U.S. patent application number 11/301386 was filed with the patent office on 2006-04-27 for micromixer apparatus and methods of using same.
This patent application is currently assigned to Agency for Science, Technology and Research. Invention is credited to Hongmiao Ji, Victor Samper.
Application Number | 20060087918 11/301386 |
Document ID | / |
Family ID | 33510759 |
Filed Date | 2006-04-27 |
United States Patent
Application |
20060087918 |
Kind Code |
A1 |
Ji; Hongmiao ; et
al. |
April 27, 2006 |
Micromixer apparatus and methods of using same
Abstract
Microfluidics mixing apparatus and methods of using same are
disclosed for mixing fluids using increasing centrifugal force as
the fluids being mixed traverse a mixing channel. One inventive
apparatus comprises a generally planar substrate having a top major
surface and a bottom major surface generally parallel to the top
major surface, and a cover plate over the top major surface. The
substrate has at least one inlet port that routes fluid to the top
major surface, and at least one outlet port for mixed fluid. The
substrate comprises a mixing channel having a depth measured from
the top surface and a width, the mixing channel adapted to route
fluids to be mixed therein in laminar flow and in a substantially
spiral flow pattern that is parallel to the top surface. Apparatus
of the invention can mix fluids flowing serially, or two or more
fluids entering the device from different feed channels.
Inventors: |
Ji; Hongmiao; (Singapore,
SG) ; Samper; Victor; (Springdale, SG) |
Correspondence
Address: |
Kelly K. Kordzik;Winstead Sechrest & Minick P.C.
P.O.Box 50784
Dallas
TX
75201
US
|
Assignee: |
Agency for Science, Technology and
Research
Centros
SG
|
Family ID: |
33510759 |
Appl. No.: |
11/301386 |
Filed: |
December 13, 2005 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
10459200 |
Jun 11, 2003 |
|
|
|
11301386 |
Dec 13, 2005 |
|
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Current U.S.
Class: |
366/341 ;
366/DIG.3 |
Current CPC
Class: |
B01J 2219/00952
20130101; B01J 2219/00995 20130101; B01L 3/5027 20130101; Y10S
366/03 20130101; B01J 2219/00889 20130101; B01J 2219/00835
20130101; B01F 2215/0431 20130101; B01J 2219/00783 20130101; B01J
19/0093 20130101; B01J 2219/00819 20130101; B01F 2215/0495
20130101; B01F 5/0646 20130101; B01F 5/0647 20130101; B01J
2219/00984 20130101; B01F 13/0059 20130101 |
Class at
Publication: |
366/341 ;
366/DIG.003 |
International
Class: |
B01F 5/00 20060101
B01F005/00; B81B 1/00 20060101 B81B001/00 |
Claims
1-26. (canceled)
27. A microfluidics mixing apparatus for mixing at least two
fluids, the apparatus comprising a substrate including one or more
fluid feed conduits for routing two or more fluids to be mixed to a
continuously curving spiral mixing channel, the mixing channel
having a depth and a width, the mixing channel adapted to route
fluids to be mixed therein in laminar flow and in a substantially
spiral flow pattern that is substantially parallel to a top surface
of the substrate, the mixing channel connected to a product
conduit.
28. The microfluidics mixing apparatus of claim 27 wherein the
substrate comprises a top major surface and a bottom major surface
generally parallel to the top major surface, the substrate having
at least one inlet port that routes fluid to the feed conduits, the
substrate having at least one outlet port connected to the product
conduit.
29. The microfluidics mixing apparatus of claim 27 comprising first
and second inlet ports, the first inlet port connected to a first
feed conduit, and the second inlet port connected to a second feed
conduit, the first and second feed conduits meeting at a mixing
point in said mixing channel.
30. The microfluidics mixing apparatus of claim 27 wherein one of
the feed conduits to the mixing channel is tangent to the
substantially spiral flow pattern.
31. The microfluidics mixing apparatus of claim 28 wherein the
outlet port is centered in the substrate.
32. The microfluidics mixing apparatus of claim 27 wherein the
mixing channel has a cross-section shape selected from the group
consisting of rectangular, circular, oval, and trapezoidal.
33. The microfluidics mixing apparatus of claim 27 further
comprising a cover plate.
