Escolar Documentos
Profissional Documentos
Cultura Documentos
a r t i c l e
i n f o
Article history:
Received 11 April 2008
Received in revised form 14 August 2008
Accepted 21 October 2008
Available online 17 November 2008
Keywords:
Microuids
Microuid manipulation
Programmable control
Multi-path power supply
Microuidic chip
a b s t r a c t
A versatile programmable eight-path-electrode power supply (PEPS) system for manipulating microuids
of a complex microuidic chip has been developed. The PEPS system consisted of a single chip microprocessor as a central control unit and a personal computer (PC) as an upper computer, and the program
could be operated under Windows98/2000/XP. The voltage output of each electrode was in the range
of 0 to +8000 V (0.1% precision) while the current output was in the range of 0 to +999 A. The voltage
of eight electrodes could be operated either independently or synchronously by random combination of
any electrodes through switching. The voltage output modes were switch-off/oating, switch-on and
grounded and fast switched at ms-level between these modes, and run time (0.1 s precision) of these
modes could be controlled as desired. The PEPS system was conveniently for controlling ow rate and
direction of electroosmotic ow (EOF) in a chip network. Six electrodes were chosen to control the repeated
injection and separation of 1.0 105 M uorescein isothiocyanate (FITC) in a six-reservoir glass-based
chip. The relative standard deviation (R.S.D., n = 4, S/N = 10) of the repeated operation was 0.9% for the
reservation time (tR ) and 2.3% for the peak height, respectively.
2008 Published by Elsevier B.V.
1. Introduction
Microuidic chip or micrototal analysis system (TAS) provides
a new technology platform for the research in chemistry, biology, microengineering and other related microsystem elds [1,2].
Microuidic chip devices offer many attractive benets such as
reducing device size, reducing sample requirements and reagent
volumes which can reduce overall cost. Combining different functions on a single microchip is an important step toward maintaining
a completely closed system that can be fully automated, reduce
contamination and eliminate human intervention and error [3].
However, in order to realize all above the benets, it is imperative to solve innovatively the problem of automatic control of
the microuids. The microuid control was dependent on two
categories of micropump techniques, mechanical displacement
micropump technique and non-mechanical micropump technique
[46]. Mechanical micropumps [4] such as syringe pumps [7], pneumatic pumps [8,9] and piezoelectric pumps [10]were dened as
those that exert oscillatory or rotational pressure forces on the
working uid through a moving soliduid (vibrating diaphragm,
peristaltic, rotary pumps), or uiduid boundary (ferrouid, phase
Corresponding author. Tel.: +86 531 86180010; fax: +86 531 86180017.
E-mail address: tangb@sdnu.edu.cn (B. Tang).
0925-4005/$ see front matter 2008 Published by Elsevier B.V.
doi:10.1016/j.snb.2008.10.066
266
Table 1
Voltage output mode and time interval.
Time interval
Run time/s
Voltage output/V
V01
V02
V03
V04
V05
V06
V07
V08
1st
2nd
3rd
4th
2.5
5.0
10
20
1
300
1000
3000
1
300
1000
3000
10
500
1500
3500
10
500
1500
3500
50
700
2000
4000
50
700
2000
4000
100
900
2500
4500
100
900
2500
4500
5th
40
60
5000
Off
5000
Off
5500
Off
5500
Off
6000
Off
6000
Off
7000
Off
7000
Off
6tha
60
60
8000
G
8000
G
8000
G
8000
G
8000
G
8000
G
8000
G
8000
G
267
(SDPSS, MBL-20, ex = 473 nm, Changchun Xinchanye Guangdianjishu Co. Ltd., China); emission light lter was narrowband lter
with the wavelength in the range of 525 10 nm (Omega Optical,
Brattleboro, VT, USA); photomultiplier (PMT, R928, Hamamatsu,
Japan) was used as the uorescence detector; refrigeration digital
camera CCD (DS-5Mc-U2, Nikon, Japan) was used for the imaging
observation. The sampling frequency of CT-22 data acquisition card
(Shanghai Qianpu Shuju Co. Ltd., China) was 20 Hz. The connecting interface between the PEPS and the chip was also shown in
Fig. 1b, by dipping the 6-Pt-electrode (0.1 mm) of the PEPS into the
six-reservoir of the microuidic chip, respectively.
A stock solution of uorescein isothiocyanate (FITC, Sigma
Aldrich) was rst prepared in borax buffer solution (BBS,
20 103 M, pH 9.2) as 1.0 103 M, and then diluted to be
1.0 105 M sample solution by BBS. The BBS (20 103 M, pH 9.2)
was used as the running buffer solutions. All chemicals were of analytical reagent grade and doubly distilled water (Milli-Q, Millipore)
was used throughout. All the solutions were prepared by ltrating through membranes with 0.22 m sieve. The experiments were
performed at room temperature.
Table 2
Typical voltage output program for sample injection and separation.
Time section
1st (injection)
2nd (separation)
a
Switch-off.
