Proceedings of 2008 ASME Summer Heat Transfer Conference

HT2008
August 10-14, 2008, Jacksonville, Florida USA

HT2008-56198
THERMAL MODELING FOR DESIGN OPTIMIZATION OF A MICROFLUIDIC DEVICE
FOR CONTINUOUS FLOW POLYMERASE CHAIN REACTION (PCR)

Sumeet Kumar/ Massachusetts Institute of

Technology, 77 Massachusetts Avenue,
Cambridge, MA 02139, USA
email: sumeetkr@mit.edu

Todd Thorsen/ Massachusetts Institute of

Technology, 77 Massachusetts Avenue,
Cambridge, MA 02139, USA

Sarit Kumar Das/ Massachusetts Institute of

Technology, 77 Massachusetts Avenue,
Cambridge, MA 02139, USA

ABSTRACT
Polymerase Chain Reaction (PCR) is a molecular
biological method for the in vitro amplification of nucleic acid
molecules which has wide applications in the area of genetics,
medicine and biochemistry. The typical three step PCR cycle
consists of heating the sample to 90-94 C to denature doublestranded DNA, cooling down to 5054 C to anneal the specific
primers to the single stranded DNA and finally increasing the
temperature to 7075 C for extension of the primers with
thermostable DNA polymerase. The temperature sensitivity of
the reaction requires precise temperature control and proper
thermal isolation of these three zones. In this paper we present
the design of a continuous flow PCR microfluidic device with
the channels fabricated in (poly) dimethylsiloxane (PDMS) and
thin film Platinum Resistance Temperature Detector (RTD)
elements fabricated on glass substrate to define the three
different temperature zones. The fluidic arrangement has a
water jacket layer to minimize evaporation from the porous
PDMS walls. A detailed thermo fluidic model of the device is
presented to predict the performance and efficacy of the
proposed design. Numerical simulations are carried out to find
the temperature distribution and temperature gradients in the
device and a parametric study is done by varying flow rate, heat
flux and channel dimensions in order to optimize the design for
achieving temperature isolation and sharp temperature gradients
between different zones.

INTRODUCTION
Polymerase chain reaction (PCR) is an enzymatic method
for the in vitro amplification of nucleic acid molecules, which
has wide applications in the area of genetics, medicine and
biochemistry [1, 2]. The major objective of PCR is to replicate
a nucleic acid sequence, ultimately yielding of the order of 105
106 copies from a single template. The amplification process
of PCR can be partitioned into three discrete temperature zones:
(A) denaturation: double-strand DNA segment is separated in
single strands at high temperature (90-94 C); (B) annealing: the
separated single-stranded DNA attaches to a complimentary
primer (50-54 C); (C) extension: DNA polymerase adds
nucleotides to the 3 end of the primer , replicating the target
DNA sequence (70-75C) [3, 4].
Commercially available PCR equipment (e.g. MJ Research,
Inc.) performs PCR simultaneously in 96 or more plastic tubes
or wells containing sample DNA and PCR mixtures. However,
conventional 96 well PCR devices usually have a thermal
ramping rate of 12 C/s, accounting for a significant
contribution to the run time of a typical 30 cycle PCR reaction
(1-2 hours). Moreover, while using conventional tube-based
PCR methods, both sample preparation and post-PCR product
detection need to be performed offline, thus resulting in the
longer analysis process and a higher risk of cross contamination
[1]. The use of micro electro-mechanical systems (MEMS)
technology offers several advantages for PCR, including faster
thermal ramping times, reduced sample volumes, disposability,
and functional integration of sample preparation and postanalysis [1, 3, 5, 6]. To date, most micro PCR devices can be
1

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classified into, static chamber PCR chips and continuous flow