34. The microfluidics mixing apparatus of claim 33 wherein the
cover plate is transparent.
35. The microfluidics mixing apparatus of claim 28 wherein the
outlet port connects to a second fluid handling apparatus.
36. The microfluidics mixing apparatus of claim 35 wherein the
second fluid handling apparatus is like that of claim 27.
37. The microfluidics mixing apparatus of claim 27 wherein the
mixing channel is comprised of a reactive material.
38. The microfluidics mixing apparatus of claim 37 wherein the
reactive material is selected from the group consisting of
catalysts, enzymes, and ligands.
39. The microfluidics mixing apparatus of claim 27 wherein the
substrate comprises materials selected from the group consisting of
silicon, metal, glass, plastic, and combinations, thereof.
40. The microfluidics mixing apparatus of claim 28 wherein the
inlet port and the outlet port open to the top major surface.
41. The microfluidics mixing apparatus of claim 28 wherein the
inlet ports and the outlet port open to a peripheral edge of the
substrate.
42. The microfluidics mixing apparatus of claim 27 wherein the
inlet ports and the outlet port lie in the same plane as the mixing
channel.
43. The microfluidics mixing apparatus of claim 27 wherein the
inlet ports and the outlet port lie out-of-plane from the mixing
channel.
44. A method of mixing fluids using the microfluidics mixing
apparatus of claim 27 to mix fluids, the method comprising the
steps of: a) selecting fluids to be mixed; b) selecting a radius of
the apparatus and a depth and a width of the mixing channel so as
to minimize dead volume; and c) applying fluids to be mixed and
flowing the fluids through the mixing channel.
45. The method of claim 44 further comprising a step of selecting
an angle .theta. between two feed conduits feeding the mixing
channel.
46. The method of claim 44 further comprising a step of monitoring
extent of mixing by measuring a property of the mixed fluid.
47. The method of claim 44 further comprising a step of reacting a
component of a first fluid with a component of a second fluid.
48. The method of claim 47 further comprising a step of monitoring
extent of reaction of said components.
49. A method of mixing two or more fluids, the method comprising
the steps of a) feeding two or more fluids into a continuously
curving spiral microfluidic mixing channel having an outlet; and b)
contacting the fluids through the influence of centrifugal force
while flowing through the mixing channel, the mixing channel having
a structure that functions to increase centrifugal force on the
fluids as they travel toward the outlet, thereby increasing the
effective contact area between the fluids while flowing in the
mixing channel and enhancing diffusional mixing.
50. A microfluidics mixing apparatus comprising: a) a substrate and
a cover plate combination defining a continuously curving spiral
mixing channel, the mixing channel having at least one inlet port
and an outlet port; and b) an apparatus radius and mixing channel
depth chosen so as to minimize dead volume.
Description
BACKGROUND INFORMATION
[0001] 1. Technical Field
[0002] The present invention relates generally to fluid dynamics.
More specifically, the invention relates to apparatus for mixing
fluids, and methods of making and using such apparatus.
[0003] 2. Background Art
[0004] A micromixer is a device used to mix small volumes of fluids
flowing in very narrow channels. A micromixer is essential in many
of the microfluidics systems targeted for use in biochemical
analysis, drug delivery, and sequencing or synthesis of nucleic
acids. Biological processes such as cell activation, enzyme
reactions, and protein folding often involve reactions that require
mixing of reactants for initiation. Mixing is also necessary in
many microfabricated chemical systems that carry out complex
chemical synthesis. See "Passive Mixing in a Three-Dimensional
Serpentine Microchannel," R. H. Liu, M. A. Stremler, K. V. Sharp,
M. G. Olsen, J. G. Santiago, R. J. Adrain, H. Aref, and D. J.
Beebe, Journal of Microelectromechanical Systems, Vol. 9, No. 2,
June 2000.
[0005] When fluids flow in channels approximately the size of a
human hair, the phenomenon, known as laminar flow, exhibits very
different properties than fluids flowing within the macro world.
Laminar flow, also associated with low Reynolds numbers, will allow
the movement of different layers of the fluid and particles next to
each other in a channel with little or no mixing, except for
diffusion.
