Agitating – Stationary deflector in flow-through mixing chamber
Reexamination Certificate
1999-05-06
2001-01-09
Cooley, Charles E. (Department: 1723)
Agitating
Stationary deflector in flow-through mixing chamber
Reexamination Certificate
active
06170981
ABSTRACT:
TECHNICAL FIELD OF THE INVENTION
The present invention generally relates to the mixing of confluent liquid streams in microfluidic systems and, more particularly, to an in situ micromachined mixer for microfluidic analytical systems.
BACKGROUND OF THE INVENTION
Merging two or more liquids to form a solution generally requires some combination of convective and diffusive transport. This is a critical element of many analytical methods. Although blending by convective transport alone can be achieved very quickly, it only provides a macroscopic level of mixing. Efficient mixing within convectively generated microenvironments requires diffusion. Diffusive mixing is most effective when the transport distance is a few microns or less.
Convective transport is a physical process requiring energy. Generally, this energy is provided in the form of mechanical agitation, as in the case of mechanical stirrers or vortex mixers. This direct addition of energy at the point of mixing is perhaps the reason this form of mixing is referred to as “dynamic mixing.” Liquids may also be mixed by transport through a bed of particles where eddy diffusion and laminar flow provide the convective mixing element. An external pump or gravity drives convection in this case. This form of mixing is often referred to as “static mixing,” possibly because there is no mechanical component at the point of mixing. Actually, any system in which there is convective transport is in a dynamic state of flux. The term static mixing is obviously both a misnomer and a contradiction but will be used herein because of its broad usage in the literature.
Mixing confluent liquid streams is an important, but difficult operation in microfluidic systems. Electroosmotically driven, microfluidic analytical systems in which mixing occurs in channels of 50-100 &mgr;m width are known in the art. Such mixing is generally achieved by laterally merging liquid streams in the same plane into a central channel at a T, Y, or + junction, where they mix by lateral diffusion. Channels of this width are too large for rapid diffusive mixing and too small to allow installation of a dynamic mechanical mixer. Some type of static mixer capable of substantial lateral transport would seem to be a better alternative. Because the volume of current microfluidic systems is generally in the range of 1-10 nL/cm and it would be desirable to achieve mixing within 0.1-1 mm of transport distance along a channel, mixing would have to be achieved in a volume of 0.1-2 nL. The question is how to build a static mixer of this volume with a high degree of lateral transport.
Designing a static mixer to solve this problem is facilitated by an analysis of mixing in particle beds. Longitudinal mixing along the flow axis through the bed results from i) laminar flow in the interparticle space, ii) poor mass transfer between stagnant pools of liquid within the particle matrix, and iii) radial differences in the rate of analyte transport. Even higher degrees of mixing can be achieved by using porous particles to increase the volume of stagnant mobile phase and limit mass transfuser further. Because this is a kinetic process, the degree of longitudinal mixing is flow rate dependent. Obviously, longitudinal mixing is most important when there is a longitudinal, or time based variation in the composition of the liquid stream entering the mixer. This is not the case in the microfluidic systems described above. The problem is a spatial difference produced by two, or more streams entering the mixer at different points. This is almost totally an issue of lateral heterogeneity. Lateral mixing is achieved in packed beds by transchannel mixing. As liquid from adjacent streams merges between particles there is both diffusive mixing and some degree of flow heterogeneity arising from packing variations within the bed. Transchannel coupling is very effective in averaging small degrees of lateral heterogeneity within chromatography columns, but does so over the length of many particles and a relatively large volume. The degree of lateral mixing in packed beds is too small to accommodate the substantial lateral heterogeneity encountered in merging two streams in microfluidic systems.
There is therefore a need for a static mixer i) of less than 500 pL total volume, ii) capable of continuously mixing two streams of liquid, and iii) having a high degree of lateral mixing. The present invention is directed toward meeting this need.
SUMMARY OF THE INVENTION
The present invention relates to an in situ micromachined mixer for microfluidic analytical systems. In a preferred embodiment, a 100 pL mixer for liquids transported by electroosmotic flow (EOF) is described. Mixing was achieved in multiple intersecting channels with a bimodal width distribution and varying lengths. Five &mgr;m width channels ran parallel to the direction of flow whereas larger 27 &mgr;m width channels ran back and forth through the network at a 45° angle. All channels were approximately 10 &mgr;m deep. It was observed that little mixing of confluent streams occurred in the 100 &mgr;m wide mixer inlet channel where mixing would be achieved almost exclusively by diffusion. In contrast, mixing was complete after passage through the channel network in the ≈200 &mgr;m length mixer. Solvent composition was altered by varying the voltage on solvent reservoirs. The high efficiency attained in this mixer was attributed to the presence of a 2 pL vortex in the center of the mixer. Video tracking of fluorescent particles with a fluorescence microscope allowed the position and volume of this vortex to be determined.
In one form of the present invention a microfluidic mixer is disclosed, comprising an inlet; an outlet, wherein the inlet and the outlet define a flow axis; a first flow channel extending between the inlet and the outlet, the first flow channel comprising a plurality of channel segments coupled for fluid flow therebetween, wherein each of the channel segments is oriented at a respective non-zero angle to the flow axis; and at least one second flow channel, each of said at least one second flow channels allowing fluid flow between two of the channel segments substantially parallel to the flow axis.
In another form of the present invention a microfluidic mixer is disclosed, comprising an inlet; an outlet, wherein the inlet and the outlet define a flow axis; a first flow channel extending between the inlet and the outlet, the first flow channel comprising a plurality of channel segments coupled for fluid flow therebetween, wherein one half of the channel segments are oriented at an acute angle to the flow axis and another half of the channel segments are oriented at an obtuse angle to the flow axis; and a plurality of second flow channels, each of the plurality of second flow channels allowing fluid flow between an acute angled channel segment and an obtuse angled channel segment.
REFERENCES:
patent: 1637697 (1927-08-01), Jacobsen
patent: 3998597 (1976-12-01), Forrest
patent: 4027857 (1977-06-01), Cunningham
patent: 4594005 (1986-06-01), Sakamoto et al.
patent: 600937 (1978-06-01), None
He Bing
Regnier Fred
Cooley Charles E.
Purdue Research Foundation
Woodard Emhardt Naughton Moriarty & McNett
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