A Novel Microfluidic Mixer Based on Successive Lamination

A NOVEL MICROFLUIDIC MIXER BASED ON SUCCESSIVE LAMINATION M.S. Munson and P. Yager Uniwrsity of Washington, Seattle Abstract The unique properties of flow in microfluidic channels make mixing a significant challenge[l] for which many ingenious solutions have been developed[2-121. We demonstrate the efficacy of a novel mixing channel based on the principle of flow lamination. A unique method for characterizing the extent of mixing is employed that allows characterization of the extent of mixing without a complete 3-dimensional resolution of the concentration field. Keywords: Diffusion, Lamination, Mixing, Static-Mixer 1. Introduction One of the most commonly implemented unit operations is mixing. Most chemical assays require the mixing of reagents with a sample and many assays requiring multiple mixing steps. For this reason, mixing has been widely studied[2-121. We focus on the well established method for accelerating mixing: fluidic lamination[2, 4, 5, 13, 141. The channel geometry proposed is the microfluidic implementation a commercially available macro-scale mixer manufactured by Sulzer-Chemtech[ 151. This mixer design is well suited for production using Mylar laminates, and has a very open geometry, which is advantageous in the processing of biological fluids. A scale drawing of the inlet region and first two “mixing units” can be seen in Figure 1. 2. Theory Mixing strategies can be broken down into three basic categories 1) active mixing, 2) passive chaotic mixing and 3) passive mixing by lamination. The passive mixing approaches rely on the reduction of the length scale over which diffusion must occur. Successive lamination is one way to exploit the square root dependence of diffusional distance on contact time. The proposed mixer design divides fluid streams perpendicular to the interface between the interdiffusing fluids and then recombines the fluids forming an additional interface parallel with the original interface. Since the characteristic dimension of the channel remains constant, the creation of additional fluid laminae results in a corresponding decrease in the thickness of each layer. The behavior of the mixer was modeled using the commercially available finite element package Coventorware. The model results from the first few mixing units of channel confirm that the design operates as anticipated. The streaklines can be seen in the lower portion of Figure 1. The area occupied by the streaklines originating from an inlet is representative of the channel volume that would be occupied by fluid entering that inlet. It can be noted that each

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successive striation does not consist of an relative resistances upstream of each constriction. At the low Reynolds (approximately 0.9 to 7.9), the diversion operation.

equal volume of each fluid. This is due to the fluid division resulting from the channel numbers at which this mixer was tested of the flow was not a significant factor in its

Figure 1: The mixer geometry and modeling results. Top: The inlets and first two mixing units are shown. Bottom: Projection of the streaklines originating from one inlet. 3. Experimental All mixers were fabricated using polymeric laminates. Sheets of Mylar or pressure sensitive adhesive coated Mylar were cut using a 25W CO2 laser. The laser is mounted on an x-y translation frame that interfaces to a computer through a print driver. After cutting the channel, layers were laminated together using a custom-built assembly jig. The central layer of each mixing channel was blackened with marker pen so that only one half of the mixing channel would be imaged. Leaching of components out of the ink may have occurred, but no appreciable effect on the fluorescence was observed. The experimental apparatus and image processing methods have been described in detail elsewhere[ 161. Briefly, the channel was imaged using epifluorescence microscopy. Images were captured using a 3-color, S-bit CCD camera and a PC-based frame grabber. Images were converted to intensity profiles that were used to determine the extent of mixing in the channel. It can be seen from Figure 1 that layering of the fluid created by this mixer occurs perpendicular to the optical axis. Conventional fluorescence

