Microfluid Nanofluid (2009) 6:763774
DOI 10.1007/s10404-008-0351-z
RESEARCH PAPER
Performance analysis of a folding flow micromixer
Z. Chen M. R. Bown B. OSullivan
J. M. MacInnes R. W. K. Allen M. Mulder
M. Blom R. vant Oever
Received: 7 July 2008 / Accepted: 28 August 2008 / Published online: 2 October 2008
Springer-Verlag 2008
Abstract The performance of a folding flow micromixer
in the Stokes flow regime is investigated computationally
and experimentally. Consistency with a previously derived
general scaling relation is demonstrated and the geometric
parameters in the scaling relation are determined for this
mixer. Measured data from a second similar mixer are
correctly predicted using the scaling relation, thus showing
that the approach allows quantitative prediction of mixing.
This paper focuses on the errors associated with such
predictions. Basic errors, expressed as variations in the
standard deviation of the concentration profile, were esti-
mated to be -10% for the computation and -30% for the
experiment at the highest values of Peclet number con-
sidered. It is shown that this experimental error was mostly
due to depth averaging of the spectroscopic technique used
for concentration measurement at the high Peclet numbers.
However, extra uncertainty is associated with chip fabri-
cation tolerances and this was investigated further.
Measurements at the outlet of nine different mixer chips of
notionally identical design revealed variations in mixing
of 26%. This variation was attributed to misalignment of
the glass layers determining the geometry of the mixer in
the chip. Thus, the combination of measurement error and
misalignment means predictions of the concentration
standard deviation for the mixer may get non-uniformity
wrong by up to 50%. Ensuring a required uniformity,
however, simply requires adding a few further elements to
Z. Chen
M. R. Bown
B. OSullivan
J. M. MacInnes (&)

R. W. K. Allen
University of Sheffield, Sheffield, UK
e-mail: j.m.macinnes@sheffield.ac.uk
M. Mulder
M. Blom
R. vant Oever
Micronit Microfluidics, Enschede, The Netherlands
the mixer to allow for this uncertainty. Application of the
scaling relation to mixer design is highlighted by a dis-
cussion of the options available for improving the
performance of the experimental mixer.
1 Introduction
Over the last several years, many different microchannel-
based approaches for mixing two or more liquid streams
have been reported. Among these are direct layering of
the streams (Koch et al. 1998; Veenstra et al. 1999;
Bessoth et al. 1999), using alternating flow of the streams
(Glasgow and Aubry 2003; MacInnes et al. 2005),
placement of ribs to produce a folding flow pattern
(Stroock et al. 2002; Howell et al. 2005; Bringer et al.
2004) and use of a microchannel network to produce a
folding flow by splitting and recombining streams (Gray
et al. 1999; Munson and Yager 2004; Park et al. 2004;
Schonfeld et al. 2004; Chen and Meiners 2004; Simonnet
and Groisman 2005; Lee and Lee 2005; MacInnes and
Allen 2005; MacInnes et al. 2007). These along with
several other specialised approaches for mixing are
reviewed in recent papers that consider micromixing
(Ottino and Wiggins 2004; Hessel et al. 2005; Nguyen
and Wu 2005). Comparison of the performance of dif-
ferent types of mixers has led MacInnes and Allen (2005)
to suggest that mixers of the folding flow type are espe-
cially promising for critical mixing applications in the
Stokes regime, where inertial effects are negligible but
rapid and highly uniform mixing is required.
A particular folding flow mixer geometry is investigated
here and its performance is determined using both com-
putation and experiment. The mixer uses tear-drop
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764
shaped elements and, as is usual, these are placed in series
to produce repeated folding and layering of the solutions to
reduce diffusion distance and thereby mixing time. These
elements have been incorporated in an experimental chip
designed for stop-flow reaction kinetics testing in ionic
liquids (to be reported elsewhere). The plan view of the
chip can be seen in Fig. 1 with the reaction network on the
left-hand side including a primary 13-element mixer
(Mixer B) to produce the uniform reaction mixture and a
7-element mixer used to stop reaction by dilution, with
subsequent sampling off-chip. On the right hand side of the
chip are two further mixing chains, each of 16 elements.
These have a lengthened outlet tail designed to allow
clear optical access for measurements. The elements of the
upper mixer (Mixer A) are identical to those of Mixer B
except for tail length. The network and mixer geometry is
formed by two outer glass layers with wet-etched channels
interconnected by powder-blasted holes in a middle glass
layer. These three layers when assembled result in the
mixing element geometry of Fig. 2 (which shows the
domain geometries used in computations of the short-tail
mixer, Mixer B).
The ionic liquids for which the chip has been designed
are Newtonian, have viscosities more than 10 times greater
than that of water and give species diffusivities that are 100
times or more smaller than in water. Diffusion time scales
are about 10 min in the ionic liquids as compared to 10 s in
water for small molecules diffusing across a 100 lm
channel. With reaction time scales of interest being of
order 1 min, the long diffusion times in the ionic liquid are
clearly unacceptable for accurate reaction kinetics testing.
