Welcome to Scribd, the world's digital library. Read, publish, and share books and documents. See more
Download
Standard view
Full view
of .
Look up keyword
Like this
1Activity
0 of .
Results for:
No results containing your search query
P. 1
01616665

01616665

Ratings: (0)|Views: 3|Likes:
Published by Shaykkh Shahbaawz
zdxfbbbbbbbbbbbb
zdxfbbbbbbbbbbbb

More info:

Categories:Types, Research
Published by: Shaykkh Shahbaawz on Aug 01, 2013
Copyright:Attribution Non-commercial

Availability:

Read on Scribd mobile: iPhone, iPad and Android.
download as PDF, TXT or read online from Scribd
See more
See less

08/01/2013

pdf

text

original

 
 Abstract 
 —This paper presents a theoretical and experimentalinvestigation of MEMS thermal biosensors in flow-throughmeasurements of metabolites. A model is developed to considerconvective heat transfer effects and enzyme kinetics using theMichaelis-Menton theory. Numerical solutions from the modelare compared with experimental data obtained from aprototype MEMS thermal biosensor. Satisfactory agreement isfound between the theoretical and experimental results,indicating that the model is useful for designing MEMS thermalbiosensors with optimized performance.
I.I
 NTRODUCTION
MEMS thermal biosensors, which measure theconcentrations of metabolites (e.g., glucose) by theheat released from enthalpy changes of associated enzymaticreactions, have important applications in metabolite detectionand monitoring [1-3]. However, the behavior of such sensorshas not been adequately analyzed, hindering optimal sensor design and exploration of new applications. While heattransfer effects in MEMS thermal biosensors have beenmodeled [4, 5], this is not sufficient to determine the overallsensor performance because of the omission of the kinetics of enzymatic reactions. We previously reported a model for MEMS thermal biosensors operating in flow-injection as wellas flow-through operation modes [6]. However, convectiveheat transfer effects in the device were not consideredadequately. In addition, the binary enzyme kinetics modelused is not valid when the substrate concentration is aroundsaturated. Consequently, while this earlier model generallyagrees with the experimental data, significant errors exist. Toaddress these issues, we pursue a systematical study of thedevice by considering convective heat transfer effects, whichoccur in the porous media of enzyme-attached beads packedinside the device, and the more accurate Michaelis-Mentonenzyme kinetics model. Numerical simulations have been performed with FEMLAB and a prototype MEMS thermal biosensor has been fabricated and characterized for glucosedetection. We have found that simulation results from thecurrent model quantitatively agree with the experimental data,indicating that convective heat transfer effects significantlyinfluences the behavior of the device. Based on the model,optimal designs of MEMS thermal biosensors can beefficiently carried out.
L. Wang is with the Mechanical Engineering Department, CarnegieMellon University, 5000 Forbes Ave., Pittsburgh, PA 15213 USA (phone:412-2682514; e-mail:liw@andrew.cmu.edu).Q. Lin is with the Mechanical Engineering Department, Carnegie MellonUniversity, 5000 Forbes Ave., Pittsburgh, PA 15213 USA (e-mail:qlin@andrew.cmu.edu).
II.MEMST
HERMAL
B
IOSENSORS
Fig. 1 illustrates a MEMS thermal biosensor for flow-through measurement. The device (Fig. 1a) primarilyconsists of two identical microfluidic chambers (i.e. sampleand reference chambers) by bonding a PDMS sheet withmicrofluidic features onto the chip surface. The chambers areconnected to their respective inlets and outlets bymicrochannels and contain beads coated with enzymes (Fig.1b). The beads are trapped in the chambers by a narrow gapformed by a weir structure and chip surface (Fig. 1b). Eachchamber contains a freestanding thin polymeric membrane asa mechanical support and sensing part. A thermopile isintegrated on-chip with its hot and cold junctions, formed between chromium and nickel, respectively on themembranes in the sample and reference chambers to measurethe temperature difference between them. Fabricated fromSU-8 photoresist, the thin membranes have a low thermalconductivity, which results in excellent thermal isolation aswell as minimized thermal mass of the biosensor structure.Fig. 2 shows a microscopic image of the sensor chip and animage of the packaged device.
(a)(b)
Fig. 1. MEMS thermal biosensor schematic: (a) top view, and (b)cross-sectional view.
Glucose oxidase and catalase enzymes are immobilized(using streptavidin-biotin chemistry) on polystyrene beads of 9.77
P
m nominal diameter, which are packed on the sensor membrane for measurements of glucose. The thermopileoutput voltage is measured to detect the enzymatic reaction of glucose. During measurements, the glucose solutions are
Theory and Experiments of MEMS Thermal Biosensors
Li Wang and Qiao Lin
M
ReferencechamberOn chipheaterMetalthermopileBlock weirInletSamplechamberAccesschannelsOutletA
 