PCR chips. Chamber-type PCR chips consist of a micro or
nanoliter volume of reservoir and integrated film
heaters/sensors that cycle under the static sample. These chips
have advantages such as rapid thermal heating/cooling, easy
temperature control, and nanoliter sample volumes. In contrast,
flow-type PCR chips typically consist of three independent,
fixed temperature zones fabricated from thin, conductive films
with the PCR sample continually flowing between them via a
microchannel with a serpentine configuration. Sample volumes
of continuous flow PCR chips are typically on the order of 1
10 l, and can be used for real-time PCR analysis, in which
amplified product is analyzed as a function of cycle number.
Additionally, thermal ramping times are even shorter for
continuous flow PCR devices (vs. static microchambers),
enabling faster PCR cycle times [5, 6, 7, 8].
The temperature sensitivity of continuous flow PCR
devices requires precise temperature control and proper thermal
isolation of the three zones. For PCR, it is desirable to minimize
ramp times between the extension, denaturation and annealing
temperatures to maximize yield and fidelity of the amplified
products [1, 2, 4].
In this paper, we present a design for a continuous flow
PCR microfluidic device with the channels fabricated in (poly)
dimethylsiloxane (PDMS) and thin film platinum Resistance
Temperature Detector (RTD) elements fabricated on glass
substrate, which define the three discrete temperature zones.
The microfluidic serpentine channel acting as a conduit for the
PCR mixture is covered by an enclosed water jacket reservoir,
separated from the sample channel by a thin (~30 m) layer of
PDMS, to minimize evaporation from the water-permeable
PDMS walls. A detailed thermofluidic model of the device is
presented to simulate the temperature profile of the fluid as it
transits between the RTD elements within the device.
Numerical simulations are carried out using the commercial
software Fluent to find the temperature distribution and
temperature gradients in the device as a function of flow rate,
heat flux and channel dimensions to optimize the design for
achieving temperature isolation and sharp temperature gradients
between different zones.
NOMENCLATURE
A = Cross sectional area of the rectangular channel
C pf = Specific heat capacity of the fluid

hair = Convective heat transfer co efficient of air

k f = Thermal conductivity of fluid
k p = Thermal conductivity of PDMS
k g = Thermal conductivity of glass

k w = Thermal conductivity of wood

L = Length of the channel

l w = Thickness of the wooden bench top

Pe = Peclet number ( f C pf uo 2 / k f L )
Q = Volume flow rate

q '' = Heat flux

Re = Reynolds number = u o Q A
T = Temperature
t = Time
u = Velocity
u o = Characteristic velocity scale = Q A
t * = Non dimensional time = uo t L
u * = Non dimensional velocity = u u o
x * = Non dimensional stream wise co-ordinate = x / L
y * = Non dimensional co ordinate perpendicular to the
stream wise direction = y /

z * = Non dimensional co ordinate perpendicular to the

stream wise direction = z /
P = Pressure head across the microfluidic channel
2 = Laplacian
f = Thermal diffusivity of the fluid = k f / f C pf

p = Thermal diffusivity of PDMS

g = Thermal diffusivity of Glass
f = Density of the fluid
= Height of the fluidic channel
p
g

= Thickness of the PDMS domain

= Thickness of the glass domain

k f T / Lq '' = Non dimensional temperature

= Fluid viscosity
DESIGN OF MICROFLUIDIC PCR CHIP
The design of the microfluidic channels follow the basic
serpentine design proposed by Manz et al. with some
modifications [8]. The reagents are designed to flow through the
three different zones, namely denaturation, annealing and
extension, as shown in Fig.1. To achieve good amplification, a
serpentine channel is implemented to pass through the zones 30
times, comparable to the 25-30 cycles used in conventional
PCR thermocyclers. The desired temperature zones are
achieved by using three sets of thin film platinum RTD elements
fabricated on glass substrate as shown in Fig.2. Each of these
sets of heaters can be independently regulated to control the
heat flux dissipated within each zone. The fluidic layer is then
bonded to the top surface of the glass layer after aligning the
fluid layer on top of the corresponding heater zones. Thus, a

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closed microfluidic device is formed in which the fluid is in

direct contact with the thin film heaters.
Zone B,
Annealing (50-54 C)

Zone C,
Extension
(70-75 C)

regions, a microchannel system typically encompasses only a

very small fraction of the substrate and thus heat transfer is
typically governed by a large timescale thermal diffusion
process through the solid region [9].
The model involves three-dimensional, unsteady conjugate
heat transfers between the fluidic and solid PDMS/glass regions
of the device when the three thin film heaters are active.
Different length scales are involved due to the large difference
in the size of the fluid domain (height ~ 75m, width ~ 100m)
and the solid domain (height ~ 1mm). Within the fluidic domain
the non-dimensional energy equation neglecting the viscous
dissipation term can be written as

2 2

Pe * u * . * *2 *2
z
x y
t
Zone A,
Denaturation (90-95 C)

1 cm

Fig. 1: PCR microfluidic device channel layout.

