Abstract:
The present embodiment describes a laminar-mixing embodiment that utilizes simple, three-dimensional injection. Also described is the use of the embodiment in combination with wide and shallow sections of channel to affect rapid mixing in microanalytical systems. The shallow channel sections are constructed using all planar micromachining techniques, including those based on isotropic etching. The planar construction enables design using minimum dispersion concepts that, in turn, enable simultaneous mixing and injection into subsequent chromatography channels.

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     This application is a Continuation-in-Part of prior U.S. patent application Ser. No. 10/456,772 originally filed Jun. 6, 2003 now U.S. Pat. No. 7,005,301 and entitled “Piecewise Uniform Conduction-Like Flow Channels and Method Therefor” from which benefit is claimed. 
    
    
     STATEMENT OF GOVERNMENT INTEREST 
     This invention was made with Government support under government contract DE-AC04-94AL85000 awarded by the U.S. Department of Energy to Sandia Corporation. The Government has certain rights in the invention, including a paid-up license and the right, in limited circumstances, to require the owner of any patent issuing in this invention to license others on reasonable terms. 
    
    
     BACKGROUND OF THE INVENTION 
     Field of the Invention 
     An embodiment of the present invention relates to a microfluidic apparatus employed for fluid processing. More particularly, the present embodiment relates to a microfluidic mixer employed as a microfluidic reactor apparatus. 
     Microfluidic devices have become increasingly important for the development of analytical sensors, particularly for the field of biotechnology and chemical assay. In particular, practical devices must function as miniature chemical reactors requiring an ability to rapidly mix constituent materials. However, at the small length scales typical in microanalytical devices, flow takes place at comparatively small Reynolds numbers, precluding the use of turbulence for mixing in a controlled and rational fashion. Under the resulting laminar flow conditions, mixing can take place from diffusion, but this is generally a time-consuming step in microanalytical systems. 
     This limitation has led to intense interest in micromixing research and development in recent years, (see for instance U.S. Pat. Nos. 5,921,678, 6,033,546, and 6,170,981; U.S. Patent Application Publication Serial Numbers 20030123322, 20030198130 and 20030207338; and Lui, et al.,  Journal of Microelectromechanical Systems,  2000, vol. 9(2) pp. 190-197; and He, et al.,  Analytical Chemistry,  2001, vol. 73(9), pp. 1942-1947). These mixing schemes are designed to induce chaotic advection in the fluids to be mixed, but tend to require complex geometries and/or relatively long channel lengths. In contrast, diffusive mixing can be employed in comparatively narrow sections of channel (see U.S. Pat. No. 5,842,787). Here, the diffusion time is reduced by optimizing the contact surface area-to-volume ratio, reducing the distance over which diffusive mixing must take place. In these schemes, mixing time is controlled by the channel width and length, and the fluid velocity within the channel. These designs require the use of deep, narrow channel sections, which are not readily constructed using common micro-manufacturing techniques such as isotropic etching; moreover, these schemes are not readily used with sample injection methods commonly used in microfluidic devices. What is needed, therefore, is a means for rapidly mixing constituent materials in as compact a geometry as possible that can be constructed using manufacturing techniques and interfacing with microfluidic sample injection methods. 
     SUMMARY 
     In the present discussion, we describe a laminar-mixing embodiment that utilizes simple, three-dimensional injection in combination with wide and shallow sections of channel to affect rapid mixing in microanalytical systems. The shallow channel sections are constructed using all planar micromachining techniques, including those based on isotropic etching. The planar construction enables design using minimum dispersion concepts that, in turn, enable simultaneous mixing and injection into subsequent chromatography channels. Moreover, the designs are employed using uniform-field channels, minimizing the uncertainty in mixing rate across the channel width, and minimizing the chances of channel clogging. The height of the mixing channel can be constructed to any desired value based on the fluid diffusivity, enabling rational design optimization for mixing small particles and molecules such as DNA and proteins in bio-analytical microchips. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIGS. 1A ,  1 B and  1 C show respective top, side, and bottom views of an embodiment of the present micro-mixer cover illustrating the fluid inlet and outlet ports and a first mixing channel. 