The high viscosity further rules out approaches based on
the complex flow motions associated with inertial flow
regimes since, with these liquids, the Reynolds number will
be below unity in practical microchannel networks and so
will be in the Stokes flow regime. High viscosity also
Mixer B Mixer A
y the scaling relation with parameters adjusted to take
x manufactured from the same mask design have been tested
Fig. 1 Plan view of the experimental chip network. On the left side is
a 13-element mixer (Mixer B) feeding a reactor as part of a stop-
flow reaction system. On the right hand side of the chip are two 16-
element mixers. The network is formed from two glass layers of wet-
etched channels connected by powder-blasted holes in a third glass
layer between these two channel layers. Top channels are shaded
black and bottom channels are shaded grey
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Microfluid Nanofluid (2009) 6:763774
Odd number
element
y Even number
x
element
z
Fig. 2 Computational domains used for the odd number and even
number elements. The sections taken as the beginning and end of each
element are shaded dark grey. This geometry corresponds to that of
experimental Mixer B
results in high pressures to produce the necessary flow rates
to mix reagents rapidly. Thus, it is crucial to predict the
pressure drop required for a given mixer geometry to
produce a required mixture uniformity in a specified time.
MacInnes et al. (2007) derived a general scaling rela-
tion which, when fitted to a particular mixer geometry,
allows mixing time and uniformity to be predicted. The
applicability of the scaling relation was demonstrated by
considering a particular F mixer geometry (shown in
Fig. 4) for which accurate three-dimensional finite volume
and Monte Carlo computations were made to determine
the geometric parameters in the relation for this geometry.
The work presented here applies the scaling relation to an
experimental mixer (Mixer A) having an entirely different
tear-drop geometry. Parameter values are determined
using a combination of results from finite volume
computations at low Peclet number and experimental
measurements at high Peclet number. The scaling relation
is used to predict the performance, i.e. pressure drop and
mixture uniformity, as a function of mixing time and
number of elements in the mixer. The effect of geometry
is also considered by comparison with the previously
characterised F mixer. A second mixer, similar to the first
but with a shorter tail, is also correctly predicted using
account of the change in non-dimensional residence time
with tail length.
As part of the experimental work, nine different chips
to assess the effect of geometric variability associated with
fabrication tolerances. Measurements are made at the outlet
of Mixer B for each one of the different chips and these
indicate that considerable variation in mixture uniformity is
associated with misalignment of the glass layers forming
the mixer geometry.
Microfluid Nanofluid (2009) 6:763774
2 Experimental details
The mixer network is constructed from three layers of glass,
the top and bottom layers having channels formed by iso-
tropic wet etching to a depth of 75 lm and the middle glass
layer having powder blasted connecting holes. Figure 1
shows a plan view of the network with four feed channels
etched into the bottom layer (shaded grey) connected to a
13-element mixer with elements arranged diagonally
(Mixer B). This mixer in turn feeds a 1 mm wide reaction
vessel etched into the top layer (shaded black). The feed
channels and the tail of each element are 275 lm wide and
the narrower loop portions of the elements are 180 lm
wide. The connecting holes taper from about 200 to 100 lm
diameter going from the bottom surface to the top surface of
the 175 lm thick middle glass layer. Micronit Microfluidics
fabricated the chips with 12 identical chip patterns on each
glass layer and the layers were bonded together into a
wafer before being diced into individual chips. The four
feed streams to Mixer B allow a variety of initial chemical
mixtures to be studied, but in the experiments presented
here, just two solutions are mixed in equal parts, one
solution supplied to the upper two feed streams and the
other to the lower two feed streams. A second mixer with
elements having a longer tail has been incorporated on the
chip so that clear optical access to the tail region is possible.
This second mixer (Mixer A in Fig. 1) has 16 elements,
which are arranged in a horizontal array rather than diag-
onally. Computations of another folding flow geometry
(MacInnes and Allen 2005) showed that the mixing was not
sensitive to the arrangement (horizontal, diagonal or
otherwise) chosen for the elements. Also, the scaling model
of MacInnes et al. (2007) suggests that the longer tail has a
negligible effect on the mixing (when account is taken of
the difference in mean residence time) since the loop and
connecting hole geometry are identical. Because of its
longer tail, the pressure drop per element will be greater for
Mixer A than for Mixer B, but for the Stokes flow of
interest, this can be taken into account using the developed
flow numerical solution of MacInnes et al. (2003).
Flow through either Mixer A or Mixer B is produced by
application of nitrogen gas pressure (6 bar gauge) to an
ionic liquid [bmim][N(Tf)2] (1-butyl-3-methylimidazolium
bis {(trifluoromethyl)sulfonyl}amide) held in supply res-
ervoirs. PEEK capillary tubes convey the liquid to the inlet
holes of the glass chip and from the outlet to waste at
atmospheric pressure. Flow rates produced in the tests are
estimated from the known viscosity of the liquid and the
channel dimensions. Average velocities calculated from the
estimated flow rates and nominal dimensions are expected
to have an uncertainty within about 10%. No direct mea-
surement of average velocity (or flow rate) was made since
the average velocity is needed only to determine Peclet
765
number and the Peclet number must vary by much more
than 10% to give experimentally detectable changes in
mixing.
Mixing was assessed experimentally by introducing
equal flow rates of two ionic liquid streams, one containing
0.6 mM of Rhodamine B fluorescent dye. An excitation
filter (546 nm band pass with 10 nm full width at half-
maximum transmission) was used in the illumination path
through the objective lens of an inverted microscope (Zeiss
Axiovert 100). Light passing to a charge-coupled device
(CCD) camera was filtered for the fluorescence emission
(600 nm long pass with a 25 nm transition width). Each
CCD pixel value can be related to the average concentra-
tion over the channel depth at that pixel location in the
image. Thus, the profile of depth-average concentration
across a channel section can be found and from this, the
volume average concentration and an approximation to the
standard deviation of concentration over the section can be
determined. A uniform mixture of equal parts of the dyed
and un-dyed solutions was also used to allow variation in
channel depth to be taken into account.