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microscopy would yield no useful information about the extent of mixing. Instead, the The solutions pH sensitivity of fluorescein was used to image the extent of mixing. pumped into either inlet consisted of identical fluorescein concentrations, but were buffered at different pH values and different buffering strengths. The buffers were chosen so that the final pH upon mixing was the nearly same as the pH of the more basic solution at the inlet. The result of this is that upon interdiffusion of H+ and OR ions, the total intensity would increase, requiring that only the total integrated intensity at a given channel cross section be measured. 4. Results and Discussion The mixing enhancement caused by the channel geometry was determined experimentally. The resulting intensity profiles at the fist mixing window are shown in Figure 2a. The extent of mixing at the fist three viewing windows as a function of varying residence time at each window is shown in Figure 2b. The three experimental curves shown are compared to a computational prediction of the extent of mixing in a straight channel of the same characteristic dimension covering the same range of residence times. The diffusion of pH was approximated as the effective diffusion of protons (9.3x10-’ cm2/sec). From these curves we see that each successive mixing unit allows for the complete equilibration of the fluid in a shorter average residence time. For a diffusing species in a straight channel of the same dimensions to have reached the level of equilibration seen at the first viewing window, the effective diffusivity of the species would have to have been 16.65x10-’ cm2/sec, and 28.37x10-’ cm2/sec at the second window. This corresponds to a 1.79-fold and a 3.05-fold increase in the effective difmsivity.

Left: normalized intensity profiles Figure 2: Experimental mixer characterization. at the first viewing window as a function of mean residence time. Right: extent of mixing, based on the total fluorescence intensity as a function of mean residence time and channel location. 5. Conclusions The mixer design presented here is a novel embodiment of the well established concept of enhancing mixing through fluid lamination. The ability to very quickly reduce

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the length scale of the fluid striations allows achievement of mixing on a convective time scale rather, which is crucial for the implementation of rapid, on-chip mixing strategies. Reduction of the length scale of the fluid lamina so that they are comparable to the sizes of single macromolecules can be achieved in relatively few mixer units. The design shown here accomplishes this without the need for small channel dimensions, which could easily be blocked by particles. Acknowledgements We acknowledge the support and helpful discussion of the Yager research group, in particular, Dr. Andrew Kamholz and Dr. Catherine Cabrera and Eric Schilling. Support for this research has been provided by the Washington Technology Center, Micronics, Inc., the Department of Bioengineering, and an IGERT fellowship in Nanotechnology. References J. P. Brody; P. Yager; R. E. Goldstein; R. H. Austin, Biophys. J. 7 1 (1996) 3430. IIll J. Branebjerg; P. Gravesen; J. P. Krog; C. R. Nielsen, MEMS ‘96, Proceedings, I21 Feb 11-15 1996; IEEE; p. 441. W. Ehrfeld; K. Golbig; V. Hessel; H. Lowe; T. Richter, Ind. Eng. Chem. Res. 38 131 (1999) 1075. F. G. Bessoth; A. J. deMello; A. Manz, Anal. Commun. 36 (1999) 213. 141 N. Schwesinger; T. Frank; H. Wurmus, J. Micromech. Microeng. 6 (1996) 99. 151 C. Erbacher; F. G. Bessoth; M. Busch; E. Verpoorte; A. Manz, Mikrochim. Acta [a 131 (1999) 19. R. 11. Liu; M. A. Stremler; K. V. Sharp; M. G. Olsen; J. G. Santiago; R. J. L7.l Adrian; H. Aref; D. J. Beebe, J. Microelectromech. Syst. 9 (2000) 190. T. J. Johnson; D. Ross; L. E. Locascio, Anal. Chem. 74 (2002) 45. [81 A. D. Stroock; S. K. W. Dertinger; A. Ajdari; I. Mezic; H. A. Stone; G. M. [91 Whitesides, Science 295 (2002) 647. i-101 P. K. Yuen; G. S. Li; Y. J. Bao; U. R. Muller, Lab Chip 3 (2003) 46. V. Hessel; S. Hardt; H. Lowe; F. Schonfeld, Aiche J. 49 (2003) 566. VII S. Hardt; F. Schonfeld, Aiche J. 49 (2003) 578. WI H. Mensinger; T. Richter; V. Hessel; J. Dopper; W. Ehrfeld, Micro Total P31 Analysis Systems, Twente, The Netherlands, November 2 l-22 1994; Kluwer Academic Publishers; p, 237. H. Mobius; W. Ehrfled; V. Hessel; T. Richter, Transducers ‘95., Stockholm, P41 Sweden, June 25-29 1995; IEEE; p. 775. 1151 htt~:~/www.s~lzerchemtech.com~. II161 M. S. Munson; C. R. Cabrera; P. Yager, Electrophoresis 23 (2002) 2642.

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