USOO8414182B2

(12) United States Patent (10) Patent No.: US 8.414,182 B2

Paul et al. (45) Date of Patent: Apr. 9, 2013
(54) MCROMIXERS FOR NANOMATERAL 6,793,831 B1 9, 2004 Paul et al.
PRODUCTION 7,507,380 B2 3/2009 Chang et al.
2008. O108122 A1 5/2008 Paul et al.
(75) Inventors: Brian Kevin Paul, Corvallis, OR (US); FOREIGN PATENT DOCUMENTS
Anna Evelyn Garrison, Philomath, OR WO 2004/072419 8, 2004
(US) WO 2006/1072O6 10, 2006

(73) Assignee: State of Oregon acting by and through OTHER PUBLICATIONS

the State Board of Higher Education Ajmera et al., “Microfabricated differential reactor for heteroge
on behalf of Oregon State University, neous gas phase catalyst testing.” Journal of Catalysis, 209:401-412,
Corvallis, OR (US) 2002.
(*) Notice: Subject to any disclaimer, the term of this Amador et al., “Flow distribution in different microreactor scale-out
patent is extended or adjusted under 35 geometries and the effect of manufacturing tolerances and channel
U.S.C. 154(b) by 900 days. blockage.” Chemical Engineering Journal, 101:379-390, 2004.
Bejanet al., “Deterministic tree networks for fluid flow: geometry for
(21) Appl. No.: 12/414,597 minimal flow resistance between a volume and one point. Fractals,
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Chan et al., “Size-controlled growth of CdSe nanocystals in
(22) Filed: Mar. 30, 2009 microfluidics reactors.” Nano Letters 3(2): 199-201, 2003.
Chang et al., “Progress towards chip-based high-throughput
(65) Prior Publication Data
dendrimer synthesis.” IMRET8–8" International Conference on
US 2009/O245O17 A1 Oct. 1, 2009 Microreaction Technology, Atlanta, GA, Apr. 2005.
Ehrfeld et al., “Characterization of Mixing in Micromixers by a Test
Related U.S. Application Data Reaction: Single Mixing Units and Mixer Arrays.” Ind. Eng. Chem.
Res. 38: 1075-1082, 1999.
(60) Provisional application No. 61/072,265, filed on Mar.
28, 2008. (Continued)
(51) Int. Cl. Primary Examiner —Yogendra Gupta
BOIF I3/00 (2006.01) Assistant Examiner — John Robitaille
(52) U.S. C. (74) Attorney, Agent, or Firm — Klarduist Sparkman, LLP
USPC ........................................... 366/341; 366/336
(57) ABSTRACT
(58) Field of Classification Search .................. 366/341,
366/336 A micromixer device has at least one fluid inlet channel and at
See application file for complete search history. least one fluid outlet channel. A plurality of pathways extend
between the fluid inlet channel and the fluid outlet channel.
(56) References Cited The width of at least some of the plurality of pathways varies
in a Substantially parabolic manner along at least one dimen
U.S. PATENT DOCUMENTS sion of the micromixer device.
5,595.712 A * 1/1997 Harbster et al. . . . . . . . . . . . . . 422/129

6,672,502 B1 1/2004 Paul et al. 13 Claims, 37 Drawing Sheets

32)
 US 8,414,182 B2
Page 2

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dendritic polymers.” Industrial Engineering Research Conference,
El Moctar et al., “Electro-hydrodynamic micro-fluidic mixer.” Lab Orlando, FL May 20-24, 2006.
on a Chip, 3:273-280, 2003. Rebrov et al., “Optimization of heat transfer characteristics, flow
Fournier et al., “A new parallel competing reaction system for assess distribution, and reaction processing for a microstructured reactor/
ing micromixing efficiency—experimental approach. Chemical heat-exchanger for optimal performance in platinum catalyzed
Engineering Science 51(22):5053-5064, 1996. ammonia oxidation.” Chemical Engineering Journal, 93:201-216,
2003.
Glasgow and Aubry, “Enhancement of microfluidics mixing using Rebrov et al., “Header design for flow equalization in
time pulsing.” Lab. On a Chip, 3:114-120, 2003. microstructured reactors.” American Institute of Chemical Engineers
Glasgow et al., “Parameters influencing pulsed flow mixing in Journal 53(1):28-38, 2007.
microchannels.” Analytical Chemistry, 76:4825-4832, 2004. Richter et al., “Metallic Microreactors: Components and Integrated
He et al., “A picoliter-volume mixer for microfluidics analytical Systems.” Process Miniaturization, 2" Annual International Con
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Ismagilov, “Integrated Microfluidic Systems.” Angew. Chem. Int. Ed. Schenk et al., “Novel liquid-flow splitting unit specifically made for
42:4130-4132, 2003. numbering-up of liquid/liquid chemical microprocessing.” Chemical
Jongen et al., “Development of a continuous segmented flow tubular Engineering Technology 26(12): 1271-1280, 2003.
reactor and the 'scale-out” concept—In Search of perfect powders.” Schenk et al., “Numbering-up of micro devices: a first liquid-flow
Chemical Engineering Technology, 26(3):303-305, 2003. splitting unit.” Chemical Engineering Journal 101:421-429, 2004.
Khan et al., “Microfluidic Synthesis of Colloidal Silica.” Langmuir, Schwarzer & Peukert, “Experimental Investigation into the Influence
20:8604-8611, 2004. of Mixing on Nanoparticle Precipitation.” Chem. Eng. Technol.
Kockmann et al., “Silicon microstructures for high throughput mix 25(6):657-661, 2002.
ing devices.” Microfluid Nanofluid 2:327-335, 2006. Schwarzer & Peukert, “Combined Experimental/Numerical Study
Krishnadasan et al., “On-line analysis of CdSe nanoparticles forma on the Precipitation of nanoparticles. AIChE Journal 50(12):3234
tion in a continuous flow chip-based microreactor.” J. Mater: Chem. 3247, 2004.
14:2655-2660, 2004. Sovran & Klomp, "Experimentally determined optimum geometries
Li et al., “Control of crystal morphology through Supersaturation for rectilinear diffusers with rectanglular, conical or annular cross
ration and mixing conditions,” Journal of Crystal Growth 304:219 section.” Fluid Mechanics of Internal Flow Proceedings of a
224, 2007. Sumposium, Warren, MI, 1965.
Liu et al., "Convergent synthesis of polyamide dendrimer using con Taylor et al., “Scale-up methods for fast competitive chemical reac
tinuous flow microreactors.” Chemical Engineering Journal tions in pipeline mixers.” Ind. Eng. Chem. Res.44:6095-6102, 2005.
135S:S333-S337, 2008. Tonomura et al., “CFD-based optimal design of manifold in plate-fin
Mohammadi & Santiago, “Simulation and Design of Extraction and microdevices.” Chemical Engineering Journal, 101:397-402, 2004.
Separation Fluidic Devices.” Mathematical Modeling and Numerical Trachsel et al., “Measurement of residence time distribution in
Analysis 35(3):513-523, 2001. microfluidics systems.” Chemical Engineering Science, 60:5729
Moody & Collins, “Effect of Mixing on the Nucleation and Growth 5737, 2005.
of Titania Particles.” Aerosol Science and Technology 37:403-424, Wiessmeier & Honicke, "Strategy for the development of microchan
2003. nel reactors for heterogeneously catalyzed reactions.” American
Nakamura et al., “Preparation of CdSe nanocrystals in micro-flow Institute of Chemical Engineers, New Orleans, USA, 1998.
reactor, Chem. Comm. 2844-2845, 2002. Yen et al., “A continuous-flow microcapillary reactor for the prepa
Paul & Peterson, “Microlamination for microtechnology-based ration of a size series of CdSe nanocrystals.” Adv. Mater.
energy, chemical and biological systems.” ASME International 15(21): 1858-1862, 2003.
Mechanical Engineering Congress and Exposition, Nashville, TN. Yen et al., “A microfabricated gas—liquid segmented flow reactor for
AES 39:45-52, 1999. high-temperature synthesis: the case of CdSe quantum dots.”
Paul. “Micro energy and chemical systems and multi-scale fabrica Angewandte Chemie International Edition, 44:5447-5451, 2005.
tion.” Chapter 14 in Micromanufacturing and Nanotechnology,
Springer-Verlag, Germany, 2005. * cited by examiner
U.S. Patent Apr. 9, 2013 Sheet 1 of 37 US 8,414,182 B2

Coupled-gradient Core-shell-gradient

Composition-gradient shape-gradient size-gradient

FIG. 1

End Cap
U.S. Patent Apr. 9, 2013 Sheet 2 of 37 US 8,414,182 B2

4 essessessessessessessessessessessessessessessessesseegergegreegeese eroes.

0. 8

0. 4

0. 2

O
O& - - - - - - s&s 180
0 degrees

FIG. 3
U.S. Patent Apr. 9, 2013 Sheet 3 Of 37 US 8,414,182 B2

10.00
--T-Mixer
or to IMM Mixer
ris-OSU-MB Mixer

OO

O. O

O.O.
O 50 OO 150 200 250 300
Reynolds Number

FIG. 4
U.S. Patent Apr. 9, 2013 Sheet 5 Of 37 US 8,414,182 B2

s
l i
0. 0.005 0.01 0.015 0.02 O.025 0.03 0.035
Y Location (m)
FIG. 6
U.S. Patent Apr. 9, 2013 Sheet 6 of 37 US 8,414,182 B2

170

.."
.. . ...
Rsss 115
s ".

