Theory and Experiments of MEMS Thermal Biosensors: Li Wang and Qiao Lin
Theory and Experiments of MEMS Thermal Biosensors: Li Wang and Qiao Lin
Theory and Experiments of MEMS Thermal Biosensors: Li Wang and Qiao Lin
c c c c
+ = + +
c c c c
(1)
2 2
2 2
( )
s s s s s
p
C C C C dC
u D
t x x y dt
c c c c
+ = + +
c c c c
(2)
Substrate
L
t
2a
y
x
Beads
Q
T
(6)
where
2
k is the turnover number of the enzyme,
M
K is the
Michaelis constant,
e
C
is the enzyme concentration and H A
is the reaction enthalpy change. Introducing dimensionless
parameters
*
0
~ / ,
s s
C C C
*
~ / ,
amb
T T T
*
~ / , x x L
*
~ / 2 , y y a
* 2
~ /( / ),
p
t t L D
*
0
~ /
M M
K K C
and
*
~ /
d d amb
T T T where C
o
and T
amb
are initial substrate concentration and ambient
temperature, and combining Eqs. (1,2,3,5,6), we can then
formulate the problem in dimensionless form
* * 2 * 2 * *
2
2 1 * * *2 *2 * *
( )
s s s s s
a
M s
C C C C C
r L B
t x x y K C
c c c c
+ = +
c c c c +
(7)
* * * 2 * 2 *
2 0 2 * * *2 *2 * *
( )
( )
s
M s
C T T T T
r r B
t x x y K C
c c c c
+ = + +
c c c c +
(8)
*
2 * 2 *
1 *2 *
2
| 0
2
p
m
y
m
T L T
x at y
=
c c
+ =
c c
(9)
where the dimensionless parameters
2
/
p
r uL D = is mass
Peclet number showing relative importance of the mass
convection rate vs. diffusion rate,
0
/
p p
r D o =
shows the
1302
relative importance of thermal conduction vs. mass diffusion
effects,
2
1 2 0
/
e p
B L k C D C =
is the ratio of the substrate
consumption rate vs. mass diffusion rate,
2
2 2 0
/ ( )
e p f
B HL k C D T c = A
is the ratio of heat production rate
from reaction vs. heat conduction rate, and
a L L
a
2 / =
is the
ratio of the length and height of the chamber. The problem is
closed by the following boundary and initial conditions.
* * *
*
* *
*
*
* *
*
*
* *
*
(0, , ) 1
(1, , ) 0
1
( , , ) 0
2
1
( , , ) 0
2
s
s
s
s
C y t
C
y t
x
C
x t
y
C
x t
y
=
c
=
c
c
=
c
c
=
c
* * *
*
* *
*
*
* *
*
* *
* *
(0, , ) 1
(1, , ) 0
1
( , , ) 0
2
(0, ) 1
(1, ) 1
m
m
T y t
T
y t
x
T
x t
y
T t
T t
=
c
=
c
c
=
c
=
=
* * *
* * *
( , , 0) 1
( , , 0) 1
s
T x y
C x y
=
=
We then carry out the numerical simulations with the
parameters in Table 1 for flow-through measurements with
different substrate concentrations and flow rates.
TABLE 1. TYPICAL PARAMETERS OF MEMS THERMAL BIOSENSORS FOR
SIMULATION OF DIFFERENT SUBSTRATE CONCENTRATIONS AND FLOW RATES
D
p
(m
2
/s) (c)
f
(J/ul.K) C
e
(M) Width (um)
9.2E-10 0.0042 1.925E-5 2000
p
(W/K.m) 2a (um) L (um)
0.4764 0.4 200 2000
H (KJ/mol) K
M
(mM)
m
(W/K.m) k
2
(s
-1
)
180 1 0.2 1000
IV. RESULTS AND DISCUSSION
To evaluate the significance of heat convection compared to
heat conduction, we can calculate dimensionless thermal
Peclet number Pe=2au/
p
, which characterizes the ratio of
heat convection and conduction effects. With a flow rate of
0.5 ml/h and using the parameters listed in Table 1, Pe=0.7,
which shows that convection heat transfer effects are of the
same order as conduction effects, and therefore should be
considered for our problem. We have performed 2D
numerical simulation using the FEMLAB finite element
analysis package [9]. Figs 4 and 5 show typical calculated
fluid temperature and glucose concentration distributions
inside the chamber. It is observed that the reaction starts from
the chamber entrance (located on the left) and the substrate
concentration drops from there, resulting in the release of heat
and rise of temperature along the chamber. We then take the
simulated temperatures at membrane center corresponding to
the thermopile junctions, and calculate the thermopile voltage
values by multiplying the thermoelectric coefficient (1.85
mV/K). By plotting the thermopile output voltage versus flow
rates or pumped substrate concentrations in Figs. 6-7, we
compare the results from current model with the experimental
data and simulation results from the previous model [6].