         FIGS. 2A and 2B  show respective top, and side views of an embodiment of the present micro-mixer base illustrating a second mixing channel designed to lie parallel to the first mixing channel. 
         FIGS. 3A and 3B  show isometric views of the micro-mixer of the present embodiment as seen from the top and from the bottom. 
         FIG. 4  shows the manner in which two separate fluids flow through the micro-mixer. 
         FIGS. 5A and 5B  show a cartoon of another embodiment of the present invention. 
         FIG. 6A  shows a photomicrograph of an actual micro-mixer constructed as described by herein below. 
         FIG. 6B  shows a close-up view of the expansion channel section of the actual micro-mixer constructed as described by herein below. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     In conventional chromatographic separations using microfluidic instruments, diffusive mixing designs with narrow, deep channels, fluids are injected using conventional techniques in the same plane as the mixing channel. The use of shallow, wide mixing channels requires the use of injection systems located in a different vertical plane with respect to the mixing channels such as is illustrated in the schematics shown in  FIGS. 1 and 2 . 
     In  FIGS. 1A-C , the mixer cover  10  is illustrated using a top, a side, and a bottom view. As shown, in  FIG. 1C  cover  10  includes a “T” shaped channel  14  etched part-way into the thickness of the cover medium; a first inlet port  11  etched or drilled completely through the thickness of the cover medium such that it is in-line with but spaced apart from “T” shaped channel  14 ; and two off-set second inlet ports  13  etched or drilled through the channel thickness so that each intersects at each end of an arm of the “T” of channel  14 . Finally, cover  10  contains a single outlet port  12  etched or drilled through the thickness of channel  14  such that it intersects the far end of the “T” of channel  14 . Inlet ports  11  and  13  are used to inject a first and a second fluid, (labeled “Fluid A” and “Fluid B” in  FIG. 4 , respectively), while single port  2  is used to extract a mixed fluid. 
     In  FIGS. 2A  and B, rectangular mixing channel base  20  is illustrated by showing a top and a side view of the part and is characterized by a single channel  21  etched into the thickness of the base medium. The channel dimensions are chosen for the sake of example only and, in fact, could take on nearly any desired width and height, although shallow channels will work particularly well. The length of channel  21  is designed to be long enough to span the distance between first inlet port  11  and outlet port  12  as well as to run parallel to the length of channel  14 . 
     After completing the fabrication of the features of both cover  10  and channel base  20 , the two are bonded together as shown in  FIGS. 3A and 3B . A similar, alternative embodiment is shown in  FIGS. 5A and 5B . 
     Fluid injection into the present embodiments can be accomplished using any method for driving fluid motion, including electrokinetic pumping, pressure pumping, gravity, magnetic fields, or any other method for moving a fluid. However, the scale of these devices limits flow speeds, which minimizes convective mixing, and the net effect is the laminar flow illustrated in the side view of  FIG. 4A . Here Fluids A and B are observed to form distinct layers as the result of this laminar flow following vertical injection. Layers such as these result only if diffusion is negligible, which takes place when the Peclet number (the dimensionless ratio of diffusion time over convection time) is infinitely large. Fortunately, the Peclet number for common microfluidic channels used in practice typically ranges from about 10 to about 100; therefore, diffusion will cause Fluid A to diffuse into Fluid B, and Fluid B to diffuse into Fluid A as is illustrated in  FIG. 4B . The degree of diffusive mixing will increase as the flow travels downstream into the channel. For ideal electrokinetic flow, therefore, the degree of mixing will be proportional to the length of the mixing section, the applied field (which results in the desired Peclet number), and the contact surface area between the two layers. 