FIG. 7(a) FIG. 7(b)

U.S. Patent Apr. 9, 2013 Sheet 7 Of 37 US 8,414,182 B2

O. 12

s
0.02

0.016 0.018 0.02 0.022 0.024 0.026 0.028 0.03 0.032

FIG. 8(a)

0.1 -

0.08

s
0.02 .

0.005 O.O. 0.015

FIG. 8(b)
U.S. Patent Apr. 9, 2013 Sheet 8 Of 37 US 8,414,182 B2

FIG. 9

FIG. 10
U.S. Patent Apr. 9, 2013 Sheet 9 Of 37 US 8,414,182 B2

Channel Width as a Function of

Distance from Micromixer Centerline

location (mm)

F.G. 11
U.S. Patent Apr. 9, 2013 Sheet 10 Of 37 US 8,414,182 B2

Channel Width as a Function of Distance

from Center of Micromixer

aa

Yany

r
E
E -i il
S.
S.
r
O
U.S. Patent Apr. 9, 2013 Sheet 11 of 37 US 8,414,182 B2

3 O 3OO

32O

FIG. 13
U.S. Patent Apr. 9, 2013 Sheet 12 Of 37 US 8,414,182 B2

300
U.S. Patent Apr. 9, 2013 Sheet 13 Of 37 US 8,414,182 B2

F.G. 15
U.S. Patent Apr. 9, 2013 Sheet 14 of 37 US 8,414,182 B2

Velocity Profile for 0.025 Factor

O : :

-O.OO25
-0.005 E
-0.0075
-0.0
-0.0125
-0.05
-O.O 75
-0.02
-0.0225
-0.025.
-0.0275 W

-0.03 i | i i
-0.004 -0.003 -O.OO2 -O.OO O O.OO O.OO2 0.003 0.004
X Location (m)
FIG. 16(a)
O
Velocity Profile for Factor = 0.04
-O.OO25

-0.0075
-O.O in or co

-0.0125

-0.0175
-0.02
-0.0225

w N-1 Y-1
-0.0275
-0.03 i
-0.004 -0.003 -0.002 -0.00 O (). OO O.OO2 O.OO3 0.004
X Location (m)
FIG. 16(b)
U.S. Patent Apr. 9, 2013 Sheet 15 Of 37 US 8,414,182 B2

no stabilization
SuperSaturation

mixing &
SuperSaturation
C build-up
s
H
wn
s
e
Y
H
d

no aggregation
(W-boo)
aggregation 20

O W stirre-as-rror-repress-----, asperor r resis r O

10 10 10' 10 O 10

precipitation time ins

FIG. 17
U.S. Patent Apr. 9, 2013 Sheet 16 of 37 US 8,414,182 B2

80s". .50e-0 3.00e-0 4.50e-0 6.00e-O 7.5Oe-O 9.00e-0

F.G. 18

Standard Deviation of Mass Fraction at Mixer Outlet

O.O6

O.49 O.5 O.51 O.52 0.53 O.54 O. 55 O.56

Flow Times)
F.G. 19

FIG. 20
U.S. Patent Apr. 9, 2013 Sheet 17 Of 37 US 8,414,182 B2

IZ“OICH
[0-9.17 ZZ"OIH

:?

105°09'
|

0 :0
U.S. Patent Apr. 9, 2013 Sheet 18 Of 37 US 8,414,182 B2

£Z"OIDH

0-30 "
|

0+3°C)
U.S. Patent Apr. 9, 2013 Sheet 19 Of 37 US 8,414,182 B2

HI
’DI
SZ 9Z"SOICI

0-30 ,
|
€

0 ,0
U.S. Patent Apr. 9, 2013 Sheet 20 Of 37 US 8,414,182 B2

Pressure Drop in 2D Mixer Models

a
x:
A.
se

C
A
u?
s
s
g
in
A.

Mixer 10

FG. 27
U.S. Patent Apr. 9, 2013 Sheet 21 Of 37 US 8,414,182 B2

Mixer Inlet Velocity

().045
0.04 &

0.035 - . .
0.03 -
0.025 - ' -- Inlet A h
s
0.02 a °, - -. .- - - -. -- Inlet B .
0.05 - . . - /

. 1.2
Flow Time (s)

FG, 28
U.S. Patent Apr. 9, 2013 Sheet 22 Of 37

N(S)QAUO'IHL

uOneAeC peputeS
U.S. Patent Apr. 9 9 2013 Sheet 23 Of 37 US 8 9414,182 B2

A(S)QOUIHL

H.
*5)I,
09
U.S. Patent Apr. 9 9 2013 Sheet 24 of 37 US 8 9414,182 B2

‘ DIBI
º
I
U.S. Patent Apr. 9, 2013 Sheet 25 Of 37 US 8,414,182 B2

I.19XIN

¿IIJoxqu-'+;-¡

?5x,-
UOle AeC plutepueS
U.S. Patent Apr. 9, 2013 Sheet 26 of 37 US 8,414,182 B2

Mixer Inlet Velocity

area
---

NY
E
>
.
d
e
C
D
D

0.

Flow Time (s)

FIG. 33
U.S. Patent Apr. 9, 2013 Sheet 27 Of 37 US 8,414,182 B2

Standard Deviation of Species Mass Fraction

at Mixer Outlet for Mixer 11

C
s
>
g -- No Reverse Flow

c -o- or With Reverse FOW

es
ra
f

Flow Time (s)

F.G. 34
U.S. Patent Apr. 9, 2013 Sheet 28 Of 37 US 8,414,182 B2

OHA3MS.NºJI!E

-90

0
|

-90S.
|
U.S. Patent Apr. 9, 2013 Sheet 29 Of 37 US 8,414,182 B2

O(ADMESNJAIGE
99"OIDH
U.S. Patent Apr. 9, 2013 Sheet 30 Of 37 US 8,414,182 B2

Standard Deviation of Species Mass Fraction

at Outlet of Mixer 11
0.075
0.073 a

0.069 3.

0.065 : &

0.06 8.

0.055

Time Step Number

FG. 37
U.S. Patent Apr. 9, 2013 Sheet 31 Of 37 US 8,414,182 B2

[][0-90S.”

|0-90 ’9
U.S. Patent Apr. 9, 2013 Sheet 32 Of 37 US 8,414,182 B2
U.S. Patent Apr. 9, 2013 Sheet 33 Of 37 US 8,414,182 B2

FIG. 42

|
A B C

Improved Mixing
with 180° out of
phase pulsing

FIG. 43
U.S. Patent Apr. 9, 2013 Sheet 34 of 37 US 8,414,182 B2

FG, 44
U.S. Patent Apr. 9, 2013 Sheet 35. Of 37 US 8,414,182 B2

FG. 47
U.S. Patent Apr. 9, 2013 Sheet 36 of 37 US 8,414,182 B2

wn 5O.800 s
Typ.

38.305.05 —-
TYP.

-H-H 6.262:0.5
TYP. 4 O

43 O 440

400 -->

Drill & tap for 8-32 (both sides)

TYP.