Zone B

Zone C

Zone A

1 cm

Fig. 2: Patterned thin film Platinum heaters (black strips) on

glass substrate (white background)
THERMAL MODELING OF THE DEVICE
A thermal model of the proposed design is useful to predict
the performance of the device. The important variables are
channel dimensions, heat flux imparted by the thin film heaters,
and the volumetric flow rate. The objective function for design
optimization is the temperature distribution within the device
and, more importantly, the temperature distribution experienced
by a fluid element as it flows through the microchannel.
Unlike momentum and species transport analysis, which is
confined to the fluidic domain, thermal modeling in
microfluidics presents some unique challenges as the presence
of thermal diffusion necessarily extends the simulation domain
from the region of interest (i.e. the fluidic domain) to
encompass the materials bounding the microchannels (glass,
PDMS). Contrasting with a macroscale system, where the
fluidic domain is most often of comparable size to the solid

(1)

The requirement of large number of cycles for effective

amplification by PCR dictates a long effective microchannel
length for continuous-flow microfluidic PCR devices to allow
sufficient residence time for samples flowing through the three
respective temperature zones (denaturation, annealing and
extension). Our design consists of 30 identical passes through
the three zones, with a total length of the microfluidic channel =
1.602 m. Modeling the channel as a cylinder with an effective
hydraulic diameter of 85.7 m and assuming the fluid viscosity
to be equal to that of water, the pressure head required to drive
the flow is P1.213x1010Q, where Q is the volumetric flow
rate. Under standard operating conditions, we would like to
operate the devices using flow rates on the order of 1 50 nl/s,
providing short loading times for sub-l scale samples while
allowing sufficient sample residence times over the temperature
zones for complete amplification. For Q ~ 1 50 nl/s, P
0.012 0.6 bar. At these flow rates, viscous forces are
dominant, with Reynolds numbers (Re) between 0.01Re0.5.
The Peclet number (Pe) for such flows, characterizing
comparison of convective to diffusive forces, ranges between
0.510-5 Pe 2.510-4.
Inside the upper substrate (PDMS) and lower substrate
(glass) zones, the energy equation takes on a simplified form,
consisting of transient and diffusion terms only, which can be
written in dimensional form as

1 T
2T
i t

(2)

where the generic thermal diffusivity () subscript, i, denotes

either PDMS (i=p) or glass (i=g).
The glass substrate has patterned thin film heaters (Fig. 2),
which act as constant heat flux sources when a current is passed
through them. The thin film heaters are subsequently sealed
with the microchannel-patterned PDMS, and the heaters are in
direct contact with the fluid when the device is operated. This
leads to a constant heat flux boundary condition at the lower
boundary of the fluidic domain. Most of the heat within the
fluid flowing through the microchannel is transferred via

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thermal diffusion due to the low Peclet number of the flow.

Since the heaters are fabricated on the glass and kg>kf>kp, the
bulk of the heat generated by the heaters is transferred to the
glass.
NUMERICAL SIMULATION AND RESULTS
As shown in Fig.3 the simulation domain consists of three
domains (fluid, glass and PDMS). The domain represents one
pass through the PCR microfluidic device (with a pass defined
as fluid flow through the denaturation, annealing, and extension
zones respectively). The dimensions of the fluidic domain for a
single pass are as follows; height = 75m, width = 100m,
length of the serpentine channel = 5.34 cm. The glass and the
PDMS domains are chosen in such a way that they encompass
the fluidic domain and represent one pass of the microfluidic
device. The thickness of the PDMS and glass domains are; p =
0.5 mm, g = 1 mm. The top face of the glass domain is
partitioned in the model according to the different heater zones,
facilitating simulation of different heat flux dissipated by
respective zones.

In the actual device, PDMS layer on top of glass provides

additional thermal resistance. For PDMS layer of thickness =
0.5 mm and kp = 0.15 W/mK, Eqn. 3 is used to calculate heff for
the top surface of the glass (= 14 W/m2K). The heat flux values
for the heater zones were chosen to be the same as the one used
for single pass simulation (justified later); Zone A = 11200 W/
m2, Zone B = 1000 W/ m2, Zone C = 7000 W/ m2. Thermal
properties of glass used are; kg = 1.3 W/mK, g = 7.8110-7
m2/s.
From Fig.5 the temperature variations in the transverse
direction (neglecting end effects) are found to be small, ~ 1-2 K
over 10 mm, equivalent to the width of 10 passes. As the
transverse temperature gradients are much smaller than the
temperature gradients in the direction of flow (between heater
regions), variations in temperature profiles between different
passes as a function of chip position were assumed to be
negligible.