Depth-average concentrations were determined from
recorded pixel values using three different images for each
location: an image (I) of the mixing flow, an image (ID)
with no illumination to correct for background noise and an
image (Io) with the uniform mixture in the channel. The
depth average concentration, Cz at each pixel position
normalised by the concentration of the uniform mixture
concentration could then be determined using
I  ID
Cz : 1
Io  ID
At the edges of the channel, the wet-etched surface
curves in an approximately quarter-circular section
resulting in the channel depth approaching zero as the
edge is approached. The ratio in Eq. 1 becomes inaccurate
near the channel edges and the results there were not
included in the determination of the mean and standard
deviation of concentration. In the case of 275 lm wide
channel sections, the data within 8 lm of either edge were
discarded and for the 1 mm wide reactor the data within
33 lm of the edges were discarded. This corresponds to
overlooking just 2% of the channel section area and this
should introduce negligible error. A composite of three
low-magnification images showing the entire 16 elements
of Mixer A is shown in Fig. 3 along with measured
concentration profiles across the outlet section of every
fourth element. One-half of the inlet flow at the lower left
in the image contains the Rhodamine B. The increasing
number of striation layers from element to element
expected for this type of mixer is evident. It is noted that
these small-scale variations in concentration are somewhat
blurred by internal reflection and other effects causing
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766 Microfluid Nanofluid (2009) 6:763774

k=4 k=8 k = 12 k = 16
Cz
1.0

0.0
0 100 200 0 100 200 0 100 200 0 100 200
Position (m) Position (m) Position (m) Position (m)

k=4 k=8 k = 12 k = 16

Fig. 3 Composite microscope image of fluorescence intensity (bot- The Peclet number based on channel depth (R) and average velocity
tom) for Mixer A and (top) profiles of measured (depth averaged) (V) is Pe = 3.2 9 105
concentration at selected element outlets (k) derived from the images.

fluorescent light emitted at one position to be received by

Table 1 Experimental conditions
the camera from adjacent positions.
Quantitative comparison with the computations and with q 1,500 kg/m3
the scaling relation is dependent on determining the con- l (at 25C) 0.0497 N s/m2
ditions of the experiment, in particular the Peclet number. D (at 25C) 1.54 9 10-11 m2/s
The Peclet number used here is Pe = VR/D where V is Sc = l/qD 2.1 9 106
average velocity in the 275 lm wide tail section of an R (channel depth) 75 9 10-6 m
element, R is the channel depth (75 lm) and D is the dif- sD 365 s
fusivity of the Rhodamine B in the ionic liquid. The
13-element 16-element
average velocity in the tail section is readily determined (diagonal) mixer (horizontal) mixer
and the channel geometry is known with satisfactory
accuracy, but the diffusivity of the Rhodamine B in the V (in 275 lm section) 0.085 m/s 0.0683 m/s
ionic liquid, although expected to be in the region of Pe = VR/D 4.0 9 105 3.2 9 105
10-11 m2/s based on values for similar molecules diffusing Re = qVR/l 0.19 0.15
in similar ionic liquids, needs to be measured. This was Mean residence time 256 ms 489 ms
accomplished by stopping dyed and un-dyed ionic liquid
solutions side by side in a channel, thereby initiating a two-
dimensional transient diffusion process in the section of the
channel. Images were recorded to give depth-average 3 Computational approach
concentration profiles as a function of time until a uniform
mixture was reached. The diffusion equation was then A continuum computational method is used here to deter-
solved numerically for the two-dimensional channel cross- mine the performance of the experimental mixer. The
section shape, beginning with an initial step profile of computations are, however, limited to low Peclet number
concentration, and the results were fitted to the experi- conditions where sufficiently fine grid size can be used to
mental profiles by adjustment of the diffusivity. The control numerical errors in the solution of the species
diffusivity so determined is judged to have an uncertainty equation. The exact equations for steady Stokes flow
of around 5% and the value determined is listed in Table 1 transporting a dilute species can be expressed in terms of
along with other experimental conditions. non-dimensional variables as:

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Microfluid Nanofluid (2009) 6:763774
op o2 ui ouj ouj C 1 o2 C
2 0 : 2
oxi oxj oxj oxj Pe ox2j
The normalising scales used are R for length, V for velocity
and the viscous scale lV/R for pressure. Concentration is
normalised by that in the inlet stream containing the dye so
concentration ranges from zero in the pure undyed solution
to unity in the pure dyed solution.
These equations are solved using finite volume discret-
isation to determine the velocity, pressure and species
fields within the mixer (using the Fluent CFD program,
Version 5). The computation is made element by element
with the solution at the outlet from one element being
transferred as the inlet boundary condition to the next
element downstream. For each element computation, suf-
ficient length of the downstream element is included for the
results at the element outlet section to be unaffected by the
outlet boundary condition imposed further downstream.
The inlet boundary condition for the first element is a lat-
eral step function in concentration and a uniform velocity
in the direction parallel to the channel. Three computa-
tional domains are used, one for the first element where
inlet conditions are imposed, a second for even-numbered
elements and a third for odd-numbered elements. Figure 2
shows the odd and even computational domains with the
coordinate system used. (Note that z corresponds to the
direction of depth averaging in the experimental mea-
surements.) The sections corresponding to the beginning
and end of the element are shown as shaded sections in
the figure.