F.G. 48
U.S. Patent Apr. 9, 2013 Sheet 37 Of 37 US 8,414,182 B2

430 440

-- 420

FIG. 49
 US 8,414, 182 B2
1. 2
MCROMIXERS FOR NANOMATERAL pathways. The structural elements can comprise channel
PRODUCTION walls that are substantially rectangular in shape.
In other specific implementations, the device comprises a
CROSS REFERENCE TO RELATED plurality of sections. Each section comprises a plurality of
APPLICATION pathways that have substantially the same width. The width of
pathways varies from section to section in a Substantially
This application claims the benefit of the earlier filing date parabolic manner. The device can also comprise a base por
of U.S. Provisional Patent Application No. 61/072,265, filed tion and two side walls that at least generally converge
Mar. 28, 2008. The entire disclosure of the provisional appli towards one another, and the fluid inlet channel can be located
cation is considered to be part of the present disclosure and is 10 Substantially at the intersection of the two converging side
hereby incorporated herein by reference. walls.
In other specific implementations, the location of the fluid
ACKNOWLEDGEMENT OF GOVERNMENT inlet channel can define a central longitudinal axis of the
SUPPORT device, and the lengths of the pathways can vary according to
15 their distance from the longitudinal axis. The lengths of the
This invention was made with government Support under pathways nearest the longitudinal inlet channel can be longer
W911NF-07-2-0083 awarded by the Army Research Office. than the lengths of the pathways furthest from the inlet chan
The United States government has certain rights in the inven nel. The structural elements can be pillars that are substan
tion. tially cylindrical and which vary in width.
In another embodiment, a microchannel array comprises a
FIELD plurality of laminae. Each lamina comprises at least one
micromixer device that has a plurality of fluid flow pathways
The present disclosure relates generally to micromixers between an inlet region and an outlet region. The inlet region
and methods of using micromixers to process nanomaterials. of the micromixer device can be located Substantially along a
25 central longitudinal axis of the micromixer device, and the
BACKGROUND fluid flow pathways can vary in length and width relative to
their distance from the central longitudinal axis.
Microchannel processing of nanomaterials can provide a In specific implementations, the width of the fluid flow
number of advantages over conventional batch processing, pathways can vary substantially parabolically relative to their
including, for example, lower production cost, safer opera 30 distance from the central longitudinal axis. In specific imple
tion, improved selectivity, reduced energy consumption and mentations, there are at least four laminae and at least four
better process control. These improvements in synthesis are micromixer devices on each of the laminae. In specific imple
largely due to the large surface-area-to-volume ratios pos mentations, the lengths of the fluid flow pathways are shorter
sible within microreactor technology leading to accelerated the further they are from the central longitudinal axis and the
heat and mass transport. This accelerated transport allows for 35 widths of the fluid flow pathways are wider the further they
rapid changes in reaction temperatures and concentrations are from the central longitudinal axis. Each micromixer
leading to more uniform heating and mixing. device can comprise a plurality of sections, with each section
One concern in micromixer design is the non-uniform comprising a plurality of fluid flow pathways that have sub
velocity profile due to laminar flow which leads to variations stantially the same width. The widths of pathways can vary
in shear-dependent mixing and a broadening of the residence 40 from section to section in a Substantially parabolic manner.
time distribution (RTD) of molecules within the channel. The fluid flow pathways can be made using any suitable
Velocity profiles become even more difficult to manage as the process, such as chemical etching.
design is scaled up through “numbering up' strategies that In another embodiment, a microchannel mixer comprises a
combine multiple microchannel structures together. Another first fluid inlet for introducing a first fluid into the mixer: a
concern in micromixer design is clogging. The size and shape 45 second fluid inlet for introducing a second fluid into the
of current microchannel structures are prone to undesirable mixer, a serpentine fluid flow pathway; a first pump device,
clogging. the first pump device being configured to introduce the first
fluid into the fluid flow pathway; and a second pump device,
SUMMARY the second pump device being configured to introduce the
50 second fluid into the fluid flow pathway. The first and second
The foregoing and other objects, features, and advantages pump devices can be configured to pump the first and second
of the embodiments described herein will become more fluids, respectively, into the fluid flow pathway using reverse
apparent from the following detailed description, which pro oscillatory flow.
ceeds with reference to the accompanying figures. In specific embodiments, the first and second pump devices
In a first embodiment, a micromixer device comprises at 55 both comprise two pump members. A first pump member is
least one fluid inlet channel and at least one fluid outlet configured for forward sinusoidal flow and a second pump
channel. A plurality of pathways are positioned between the member is configured for reverse sinusoidal flow. In other
fluid inlet channel and the fluid outlet channel. The width of specific implementations, the first and second pump devices
at least some of the plurality of pathways vary in a Substan are configured to pump the first and second fluids, respec
tially parabolic manner along at least one dimension of the 60 tively, into the fluid flow pathway at 180 degrees out of phase
micromixer device. with each other.
In a specific implementation, the fluid inlet channel is In other specific implementations, the fluid flow pathway is
located at a substantially central location relative to the plu machined to be about 200 micrometers or greater in width.
rality of pathways and the width of the pathways varies in a The serpentine fluid flow pathway can be defined by a top and
Substantially parabolic manner as a function of the distance of 65 bottom member. The serpentine fluid flow pathway can be
the pathway from the fluid inlet channel. In another specific machined into the top and bottom members. The top and
implementation, a plurality of structural elements define the bottom members can be removably coupled together. In
 US 8,414, 182 B2
3 4
another specific embodiment, the standard deviation of mass FIG. 24 illustrates an analysis of residence time distribu
fractionatan outlet of the serpentine fluid flow pathway is less tion with the micromixer channel shown in FIG. 23.
than about 0.06. FIG.25 illustrates an embodimentofa micromixerchannel
with alternating increasing width (expanded) regions and
BRIEF DESCRIPTION OF THE DRAWINGS 5 decreasing (constricted) width regions.
FIG. 26 illustrates a residence time distribution of the
FIG. 1 is a schematic drawing illustrating embodiments of micromixer channel of FIG. 25.
hierarchical nanostructures that can be made using embodi FIG. 27 illustrates pressure drops across the micromixer
ments of disclosed micromixers. channels of FIG.20 (i.e., Mixer 3), FIG.23 (i.e., Mixer 4), and
FIG. 2 is a microlaminationarchitecture that can be used to 10 FIG. 25 (i.e., Mixer 10).
fabricate a dual micro-channel array. FIG. 28 illustrates a mixer inlet velocity that has a sinusoi
dal switched flow.
FIG.3 illustrates as loss co-efficient K, for a typical conical FIG. 29 illustrates a comparison of mixer outlet mass frac
diffuser.
FIG. 4 shows absorption data for several types of micro tion between the micromixer channels of FIG. 20 (i.e., Mixer
mixers having a flow rate dependence. 15
3) and FIG. 23 (i.e., Mixer 4).
FIG. 30 illustrates a comparison of standard deviations of
FIG.5 illustrates a micromixer with cylindrical pillars. The species mass fraction at outlet for the micromixers of FIG. 23
outlined geometry illustrates an adjacent bonded lamina. (i.e., Mixer 4) and FIG. 25 (i.e., Mixer 10).
FIG. 6 illustrates the velocity profile of the micromixer FIG. 31 illustrates a comparison of standard deviations of
model shown in FIG. 5. species mass fraction at outlet for the micromixers of FIG. 25
FIG. 7(a) shows a micromixer with a linear variation in (i.e., Mixer 10) and Mixer 11 (similar to FIG. 25, but with the
pillar diameter. inlet relocated as shown in FIG. 31).
FIG.7(b) shows a micromixer with a parabolic variation in FIG.32 illustrates a comparison of standard deviations for
pillar diameter. the micromixers of FIG. 20 (i.e., Mixer 3), FIG. 23 (i.e.,
FIG. 8(a) shows a velocity profile distribution for the Mixer 4), FIG. 25 (i.e., Mixer 10), and Mixer 11 (shown in
micromixer shown in FIG. 7(a). 25 FIGS. 31 and 32).
FIG. 8(b) shows a velocity profile distribution for the FIG. 33 illustrates an embodiment of inlet velocity for a
micromixer.
micromixer shown in FIG. 7(b). FIG. 34 illustrates a standard deviation of species mass
FIG. 9 illustrates a micromixer channel width that varies
according to a parabolic function. fraction at mixer outlet for Mixer 11 (shown in FIGS. 31 and
FIG. 10 illustrates dimensions used to determine hydraulic 30 32).
diameter for a rounded microchannel. FIG.35 illustrates CFD analysis of the contours of species
mass fraction at beginning of the cycle without and with
FIG. 11 illustrates a comparison of actual versus modeled reversed flow.
channel width as a function of micromixer width, using a FIG. 36 illustrates residence time distributions without and
slope factor of c=0.04. with reversed flow.
FIG. 12 illustrates channel width as a function of distance 35
FIG. 37 illustrates a comparison of standard deviations of
from the center of a micromixer. species mass fraction at outlet for Mixer 11 with a pulse
FIG. 13 illustrates a portion of a microchannel array com frequency of 5 Hz and 20 Hz.
prising a plurality of laminae coupled together. FIG. 38 illustrates a CFD analysis of the contours of spe
FIG. 14 illustrates an exploded view of the microchannel cies mass fraction for 5 Hz and 30 Hz systems.
array shown in FIG. 13, shown with the laminae separated 40 FIG. 39 illustrates a residence time distributions for a
from one another in an exploded view. pulsed flow frequency of 5 Hz.
FIG. 15 illustrates a triangular mesh used in regions of FIG. 40 illustrates a residence time distributions for a
complex geometry while a structured grid is applied in rect pulsed flow frequency of 20 Hz.
angular channels. FIG. 41 illustrates a residence time distributions for a