Fig. 4. Temperature map in the chamber from FEMLAB simulation (initial
substrate concentration: 31.25 mM)
Fig. 5. Concentration map in the chamber from FEMLAB simulation (initial
substrate concentration: 31.25mM)
0
2
4
6
8
0 1 2 3 4
Flow Rate (ml/h)
D
e
v
i
c
e
O
u
t
p
u
t
(
V
)
Ref. [6]
Model
Experiment
Fig. 6. Device output at different flow rates (glucose concentration: 31.25
mM)
In Fig. 6, we can observe that results from the current
model are in much improved agreement with the
experimental data in the entire flow rate range. When flow
rates are smaller than 0.05 ml/h, the current model is close to
the experimental as well as the previous model. This is
explained by the small Pe value (<0.07), which implies that
convective heat transfer effects are almost negligible. At
larger flow rates, the heat loss via convective heat transfer is
more pronounced as Pe becomes larger. The current model,
which considers these effects, gives lower thermopile voltage
Chamber
Membrane
Membrane Chamber
1303
predictions compared with the previous model [6] and is
more accurate.
In flow-through mode, part of the heat generated by the
enzymatic reaction is taken away by the flowing substrate
solution via forced convection, which is more pronounced at
larger flow rates. On the other hand, a larger flow rate
supplies more substrate to the reaction chamber, generating
larger thermal power. These are two competitive effects, and
therefore, an optimal flow rate exists that maximizes the
thermopile output. In the experiment, an optimal flow rate of
0.5 ml/h is observed, which is same as predicted by the
current model. In contrast, the previous model that ignores
convection effects is in error by 40% in the predicted optimal
flow rate.
Fig. 7 shows the simulated and experimental results of
device output when glucose solutions of different
concentrations are pumped through the chamber with a fixed
0.5 ml/h flow rate. We see that the simulated and
experimental thermopile output both increase when the
glucose concentration becomes larger. This can be attributed
to the small flow rate (Q=0.5 ml/h) we used in the
measurements. Flow rates can influence the extent of
completion of the enzymatic reaction inside the chamber.
When Q is small, the substrate has sufficient residence time in
the chamber to interact with the enzymes and therefore is
completely consumed. When Q becomes larger, the substrate
in the chamber is replenished before it is completely reacted.
The critical flow rate Q
c
=k
2
C
e
V/C
s
can be calculated by
comparing the residence time t
r
=V/Q and consumption time
t
c
= C
s
/k
2
C
e
of substrate solution in the reaction chamber. Here
we used a fixed flow rate Q=0.5 ml/h. This is smaller than the
critical flow rate Q
c
=1.77 ml/h when the glucose
concentration is 31.25 mM. The critical flow rate is even
larger for smaller glucose concentrations. Therefore, the
glucose solutions used in our experiment are all completely
consumed in the chamber and the reactions are limited by
substrate supply. This results in the increase of thermopile
output when the concentrations of supplied glucose solution
become larger.
The current model predicts that the device output is
nonlinear at higher glucose concentrations (Fig. 7). This
nonlinearity, which is not predicted by the previous model,
can be explained by the non-uniformity of substrate
consumption in the chamber. When the concentration is small,
the glucose solution is completely consumed near the
entrance to the chamber, and there is no reaction towards the
chamber exit. This results in non-uniform distributions of
reaction power density inside the chamber and significant
temperature non-uniformities, with the thermopile junctions
at a large distance from locations of maximal temperatures.
As the concentration increases, the substrate will be available
for reaction in a larger portion of chamber, resulting in
improved power and temperature uniformities. In this case,
the thermopile junctions will become closer to locations of
maximal temperature, and the thermopile signal will therefore
increase faster when the substrate concentration becomes
higher.
0
2
4
6
8
0 10 20 30 40
Glucose Concentration (mM)
D
e
v
i
c
e
O
u
t
p
u
t
(
V
)
Ref. [6]
Model
Experiment
Fig. 7. Device output at different glucose concentrations (flow rate: 0.5 ml/h)
V. CONCLUSION
We have conducted theoretical and experimental analysis of
MEMS thermal biosensors. Convective heat transfer effects
and Michaelis-Menton enzyme kinetics are included in the
model. Numerical solutions of the model have been
performed and compared with experimental data as well as
results from a previous model that does not include
convection effects. Satisfactory agreement between the
current model and experimental data has been observed.
Nonlinear behavior at larger rates in flow-through glucose
detection is also predicted.
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