A grid cell size of 0.04 times the channel depth proved
to be the practical limit with available computer resources
(AMD Opteron X50 processors with nominal speed of
2.2 GHz). This cell size was used uniformly throughout the
domain to produce a mesh of tetrahedral cells. Second
order differencing was used for the convective terms in the
species equation and computed values of concentration
standard deviation are expected to have an error of about
1% at a Peclet number of 1,000, the error increasing with
Peclet number. This error was estimated from computa-
tions at Pe = 1,000 made for a series of different grid sizes
with small enough grid size being reached to judge the
exact result and also from related previous computational
studies where error was assessed by comparison with exact
solutions (MacInnes 2002). The error scales directly with
the Peclet number for fixed grid size, so at the highest
Peclet number computed here (10,000) the error is around
10%. The computations required up to 60 h CPU time at
each Peclet number, depending on the number of elements
computed. Figure 4 (tear-drop mixer) illustrates the char-
acter of the species distribution, where computed
concentration at the channel wall surfaces for the first
element of the mixer at Pe = 1,000 is shown. It is
767
Fig. 4 Computed contours of concentration at the wall surfaces for
the first element of the tear-drop mixer geometry (Mixer B) and for
the F mixer geometry (MacInnes et al. 2007). The Peclet number is
1000 in each case. Red corresponds to one of the pure solutions, blue
to the other and intermediate shades to mixtures of the two
encouraging to note that in the computation, more of the
dyed solution flows into the left hand branch when the flow
divides at the beginning of the second element, which is
also found to be the case in the experimental result in
Fig. 3.
4 Mixer scaling relation
The experimental and computational results will be used to
determine the parameters in the scaling relation developed
by MacInnes et al. (2007) for concentration non-uniformity
as a function of the number of elements in the mixer and
Peclet number. The scaling relation allows both the overall
consistency of the results to be judged and the use of
limited results to predict performance for mixer design
purposes. The most direct measure of mixture non-unifor-
mity is the standard deviation of concentration normalised
by the concentration of the fully mixed state. This relative
standard deviation, r, is defined by
v
u 2
u C
r t 2  1 3
C
where C is concentration and the over bar represents an
averaging operation (here volume weighted averaging over
a flow section is used). For volumespof two solutions
combined in the ratio /, r equals 1 / in the initial
unmixed state (MacInnes et al. 2005) and approaches zero
as progress is made towards complete uniformity. So equal
flows of two solutions, as is the case here, correspond to an
initial relative standard deviation of r = 1.
The standard deviation is reduced from element to
element by diffusion between layers of the solutions.
MacInnes et al. (2007) derived a general relation for decay
of standard deviation with number of elements that applies
over the entire range of Peclet number. The relation blends
high Peclet number scaling with that at low Peclet number.
At high Peclet number, mixing is delayed by a certain
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768 Microfluid Nanofluid (2009) 6:763774

number of elements as the smallest length scales of the non-dimensional variables. Three equations are needed:
concentration field are progressively reduced to the size the scaling relation (Eq. 4) provides one equation, the
where diffusion can play a significant role, the delay definition of Peclet number provides a second and the
increasing with Peclet number. Then, the standard devia- third is provided by the Stokes flow pressure drop relation
tion of concentration decreases exponentially at a rate that for one element (Dpe = j/se where j is the pressure drop
is independent of Peclet number and dependent only on the coefficient and Dpe is the element pressure drop norma-
continual folding produced by flow through the element lised using the viscous scale lV/R). The design constrains
geometry. Three geometric parameters a, k and c are are element size, mixing time and mixture uniformity.
needed to quantify, respectively, the dissipation rate of These three constraints with the three equations determine
standard deviation, the effectiveness of the elements at the number of elements required and the pressure drop
folding the solutions and the delay to the beginning of the and Peclet number of operation. The three design
exponential decay. At low Peclet number the decay rate is equations in terms of the non-dimensional design
proportional to the inverse of the Peclet number and a constraints are:
fourth geometric parameter (b) is needed to quantify the    
s
transition between the two Peclet number regimes. The r exp ase k 2 kr  c max0; lnkse kr =s
b se k r
relation derived for relative standard deviation is
    5
1
r exp ase k 2 k  c maxlnkPe; 0 4 jkr2
b Pe Dp 6
s
where k is the number of elements the flow has passed
k r se
through, Pe is the Peclet number as previously defined and Pe 7
s
se is mean residence time in a single element non-dimen-
sionalised by the convective time scale R/V. The The design criteria are imposed by specification of the
parameters in Eq. 4 are functions only of element geometry required mixture uniformity (r) and mixing time (sr). The
in the Stokes regime considered here. It should be noted mixing time is taken as the total mean residence time of the
that beyond the Stokes regime they become functions of mixer, sr = krseR/V. This mixing time is present in the
Reynolds number as well. above equations as the non-dimensional time s = sr/sD,
The computations consider just the short-tail mixing where sD = R2/D is the diffusion time scale based on
element of Mixer B whereas the most detailed experiments channel size, R. Note that the non-dimensional mean resi-
are made for the long-tail mixing element of Mixer A. As dence time of the mixing element (se) is a purely geometric
has been mentioned, since the part of the geometry parameter and is a known constant for a particular element
responsible for folding is identical in the two geometries, it geometry (values given in Table 2). With r and s specified,
is possible to translate results from one to the other in a the number of mixing elements (kr) is uniquely determined
straightforward manner, taking account of the different by solution of Eq. 5. The non-dimensional pressure drop
values of se and pressure drop coefficient (j) for the two across the mixer (Dp) is then determined by Eq. 6 and
mixers. The product sek determines the scale reduction per the Peclet number by Eq. 7 (note that the physical pres-
element at large Peclet number and the product ase deter- sure drop has been normalised by the stress scale lD/R2 to
mines dissipation of concentration variance over the form Dp).