[0006] As explained by Liu et al., using a classification that is
adapted here, micromixers can be classified as either active or
passive. Passive stirring schemes include simple in-plane
lamination and chaotic advection stirring (defined by Liu et al. as
the rapid distortion and elongation of material interfaces). Active
mixers have moving parts or externally applied forcing functions
such as pressure, electric field, or ultrasound. Passive mixers
typically use channel geometry to increase the interfacial area
between the liquids to be mixed, thus improving the odds for
diffusional mixing. These mixers can be categorized into two
subclasses: in-plane mixers, which divide and mix streams within a
fluid network confined to one level, and out-of-plane or lamination
mixers, which use three-dimensional channel geometries. The
above-referenced Liu et al. article describes a three-dimensional
serpentine channel out-of-plane passive mixer, which relies on
chaotic advection, as well as two in-plane mixers: square-wave
channel, and straight channel. The simplest in-plane mixers merge
two fluid streams into a single channel and accomplish mixing by
molecular diffusion, relying on time and high diffusion
coefficients to mix the fluids or move solutes between fluids. This
is troublesome for biologic samples, whose constituent molecules
are frequently complex oligomeric or polymeric structures.
Out-of-plane, lamination mixers sequentially split and stack fluid
streams in a three-dimensional fluidic network. Lamination mixers
typically require multi-layer microfabrication techniques, which
make them less attractive to bioanalysis system designers where
targets are simple fabrication, planar designs, and ease of
integation into microfluidic systems.
[0007] Several other microfluidic devices have been developed
recently which attempt to improve fluid mixing within microscale
devices. U.S. Pat. No. 6,136,272, which issued on Oct. 24, 2000,
and is assigned to the University of Washington, describes a device
for rapidly joining and splitting fluid layers within microfluidic
channels which allow for diffusional mixing in two directions, in
the depth direction and in the width direction. Unfortunately, the
devices described in this patent, which refer to curved bridge
channels used in "mixing mode," do not describe centrifugal mixing
in these channels, and in fact appear to be devoted to keeping the
laminar flow streams separated in the bridge channels. The only
mixing occurring in these devices appears to be in parallel,
straight channels downstream from any curved bridge channel.
[0008] Patent Cooperation Treaty WO 01/89675 A2, published Nov. 29,
2001 and assigned to Micronics, Inc., describes a jet vortex mixer,
generally circular-shaped, containing no moving parts, and capable
of mixing both serial and laminar flow streams. This device may be
termed an active mixer, in that the inlets of this device are
connected with pumping valves that provide the power to the mixer
and transport fluids forward and backward inside the mixer. The
device requires converging sections for the fluid entering the
device, thereby increasing linear velocity of the fluid prior to
entering the mixing chamber. These converging sections may lead to
difficulties in cleaning the device for repeated use.
[0009] U.S. Published Patent Application No. 2002/0097632 A1,
published Jul. 25, 2002, describes microsystem platforms for
achieving efficient mixing of one or a plurality of fluids on the
surface of the platform when fluid flow is motivated by centripetal
force produced by rotation, similar to a CD-ROM disc. These devices
appear to be able to mix fluids only in serial fashion, not in
laminar layers.
[0010] Despite recent advances, there is an unmet need in many arts
for efficient, reliable, and repeatable mixing of reagents or
reagents and samples in microfluidic devices. For example,
biochemical analysis, drug delivery, sequencing or synthesis of
nucleic acids, biological processes such as cell activation, enzyme
reactions, and protein folding often involve reactions that require
mixing of reactants in microspace for initiation. Mixing is also
necessary in many microfabricated chemical systems that carry out
complex chemical synthesis, such as combinatorial chemistry.
SUMMARY OF THE INVENTION
[0011] The apparatus and methods of the present invention reduce or
overcome many of the noted problems of previous microfluidics
apparatus and methods.
[0012] A first embodiment of the invention are microfluidics mixing
apparatus for mixing at least two fluids, one inventive apparatus
comprising a substrate comprising one or more fluid inlet conduits
and a mixing channel, the mixing channel having a depth and a
width, the mixing channel adapted to route fluids to be mixed
therein in a substantially spiral flow pattern that is
substantially parallel to a top surface of the substrate, the
mixing channel connected to a product conduit.