FIG. 16(a) illustrates a velocity profile for a micromixer 45 pulsed flow frequency of 5 Hz.
having a slope factor of c=0.025. FIG. 42 illustrates a residence time distributions for a
FIG. 16(b) illustrates a velocity profile for a micromixer pulsed flow frequency of 20 Hz.
having a slope factor of c=0.04. FIG. 43 illustrates several inlet configurations for a micro
mixer.
FIG.17 illustrates an example of the time scales over which FIG. 44 illustrates a pump system for sinusoidal flow.
Supersaturation, nucleation, and aggregation occur within 50
FIG. 45 illustrates a pump system for sinusoidal flow.
typical precipitation chemistry reactions. FIG. 46 illustrates a drawing showing an exploded view of
FIG. 18 shows computational fluid dynamic analysis of an a device withinlet headers and an embedded serpentine chan
axial cross-section of flow. nel system machined into the bottom plate.
FIG. 19 shows resultant standard deviation of concentra FIG. 47 illustrates a cross-section view of the top and
tion at outlet as a function of time. 55 bottom plates shown in FIG. 46 and reflecting dimensions
FIG.20 illustrates an embodimentofa micromixerchannel that can be machined using conventional cutting tools.
with a serpentine construction. FIG. 48 illustrates another embodiment of a micromixer
FIG. 21 illustrates a CFD analysis of the structure of FIG. channel that can be machined using conventional cutting
20 with an inlet velocity of 0.02 m/s (about 3.5 mL/min). tools.
FIG. 22 illustrates an analysis of residence time distribu 60 FIG. 49 illustrates another embodiment of a micromixer
tion with the same micromixer channel. channel that can be machined using conventional cutting
FIG.23 illustrates an embodimentofa micromixerchannel tools.
comprising a serpentine channel that expands at areas or
regions where the flow changes direction (e.g., at turns in the DETAILED DESCRIPTION
microchannel) and contracts where the flow is in a region 65
where the flow continues in one direction (e.g., where the flow The following description is exemplary in nature and is not
does not change direction). intended to limit the scope, applicability, or configuration of
 US 8,414, 182 B2
5 6
the invention in any way. Various changes to the described TALLIC STRUCTURES AND INTERMETALLIC
embodiment may be made in the function and arrangement of DEVICES MADE THEREBY: International Patent Applica
the elements described herein without departing from the tion No. PCT/US2004/03452, filed Oct. 25, 2004, titled
Scope of the invention. HIGH VOLUME MICROLAMINATION PRODUCTION
As used in this application and in the claims, the singular OF DEVICES; U.S. patent application Ser. No. 11/086,074,
forms “a,” “an,” and “the include the plural forms unless the filed Mar. 21, 2005 and issued as U.S. Pat. No. 7,507,380 on
context clearly dictates otherwise. Additionally, the terms Mar. 24, 2009, titled MICROCHEMICAL NANOFACTO
“having and “including' mean "comprising.” Further, the RIES; and U.S. patent application Ser. No. 1 1/897.998, filed
terms “coupled and “associated generally means electri Aug. 31, 2007, titled MICROCHEMICAL NANOFACTO
cally, electromagnetically, and/or physically (e.g., mechani 10 RIES.
cally or chemically) coupled or linked and does not exclude Microreactors can also improve cycle times and yields
the presence of intermediate elements between the coupled or associated with the production of precision macromolecules,
associated items. For the purposes of this disclosure, nano Such as dendrimers. Further, microreactor technology can
materials refer to applications with features smaller than minimize the environmental impact of hierarchical manufac
about one tenth of a micrometer in at least one dimension. 15 turing through solvent-free mixing, integrated separation
Although the operations of exemplary embodiments of the techniques, and reagent recycling. Finally, the possibility of
disclosed method may be described in a particular, sequential synthesizing nanomaterials in the required Volumes at the
order for convenient presentation, it should be understood point-of-deposition eliminates the need to store and transport
that disclosed embodiments can encompass an order of potentially hazardous materials while providing new oppor
operations other than the particular, sequential order dis tunities for tailoring novel, functionally gradient structures.
closed. For example, operations described sequentially may For example, microreactor technology can be used to form
in Some cases be rearranged or performed concurrently. Fur coupled-gradient, core-shell-gradient, composition-gradient,
ther, descriptions and disclosures provided in association shape-gradient, and size-gradient structures such as those
with one particular embodiment are not limited to that shown in FIG. 1.
embodiment, and may be applied to and/or combined with 25 To improve and establish the industrial viability of micro
any other description or disclosure provided herein relating to channel processing of nanomaterials, it is desirable to estab
alternative or different embodiments. lish that parallel microchannels can be scaled-up with each
Moreover, for the sake of simplicity, the attached figures microchannel processing equivalent amounts of fluid under
may not show the various ways (readily discernable, based on precise concentrations and temperatures and with Small resi
this disclosure, by one of ordinary skill in the art) in which the 30 dence time distributions. Accordingly, improvements in the
disclosed system, method, and apparatus can be used in com scale-up issues associated with the microchannel processing
bination with other systems, methods, and apparatuses. Addi of nanomaterials are desirable.
tionally, the description sometimes uses terms such as “pro Scale-up fundamentally involves increasing the Volumetric
duce” and “provide to describe the disclosed method. These flow rate through the microreaction system according to the
terms are high-level abstractions of the actual operations that 35 equation:
can be performed. The actual operations that correspond to
these terms can vary depending on the particular implemen avg (1)
tation and are, based on this disclosure, readily discernible by where v is the volumetric flow rate of reactants through
one of ordinary skill in the art. microchannels, V is the average velocity of the reactants
Various embodiments of interdigital micromixers are 40 through the microchannels and A is the flow cross-section,
described herein. Such micromixers are capable of scaling up which is a product of the flow cross-section of each micro
liquid-phase nanosynthesis. By providing a uniform Velocity channel by the number of microchannels. Increasing the aver
profile, more uniform mixing and more uniform RTD can be age velocity through the microchannels increases the pres
achieved. Application of the embodiments disclosed hereinto Sure drop across the microchannel, which is practically
higher temperature liquid phase and gas phase reactions can 45 limited by the size of the pump. A more reasonable strategy
be accomplished by incorporating integrated microchannel involves increasing the cross-section of flow. Given that the
heat exchangers. flow in microchannel technology is predominately laminar
In nanoparticle synthesis, microreactor technology offers and therefore the size of the channel is generally constrained
large Surface-area-to-volume ratios within microchannel by the application (e.g., the speed of heat transfer or diffu
structures to accelerate heat and mass transport. This accel 50 sional mixing), microchannel scale-up requires a strategy for
erated transport allows for rapid changes in reaction tempera arraying parallel microchannels. In the general microreactor
tures and concentrations leading to more uniform heating and literature, this scale-up strategy is sometimes called “num
mixing. Consequently, microreactors can provide dramatic bering up.” As used herein, scale-up is intended to refer to be
reductions in the dispersity of quantum dot size distributions. the processing of an industrially relevant flow rate Sustained
The following references, the entire disclosures of which are 55 by an array of parallel microchannels.
incorporated herein by reference, disclose micromixers and/ At least three levels (or different types) of numbering-up
or microreactor technology: U.S. patent application Ser. No. can be considered for increasing the flow cross-section of
09/369,679, filed Aug. 5, 1999 and issued as U.S. Pat. No. microchannel architectures: “device up.” “layer up.” and
6,793,831 on Sep. 21, 2004, titled MICROLAMINATION “channel up' structures. “Device up' structures generally
METHOD FOR MAKING DEVICES; U.S. Provisional 60 include identical devices that are connected in parallel with
Patent Application No. 60/253,383, filed Nov. 28, 2000, titled interconnects. "Layer up' structures generally include iden
METHOD AND APPARATUS FOR MAKING MONO tical layers or laminae that are stacked and/or coupled (e.g.,
LITHIC INTERMETALLIC STRUCTURES AND INTER bonded) together. “Channel up' structures generally include
METALLIC DEVICES MADE THEREBY U.S. patent identical channels that are arrayed on a single lamina
application Ser. No. 09/996,621, filed Nov. 28, 2001 and 65 “Channel up' is the most fundamental level of scale-up and
issued as U.S. Pat. No. 6,672,502 on Jan. 6, 2004, titled typically involves arraying identical channels within a con
METHOD FOR MAKIN DEVICES HAVING INTERME fined material layer or lamina. Ultimately, this strategy is
 US 8,414, 182 B2
7 8
generally constrained by the size of the microchannel and the (See Trachsel, F., Günther, A., Khan, S. and Jensen, K. F.,
size of the lamina used. Manufacturing processes are typi (2005), “Measurement of residence time distribution in
cally limited in the size of the laminae that can be processed microfluidic systems. Chemical Engineering Science, Vol.
and so impose the ultimate constraint on channel-up strate 60, pp. 5729-5737.) Khan et al. has compared the single phase
gies. Additional channels can be added using a “layer up' laminar flow reactor (LFR) with a segmented flow reactor
strategy where additional laminae are added, with each (SFR) for producing silica nanoparticles. (See Khan, S.A.,
lamina containing, for example, identical channel-up arrays. Gunther, A., Schmidt, M. A. and Jensen, K. F., (2004),
The constraint on this strategy is typically the thickness of the “Microfluidic Synthesis of Colloidal Silica. Langmuir, Vol.
laminae and the work envelope of the bonding process used to 20, pp. 8604-8611.) The results showed that the latter one has
convert the laminae into a monolithic structure. 10
As shown in FIG. 2, microlaminationarchitectures, involv Smaller particle size distribution compared to continuous
ing the patterning and bonding of thin laminae, employ at single phase microreactor (LFR: residence time: 6.5 min,