element. Lengthening the tail does not affect scale at high
Peclet number so the former must remain constant for the
two similar mixers. The later should remain approximately
constant since strongest dissipation occurs in the loop
Table 2 Parameter values in the scaling relation (Eq. 4 or 5) for tear-
where the layers are stretched and diffusion distance is drop Mixers A and B and the F mixer (MacInnes et al. 2007)
reduced, the increase in residence time due to lengthening
Tear-drop mixer F mixer
the tail being countered by a reduction in average dissi-
pation rate and hence in a. Mixer A (long tail) Mixer B (short tail)
Once the scaling relation for a particular mixing element se 26.9 21.6 11
geometry is accurately established, one can reliably design a 21.0 26.2 28
any mixer based on that same element geometry. Questions
k 0.000353 0.000439 0.00162
of optimum number of elements, the effect of size and of
b 3.22 3.22 1.63
performance relative to other element geometries can be
c 0.564 0.564 0.776
decided based on the scaling relation. MacInnes et al.
j 9,610 5,940 1,190
(2007) develop the necessary design relations in terms of

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Microfluid Nanofluid (2009) 6:763774
5 Results
Computations at four different values of the Peclet number
up to 10,000 for Mixer B and experimental measurements
at Pe = 320,000 for Mixer A were made. In all cases, the
Reynolds number was much lower than unity, so Stokes
flow prevailed. The experimental condition used corre-
sponds to typical operation of the mixer in the reaction
device and, indeed, to conditions commonly of interest in
microchannel networks. Finite volume computations at
Peclet numbers greater than 10,000 produce unacceptably
large errors and experiments at lower Peclet number could
not be controlled accurately using the available apparatus.
Rather than a direct comparison of computational predic-
tion with experimental measurement, agreement of the
computation and experiment will be judged indirectly
based on how well the scaling relation fits all of the results
together.
Figure 5 shows the results with open symbols for the
computations and solid symbols for the experiment. The
lines are the scaling relation (Eq. 4) fit to all data in the
final stage of decay, with the parameters listed in Table 2
giving the least-squared-error best fit. It is the final expo-
nential stage of decay that determines mixer performance
and to which the scaling relation applies. The starting
element used to determine the best fit was selected based
on where the error in fitting the final decay settled to an
approximately steady level, the error increasing as more
elements from outside the exponential region were inclu-
ded. This was determined individually for each Peclet
number data set (computational or experimental). In the
figure, a significant initial delay at high Peclet number can
be observed, as expected, with little mixing occurring
before the exponential decay begins. The origin of expo-
nential decay for Pe = 320,000 is at about the third
1.00
Pe = 320,000
0.10
10,000
1,000
100
320
0.01
0 5 10 15 20
k be the case for the F mixer investigated in MacInnes et al.
Fig. 5 Comparison of r results from computation (open symbols) and
measurement of Mixer A (solid symbols) with the scaling relation
fitting all results. Parameter values used in the scaling relation (Eq. 4)
are listed in Table 2
769
element, i.e. three elements are required to develop small
enough layer thickness for significant mixing to begin. The
actual data in fact show a gradual transition to the final
decay rate, with initially slow decay rather than no decay
for the first three elements and the final constant decay rate
being reached by about the ninth element. The fact that
standard deviation values in this transition region are rather
erratic and unexpectedly low compared to the computation
at Pe = 10,000, suggests that error due to depth averaging
may be especially important during transition. Clearly,
though, the scaling relation gives an excellent account of
all of the data, both computational and experimental, in the
final decay region, where mixing performance will be
judged.
Of course, the scaling relation is only as good as the
quality of the data on which it is based. As mentioned,
the computations have a numerical error of about 10% at
Pe = 10,000, which decreases with Peclet number, and
this error will give a lower standard deviation than is
actually present. A second important error is that caused
by the depth averaging of the experimental measurement
of concentration (e.g. Schonfeld et al. 2004; Nguyen and
Wu 2005). With variation of concentration in the direc-
tion perpendicular to the image not captured by the
measurement, striation layers that are not perfectly per-
pendicular to the image plane result in falsely low
standard deviation values. The magnitude of this error can
be estimated using the computational results. Applying
depth averaging to the computational results reduces
values of r by between 0 and 0.6% (depending on which
element is considered) for Pe = 100, by 2.26.9% for
Pe = 1,000 and by 5.312.1% for Pe = 10,000. This
increasing effect with Peclet number suggests the reduc-
tion at the high Peclet number of the experiment might be
around 30%. Blurring of image intensity mentioned ear-
lier will introduce somewhat further error also reducing
the measured deviation.
Thus, while the fitted scaling relation represents the data
well the error present in these data may be allowing a
fortuitously good match with the scaling relation. To test
this, the data at Pe = 10,000 and 320,000 were increased to
account for the errors estimated above (by 10 and 30%,
respectively) and the scaling relation was refitted to the
adjusted data. The resulting scaling relation gave an
equally good fit to the adjusted data as that shown in Fig. 5
for the original data. Thus, the general scaling relation does
seem to allow an excellent account of the mixing behaviour
of the tear-drop mixer considered here, just as was found to
(2007). One must bear in mind that since the parameters for
the tear-drop mixer in Table 2 fit the original unadjusted
data the corresponding scaling relation will under-predict
the mixture standard deviation.