BC
PDMScoverBonding padMetal thermopileOn-chip heaterInletOutletChamberMembraneChannelMembraneBeadsWeirPDMScoverBonding pad
 
Metal thermopileInletOutletChamberMembraneChannelMembraneBeadsWeir
Proceedings of the 2005 IEEEEngineering in Medicine and Biology 27th Annual ConferenceShanghai, China, September 1-4, 2005
0-7803-8740-6/05/$20.00 ©2005 IEEE.
1301
 
 pumped through the sample chamber and the buffers for reference chamber. The temperature difference between thesample and reference chambers due to the heat differencereleased from the enzymatic reactions reflects theconcentration difference between the sample and buffer solutions. The temperature difference is measured by thethermopile and used to obtain the concentrations of thesample substrate. To obtain experimental data to verify theMEMS thermal biosensor model, we have performed theexperiments by fixing the glucose concentration and varyingflow rates at which samples and buffers are introduced.
PolymermembraneOn chip heaters
100 µm
Metalther
 
mopile
TubingChamber
Fig. 2. Images of a (a) microscopic view of bare and (b) packaged MEMSthermal biosensor.
III.MEMS
THERAL
B
IOSENSOR 
M
ODELING
Our MEMS thermal biosensor model is in Fig. 3, whichshows the cross-section schematic of the sensor chamber along the fluid flow. In this 2D problem, substrate andreference solutions flow through the chambers packed withenzyme-functionalized beads. The kinetics of enzymaticreactions of the substrate, forced mass and heat convection inthe fluid and heat conduction in the membranes areconsidered. The membrane center is the location of hot junctions of the thermopile temperature sensor whose voltagegives the temperature change due to the enzymatic reactions.The thermopile thickness is ignored, as it is far less than the polymer membrane thickness. However, the conduction heatloss via the thermopile lines is included in terms of theaverage thermal conductivity of the membranes. With the lowthermal conductivity and large thickness of the PDMS cover compared with the thin membrane, the upper boundary of thechannel is assumed to be thermally insulated. Since thedevice inlet and outlet are located far away from the chambers,the fluid flow in the chambers can be regarded as being fullydeveloped through a porous media formed by the packed beads. Then in the Darcy flow regime [7] the longitudinalvolume-average velocity
u
is uniform over the channel crosssection, which implies that
u=-Q/2a
, where
Q
is the flow rate per unit channel width.Forced convection of heat and substrate mass in the fluid isgoverned by [7]
2222
()()
 p p f 
qT T T ut x x y c
 U 
wwwwwwww
(1)
2222
()
 s s s s s p
C C C C du Dt x x y d
wwwwwwww
(2)
Substrate
L2a
 
 x 
Beads
Q
T
T
Polymeric membraneTemperature sensorSubstrate
L2a
 
 x 
Beads
Q
T
T
Polymeric membraneTemperature sensor
Fig. 3.
Model of MEMS thermal biosensor in flow-through mode.
Where
/()
 p p
c
D O
is thermal diffusivity of the porousmedia,
 p
q q
is the average density of power generated inthe chamber,
is the chamber temperature,
 f 
q
is thermal power density in the substrate solution,
is porosity of the porous media,
()
 f 
c
 U 
is the heat capacity of the solution,
 s
is the substrate concentration,
 p
 D
is the substratediffusivity and
 p
is the average thermal conductivity of  porous media. Heat conduction in the membrane is governed by
22
|0
mm p y a
 x y
O

wwww
(3)
|
m y a
T

(4)where
m
and
m
are the average temperature over themembrane thickness
(
t<<L
) and average thermalconductivity of the membrane, respectively.Heat is released from the enzymatic reactions, whosekinetics is governed by the Michaelis-Menten equation [8]
2
 s e s M s
dC k C dt K C 
(5)
2
 s e s f  M s
dC Hk C q dt K
''
(6)where
2
is the turnover number of the enzyme,
 K 
is theMichaelis constant,
e
is the enzyme concentration and
 H 
'
is the reaction enthalpy change. Introducing dimensionless parameters
*0
~/,
 s s
C C
*
~/,
amb
T T
*
~/,
 x x L
*
~/2,
 y y a
*2
~/(/),
 p
t t L D
*0
~/
 M
 K K
and
*
~/
d d amb
T T
where
o
and
amb
are initial substrate concentration and ambienttemperature, and combining Eqs. (1,2,3,5,6), we can thenformulate the problem in dimensionless form
**2*2**221***2*2**
()
 s s s s sa M s
C C C C r L Bt x x y K
wwwwwwww
(7)
***2*2*202***2*2**
()()
 s M s
T T T r r Bt x x y K
wwwwwwww
(8)
*
2*2*1*2*2
|02
 pm ym
L  x at y