least these two strategies for Scaling-up microchannel arrays. average particle size: 281 nm with a standard deviation of
FIG. 2 illustrates both channel-up and layer-up strategies, 20%; SFR: residence time: 10 min, average particle size: 277
with arrows illustrating the direction of flow. Beyond this, a 15 nm with a standard deviation of 9.5%). The thickness of the
“device up' strategy can be used to further increase through film depends on the relative magnitude of viscous to Surface
put by adding identical devices in parallel. tension forces using the dimensionless capillary number, C.
These scale-up strategies, however, have various difficul
ties and/or undesirable effects. One undesirable effect of a
(2)
parallel microchannel reaction architecture is a variation in
reaction conditions. Variations in concentration, temperature
and residence time can all be detrimental to nanoparticle size
distributions. One of the more difficult elements to control is where u is the liquid viscosity, U, is bubble velocity and O is
residence time. Poor residence time distributions can be due the interfacial tension. Based on Betterton's model, it was
to both flow velocity profiles within microchannels, as well as 25 predicted that rectangular channels would have an increase of
flow maldistribution between microchannels. approximately two to three times increase in the communi
For the large class of homogeneous liquid-phase reactions, cation between neighboring liquid slugs than circular chan
microreactors are frequently based on single-phase laminar nels with the same cross-sectional area. Other techniques to
flow designs. However, such designs can be restricted in introduce segmented (slug) flow inside a microchannel sys
terms of large residence time distributions (RTDs). Yen et al. 30 tem are typically based on the application of external fields
showed progress toward improving RTDs by using recircu like pneumatically, magnetically, ultrasonically, or electri
lation within two-phase segmented flows (gas-liquid or liq cally applied external fields.
uid-liquid) to eliminate axial dispersion as encountered in It is desirable to improve the equalization of flow distribu
single phase laminar flow. (See Yen, B. K. H., Gunther, A., tions across microchannel arrays. This can be particularly
Schmidt, M.A., Jensen, K. F. and Bawendi, M.G. (2005), “A 35 true in the field of nanomaterial synthesis. In addition to
microfabricated gas-liquid segmented flow reactor for high effecting residence time distributions, fluid velocities across
temperature synthesis: the case of CdSe quantum dots.” microchannels affect the heat and mass transfer throughout
Angewandte Chemie International Edition, Vol. 44, pp. 5447 the device. To equilibrate flow velocities, an appropriate
-5451.) Jongen et al. has precipitated out CaCO using seg “channel-up' structure preferably distributes the flow from a
mented flow microreactor and established that the particle 40 common reactant reservoir through the microchannels to a
size distribution is narrower than the commercially available common product reservoir. Amador et al. studied two differ
powders. (See Jongen, N., Donnet, M., Bowen, P. Lemaitre, ent kinds of manifold structures, namely consecutive and
J., Hofmann, H., Schenk, R., Hofmann, C., Aoun-Habbache, bifurcated, using a method based on electrical resistance cir
M., Guillemet-Fritsch, M., Sarrias, J., Rousset, A., Viviani, cuit analysis and validated against finite element simulations.
M., Buscaglia, M.T., Buscaglia, V., Nanni, P., Testino, A. and 45 (See Amador, C., Gavriilidis, A. and Angeli, P., (2004), “Flow
Herguijuela, J. R. (2003), “Development of a continuous distribution in different microreactor scale-out geometries
segmented flow tubular reactor and the “scale-out” concept— and the effect of manufacturing tolerances and channel block
In search of perfect powders. Chemical Engineering Tech age.” Chemical Engineering Journal, Vol. 101, pp. 379-390.)
nology, Vol. 26(3), pp. 303-305.) The span is reduced from An analytical model was also developed to study the effects of
1.69 to 1.09. The experiments were also conducted with 50 manufacturing tolerances and of channel blockage on flow
BaTiO. The produced powder had a much smaller particle distribution. The bifurcated manifold structure can provide
size (30 nm) with a high specific surface area (40 m/g) better uniform flow distribution. Commenge et al. evaluated
compared to commercially available high purity fine powder flow distribution in a multichannel microreactor having a
having particle size (60 nm) with specific surface area of 17 consecutive type of manifold structure to distribute the reac
m?g. Recirculation has the dual effect of narrowing the RTD 55 tant fluid to the microchannels. (See Commenge, J. M., Falk,
as well as improving mixing. In contrast to single-phase L., Corriou, J. P. and Matlosz, M., (2002), “Optimal design
designs, segmentation makes it possible to drive reactions to for flow uniformity in microchannel reactors.” American
required yields over significantly shorter times owing to the Institute of Chemical Engineers Journal, Vol. 48(2), pp. 345
enhanced mixing, while maintaining narrow RTDS and pro 348.) A reactor design was found for a single-phase flow
ducing monodispersed powder particles. 60 distribution that provided a more uniform flow distribution.
However, this condition is strictly true only if neighboring The analysis was performed using a resistance network
slugs of the phase of interest are completely disconnected method combined with an optimizing function to calculate
from each other. Therefore, in designing microchannel reac varying diameters for flow distributing and collecting chan
tors, it can be helpful to minimize sharp changes in flow nels.
direction. Using a segmented gas-liquid flow system, Trach 65 Bejan et al. compared the fractal tree-like structure to natu
sel et al. found, in maneuvering around sharp radii, adjacent rally available structures like lungs, arteries, veins etc and
liquid slugs are connected across thin liquid films or menisci. found that these structures not only provided flow uniformity
 US 8,414, 182 B2
10
but also minimized flow resistance through a Volume-to-point geometry of the system. The most common method to deter
path. (See Bejan, A. and Errera, M.R., (1997), “Deterministic mine these head losses or pressure drop is to specify a loss
tree networks for fluid flow: geometry for minimal flow resis factor, K.
tance between a volume and one point.” Fractals, Vol. 5 pp.
685-695.) Ajmera et al. developed a novel design of a silicon
cross-flow microreactor for parallel testing of porous catalyst 2Ap (4)
K (V/2g) p. V.
beds. (See Ajmera, S. K., Delattre, C. Schmidt, M. A., and
Jensen, K. F., (2002), “Microfabricated differential reactor
for heterogeneous gas phase catalyst testing.” Journal Cata
lysts, Vol. 209, pp. 401-412.) A more uniform flow distribu 10 where h is the head loss between sections having areas A
tion was achieved by bifurcating the inlet stream into 64 (inlet) and A (outlet), V is the average velocity of the fluid,
parallel microchannels. The experimental data was validated Ap is the pressure drop and p is the density of the fluid. K is
using computational fluid dynamics (CFD) models. a function of geometry of the component and Reynolds num
Uniformity of the flow distribution, however, preferably ber, R. A fluid may flow from a reservoir into a pipe through
also involves equalizing and distributing flow between layers 15 any number of different shaped entrance regions, namely
and devices. At a device level, the non-uniformity of fluid square, round, conical (downstream) or vice versa (up
flow in a microchannel reactor system is primarily attributed stream). As a fluid enters into a square-edged entrance, there
to the difficulty in making a smooth transition from the cross is vena contracta (which results in a dead volume region
sectional shape of a reactor to that of the upstream and down because of contraction or expansion) developed because the
stream connectors without any dead volume. At a layer level. fluid cannot make a sharp right-angled corner. At the Vena
the methods for uniformly distributing fluid within multilay contracta region, the kinetic energy of the fluid is partially lost
ered structures can vary based on differences in the geometry because of Viscous dissipation and an entrance or exit head
of the inlets and the outlets of the reactor units. Baffles can be loss is generated. For a micromixer, this vena contracta on the
used to create a backpressure upstream of the array. Screens outlet side can significantly affect the flow distribution. Coni
have been found to be a simple and effective means to dis 25 cal diffusers, with varying area ratios, A/A can be used to
tribute the flow uniformly throughout the cross section of better regulate the flow distribution. FIG. 3 shows a loss
macro-scale reactors. Several researchers have evaluated the co-efficient K, for a typical conical diffuser, including the
use of different kinds of meshes and screens for solving the effect of the included angle of the diffuser, 0, on the velocity
problem of flow equilization between microchannel layers. head through an expansion which is the typical situation for a
The screen leveling properties depend on the geometrical 30 microreactor outlet. Sovran et al. reported that the optimum
parameters like effective (open) cross-section and the thick angle for minimum loss co-efficient under these conditions is
ness of the screen. The drag co-efficient, , of the screen can 0=8. (See Sovran, G. and Klomp, E. D., (1967) “Experimen
be defined as tally determined optimum geometries for rectilinear diffusers
with rectanglular, conical or annular cross-section. Fluid
35 Mechanics of Internal Flow, Elsevier, Amsterdam.)
2A
g =Tp.fiV. 3
(3) Generally, mixing within microchannel reactors is rapid
enough for most liquid-phase nanoparticle reactions. Even
under simple diffusive conditions, mixing times well below
one second have been reported. Some attempts have been
where Ap is pressure drop along the screen, p is the density of 40 made to improve upon these conditions. Burke and Regnier
the fluid and V is the average velocity. A flow distribution used a series of “short cut tributaries to promote mixing
system is suggested if of the screen is less than 1000. Riman inside a microreactor. (See He, B., Burke, B. J., Zhang, X.
et al. proposed a method for calculating the distortion in Zhang, R. and Regnier, F. E., (2001), “A picoliter-volume
Velocity profile using a similar grid concept. Most of these mixer for microfluidic analytical systems.” Analytical Chem
methods have been developed for macro-scale reactors under 45 istry, Vol. 73(9), pp. 1942-1947.) Enhancement in mixing has