Run time/s
20
70
Voltage applied/V
V01 (S)
V02 (SW)
V03 (B)
V04 (BW)
V07 (F1 )
V08 (F2 )
400
1400
0
1400
250
2000
380
0
240
Offa
240
Offa
268
The reported design took full usage of software for controlling the PEPS system, the process and the display functions of PC.
All the operations and displays would be completed within the
PC display windows, and only an on/off and a reset button were
remained in the exterior of power supply. The reported design
improved the instrumental stability, reduced the usage of hardware
and decreased the power supply and instrumental size.
3.1.2. Electrode voltage generation
The generating of electrode voltage was schematically shown
in Fig. 3. The preset voltage parameters were input through the
keyboard of the PC, and the input value was memorized into the
random access memory (RAM). The input value was transformed
to be binary numeral (for example, 110101100110) according to the
preset voltage range of PEPS program software, and the number was
transferred to SCM by serial port. Then, the numeral memorized in
the RAM was transferred to the D/A. Based on the reference voltage
value, D/A transformed the number to be relevant standard 05VDC
simulate signal at s level. The signal could control the DCDC module to output the corresponding voltage (Vo ) at ms level after it
was adjusted using amplier (equal to the voltage input value from
keyboard). These DCDC converters modules used an input voltage range between 0 and +5 V and voltage output between 0 and
+8000 V and a maximum current output of 1000 A. These specications are able to meet the power requirements at the microchip
scale.
269
Fig. 4. (a) Schematic diagram of voltage output mode for each electrode; (b) time sequence for SCM controlling the voltage output. Vo , voltage output; DCDC, high-voltage
module; W1 W2 , W3 W4 , control winding of grounded and oating of voltage switching relays, respectively; VIN , input voltage of DCDC; VJ , VK voltage control of W1 W2 ,
W3 W4 , respectively.
270
Table 3
The experimental results for PEPS output.
Electrode
output
Voltage
range (V)
Current
range (A)
Voltage
stability (%)
Run time
precision (s)
V01
V02
V03
V04
V05
V06
V07
V08
08002
08003
08008
08007
08006
08006
08005
08003
0999
0999
0999
0999
0999
0999
0999
0999
0.025
0.038
0.1
0.088
0.075
0.075
0.063
0.038
0.097
0.096
0.099
0.098
0.097
0.093
0.096
0.091
On
13
12
12
11
13
14
14
13
47
46
48
44
47
48
49
43
9.7
9.2
10
9.1
10
10
9.8
10
Voltage display
error (%)
0.13
0.14
0.16
0.18
0.19
0.17
0.15
0.17
Current display
error (%)
0.53
0.55
0.57
0.58
0.59
0.56
0.54
0.59
(3) add de-dipole capacitance at the input power supply of the PEPS
system to decrease high-frequency interferences;
(4) avoid the grounded/oating switching relays from highvoltage switching (Fig. 4b) and cancel the onoff switching
interferences;
(5) use a watch-dog circuit to avoid the SCM from status of a dead
running cycle and/or a departure and to prevent SCM from
out of control status that possibly lead illegal operation of the
controlled bit;
(6) moreover, optimize the distribution of the electric board, for
example, to separate the SCM and relay as far as possible that
decrease the conduct interference.
3.2. Evaluation of PEPS
The experimental results for PEPS system were shown in Table 3.
The results indicated that the experiment parameters such as
electrode path (18 path), voltage output mode for each electrode (switch-off/oating, on and grounded), time section
(16 section), run time (09999 s) and repeated running time
(09999 times) could be randomly preset as desired. The voltage
output of the eight electrodes could be operated synchronically
according to time section preset and the voltage mode for each electrode could be automatically controlled and quickly transformed
without any interference. For each electrode, the parameters such
as the status of voltage mode, the voltage output, curves of current output vs time were all real-time displayed at the same time.
When the output load of resistance changed with 200%, the voltage output and current output were in the range of 0 to +8000 V
and 0 to +999 A, respectively. The precision of voltage output and
the run time for PEPS were less than 0.1% and 0.1 s, respectively,
the display precision of voltage output and current output were
less than 0.2% and 0.6%, respectively, and the switching time of
switch-off/oating, on and grounded output mode was less
than 15 ms, 50 ms and 10 ms, respectively.
The characteristics such as eight electrodes (operated independently for single electrode or output synchronously for multiple
electrodes combination), programmable control the voltage output
and running time, and output stable, indicated that the PEPS system
could conveniently and automatically control the ow rate and the
direction of uids in the microchannel network, which could be
easily realized by randomly regulating the electric eld strength
and direction applied in the channel network.