[0013] Apparatus of the invention may comprise a generally planar
substrate having a top major surface and a bottom major surface
generally parallel to the top major surface. The substrate may have
one or more inlet ports that route fluids to be mixed to the top
major surface. For example, apparatus of the invention could mix
two or more fluids entering through the same inlet port but at
different times. The substrate may also have an outlet port for
mixed fluid, if necessary, in accordance with the specific use of
the apparatus. More commonly, apparatus of the invention will mix
two or more fluids flowing from different feed streams, and if
inlet ports are necessary, the apparatus will comprise first and
second inlet ports, the first inlet port connected to the feed
conduit, and the second inlet port connected to a second feed
conduit, the first a second feed conduits meeting at a mixing point
in the mixing channel. At least one of the feed conduits to the
mixing channel is tangent to the substantially spiral flow pattern.
The mixing channel may comprise first and second mixing channel
sections, the first mixing channel section adapted to route the
fluids to be mixed from a periphery of the substrate to a center of
the substrate. Thereafter, the first mixing channel section feeds
the second mixing channel section, wherein the fluids being mixed
flow in a reverse spiral pattern compared to the spiral pattern of
the first mixing channel section. The second mixing channel section
may or may not be adjacent the first mixing channel section. The
outlet port may be centered in the substrate, or located on the
periphery of the substrate. The outlet port may connect to a second
fluid handling device, wherein the second fluid handling device is
a second apparatus of the invention or a different device. The
apparatus may include a cover plate, which may be transparent
allowing optical access. Alternatively, the mixing channel may be
closed by growing up the edges of the channel, or the mixing fluids
may form a solidified top surface, while the bulk of the mixing
fluids traverse the mixing channel beneath the solidified top
surface. The mixing channel has a cross-section shape selected from
the group consisting of rectangular, circular, oval, and
trapezoidal.
[0014] The mixing channel may be comprised of a reactive material
or an inert material. Reactive materials may be either organic or
inorganic, and selected from the group consisting of catalysts,
enzymes, ligands, oligomers, oligonucleotides, and the like. The
substrate comprises materials selected from the group consisting of
silicon, metal, glass, ceramic, and combinations thereof. The inlet
port and the outlet port may open to the top surface or to the
peripheral edge of the substrate to another in-plane device.
[0015] Another embodiment of the invention are methods of mixing
fluids using the mixing apparatus of the invention, the method
comprising the steps of: [0016] a) selecting fluids to be mixed;
[0017] b) selecting a radius R of the apparatus and a depth and a
width of the mixing channel according to the principles: [0018] i)
dead volume is low as possible; [0019] ii) flow rate of mixed
fluid; [0020] iii) viscosity of mixed fluid; [0021] iv)
0<t.sub.r<t.sub.c, [0022] where t.sub.r is residence time of
fluids flowing in the mixing channel, and t.sub.c is time required
for complete mixing of fluids in an ideal mixer; and [0023] c)
applying fluids to be mixed and flowing the fluids through the
mixing channel.
[0024] The methods of using the apparatus may include the step of
selecting an angle .theta. between two feed conduits; maintaining
temperature of the fluids being mixed; and removing heat energy
generated during mixing or adding heat energy to the apparatus
during mixing. The methods may also include monitoring extent of
mixing and/or an extent of reaction by measuring a property of the
mixed fluid selected from the group consisting of color,
temperature, change in temperature from one point to another point
in the mixing channel, radioactivity, binding affinity, NMR
spectra, mass spectra, IR spectra, X-ray fluorescence spectra,
Raman spectra, conductivity, resistivity, zeta potential, surface
plasmon resonance, viscosity, index of refraction, fluorescence,
viscosity, index of refraction, pH, and combinations of the
foregoing.
[0025] Further aspects and advantages of the invention will become
apparent by reviewing the description of embodiments that
follows.
BRIEF DESCRIPTION OF THE DRAWING
[0026] For a more complete understanding of the present invention,
and the advantages thereof, reference is now made to the following
descriptions taken in conjunction with the accompanying drawings,
in which:
[0027] FIG. 1 is a schematic plan view (enlarged) of an apparatus
of the invention, with some components illustrated in phantom;
[0028] FIGS. 2A, 2B, 2C, and 2D are cross-sections (enlarged) taken
along the lines indicated in FIG. 1;
[0029] FIG. 3 is a schematic plan view (enlarged) of another
apparatus of the invention;
[0030] FIG. 4 is a schematic plan view (enlarged) of another
apparatus of the invention;
[0031] FIG. 5 is a cross-section taken along the section 5-5 of
FIG. 4; and
[0032] FIGS. 6A-C are schematic plan views (enlarged) of three
apparatus of the invention.