turbulent flow regimes having high Reynolds number, which also been investigated by introducing time pulsed cross flows
is not the case in microreactor systems. However, Rebrove et into the main stream flowing in a channel. Efforts have been
al. proposed a conical diffuser connected to a thick-walled made to study the effect of varying the timing of lateral pulses
screen to enhance the uniformity of fluid flow distribution with respect to the flow rate inside the main fluid stream on the
within micro-scale reactors. (See Rebrov, E.V., Duinkerke, S. 50 mixing quality. (See Moctar, A. O. E., Aubry, N. and Batton,
A. and Schouten, J. C., (2003), “Optimization of heat transfer J., (2003), Electro-hydrodynamic micro-fluidic mixer, Lab on
characteristics, flow distribution, and reaction processing for Chip, Vol. 3, pp. 273-280.) Glasow etal. examined the mixing
a microstructured reactor/heat-exchanger for optimal perfor of two reagents by simply varying the inlet stream flow rates
mance in platinum catalyzed ammonia oxidation. Chemical without using any additional geometric features, parts or
Engineering Journal, Vol. 93, pp. 201-216; and Mies, M. J. 55 external fields. (See Glasgow, I., Lieber, S. and Aubry, N.,
M., Rebrov, DeCroon, M. H. J. M., Schouten, J. C. and (2004), Parameters influencing pulsed flow mixing in micro
Ismagilov, I. Z. (2006), “Inlet Section for Micro-Reactor.” channels, Analytical Chemistry, Vol. 76, pp.4825-4832.)
PatentPCT/NL2006/050074; 2006.) The design of the header Generally, as average velocity increases within an inter
was optimized using CFD simulations. Numerical simula digital micromixer, mixing performance improves. FIG. 4
tions suggested that the proposed header configuration 60 illustrates data for a standard test reaction used to qualify
including screens can effectively improve the performance of mixing quality. The Y-axis of FIG. 4 is a measure of mixing
the microreactor, decreasing the ratio of the maximum veloc efficiency based on the amount of side product produced in a
ity to the mean flow velocity to between 1 and 2 for a wide competing reaction. Absorption data indicates the amount of
range of Reynolds numbers (e.g., 0.5-10). secondary (unpreferred) product. The improved mixing qual
The head loss associated with a flow through an intercon 65 ity is likely due to increased shear between interdigitated flow
nect-header interface is a common minor loss. The purpose of lamella and velocity distribution is likely not only important
a header is to regulate the flow distribution by changing the for residence time distribution, but also for uniform mixing.
 US 8,414, 182 B2
11 12
Commengeet. al (2002) proposed an approximate pressure By introducing the inlet flow in the center of the mixer,
drop model based on division of a mixer into a series of instead of from the side, there is less flow nonuniformity to
rectangular ducts. (See Commenge, J. M., Falk, L., Corriou, counteract. Referring to FIGS. 7(a) and 7(b), two portions
J. P. Matlosz, M., “Optimal Design for Flow Uniformity in 105, 115 of a micromixer channel are shown. Portions 105,
Microchannel Reactors.” AIChE Journal February 2002 Vol. 5 115 are formed with inlet regions 150, 160 in a center of the
48 no.2345-358.) The channel widths remain constant while respective micromixer channel. Pillars 170 are spaced apart
the taper of the inlet chamber is varied based on the model. throughout both portions 105, 115. For convenience, FIGS.
The model was applied to optimizing a 26-channel mixer inlet 7(a) and 7(b) each illustrate half of a micromixer channel,
chamber shape described by 26 sectional widths. The result with the other half of the micromixer channel being a mirror
ing geometry was nearly linear but with slight curvatures 10 image taken from the centers 155, 165 of the portions shown.
adding complexity. This complex shape, however, is difficult Because the geometry in these embodiments is symmetric
to manufacture. Linear variation of the chamber inlet taper about the mixer centerline, more options are available for
was determined to be inadequate for achieving a uniform pillar sizing and placement while still adhering to alignment
velocity profile but was deemed sufficient for practical appli constraints. Pillar diameter can be adjusted so that those
cations. 15 pillars further from the center are reduced in diameter relative
Tonomura et. al (2003) used CFD analyses to confirm that to the pillars closer to the center, which increases flow area
flow uniformity among microchannels depends on the mani and thereby reduces pressure drop across the micromixer.
fold shape. (See Tonomura, O., Tanaka, S., Noda, M., Kano, In portion 105, the pillar diameter varies linearly across the
M., Hasebe, S., Hashimoto, I., “CFD-based optimal design of width of the mixer. Each half of the micromixer portion 105
manifold in plate-fin microdevices’. Chemical Engineering was divided into four sections corresponding to four different
Journal 101 (2004) 397-402.) A CFD-based optimization pillar diameters. Thus, as shown in FIG. 7(a), micromixer
method was proposed. They first demonstrated how flow portion 105 has pillars 170 of four different sizes, which vary
uniformity is improved by increasing the length of the chan based on the distance from the center 155 of the micromixer
nels. All channels were the same length and all other variables portion 105. As shown in FIG. 8(a), the resulting velocity
were held constant. Another investigation demonstrated that 25 profile indicated that flow resistance should be desirably
expansion of the outlet manifold could improve flow unifor reduced in the outer regions.
mity. They further demonstrated how introducing a taper into In the next embodiment illustrated by FIG. 7(b) pillar
the outlet manifold region can improve flow uniformity. An diameter varies as a function of distance from mixer center
automated optimization using CFD was performed using a line according to the following equation:
single variable defining outlet region taper angle. Tonomura 30
etal. stated that combining their work with that of Commenge
et. al in a sequential optimization process is promising.
The methods of Commenge et al. and Tonomura et al., d-(if (d. -dii) (5)
however, do not allow a large manifold region using the
manufacturing process described herein. That process 35
where d, and d are the minimum and maximum pillar
requires, for structural integrity, that the micromixer does not diameters, X is the distance from the centerline of the mixer,
contain an etched feature larger than 300 um in width. If these and L is the total width of the micromixer. Thus, the micro
models discussed above were applied to the processes and mixer shown in FIG. 8(b) has pillars that vary in size (e.g., in
designs disclosed herein the total size of the mixer would be diameter) parabolically. In addition, it was determined that
impractically Small. 40
parabolic variations in the size of the pillars provides
Richter et al. (1998) used CFD to design a gas phase improved flow uniformity. If desired, the plurality of sections
microreactor with concentric radial channels of equal Volu described above with respect to linear variation of pillar size
metric flow rate. (See Richter T., Ehrfeld W., Gebauer K. can also be used with parabolic variation in size. In such an
Golbig K., Hessel V., Lowe H., Wolf A., “Metallic Micfrorea embodiment, the size of the pillars would still vary in a
cors: Components and Integrated Systems’. Process Minia 45 Substantially parabolic manner, even though adjacent pillars
turization; 2nd Annual International Conference on Microre may be the same size.
action Technology, AIChE, 1998.) Curved channels were In another embodiment, a micromixer design with even
introduced to improve mixing performance. Channel length further improved flow uniformity and simpler geometry is
increased with radius of path and, to compensate for this, provided. As shown in FIG.9, a micromixer 200 comprises an
outer channels were wider than inner channels. The flow 50
inlet region 210 and a plurality of channel members 220. The
Velocity of the shortest compared to the longest channels was micromixer 200 preferably comprises channels 220 of vary
faster by a factor of about ten. While the volumetric flow rate ing width along at least one dimension of the micromixer
across the flow channels is uniform, the residence time is (e.g., along the width of the micromixer). For a fixed channel
highly non-uniform. height, the channel width preferably varies across the width
The lamina chemical etching process defines a minimum 55
of the micromixer according to the parabolic function:
feature size, and the mechanical bonding process defines a channelwidth=Cx'+w, (6)
maximum allowable distance between mechanical Supports.
Mechanical Supports must be aligned layer to mirrored layer. where c is a slope constant, X is the distance from the center
In the embodiment shown in FIG. 5, two adjacent bonded line of the mixer, and W, is the minimum channel width
layers 100, 110 are shown. Layer 100 has an inlet region 130 60 defined by manufacturing constraints. Accordingly, the width
and layer 120 has an inlet region 140. Cylindrical support of the channels vary substantially parabolically, similarly to
pillars 120 (shown as white dots on layer 100 and as circles on the variation of pillar diameter disclosed in the previous
layer 110) were placed throughout the tapered manifold embodiment.
region to provide Support and encourage flow dispersion. The Channels of increasing width can be formed in the micro
velocity distribution of this design, calculated by a three 65 mixer 200 until the maximum desired channel width is
dimensional CFD analysis and shown in FIG. 6, was highly reached. In one embodiment, the channel width of the micro
nonuniform. mixer varies as a function of distance from the center of the
 US 8,414, 182 B2
13 14
micromixer using c=0.040 (e.g., as shown in FIG. 9). The FIGS. 13 and 14 illustrate a microchannel array with a
minimum and maximum allowable channel widths thus plurality of micromixers 300 formed adjacent to one another
define the total number of channels and total mixer width. on the same lamina and bonded to other lamina to provide a
If desired, the micromixer can beformed with a plurality of layered-up device. The microchannel array comprises a plu
sections, with the width of the channels (pathways) in each 5 rality of micromixers 300 with inlet regions 310 and formed
section being Substantially the same. Adjacent sections, how of a plurality of channels 320 that vary parabolically in size
ever, can have channels of different widths, with the widths (e.g., width of channel) in the manner described above with
varying parabolically from one another. Forming sections in respect to FIG. 9. Referring to FIG. 13, a close up of the
this manner can simplify construction since one or more 10