PDMS (p)
Fluid
Domain (f)

Glass (g)

1mm

Fig.3: Computational domain for simulation

Since the pattern of heaters and fluidic channel is
geometrically periodic in the microfluidic device, it should be
sufficient to simulate one pass to understand the temperature
profile in the device. We first support this assumption by
presenting the simulation of heat diffusion in the glass substrate
with ten repeating pattern of heaters. The glass domain is
meshed using Hybrid Hexcore scheme of size 0.25 mm. 3
dimensional unsteady solver with energy equations was used in
order to obtain the temperature distribution in glass domain
with time. Figure 4 shows the isotherms to be perpendicular to
the flow direction under steady state conditions. Convective
heat transfer boundary conditions were given on the side walls
with hair = 15 W/m2K. An effective heat transfer coefficient for
the lower surface of the glass was calculated to account for the
fact that the microfluidic device will be operated on a wooden
bench top of thickness lw ~ 1cm. Assuming 1-D heat transfer
model for heat transfer from the glass to air through wooden
base we can write;
1 / heff 1 / hair l w / k w (3)
For kw = 0.1 W/mK, Eqn. 3 is used to calculate heff = 6
W/m2K.

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Flow direction
Transverse direction
Fig.4: Unsteady simulation of heat diffusion in the glass
domain at different times. Simulation predicts the system to
reach steady state at t ~ 410 s.

distribution consistent with our target zonal temperature

requirement; Zone A = 11200 W/ m2, Zone B = 1000 W/ m2,
Zone C = 7000 W/ m2. The inlet velocity for the simulation was
uo = 0.5 mm/s. or Q = 3.75 nl/s. The inlet temperature (360 K)
was defined to match the outlet temperature in order to simulate
the periodicity in flow.

100

Temperature (C)

90

80
Zone A
70

Zone C
Zone B

60

50
40
0

0.002

0.004

0.006

0.008

0.01

Distance (m )

Fig.5: Variation of temperature in transverse direction for

the 3 zones.
Simulations were carried out with a three-dimensional,
segregated, steady/unsteady solver. Hexahedral meshing of
Submap scheme was used to mesh the three domains. The three
domains had mesh of different resolutions. The fluid domain
had cubic mesh elements of volume = 25 m 25 m 25 m;
glass domain had cubic mesh elements of size = 25 m 25 m
100 m; PDMS domain had cubic mesh elements of size = 25
m 25 m 100 m. Thermal boundary conditions are as
follows; 1) a convective heat transfer coefficient of hair = 15
W/m2K on the side walls of glass and the top PDMS surface
exposed air, 2) zero heat flux boundary conditions on the side
walls of PDMS and glass which form the cutting plane along
which the simulation domain is separated from the actual
device, 3) an effective heat transfer coefficient for the lower
surface of the glass (described earlier) of heff = 6 W/m2K.
Thermal properties of the fluid, PDMS and glass used are; kf =
0.6 W/mK, f = 1.4410-7 m2/s, kp = 0.15 W/mK, p = 9.34108
m2/s, kg = 1.3 W/mK, g = 7.8110-7 m2/s. The fluid properties
were taken to be that of water which were assumed to be
constant during the PCR cycle. The concentration of reagents in
the PCR mixture is of the order of millimolar (mM). There will
be some change in the fluid properties as the reaction
progresses but since we are considering dilute solutions of
nucleotides, the variations can be neglected.
Steady state temperature profiles in the fluid, glass and
PDMS domain are shown in Fig.6. Numerical experimentation
was carried out by changing heat flux values of the different
heaters in order to achieve the desired temperature distribution.
The following values of heat fluxes gave the temperature

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Furthermore, as conduction is the dominant mode of heat

transfer in the fluid regime, and thermal resistance across the
height of the fluidic channel is small (/kf ~ 1.2510-4 Km2/W),
there is little variation in temperature as a function of height of
the fluidic channel (<1K) (Fig.8).
95
90

Temperature (C)

85
80
75
70

Zone A
Zone B

65

Zone C
60
55
50
0.00

Fig.6: Steady state temperature distribution in fluid, PDMS

and glass domain respectively.
From Fig.6, we can observe the extent of lateral diffusion
in glass and PDMS and their contributions to the temperature
distribution in the fluid domain. The dominance of conduction
over convection is illustrated by the similarity of spatial
temperature distribution between fluid and glass or PDMS
domain.
Simulations were carried by varying the inlet velocity in the
range 0.5 mm/s uo 5 mm/s or 3.75 nl/s Q 37.5 nl/s. The
spatial temperature distribution in the fluid domain is shown in
Fig.7. The results show that change in volume flow rate has a
negligible effect on spatial temperature distribution over the
defined flow rate range due to the dominance of conduction
over convection.
95
90

Temperature (C)

85
80

u=0.0005 m/s
u=0.001 m/s

75

u=0.002 m/s
70

u=0.003 m/s

65

u = 0.005 m/s

60
55
50
0

0.01

0.02

0.03

0.04

0.05

0.06

Distance (m)

Fig.7: Steady state spatial temperature distribution in the

fluid domain along the flow direction.