DETAILED DESCRIPTION
[0033] The inventors have developed unique apparatus and methods of
using same to mix fluids. Apparatus and methods of use of the
invention rely on mixing resulting from a centrifugally enhanced
diffusion process. The non-uniform velocity profile across the
section of the mixer arises from the combination of viscous forces
and centrifugal (inertial in the radial direction) forces. The
viscous forces give rise to the typical quadratic velocity profile
whilst the centrifugal forces are proportional to the tangential
velocity, the fluid mass, and the radius of the mixing channel from
the center of the apparatus to the point of interest. The solution
of all forces on the liquid results in a flow pattern that
continuously circulates the liquid from an inner inlet channel into
the fluid entering a second, or outer channel. Depending on the
size of the apparatus and the intent of the user, more than one
fluid can be mixed in apparatus of the invention.
[0034] Referring now to the drawing figures, FIG. 1 is a schematic
plan view (enlarged) of an apparatus 100 of the invention, with
some components illustrated in phantom. Apparatus 100 has a first
fluid feed conduit 2, a second fluid feed conduit 4, and a mixing
point 6. First and second feed conduits 2 and 4 form an angle
.theta., which ranges from about 10 to about 90 degrees, more
preferably from about 20 to about 45 degrees. First and second feed
conduits feed a mixing channel 7, which winds in a spiral toward a
center point C of the apparatus. After reaching center point C, in
this embodiment fluids being mixed continue in a second mixing
channel 7', which lies adjacent mixing channel 7, and the fluids
being mixed flow in the opposite angular direction compared to the
fluids traversing channel 7. Apparatus 100 also has inlet ports 14
and 16, and a product conduit 8 leading to an outlet port 18. A
cover plate 10 and substrate 12 are illustrated in phantom. Also
illustrated is a radius R, measured along the line C-P, where P is
a point on the periphery of the substrate. It should be mentioned
that the radius R of apparatus of the invention is continually
changing as the point P moves around the periphery of the
substrate.
[0035] In general, the following principles are abided by in the
methods and apparatus of the invention in selecting a radius R of
the apparatus and a cross-sectional area A and width of the mixing
channel: [0036] i) dead volume is low as possible; [0037] ii) flow
rate of mixed fluid; [0038] iii) viscosity of mixed fluid; and
[0039] iv) 0<t.sub.r<t.sub.c, where t.sub.r is residence time
of fluids flowing in the mixing channel, and t.sub.c is time
required for complete mixing of fluids in an ideal or perfect
mixer.
[0040] FIGS. 2A, 2B, 2C, and 2D are cross-sections (enlarged) taken
along the lines 2A, 2B, 2C, and 2D, respectively, and designated
110, 120, 130, and 140. Cross-section 110 (FIG. 2A) indicates where
in embodiment 100 the inlet and outlet ports 14 and 16 are
positioned, as well as feed conduits 2 and 4. Cross-section 120
(FIG. 2B) indicates the position of feed conduits 2 and 4.
Cross-section 130 (FIG. 2C) indicates first and second mixing
channels, 7 and 7'. Finally, cross-section 140 (FIG. 2D) indicates
the position of outlet port 18.
[0041] FIG. 3 is a schematic plan view (enlarged) of another
apparatus of the invention, embodiment 150. Embodiment 150 is
similar to embodiment 100 of FIG. 1, but includes a third inlet
port 14' and third feed conduit 4', which connect with second feed
conduit 4 at a junction 6'. More than three fluids may be mixed in
a given apparatus embodiment, as long as appropriate inlets ports
and flow channels are available.
[0042] FIG. 4 is a schematic plan view (enlarged) of another
apparatus of the invention, embodiment 160. Embodiment 160 allows
mixing of two fluids through inlet ports 14 and 16 and feed
conduits 2 and 4, however, this embodiment is not limited to mixing
of two fluids, and can be adapted to mixing three fluids, as
depicted in FIG. 3. In embodiment 160 of FIG. 4, two fluids meet at
junction 6, and flow in a single mixing channel 7 toward and
eventually into an outlet 20 positioned in the center of the
device.