microchannel array illustrates several lamina 330, 332, 334,
pathways (channels) are constructed with the same width. 336 bonded together to form a single unit. FIG. 14 illustrates
The inlet region 210 is desirably positioned at a central an exploded view of the laminae 330,332,334,336. As seen
longitudinal axis of the micromixer 200, as shown in FIG. 9. in FIG. 14, each of the lamina comprises a plurality of micro
In other words, the inlet region 210 is located at one end of the mixers 300.
micromixer 200 at substantially the center of the width of the 15 The outlet regions 340 of the micromixers 300 can com
micromixer 200. prise a mixing region for mixing different fluids. For example,
Because of the constraints on minimum and maximum a first fluid can be introduced into the microchannel array in
channel widths, channel length is preferably varied to further alternating lamina (e.g., 330 and 334) and a second fluid can
adjust pressure drop. As shown in FIG.9, this results in long, be introduced into the microchannel array in the remaining
narrow channels towards the center of the mixer and shorter, alternating lamina (e.g., 332 and 336). In this manner, two
wider channels at the outer limits. different fluids can exit the microchannel array and enter the
Because the mechanical Supports necessary for the bond mixing region for mixing. Of course, if desired each lamina
ing process to construct a micromixer as shown in FIG. 9 could comprise a plurality of channels, with each lamina
(e.g., the Substantially rectangular wall structures) are simpler being configured to introduce more than one fluid into the
in shape and construction than the numerous pillars in previ 25 mixing region.
ous embodiments, the production process can be simplified As shown in FIG. 15, a hybrid mesh can be configured to
and the multiple laminae can be more easily aligned for discretize the micromixer. The mesh can comprise a mix of
bonding. This design can also improve the uniformity of load triangles and rectangles linearly extruded to a thickness equal
distribution throughout the micromixer, which can reduce to the etch depth. Downstream, in the reservoir region, the
buckling and deformation during bonding and operation of 30
grid can comprise triangles and rectangles extruded to a total
the micromixer. thickness equal to that of the lamina. A structured grid can be
Generally, chemically etched microchannels are substan used in rectangular sections of the geometry and triangles can
tially rectangular, but not completely rectangular, and may be used in areas of complex geometry and to transition from
have a cross-section as shown in FIG. 10. To include these
35 fine to coarse regions of the grid.
geometric details, which have an impact on the fluid flow, into The velocity profile associated with a mixer geometry with
the CFD model would be prohibitively time consuming. a slopefactor of 0.025 (c=0.025) is shown in FIG.16(a). FIG.
Therefore, when modeling rectangular channels it is neces 16(b) shows a velocity profile associated with a mixer geom
sary to correct the model relative to a channel having a Sub etry with a slope factor of 0.040 (c=0.040). As shown in FIG.
stantially round cross section using the generic parameter
hydraulic diameter. For the purposes of this disclosure, the 40 16(b), the flow uniformity is improved for c=0.040 relative to
hydraulic diameter of a rounded (quarter-moon) channel was c=0.025. In addition, the width of the outermost channels can
calculated using the following equation: be reduced to eliminate or reduce the velocity spikes in that
region, further improving flow uniformity.
Accordingly, the micromixers described above are capable
(7) 45 of producing a highly uniform Velocity distribution. In addi
tion, because of the relatively simple geometry, the manufac
ture and construction of such micromixers can be simplified.
Also, to further optimize the geometry, only one parameter
(i.e., the slope factor) need be considered. Moreover, if
where h is the height of the channel and a is the width of the 50 desired and/or useful, other design parameters can be used to
rectangular region of the shape (FIG. 10). further adjust and/or improve the functioning of the micro
As shown in FIG. 11, a comparison of the hydraulic diam mixer. For example, channel length can be used to help
eter for the half-moon with the rectangle reveals a significant achieve a desired pressure drop.
difference in channel width. Therefore, when designing the Moreover, it should be understood that the embodiments
micromixer using rectangular channels in CFD, the dimen 55 described herein are exemplary and micromixers can be pro
sions of the rectangular channels were adjusted to compen duced with channels of different shapes and manufacturing
sate for the hydraulic diameter of the half-moon shape of a techniques (e.g., chemically etched, laser engraved,
chemically etched channel. machined) without departing from the scope of the inventions
Two values for the slope factor c were investigated for disclosed herein.
linear variation of channel length: 0.040 and 0.025. The slope 60 Another concern in micromixer design for nanoparticle
factoric can vary based on the desired size and/or other desired synthesis is clogging. High Surface-area-to-volume ratios
parameters the micromixer. FIG. 12 reflects the differences within microchannel mixers permit shorter diffusional dis
between the channel widths as a result of the different slope tances allowing for rapid and precise mixing. Throughput can
factors. Three-dimensional CFD analyses were conducted be directly scaled by “numbering-up' the number of channels
using CFD-ACE+ for both configurations. Manifold channels 65 in parallel. Acceleration of passive (diffusional) mixing in
were modeled as rectangular with hydraulic diameter equal to microchannel structures is generally governed by decreas
that of the required rounded channel. ingly smaller channels. Channels down to 25 micrometers in
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15 16
hydraulic diameter can be implemented; however, smaller FIGS. 23 and 24 illustrate an embodiment of a micromixer
channels can lead to problems with channel clogging for channel comprising a serpentine flowpath that expands in
nanoparticle synthesis. width at areas or regions where the flow changes direction
To reduce the effect of clogging, the following embodi (e.g., at turns in the microchannel) and contracts in width
ments disclose larger microchannel structures (e.g., about 5 where the flow is in a region where the flow continues in one
300 micrometer diameter) that achieve rapid, high-quality direction (e.g., where the flow does not change direction). The
mixing using reversed oscillatory flow through microchan standard deviation of species mass fraction at outlet is about
nels with at least some portion that is not straight, Such as a 0.41256,413. FIG. 24 illustrates an analysis of residence time
serpentine microchannel. For the purposes of this application, distribution with the micromixer channel shown in FIG. 23.
serpentine refers to a shape that repeatedly changes direction, 10 Because of the increase in channel sizes (e.g., in the width of
either slowly (e.g., with rounded turns) or sharply (e.g., with the channel at the regions where the flow changes direction),
turns of about 90 degrees). Larger microchannel dimensions the residence time distribution of FIG. 24 is somewhat higher
can also make the device easier to fabricate and more difficult
to clog. Reversed oscillatory flow through a serpentine chan than that of FIG. 22.
FIGS. 25 and 26 illustrate an embodiment of a micromixer
nel results in much faster mixing over conventional flow 15 channel with alternating increasing width (expanded) regions
patterns. Further, the design can be assembled and disas
sembled to make cleaning easier. and decreasing (constricted) width regions. That is, the
For the formation of nanoparticles by precipitation chem micromixerchannel comprises a serpentine channel in which
istry, high levels of supersaturation are desired. FIG. 17 the flow repeatedly changes directions. In a first region where
shows an example of the time scales over which Supersatura the flow changes direction, the channel comprises an
tion, nucleation, and aggregation occur within typical pre expanded region. In a second region, however, where the flow
cipitation chemistry reactions. The use of micromixers can changes direction, the channel comprises a constricted
greatly decrease mixing times by allowing for higher levels of region. If desired, the expanded and constricted regions can
Supersaturation prior to nucleation. Higher levels of Super alternate throughout the micrmixer channel. FIG. 25 illus
saturation can also lead to less variability in the onset of 25 trates a CFD analysis of such a micromixer channel. The
homogeneous nucleation and more uniform particle growth. standard deviation of species mass fraction at outlet is about
To improve mixing and shorten mixing times, the mixing 0.40872991. FIG. 26 illustrates a residence time distribution
systems disclosed herein do not necessarily rely solely on of the same micromixer channel.
passive (diffusional) mixing mechanisms. Instead, the sys FIG. 27 illustrates pressure drops across the micromixer
tems herein use reverse oscillatory flow in combination with 30 channels of FIG.20 (i.e., Mixer 3), FIG.23 (i.e., Mixer 4), and
nonlinear, serpentine microchannels to provide additional FIG. 25 (i.e., Mixer 10). FIG. 28 illustrates a mixer inlet
convective mechanisms for the rapid mixing of materials. velocity that has a flow that varies sinusoidally. As shown in
Consequently, larger channels can be used while maintaining FIG. 28, the flow of the two inlets (inlet A and B) are config
rapid mixing times. Also, if desired, the micromixers can be ured to be 180 degrees out of phase. The outlet velocity,
constructed of metal (instead of having brittle Si inserts which 35 however, remains Substantially constant.
many conventional passive mixers use). The metal construc FIG. 29 illustrates a comparison of mixer outlet mass frac
tion can simplify cleaning. tion between the micromixer channels of FIG. 20 (i.e., Mixer
Passive mixing models have been developed, such as the 3) and FIG.23 (i.e., Mixer 4). FIG.30 illustrates a comparison
passive T-mixing of colored water within a 275um channel as of standard deviations of outlet species mass fraction for the
disclosed in Glasgow and Aubry 2003. (See Glasgow, I. and 40 micromixers of FIG.23 (i.e., Mixer 4) and FIG.25 (i.e., Mixer
Aubry, N., (2003), “Enhancement of microfluidic mixing 10). FIG.31 illustrates a comparison of standard deviations of
using time pulsing. Lab on Chip, Vol. 3, pp. 114-120.) Flow species mass fraction at outlet for the micromixers of FIG. 25
from both inlets is continuous and steady and does not result (i.e., Mixer 10) and Mixer 11 (similar to FIG. 25, but with the
