Académique Documents
Professionnel Documents
Culture Documents
I. I NTRODUCTION
XUE AND YAN : GLASS-BASED CONTINUOUS-FLOW PCR CHIP WITH A PORTABLE CONTROL SYSTEM FOR DNA AMPLIFICATION
TABLE I
C OMPARISON A MONG T HREE T YPES OF PCR D EVICES
1915
2.8 cm
2.7 mm
4 mm
Minimum
required
sample
volume
Reaction
time
(30 cycles)
Cost
of
device
Integration
with other
micro-chips
Conventional
PCR machine
20 l
30-60 min
High
No
Microfabricated
continuous-flow
PCR chip
< 10 l
2-30 min
Low
Easy
Microchamber
PCR chip
10-50 l
15-30 min
Low
Difficult
1 cm
NiCr heater
Fig. 3.
Ni thermometer
Not to scale
Cover-glass
(a)
(b)
(c)
(d)
Substrate-glass
2.5 cm
DNA denaturation zone
1 cm
1 cm
1 cm
DNA annealing zone
Sample inlet
Fig. 2.
Sample outlet
Fig. 4. Thermal distribution analysis of continuous-flow PCR chip. Thicknesses of glass are (a) 0.6 mm, (b) 1.4 mm, and (c) 2.2 mm. (d) Cross-sectional
thermal distribution of 1.4-mm-thick glass.
1916
Mask
Photoresist
Cr
Glass
SiN
SiO2
Silicon
(a)
(f)
NiCr Ni NiCr
(b)
(g)
(c)
Glass lid
Glass substrate
(d)
Glass lid
Glass substrate
(e)
(h)
Not to scale
Fig. 5.
Fabrication process of continuous-flow PCR chip. (a)(e) Glass
fabrication: (a) Cr patterning, (b) Cr etching, (c) glass etching, (d) protection
layers removal, (e) thermal bonding of two glasses to form sealed channel.
(f)(g) Silicon fabrication: (f) SiN deposition, (g) Ni thermometer and NiCr
heater patterning. (h) Bonding of glass and silicon.
Amplifier and
A/D
LCD display
95 C
700
600
Temperature (C)
Fig. 7.
Micro
processer
72 C
500
55 C
Keypad control
400
PE coupler
and amplifier
100
Fig. 8.
0
0
Fig. 6.
100
200
600
700
C. Fabrication
D. Temperature-Control System
XUE AND YAN : GLASS-BASED CONTINUOUS-FLOW PCR CHIP WITH A PORTABLE CONTROL SYSTEM FOR DNA AMPLIFICATION
1917
140
Data window
T/C
120
110
100
90
80
70
60
50
40
30
20
10
00
Temperature (C)
120
100
80
5
Time/min
60
40
Fig. 11. PCR chip testing setup with control circuit and PC interface control.
20
0
10
Fig. 9.
Resistance (k)
95 C
72 C
55 C
20
30
Voltage (V)
40
50
0.70
0.68
0.66
0.64
0.62
0.60
0.58
0.56
0.54
0.52
0.50
0.48
Resistance 1
Resistance 2
Resistance 1 36 h later
Resistance 2 36 h later
20
40
60
80
Temperature (C)
100
1918
R EFERENCES
[1] H. Nagai, Y. Murakami, K. Yokoyama, and E. Tamiya, High-throughput
PCR in silicon based microchamber array, Biosensors Bioelectron.,
vol. 16, nos. 912, pp. 10151019, Dec. 2001.
[2] C. T. Wittwer, G. C. Fillmore, and D. J. Garling, Minimizing the
time required for DNA amplification by efficient heat-transfer to small
samples, Anal. Biochem., vol. 186, no. 2, pp. 328331, May 1990.
[3] E. T. Lagally, P. C. Simpson, and R. A. Mathies, Monolithic integrated
microfluidic DNA amplification and capillary electrophoresis analysis
system, Sensors Actuat. B, vol. 63, no. 3, pp. 138146, May 2000.
[4] M. A. Northrup, L. A. Christel, W. A. McMillan, K. Petersen, F.
Pourahmadi, L. Western, S. Young, A. I. Michael, H. G. David, and
J. S. John, A new generation of PCR instruments and nucleic acid
concentration systems, in PCR Applications. San Diego, CA: Academic,
1999, pp. 105125.
[5] Z. Q. Zou, X. Chen, Q. H. Jin, M. S. Yang, and J. L. Zhao, A novel
miniaturized PCR multi-reactor array fabricated using flip-chip bonding
techniques, J. Micromech. Microeng., vol. 15, no. 8, pp. 14761481,
Aug. 2005.
[6] K. Sun, A. Yamaguchi, Y. Ishida, S. Matsuo, and H. Misawa, A heaterintegrated transparent microchannel chip for continuous-flow PCR,
Sensors Actuat. B, vol. 84, nos. 23, pp. 283289, May 2002.
[7] T. Fukuba, T. Naganuma, and T. Fujii, Microfabricated flow-through
PCR device for underwater microbiological study, in Proc. Int. Symp.
Underwater Technol., 2002, pp. 101105.
Ning Xue (S11) received the B.S. and M.S. degrees in electrical engineering
from the Dalian University of Technology, Dalian, China, in 2005 and
2008 respectively. He has worked in the bioMEMS microfluidc devices for
his master research. He is currently pursuing the Ph.D. degree with the
Department of Electrical Engineering, University of Texas, Dallas.
He joined Micro-Nano Devices and Systems Laboratory, Microelectromechanical Systems (MEMS) Research Group, University of Texas at Dallas,
Richardson, TX, in 2009. His current research interests include MEMS fabrication, microfluidic device, bioMEMS for wireless implantable applications,
pressure sensors, and radio frequency (RF) MEMS of on-chip inductor and
capacitor.
Weiping Yan received the M.S. degree in physics and devices of semiconductors from Jilin University, Changchun, China, in 1975 and 1989, respectively.
She was with the Department of Electronic Science, Jilin University, from
1975 to 1990. She has been with the Department of Electronic Engineering,
Dalian University, Dalian, China, since 1990. Her current research interests
include the fabrication of the integrated biochip, design, and fabrication of
semiconductor sensors.