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770
6 Effect of misalignment
In addition to the element-by-element measurements for
Mixer A, further measurements were made at the outlet
from Mixer B when it was realised that different chips of
identical design gave noticeably different mixing perfor-
mance. Chips were available from three different wafers
(A, B and C) and from different positions on the wafers.
Figure 6 shows the fluorescence images of the reactor
region (i.e. the outlet from Mixer B) and the corresponding
measured values of relative standard deviation in the
reactor produced by nine different chips of identical design
taken from Wafers A, B and C. The images are arranged in
increasing order of r and one can see the progression quite
clearly from a relatively low non-uniformity of 6.9% to
relatively high non-uniformity of 25%. Interestingly, there
is not necessarily a consistent relationship between uni-
formity for a chip and the wafer from which it was taken.
In the case of the chips from Wafer B, several give the
lowest levels of non-uniformity while another gives rela-
tively high non-uniformity.
Misalignment of the glass layers during fabrication is
the most obvious cause of the observed variability. The
misalignment of the top and bottom layers could be
Fig. 6 Fluorescence intensity
images showing the mixture
non-uniformity in the reactor
region (outlet from Mixer B) at
Pe = 4 9 105. The wafer from
which each chip has come is
indicated along with the
measured value of r. The
images are arranged in order of
increasing relative deviation
going from left to right and from
Wafer B #10 6.9%
top to bottom
Wafer C #10 9.5%
Wafer C #2 10.9%
123
Microfluid Nanofluid (2009) 6:763774
estimated for Wafer A to be about 12 lm based on com-
parison of the fabricated channels and the design pattern. In
the case of Wafer B, alignment marks on individual glass
layers could be used to determine within a couple of
microns the actual displacement of the top and bottom
layers relative to the middle layer. Since chips from the
same wafer are bonded before dicing, misalignment of each
chip is determined by the misalignment of the glass layers
and the position of the particular chip on the wafer. The
misalignment of the glass layers was determined in terms
of a rotation angle about the wafer centre followed by
translation. The rotation and translation were determined
by best fit to the measured offset of the alignment marks.
From this information, the displacement of the top and
bottom layers relative to the middle layer can be worked
out for the centre of Mixer B in the case of each chip from
Wafer B. The values determined are given in Table 3 and
one can note that these chips have been better aligned than
the one from Wafer A, i.e. to within around 5 lm as
compared with 12 lm. Though not measured, the chips
from Wafer C are expected to have similar levels of mis-
alignment to those of Wafer B.
Returning to Fig. 6, one does find a similarity in the
pattern of dye distribution across the reactor for chips from
Wafer B #8 8.0% Wafer B #11 8.4%
Wafer C #11 10.1% Wafer C #3 10.8%
Wafer B #4 11.8% Wafer A #2 25.0 %
Microfluid Nanofluid (2009) 6:763774 771

the same wafer, e.g. those from Wafer B tend to have some offset, while for Case S15, the mixing is improved by the
streaks of high dye concentration to the left of the reactor offset. Relative standard deviation has been altered by
centre, those from Wafer C a sharp high concentration around 50% of the value reached when the channels are
streak just near the reactor centre. This might be expected perfectly aligned. Further computations for these two cases
since all are affected by the same offset rotation and at lower Peclet numbers suggest also that the deviation in
translation. However, quite large variations in mixing mixing due to offset increases with Peclet number. The
evidently result from apparently subtle differences in offset eight different experimental chips from Wafers B and C are
even for chips from the same wafer. For example, chip #4 found to have a 26% variation in mixing and this appears
from Wafer B gives a r value almost twice that of chip #10 to be consistent with the computational result, taking
from the same wafer and yet the offsets are similar in account of the increased variation due to larger Peclet
magnitude (Table 3). Chip #8 has the largest offsets of the number and the decreased variation due to the smaller
four tested, yet the value of r produced is among the offset magnitude for those wafers (of around 5 lm) com-
lowest. pared to that used in the computations. Therefore,
To quantify the effect of misalignment, two further misalignment appears to explain the observed variation in
computations with intentional misalignment were made for mixing for the different chips. For the fabrication toler-
Pe = 1,000. In the first, the top layer of channels were ances maintained for Wafers B and C, two or three extra
offset in the x direction (coordinate system of Fig. 2) rel- elements would need to be added to ensure the required
ative to the middle layer and the bottom layer of channels uniformity is achieved, and perhaps four or five extra for
were offset in the y direction relative to the middle layer, the larger fabrication tolerances of Wafer A.
each by 15 lm (similar to the offset magnitude for Wafer
A). This misalignment moves the outlet of each connecting
hole to one side of the receiving channel (Case R15). In the 7 Application of the scaling relation
second computation, the offset is such that the inlet of each
connecting hole is moved to one side of the supplying At the highest Peclet number, which is most typical of
channel (Case S15). The resulting change in decay of rel- conditions of interest, the standard deviation of concen-
ative standard deviation for these two cases is shown in tration remains around 8% at the outlet of the mixers
Fig. 7. Case R15 worsens the mixing compared with no (Fig. 5 for Mixer A, Fig. 6 for Mixer B). Arguably, for
many applications good uniformity would correspond to
Table 3 Offset coordinates of the centre of Mixer B for chips from r = 1% or lower and thus the performance of the mixers
Wafer B studied here would be unacceptable. The design equations
Chip Top relative to middle Bottom relative to middle
(Eqs. 57) will now be used to assess the ways in which the
mixer could be improved.
dx (lm) dy (lm) dx (lm) dy (lm) First, exactly the same element geometry could be used
#4 -2.9 0.5 -2.5 5.9 but with more elements or operating at a lower flow rate.