in complete mixing by the end of the channel. Moreover, inlet relocated as shown in FIG. 31). FIG. 32 illustrates a
while adding reverse oscillatory flow to or both inlets some 45 comparison of standard deviations for the micromixers of
what improved the results of the mixing, it did not result in FIG. 20 (i.e., Mixer 3), FIG. 23 (i.e., Mixer 4), FIG. 25 (i.e.,
flows that are fully mixed by the end of the channel. Mixer 10), and Mixer 11 (shown in FIGS. 31 and 32).
Applicants have found that by replacing the T-mixer with a FIG.33 illustrates an embodiment where inlet velocity is
microchannel mixer having a serpentine channel results in varied for a micromixer having two inlets A and B. The flow
significant, unexpected improvement in the standard devia 50 of the two inlets is 180 degrees out of phase with flow velocity
tion of the outlet concentration. In addition, if desired, the varying between -0.01 m/s and +0.03 m/s. FIG.34 illustrates
serpentine flow features can be machined, which can simplify a standard deviation of species mass fraction at mixer outlet
production and reduce manufacturing costs. for Mixer 11 (shown in FIGS. 31 and 32). As shown in FIG.
Referring to FIGS. 18 and 19, computational fluid dynamic 34 reversed switched flow significantly improves mixing. In
results of reverse oscillatory flow 180 degrees out of phase in 55 addition, the segments of liquid A and B are better formed.
both inlets of a micromixer show significant improvement in FIG.35 illustrates CFD analysis of the contours of species
mixing. FIG. 18 shows axial cross-section offlow and FIG. 19 mass fraction at the beginning of the cycle without and with
shows resultant standard deviation of outlet concentration as reversed flow. FIG. 35 clearly shows the improvement in
a function of time. As shown in FIG. 19, mixing is improved mixing that is obtained with reversed flow. FIG. 36 illustrates
to a standard deviation of concentration as low as about 0.02. 60 residence time distributions without and with reversed flow.
FIGS. 20-22 illustrate an embodiment of a micromixer The residence time distributions were broadened by reversed
channel with a serpentine construction. FIG. 21 illustrates a flow.
CFD analysis of the structure of FIG. 20 with an inlet velocity If desired, pulse Volume can be adjusted to improve mixing
of 0.02 m/s (about 3.5 mL/min). The standard deviation of and residence time distributions. Pulse volume determines
species mass fraction at outlet was about 0.4024311. FIG.22 65 the volume of fluid flowing into the microchannel per cycle.
illustrates an analysis of residence time distribution with the Pulse volume can be adjusted by altering the flow velocity
same micromixer channel. magnitude and/or the pulse duration/frequency.
 US 8,414, 182 B2
17 18
The higher the pulse frequency, the better the mixing that is of this geometry with reverse oscillatory flow pumping can
achieved. FIG.37 illustrates a comparison of standard devia yield significantly reduced mixing times which is ideal for
tions of species mass fraction at outlet for Mixer 11 with a nanomaterial synthesis.
pulse frequency of 5 Hz and 20 Hz. FIG.38 illustrates a CFD In view of the many possible embodiments to which the
analysis of the contours of species mass fraction for 5 Hz and 5 principles of the disclosed invention may be applied, it should
30 Hz systems. be recognized that the illustrated embodiments are only pre
FIGS. 39–42 illustrate the influence of frequency on resi ferred examples of the invention and should not be taken as
dence time distributions, which appears to be substantially limiting the scope of the invention. Rather, the scope of the
linear. For example, the residence time distribution decreased invention is defined by the following claims. We therefore
about 4 times with a 4 times increase in frequency and Veloc 10 claim as our invention all that comes within the scope and
ity magnitude. spirit of these claims.
FIG. 43 illustrates improvements in mixing based on the We claim:
inlet orientations. As shown in FIG. 43, with a reverse flow 1. A micromixer device, comprising:
that is 180 degrees out of phase, it is preferable that the inlet at least one fluid inlet channel and at least one fluid outlet
orientation be such that the two inlets are oriented in opposing 15 channel; and
flow directions. a plurality of pathways between the at least one fluid inlet
FIGS. 44 and 45 illustrate a pump system for sinusoidal channel and the at least one fluid outlet channel, a width
flow. As shown in FIG. 44, two fluids can be introduced to of at least some of the plurality of pathways varying in a
inlets of a microreactor as described above via two reservoirs Substantially parabolic manner along at least one dimen
or tanks. Two pumps can be associated with each reservoir sion of the micromixer device.
(tank) with one pump being configured for forward sinusoidal 2. The device of claim 1, wherein the fluid inlet channel is
flow and the other pump being configured for reverse sinu located at a substantially central location relative to the plu
soidal flow. In addition, pumps associated with the first res rality of pathways and the width of the pathways varies in a
ervoir (e.g., Pumps 1 and 2) can be configured to always be Substantially parabolic manner as a function of the distance of
180 degrees out of phase with the pumps associated with the 25 the pathway from the fluid inlet channel.
second reservoir (e.g., Pumps 3 and 4). 3. The device of claim 1, wherein a plurality of structural
Another advantage is that these features can be embedded elements define the pathways.
within a structure that can be scaled-up and disassembled as 4. The device of claim 1, wherein the structural elements
shown in FIG. 46. The serpentine fluid flow pathway of FIG. comprise channel walls that are substantially rectangular in
46 is machined into the top and bottom members. The top and 30 shape.
bottom members are removably coupled together and an end 5. The device of claim 1, wherein the device comprises a
cap is added to both ends of the top and bottom members. plurality of sections, with each section comprising a plurality
Because the top and bottom members are removably coupled of pathways that have substantially the same width, wherein
together, the serpentine fluid flow pathway can be accessed by the width of pathways vary from section to section in a sub
disassembling the device for cleaning. In addition, the fabri 35 stantially parabolic manner.
cation of the mixing region can be machined using, for 6. The device of claim 2, wherein the device comprises a
example, commercially available tools (e.g., bits). Such as base portion and two side walls that at least generally con
those available from Kyocera. FIGS. 48 and 49 illustrate Verge towards one another, and the fluid inlet channel is
additional examples of embodiments that are capable of located Substantially at the intersection of the two converging
being machined. As shown in FIGS. 48 and 49, micromixers 40 side walls.
400 comprises a first pump device 410 for pumping a first 7. The device of claim 6, wherein the location of the fluid
fluid, a second pump device 420 for pumping a second fluid, inlet channel defines a central longitudinal axis of the device,
a serpentine pathflow 430, and a fluid outlet 440. and the lengths of the pathways vary according to their dis
If desired, heating inserts can be placed above and below tance from the longitudinal axis, with the lengths of the path
nucleation regions to permit more precise control oftempera 45 ways nearest the longitudinal inlet channel being longer than
ture in the process. These structures can be optimized to allow the lengths of the pathways furthest from the inlet channel.
for scale-up by lamination. Because channel sizes are much 8. The device claim 3, wherein the structural elements are
larger, fabrication is made easier. As noted above, FIG. 47 pillars that are substantially cylindrical and which vary in
shows that cutting tools exist that can be used to make the width.
needed structure in FIG. 46. Other methods also exist for 50 9. A microchannel mixer, comprising:
making this geometry including wire electrodischarge a first fluid inlet for introducing a first fluid into the mixer:
machining. However, these features would not be machine a second fluid inlet for introducing a second fluid into the
able by these methods if they were below about 100 microme mixer,
ters. Preferably, however, to help reduce clogging, the chan a serpentine fluid flow pathway;
nel sizes are machined at a size that is greater than about 150 55 a pump system with a first oscillatory flow pump device
micrometers, more preferably greater than about 200 and a second oscillatory flow pump device, the first
micrometers, and even more preferably greater than about oscillatory flow pump device being operative coupled to
250 micrometers. Accordingly, if desired, other known meth the first fluid inlet and the second oscillatory flow pump
ods can be implemented to manufacture the above described device being operative coupled to the second fluid inlet
structures at Smaller sizes. 60 configured
Accordingly, the above embodiments disclose structures wherein the first oscillatory flow pump device and second
and methods for reducing mixing times within a scaled-up oscillatory flow pump device pump the first and second
geometry. Desirably, the geometry is relatively easy to fabri fluids, respectively, into the fluid flow pathway using
cate and can be disassembled for cleaning. In some embodi reverse oscillatory flow:
ments, the microchannels can be much larger than conven 65 wherein the first and second oscillatory flow pump devices
tional interdigital mixers and, therefore, are less likely to clog both comprise two pump members, with each pump
and easier to fabricate by multiple methods. The combination device having a first pump member configured for for
 US 8,414, 182 B2
19 20
ward sinusoidal flow and a second pump member con
figured for reverse sinusoidal flow.
10. The mixer of claim 9, wherein the first and second
oscillatory flow pump devices are configured to pump the first
and second fluids, respectively, into the fluid flow pathway, 5
with the first and second pump devices being 180 degrees out
of phase with each other.
11. The mixer of claim 9, wherein the fluid flow pathway is
machined to be about 200 micrometers or greater in width.
12. The mixer of claim 9, wherein the serpentine fluid flow 10
pathway is defined by a top member and bottom member, the
serpentine fluid flow pathway being machined into the top
and bottom members, the top and bottom members being
removably coupled together.
13. The mixer of claim9, wherein the standard deviation of 15
mass fraction at an outlet of the serpentine fluid flow pathway
is less than about 0.06.