[0043] FIG. 5 is a cross-section taken along the section 5-5 of
FIG. 4, further illustrating outlet port 20 and mixing channel
7.
[0044] FIGS. 6A-C are schematic plan views (enlarged) of three
apparatus of the invention. FIG. 6A illustrates an embodiment 170
having two centers as opposed to one center as in FIGS. 1-5. Fluid
inlet conduits 2a and 4a direct two fluids to be mixed to a first
mixing channel 7a, then to a second mixing channel 7a'. Mixing
continues in mixing channel 9a, which also function as a connection
to the second stage and mixing channels 11a and 13a. Mixed fluid
exits the apparatus through outlet channel 8a. FIG. 6B illustrates
an embodiment 180 similar to embodiment 170 of FIG. 6A. Two fluids
to be mixed enter through fluid inlet conduits 2b and 4b, which
direct the fluids to mixing channels 7b and 7b', then mixing
channels 9b, 11b, and 13b, and finally the mixed fluid exits
through outlet channel 8b. Embodiments 170 and 180 differ
essentially in that embodiment 170 has longer channels, and thus
the mixing fluids experience longer residence time (t.sub.r). FIG.
6C illustrates an embodiment 190 having four centers, which may be
viewed as two apparatus of embodiment 180 connected in series. Two
fluids to be mixed enter through fluid inlet conduits 2c and 4c,
which direct the fluids to mixing channels 7c and 7c', then mixing
channels 9c, 11c, and 13c. A connecting channel 9c' connects mixing
channel 13c with mixing channel 15c, which in turn routes mixing
fluids through channels 17c, 9c'', 19c, 21c, and finally the mixed
fluid exits through outlet channel 8c. In each embodiment 170, 180,
and 190, the length of the mixing chambers (number of the circles)
can be more or less, depending on mixing efficiency.
[0045] The apparatus and methods of the invention can accommodate
many variations, including but not limited to mixing non-reactive
fluids, mixing one reactive fluid with one inert fluid, mixing cold
fluids with hot fluids, as long as the materials of construction
used are sufficient to withstand at least one such mixing use.
Parallel and series versions of the embodiments of FIGS. 1, 3, and
4 are possible, for example where two fluids are mixed in a first
apparatus, then the mixture mixed with a third fluid in a second
apparatus, where the second apparatus is the same or different from
the first. Embodiments may be envisioned herein the mixing channel
comprises reactive sites, or reactive moieties, receptors, and the
like, and the apparatus used as a filter or chromatograph.
[0046] The substrate material may be any material that can be
shaped or formed into a planar shape and have channels formed
therein or thereon. The mixer can be fabricated on or from any
substrate suitable for the fluids of interest. The spiral mixing
channels are typically in the range of 20-200 .mu.m wide and 20-200
.mu.m deep. The profile of the channels can be rectangular,
trapezoidal, circular, oval, or any other shape that can be
patterned on the substrate. The substrate may be silicon and the
cover plate may be glass or plastic. The two materials can be
bonded together with anodic binding with silicon and glass. Inlet
ports and outlet ports of the mixer can be in-plane or
out-of-plane. The out-of-plane embodiment is illustrated in FIG. 1.
The access holes are illustrated in the silicon substrate that
contains the spiral channel, however, apparatus of the invention
have also been shown to function equally well for holes drilled in
the cover material. The fluid inlet and outlet ports can also lead
to the edge of the substrate for edge type connections. The
apparatus of the invention may employ any other materials
including, but not limited to, polymer substrates such as
polyester, for example polycarbonate, or polydimethylsulphoxane
(PDMS), metallic substrates such as aluminum, stainless steel, or
titanium, glass substrates such as borosilicate glass, and ceramic
substrates. Likewise the cover layer is illustrated for glass, but
can be any other material suitable for sealing the channels. The
apparatus embodiments illustrated herein depict etched channels
produced in the substrate, however apparatus of the invention may
also be fabricated by techniques that result in channels on the
substrate, such as thin film and thick film surface micromachining
including, but not limited to, channels fabricated using
electroplated metal walls, polysilicon walls, silicon dioxide
walls, or silicon nitride walls.