#8 -5.7 -3.7 -6.4 0.1 To determine the required adjustments, Eq. 5 can be used
#10 -2.9 -3.7 -2.5 0.1 to develop a general performance plot, i.e. the mixture
#11 -1.5 -3.7 -0.6 0.1 uniformity as a function of non-dimensional mixing time
for mixers having different numbers of elements. For the
Mixer B element (short tail), the plot of Fig. 8 results for
1 mixers differing only in the number of elements, k. For
mixing of Rhodamine B in ionic liquid as in the experi-
Perfect alignment
ments, the channel diffusion time is sD = 365 s. If a
0.1 mixing time of 0.365 s is required, for example, s must be
Case R15 10-3. From the figure, the current 13 element mixer gives r
of about 8% for s = 10-3, and one can see that this could
Case S15
0.01
be reduced to below 1% for the same mixing time by
increasing the number of elements to about 22. However,
Eq. 6 shows that this approximate doubling in the number
Pe = 1000
of elements would be accompanied by a quadrupling of the
0.001
0 3 6 9 12 15 18 21 pressure drop across the mixer. Thus, the 2 bar pressure
k drop required with 13 elements would increase to about
Fig. 7 Computed effect of misalignment on r at Pe = 1,000 for two 8 bar to reduce standard deviation to 1%. Alternatively, the
example offsets, Cases S15 and R15 existing 13-element mixer could be operated at a larger

123
772
1.E+00
Tear Drop Mixer
k =5 (short tail)
9
1.E-01
13
17
1.E-02
21
25
1.E-03
1.E-04 1.E-03 1.E-02 1.E-01 1.E+00
Fig. 8 Predicted performance of the tear-drop mixer. Curves are the
scaling relation (Eq. 4) with the values listed in Table 2 for Mixer B.
Symbols show measured values at the outlet of Mixer B for the nine
different experimental chips from Wafers A, B and C
value of mixing time. Increasing s to 0.6 reduces r to
below 1% according to Fig. 8. However, the mixing time is
then very long (3.6 min) and similar to that for a simple
channel, i.e. the channel diffusion time. Lengthening the
mixing time reduces the Peclet number (Eq. 7) which
corresponds to increasing the decay rate of r (Fig. 5).
The data from the nine different chips at the outlet from
Mixer B is also plotted in Fig. 8 and the scatter due to
misalignment is evident. The scaling relation determined
by computation and Mixer A measurements passes through
the middle of the data, which represents a successful pre-
diction (albeit a somewhat modest one since the geometry
is so close to the one used to determine parameter values of
the scaling relation). The effect of misalignment may be
thought of as effectively increasing or decreasing the
number of elements in the mixer. The highest value of r is
produced by the chip from Wafer A and has in effect
reduced the number of elements by 5 (from 13 to 8). For
the data from Wafers B and C chips, the effective number
of elements is only changed by one or two elements.
A further possibility for reducing r is to reduce the size
of the mixer. To see the effect of size, which is represented
by the channel depth, R, all non-dimensional quantities
depending on R must be expanded. One finds that, for a
given number of elements and for a constant mixing time,
pressure drop remains constant as size is decreased but the
Peclet number decreases in proportion to R2. The reduction
in Peclet number with size again serves to increase the
decay rate of r, but the effect is modest until quite low
levels of Peclet number are reached. Until one reduces the
Peclet number to around 1000, corresponding to a reduc-
tion in channel depth from 75 lm down to about 4 lm, the
improvement remains small. Such small channel size may
be impractical in relation to achieving required fabrication
tolerances and avoiding blockages. In addition, as channel
size is decreased, the flow rate decreases in proportion to
R3 which may or may not be desirable.
123
Microfluid Nanofluid (2009) 6:763774
In practice, one would like to design a mixer in a direct
manner. The problem reduces to seeking the best mixer
for a particular application. Two mixing criteria are asso-
ciated with a given application: the mixture uniformity to
be produced by the mixer and the time within which that
uniformity must be produced. Thus, to determine the mixer
design requires r and sr to be decided. A third parameter
must be decided on practical grounds and that is the size of
the mixer, i.e. R. Once R, r and sr are decided, there is one
further choice and that is the element geometry to be used.
For, in principle, any particular folding flow mixing
geometry can be operated such that the three criteria are
satisfied. One simply solves the design equations (Eqs. 5
7) for kr, Dp and Pe, thereby determining the required
number of elements for that mixer and the conditions of
operation. However, each element geometry will lead to a
different operating pressure drop and a different chip
footprint area for the same size R. The pressure drop and
chip area occupied by the mixer are closely related since,
for fixed R, each is approximately proportional to the
overall flow path length. In nearly all applications, mini-
mising either the mixer pressure drop or mixer footprint
area or both will be important. One can thus identify a
theoretical best mixer to be the one giving minimum
pressure drop.