20.00

40.00

60.00

80.00

Height (microns)

Fig.8: Temperature variation along the height of the

microfluidic channel at three different locations which are
representative of the respective zones
From an engineering perspective in the design of PCR
devices, the most important parameter is the temperature
variation which a fluid particle experiences as it passed through
the fluidic channel. The material derivative of temperature can
be written as

DT T
T

u
Dt
t
x

(4)

The material derivative represents the rate of change of T

moving with a fluid element. The first term represents the local
rate of change of T at a particular point and the second term
represents the change in T as a result of advection of fluid from
one location to other. Since we are considering fully developed
flow at low Reynolds number, the advective term has
contribution only from the streamwise velocity u.
Figure 9 shows the variation in temperature profile of the
fluid with time as it flows through the channel. The spatial
variation of temperature with flow rate being negligible, the
total derivative or the material derivative of temperature varies
linearly with flow rate.
The ramp rate of a zone was calculated as the average rate
of change of temperature moving from the zone to the next
zone. The residence time was calculated as the average time for
which the fluid remains in a particular zone. Their variations
with mean velocity are plotted in Fig. 10. The ramp rate (being
the average of material derivative) under steady state conditions
depends on the mean flow rate and the spatial temperature
distribution (Eqn. 4). The spatial temperature distribution is
controlled by the thin film heaters geometry, their spatial

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arrangement and the heat flux dissipated by them. The design

presented here creates temperature distribution which helps in
getting higher ramp rates at reasonable volume flow rates (Fig.
10). The residence time of the fluid in a particular zone varies
inversely with flow rate (Fig.10). Hence a trade off exists
between ramp rate and residence time. Addition of nucelotides
during the extension phase of PCR is processive, as the Taq
polymerase enzyme replicating the DNA sequence adds bases to
the 3 end of the sequence at a rate of 10-60 bases s-1. Hence,
longer replication sequences require longer extension times,
achieved by reducing the linear flow rate across the zones.

95
90

Temperature(C)

85
80
75
70

u=0.001 m/s

65

u=0.002 m/s
u=0.003 m/s

60

u=0.005 m/s
55

u=0.0005 m/s

50
0

20

40

60

80

100

120

Time(s)

Fig.9: Variation of temperature with time (as experienced

by a fluid particle) for different flow rates
24
21
Zone A ramp rate

18
15

Zone B ramp rate

12
Zone C ramp rate

9
6

Zone A residence
time

3
0
-3 0

0.001 0.002 0.003 0.004 0.005 0.006

Zone B residence
time

CONCLUSION
A detailed thermo-fluidic simulation has been developed to
model the temperature profile in a continuous flow microfluidic
PCR device. A single pass of the microfluidic device has been
simulated as a representative model for the entire microfluidic
device consisting of 30 passes. The above model was justified
by carrying out numerical simulation on a glass substrate having
10 sets of patterned heaters. The results show that the single
pass model is valid for understanding the temperature
distribution within the device when edge effects are neglected.
The heat flux values dissipated by the heaters were chosen to be
the same for the entire glass simulation and single pass
simulation. The results show a good correlation in spatial
temperature distribution for the glass regime in both
simulations.
Simulations clearly showed the dominance of conduction
over convection in the chosen range of flow and thermal
variables. Hence the most important factor in determining
temperature distribution is the spatial arrangement of heaters
and the heat flux dissipated by them. The results show that our
design meets the requirement of defined temperature zones for
PCR.
The temperature variation experienced by a fluid particle
moving through the channel depends on the volume flow rate
and the spatial temperature distribution. The simulations
suggest that higher ramp rates compared to the conventional
thermocyclers can be achieved in the continuous flow
microfluidic PCR device. An important trade off exists between
the ramp rate and the residence time. Different PCR reactions
have different residence time requirements and hence the
operating conditions need to be tuned for optimum
amplification.
We anticipate that numerical simulations for thermofluidic
modeling of microfluidic devices for applications like PCR will
serve as valuable tools in the physical microfluidic chip design
process, reducing the time required to fabricate functional
prototypes while maximizing reliability and robustness.
ACKNOWLEDGMENTS
This work was supported in part by a grant from the
Singapore/MIT alliance (SMA2-MST).
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Fig.10: Variation of ramp rate between the zones (C/s) and

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