wwww
(9)where the dimensionless parameters
2
/
 p
r uL D
is massPeclet number showing relative importance of the massconvection rate vs. diffusion rate,
0
/
 p p
r D
shows the
1302
 
relative importance of thermal conduction vs. mass diffusioneffects,
2120
/
e p
 B L k C D
is the ratio of the substrateconsumption rate vs. mass diffusion rate,
2220
/()
e p
 B HL k C D T c
M
'
is the ratio of heat production ratefrom reaction vs. heat conduction rate, and
a L L
a
2/
is theratio of the length and height of the chamber. The problem isclosed by the following boundary and initial conditions.
***************
(0,,)1(1,,)01(,,)021(,,)02
 s s s s
C y  y  x x  y x  y
wwwwww
***************
(0,,)1(1,,)01(,,)02(0,)1(1,)1
mm
T y  y  x x  yT T
wwww
******
(,,0)1(,,0)1
 s
T x yC x y
We then carry out the numerical simulations with the parameters in Table 1 for flow-through measurements withdifferent substrate concentrations and flow rates.
T
ABLE
1.T
YPICAL PARAMETERS OF
MEMS
THERMAL BIOSENSORS FOR SIMULATION OF DIFFERENT SUBSTRATE CONCENTRATIONS AND FLOW RATES
 D
 p
(m
2
/s)
 ȡ
c)
 f 
(J/ul.K)
e
(M) Width (um)9.2E-10 0.0042 1.925E-5 2000
Ȝ
 p
(W/K.m)
2a
(um)
 L
(um)0.4764 0.4 200 2000
 ǻ
 H 
(KJ/mol)
 K 
 M 
(mM)
 Ȝ
m
(W/K.m)
2
(s
-1
)180 1 0.2 1000
IV.
RESULTS AND
D
ISCUSSION
To evaluate the significance of heat convection compared toheat conduction, we can calculate dimensionless thermalPeclet number Pe
=2au/ 
Į
 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 thesame order as conduction effects, and therefore should beconsidered for our problem. We have performed 2Dnumerical simulation using the FEMLAB finite elementanalysis package [9]. Figs 4 and 5 show typical calculatedfluid temperature and glucose concentration distributionsinside the chamber. It is observed that the reaction starts fromthe chamber entrance (located on the left) and the substrateconcentration drops from there, resulting in the release of heatand rise of temperature along the chamber. We then take thesimulated temperatures at membrane center corresponding tothe thermopile junctions, and calculate the thermopile voltagevalues by multiplying the thermoelectric coefficient (1.85mV/K). By plotting the thermopile output voltage versus flowrates or pumped substrate concentrations in Figs. 6-7, wecompare the results from current model with the experimentaldata and simulation results from the previous model [6].
Fig. 4. Temperature map in the chamber from FEMLAB simulation (initialsubstrate concentration: 31.25 mM)Fig. 5. Concentration map in the chamber from FEMLAB simulation (initialsubstrate concentration: 31.25mM)
 
0246801234
Flow Rate (ml/h)
   D  e  v   i  c  e   O  u   t  p  u   t   (
P
   V   )
Ref. [6]ModelExperiment
Fig. 6. Device output at different flow rates (glucose concentration: 31.25mM)
In Fig. 6, we can observe that results from the currentmodel are in much improved agreement with theexperimental data in the entire flow rate range. When flowrates are smaller than 0.05 ml/h, the current model is close tothe experimental as well as the previous model. This isexplained by the small Pe value (<0.07), which implies thatconvective heat transfer effects are almost negligible. Atlarger flow rates, the heat loss via convective heat transfer ismore pronounced as Pe becomes larger. The current model,which considers these effects, gives lower thermopile voltage
ChamberMembraneMembraneChamber
1303

You're Reading a Free Preview

Download
scribd
/*********** DO NOT ALTER ANYTHING BELOW THIS LINE ! ************/ var s_code=s.t();if(s_code)document.write(s_code)//-->