence of operations and serves as a reservoir (9) LaCroix-Fralish, A.; Clare, J.; Skinner, C. D.; Salin, E. D. Talanta 2009, 80, 670–675. (10) LaCroix-Fralish, A.; Templeton, E. J.; Salin, E. D.; Skinner, C. D. Lab Chip 2009, 9, 3151–3154. (11) Duford, D. A.; Peng, D. D.; Salin, E. D. Anal. Chem. 2009, 81, 4581–4584.
8040
Analytical Chemistry, Vol. 82, No. 19, October 1, 2010
for the sample just prior to the pump operation. Channel C is used to transfer the sample to Chamber D, which represents the first chamber in a second sequence of operations to be undertaken. Chamber E represents the second chamber in a second sequence of operations. F and G are capillaries of inner diameters 322 and 150 µm respectively. H and I are air vents of the various chambers. When the pumping operation is desired, extra dry compressed air (MEGS, QC, Canada) flowing at a steady rate of 2.1 SCFM (standard cubic feet per minute) (58.8 L min-1) flows through an outlet tube (160 cm in length, 1/8 in. (3.175 mm) inner diameter, 1/4 in. (6.35 mm) outer diameter) at 20 psi (137.9 kPa). The air pressure is controlled by a standard regulator, and the flow rate is measured by a rotameter (FL7311, Omega, QC, Canada). The outlet tube is positioned directly above and perpendicular to Vent H, at a distance of 7.5 mm from the surface of the disk. In our experiments, the pumping technique was applied at rotational frequencies of 180 (3.0 Hz), 150 (2.5 Hz), 120 (2.0 Hz), 90 (1.5 Hz), 60 (1.0 Hz), and 30 rpm (0.5 Hz). RESULTS AND DISCUSSION Operation of this pumping technique is shown as strobed images in Figure 3. A volume of 68 µL of blue food coloring in DDW was introduced into Chamber A (Figure 3a). The sample was then forced through the capillary valve (Figure 1, F) into Chamber B by spinning the disk at 500 rpm (8.3 Hz) (Figure 3b). This signaled the completion of the final operation prior to the pumping operation. With the rotational frequency of the disk lowered to 180 rpm (3.0 Hz) and the gas flow initiated, liquid was pumped through Channel C (Figure 3c) by the gas pressure acting on the fluid. As periodic pulses of gas entering Chamber B through Vent H exerted pressure on the fluid, it allowed for effective transfer of the fluid into Chamber D (Figure 3d). The strobed images in Figure 4 show that the pumping action can be repeated. This demonstrates that sequences of centrifugally pumped operations can be linked by single channels allowing an almost arbitrarily long sequence of operations. Video S-1 in the
Figure 3. Strobed images of pumping technique in operation: t indicates time elapsed; gas flow was initiated at t ) 35 s. (a) 0 rpm (0.0 Hz), t ) 0 s; (b) 500 rpm (8.3 Hz), t ) 30 s; (c) 180 rpm (3.0 Hz), t ) 60 s; (d) 180 rpm (3.0 Hz), t ) 90 s.
Figure 4. Strobed images of multiple pumping operations: t indicates time elapsed; gas flow was initiated between t ) 35 s and t ) 90 s and between t ) 125 s and t ) 180 s. (a) 0 rpm (0.0 Hz), t ) 0 s; (b) 180 rpm (3.0 Hz), t ) 90 s; (c) 180 rpm (3.0 Hz), t ) 180 s.
Supporting Information demonstrates this pumping technique in operation. The experiments shown in Figure 4 and in the Supporting Information were all conducted with 68 µL volumes. Additional experiments were conducted to show that this pumping technique was also applicable to significantly smaller sample volumes of 10 and 15 µL. The pumping operation can be implemented as long as the pressure exerted by the gas flow is greater than the opposing pressure experienced by the liquid due to centrifugal force. Although sufficient pressure had to be generated by the gas, too much pressure would cause the fluid to either escape through the air vent of Chamber D or burst through the capillary valve (Figure 1, G) into Chamber E. At rotational frequencies of 90 rpm (1.5 Hz) and under, there was a tendency for the fluid to escape through the air vent of Chamber D, as the limited centrifugal force caused by the low rotational frequency was not sufficient to retain the fluid in Chamber D. For rotational frequencies of 120 (2.0 Hz), 150 (2.5 Hz), and 180 rpm (3.0 Hz), the pumping operations were successfully carried out without visible loss of fluid. Therefore, for a given flow rate of gas, there exists a wide range of rotational frequencies at which the pumping operation can be accomplished. This shows that this technique is robust in terms of its insensitivity to possible fluctuations in rotational frequency. This technique for pumping fluids was not tested at higher rotational frequencies as it would require higher flow rates of the gas and does not provide any significant advantages. In fact, higher rotational rates are undesirable as they then require a smaller passive capillary valve in between Chambers D and E, propagating the necessity of even smaller passive capillary valves during subsequent operations. Being able to pump fluids at relatively low rotational frequencies allows for the use of common and easily implemented valving techniques (such as the 150 µm inner diameter capillary
used here) to retain the liquid in Chamber D without liquid transfer into Chamber E. In this disk design, the volume of Chamber D was made larger than that of subsequent or preceding chambers. This was to ensure that there was excess volume in the chamber into which liquid would be pumped, thereby minimizing the chance for liquid to escape through the air vent of Chamber D. This means that the chambers at the most-inward radial positions must consume slightly more space on the platform. CONCLUSIONS This experiment demonstrates a simple and effective technique for pumping fluids toward the center of the disk. This robust pumping technique does not require that a disk be stopped, uses a simple design, and does not impose limits on the properties of fluids used in experiments. Since each operation consumes space on the platform, the number of parallel analyses that can be performed on a single platform is decreased; however, the technique essentially allows the entire body of the disk to be used for an almost unlimited number of sequential operations, thereby eliminating one of the major limitations of centrifugal microfluidics. ACKNOWLEDGMENT The authors gratefully acknowledge Discovery Grant support from the National Sciences and Engineering Research Council of Canada. E.D.S. wishes to thank Horacio Kido for a provocative conversation on gas pumping. SUPPORTING INFORMATION AVAILABLE Additional information as noted in text. This material is available free of charge via the Internet at http://pubs.acs.org. Received for review August 5, 2010. Accepted August 27, 2010. AC102071B Analytical Chemistry, Vol. 82, No. 19, October 1, 2010
8041