     The mixing channels illustrated in  FIGS. 1-3 , and  5 , however, have an aspect ratio near unity such that the width and height of the channel are similar. Since the surface area of the contact layer between Fluids A and B is small, this design is not optimized for diffusive mixing. Increased mixing rates are achieved by increasing the channel aspect ratio. As is well known by those skilled in the art of microanalytical design, injection is accomplished preferably in a channel of modest aspect ratio. Alternatively, the two fluids can be directed through a channel section in which the channel aspect ratio is altered substantially expanding the channel from a modest width to a large width. Unfortunately, haphazard channel expansion has the disadvantage of creating large variations in local fluid speed across the channel resulting in unwanted dispersion and increased probability of channel clogging. A further risk is unwanted recirculation zones that increase the local residence time, effectively increasing the operating time of the microanalytical chip, and complicating chip design, operation, and interpretation of results. 
     BEST MODE 
     Fortunately, a method exists for changing channel dimensions while minimizing dispersion. As is described in detail in commonly owned U.S. patent application Ser. No. 10/456,772, now Published Application Serial Number 20030230489, herein incorporated by reference, a flow channel can be constructed as a set of connected rectangular regions each of which has the geometry of a faceted prism. As described previously, these regions can be designed to change the conductance, or permeability, of the channel by changing the channel size, particularly the depth, and the shape in the region of the facet junctions so that fluid flow is piece-wise uniform. By carefully designing the regional geometries to provide low- and high-permeability regions in the channel, dispersion produced by the junctions is essentially eliminated. The terms “deep” and “shallow,” as applied in the following paragraphs, are used in a relative sense to describe widely differing channel depths as a means for changing the permeability of the flow channel as illustrated in Published Application Serial Number 20030230489. In general, the ratio of “deep” to “shallow” will mean a minimum ratio of greater than 10:1. A ratio of such a magnitude minimizes deviations from flow uniformity caused by deviations from perfect designs that can be expected due to variability introduced when using isotropic etching methods. If such effects are not important for a given design, smaller ratios may be employed. 
     For example, consider the etched channel features shown in  FIG. 6A . Here three microscope images are compiled to obtain a panoramic view of micro-mixer  100  which is comprised of an injector section  110  at the top of the image that delivers fluid into expansion section  120  and thence into to a wide, shallow central channel region  130  where diffusive mixing can proceed. Central channel region  130  is followed again by a constriction section  140  (the inverse of expansion region  120 ) and outlet section  150 . 
     Injector section  110  is itself comprised of inlet ports  111  and  112  for introducing Fluids A and B into intersecting channel lengths  113  and  114 . Respective expansion/contraction sections  120  and  140 , disposed at either end of shallow, central channel region  130 , are made up of shallow-faceted prism channel portions  121  and  141 , respectively, and deep-faceted prism channel portions  122  and  142 , respectively. Expansion section  120  re-directs injected Fluids A and B into a shallow, central channel region  130 , in such a way as to minimize or eliminate dispersion in the moving fluids, where diffusive mixing is advantaged due to the relative depth of this region  130 . Finally, the mixed fluid is channeled away from the central channel region  130 , through contraction section  140  and into outlet section  150  comprised of channel length  151  and outlet port  152  which delivers the mixed fluids for further processing or disposal. 
     The length of the wide, shallow region can be chosen to have any desired value, limited only by the size of the device substrate employed. After the wide region, the channel can be contracted back to a narrow section, which is desirable in many instances as, for example, when detection using laser-induced fluorescence in a narrow region is of benefit. The respective position of deep and shallow regions is illustrated further in the magnified image of  FIG. 6B . Here, the angles between deep and shallow regions correspond to an 85° incidence angle for a 10:1 permeability ratio for a 3-interface, 30× expander without skew compensation, as described in U.S. Patent Application Serial Number 20030230489, herein incorporated by reference. 
     Those skilled in the art will recognize that the use of faceted prismatic sections is provided only as an example: the concept presented herein will function properly for any approach that expands the mixer channel. However, methods that retain substantially uniform fields while minimizing dispersion are highly advantageous.