Identifying the best mixer geometry would be an
immense task requiring investigation of all possible geo-
metric variations of all possible mixing element types (F,
tear-drop, ribbed, etc.). It is not clear that such extreme
optimisation would ever be advantageous. Gradual
improvement of mixer geometry accepting the modest
penalties in pressure drop and chip footprint, because the
design is not absolutely optimum, is likely to be the way
ahead. One obvious shortcoming of the tear-drop mixer
considered is its large aspect ratio. This is a result of the
wet-etching employed to create the channels. The large
channel width to depth ratio associated with isotropic
wet-etching of glass means that the diffusion distance is
relatively large compared to the channel depth on which
pressure drop directly depends. The large aspect ratio,
perhaps combined with the fact that the connecting holes
are small in relation to the channel width, seems also to
reduce the effectiveness of the folding produced by the
geometry. In Fig. 4, the uneven bulk distribution of dyed
liquid between the two branches of the second element may
be caused by these factors. It would be possible to produce
a more compact version of a tear-drop mixer that would
give much improved folding efficiency. To illustrate this
prospect, the present tear-drop mixer can be compared with
the more compact F mixer design (Fig. 4; Table 2) char-
acterised in MacInnes et al. (2007). Solution of the design
equations for an assumed mixture uniformity requirement
of r = 1% produces the plots of Figs. 9 and 10, for
Microfluid Nanofluid (2009) 6:763774
1.E+12
1.E+10
p compact than the F element, resulting in the far larger value
1.E+08
Tear-drop Mixer
1.E+06
= 0.01
F Mixer
1.E+04
1.E-04 1.E-03 1.E-02 1.E-01
Fig. 9 Non-dimensional pressure drop as a function of the reduction
in mixing time required to give r = 1%
25
20
Tear-drop Mixer
15
k is a factor giving effective diffusion distance relative to
10
F Mixer
5
= 0.01
0
1.E-04 1.E-03 1.E-02 1.E-01
Fig. 10 The number of mixing elements required as a function of the
reduction in mixing time, again for r = 1%
non-dimensional pressure drop and number of elements,
respectively, as a function of non-dimensional mixing time.
For a given liquid system and channel size, the normalising
scales for pressure and mixing time are fixed and the same
for both element geometries. Thus, since the pressure
required at any given mixing time can be seen from the
figure to be the greatest for the tear-drop mixer considered,
one can conclude that this F mixer element is more
effective than this tear-drop mixer. In fact, over the entire
range of mixing time spanned by the plot, the F mixer
element requires less than 10% of the pressure drop needed
for the tear-drop mixer. In addition, considerably fewer
elements are required to achieve the same mixing (Fig. 10),
which demonstrates the relation between pressure drop and
chip footprint. It must be emphasised that this result does
not show that the F mixer is inherently better than the tear-
drop mixer, only that this particular version of an F mixer
is better than this particular version of a tear-drop mixer.
Indeed, a tear-drop mixer of a more compact design was
considered computationally in MacInnes and Allen (2005)
that would outperform the F mixer of Figs. 4, 9 and 10.
It is interesting to compare the parameter values in the
scaling relation determined for the two different mixers.
These values are listed in Table 2 and the concentration
773
distribution at the channel wall in the first couple of ele-
ments for the two mixers is shown in Fig. 4. From the
figure, it is clear that the tear-drop element is far less
of non-dimensional residence time listed for the former in
Table 2. The parameter a is slightly smaller and k is much
smaller for the tear-drop mixer. As mentioned, k is related
to the effectiveness of the folding, i.e. the increase in
mixing interface, produced by passage through each ele-
1.E+00 ment; a represents the effectiveness of dissipation of
concentration non-uniformity associated with the folded
concentration field. Thus, both effects are greater in the F
mixer element considered, with folding being far more
effective (k = 0.00162 as compared to 0.000439) and this
lesser folding in the tear-drop is perhaps evident in the wall
concentration plots of Fig. 4. Other parameter differences
to note are the higher values of b and friction coefficient, j,
for the tear-drop. The latter is an obvious result of the
longer flow path of this tear-drop design. The parameter b
channel scale R for the low Peclet number limit. Since
channel depth has been used for both mixers, the larger
value of b for the tear-drop is simply taking account of the
greater channel width to depth ratio in that case. Thus,
1.E+00 differences in the parameter values can be related to dif-
ferences in performance and these could help to identify
shortcomings of a particular element geometry and, hence,
guide development towards optimum geometries.
8 Conclusion
A folding flow mixer formed from a chain of 16 tear-drop
elements (Mixer A) has been investigated in the Stokes
flow regime, both computationally and experimentally,
with the aims of establishing the characteristics of this
geometry and testing the scaling relation developed by
MacInnes et al. (2007). The results are found to be fully
consistent with the scaling relation and the approximate
performance of the mixer has thus been determined to
within the error of the experiment and computations.
The study also reveals a significant effect on mixing
from small misalignment of the glass layers that form the
mixer geometry. A layer offset of 5 lm (1.5% of channel
width) is found to produce up to about a 26% variation in
the standard deviation of measurements of mixture uni-
formity. The offset can lead to improved or worsened
mixing depending on the precise offsets of the layers. This
variation can, however, easily be taken into account by the
addition of a few extra elements, the number added
depending on the fabrication tolerances maintained.
The scaling relation determined for Mixer A is used
to predict the performance of a second similar mixer
123
774
(Mixer B) incorporated in a reaction test device. Mea-
surements for nine different mixer chips of identical
design show a range of relative standard deviation from
7 up to 12% for this mixer, which is consistent with the
predicted value of 8%. Reducing this relatively high non-
uniformity is considered using the design equations for
the mixer to quantify the potential improvements. Mix-
ture uniformity is improved either by increasing the
number of elements, which greatly increases pressure
drop, or by accepting a much longer mixing time. The
prospect of improving the performance of a mixer by use
of more efficient element geometry is also highlighted by
comparison with results for an F mixer element charac-
terised previously.
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