[0047] Polymer inking techniques, as taught in copending
application Ser. No. 10/______, filed Apr. ______, 2003,
incorporated herein by reference, may be used to form mixing
channels, depending on the properties of the fluids to be mixed. In
polymer inking processes, a polymer, such as a polymer film, is
applied, possibly spin coated, onto a patterned mold, and
ultimately transferred to a substrate and a positive image of the
pattern is obtained. Selective surface treatments (also referred to
sometimes as differential surface energy treatments) have been
developed with a goal being to improve the edge smoothness of the
"inked" pattern. During selective surface treatment, protruded
surfaces of the transfer member (referred to herein as protrusions)
are first treated, such as with a flexible stamp (also referred to
herein as an applicator) impregnated or simply coated with a silane
to produce a medium energy surface on the protrusions. The transfer
member is then exposed to a second surface energy modifier, such as
with immersion in a liquid organosilane, to treat the recesses or
trenches of the transfer member and produce a surface energy lower
than the first treatment. Because the surface energy of the
sidewalls and bottoms of the recesses is lower than that of the
protrusions, polymer dewetting from the sidewalls is promoted.
Dewetting from the sidewalls causes the polymer to become
discontinuous near the protrusion edges (also referred to herein as
feature edges). Therefore, the polymer on the protrusion surface of
the transfer member can be inked to the substrate with smooth
edges. Other high throughput patterning techniques, such as
microcontact printing (.mu.CP) and nanoimprint lithography (NIL)
may also be employed.
[0048] FIGS. 1 and 2 illustrate plan view and cross section
schematic views of an apparatus 100 of the invention designed with
dual helical passages, spiraling inwards to the center and back out
to the perimeter. In this embodiment, the device is formed in
substrate 12 and covered by a glass wafer 10. Cover 10 is
transparent to allow optical access to the channels 2, 4, and 7.
Backside openings form the inlets 14 and 16 and outlet 18. In
embodiment 100 of FIG. 1, feed channel 2 joins with feed channel 4
to form a junction 6. Feed channel 2 is tangent to the outer
periphery of the apparatus. Mixed fluid conduit 8, termed herein
the mixer end, can be connected to another microfluidic components
such as reaction chambers, binding chambers, liquid reservoirs, or
other in plane microfluidic channels (not shown). It also can
connect to outlet port 18 to withdraw fluids from the microdevice
of the invention.
[0049] The circulation flow of apparatus of the invention increases
the effective contact area between fluids of interest for mixing
and therefore enhances the process of mixing by diffusion. It can
be shown that increasing the flow velocity enhances the circulatory
flow however it reduces the overall time the fluids are resident in
the mixer and therefore suffers from reduced time for diffusion.
For example, slow liquid velocities suffer from poor circulatory
flow although the resident time in the mixer is large. In such
cases the spiral geometry has little enhancement on the process of
diffusion based mixing.
[0050] Apparatus of the invention are suitable for asymmetric flow
rates through the inlet ports and feed channels. They can also be
used with fluids of the same or different mass densities. The
spiral geometry increases the centrifugal component of force as the
fluid travels towards the mixer center. At the outer radius the
centrifugal force is at its minimum. The optimum mixer design
balances the parameters of dead volume and residence time given the
range of fluid velocities. Increasing the overall radius of the
mixer increases the dead volume and has an ever-decreasing
enhancement by centrifugal forces, however it is often necessary to
provide sufficient residence time for fluid mixing as the fluid
velocity increases. In such cases the advantage of the inventive
mixers' compact form can also be seen.
[0051] The extent of mixing may be observed, monitored, controlled
and/or maintained by any number of analytical techniques, including
but not limited to: measuring a property of the mixed fluid
selected from the group consisting of color, temperature, change in
temperature from one point to another point in the mixing channel,
radioactivity, binding affinity, NMR spectra, mass spectra, IR
spectra, X-ray fluorescence spectra, Raman spectra, conductivity,
resistivity, zeta potential, surface plasmon resonance, viscosity,
index of refraction, fluorescence, viscosity, index of refraction,
pH, and combination of the foregoing.
[0052] Although the foregoing examples and description are intended
to be representative of the invention, they are not intended to in
any way limit the scope of the appended claims.
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