3.3. PEPS applied for chip CE
3.3.1. Choice of electrode voltage
The optimal voltage output of the electrode applied in the reservoirs could control the process of chip CE injection and separation
with high efciency [24]. The pinched sample injection, electroki-
271
VB /RB + VF1 /RF1 + VS /RS + VF2 /RF2 + VBW /RBW + VSW /RSW
1/RB + 1/RF1 + 1/RS + 1/RF2 + 1/RBW + 1/RSW
(3)
and assumed that the cross-sectional area and the electrolyte in the
channel are the same, and Eq. (3) is
VC =
VB /LB + VF1 /LF1 + VS /LS + VF2 /LF2 + VBW /LBW + VSW /LSW
1/LB + 1/LF1 + 1/LS + 1/LF2 + 1/LBW + 1/LSW
(4)
Vi VC
Li
(5)
vieo = eo Ei =
eo (Vi VC )
Li
(6)
viep = ep Ei =
ep (Vi VC )
Li
(7)
Fig. 6. (a) Schematic diagram of voltages applied to the six reservoirs of the glassbased chip at injection step and the movement of EOF. (b) EER of microchannel
network. Thin lines, the external electrical connections and applied voltages; S,
sample reservoir; SW, sample waste reservoir; B, buffer reservoir; BW, buffer waste
reservoir; F1 , F2 , focus reservoir.
Vi VC
Ri
(1)
(2)
(8)
272
Fig. 7. The sample streamline in cross, C, using pinched injection method. (a) Injection step; (b) separation step.
The preset parameters of PEPS system for controlling FITC chipbased CE operations such as injection, separation were
(1) injection step, the voltages value applied on reservoirs of S, SW,
B and BW (V01 , V02 , V03 , V04 ) was kept invariable according to
the program listed in Table 2, and the focusing voltage value of
F1 and F2 (V07 , V08 , V07 = V08 ) was set as 240, 260, 280 and 300 V,
respectively; In this work, the volume of cross C was estimated
as 140.6 pL, as shown in Fig. 7a, the sampled volume was one
third of the above volume, i.e. 46.9 pL;
(2) separation step, the voltage value applied on reservoirs of S, SW,
B, BW, F1 and F2 was kept invariable according to the program
listed in Table 2.
The results detected by LIFD were shown in Fig. 8. From Fig. 8a
and b, the voltage change applied on the reservoirs of two offset
channel could affect the sample volume and nal sample peak (peak
height and peak area). The reason of the focus voltage affect the
sample volume was that the focused voltage change would change
the ow rate and thereby change the volume ratio as well the ow
shape of the two phases (the running buffer and the sample solution) [29], and further change the stored sample volume in the
cross, C, and nally the width and location of sample in the sampling
channel could be controlled indirectly. The higher of the voltage
applied and the narrower sample ow. Under these conditions, the
sampling volume was the function of focused voltage, sampling
time, sampling volume (in the cross, C) and running buffer ow
rate. Hence, combining the optimal design of the microuidic structure with the precise control and steady output and run time could
adjust the sample volume. The voltage output program of the PEPS
system in Table 2 was used for controlling the operation of the FITC
CE sample injection and separation based on above observation and
the detection of LIFD.
3.3.3. Continuous control injection/separation operation
According to the voltage program listed in Table 2, PEPS system was used for continuously controlled FITC injection/separation
operation four times and detected by LIFD, the results were shown
in Fig. 9. We could conclude that the voltage with synchronous
switch and steady output of PEPS system in each reservoir (S, SW,
B, BW, F1 and F2 ) can automatically realize the continuous injection and separation of chip-based CE operation, and also ensure
the relative standard deviation (R.S.D., n = 4, S/N = 10) of the analysis results with 0.90% for the reservation time (tR ) and 2.3% for the
peak height, respectively.
The main reason for this was, in the sample injection step,
the voltage in the reservoirs (S, B, BW, F1 and F2 ) was all
higher than that at the cross node, C (about 230 V according
to Eq. (4)) and the voltage in the sample waste reservoir, SW,
was the lowest (V02 = 0 V, grounded). The distribution of electric eld strength between the six reservoirs and cross, C, was:
ECSW > ESC > EBC /EBWC > EF1C /EF2C . Hence, the conuent ows
of the major ow from the sample reservoir, S, and minor ows
running buffer reservoirs, F1 and F2 , forming three-layer parallel
laminar ow, and then the uid owed into SW after passing the
cross; the buffer from B and BW compressed the sample ow at
the cross, C, which reduced the pervasion accumulation when the
sample was injected into the separation channel (Fig. 7a). It should
be pointed out that the liquid at lower ow velocity in microchannel formed a laminar ow, and the advection effect at the interface
273
Fig. 8. (a) Inuence of focusing voltage on sample volume and corresponding sample peak; (b) variations of sample peak height and sample peak area vs focusing
voltage.
[1] G.M. Whitesides, The Origins and the future of microuidics, Nature 442 (2006)
368373.
[2] P.S. Dittrich, K. Tachikawa, A. Manz, Micro total analysis systems. Latest
advancements and trends, Analytical Chemistry 78 (2006) 38874908.
[3] A. Wolff, I.R. Perch-Nielsen, U.D. Larsen, P. Friis, G. Goranovic, C.R. Poulsen,
J.P. Kutter, P. Telleman, Integrating advanced functionality in a microfabricated
high-throughput uorescent-activated cell sorter, Lab on a Chip 3 (2003) 2227.
[4] D.J. Laser, J.G. Santiago, A review of micropumps, Journal of Micromechanics
and Microengineering 14 (2004) R35R64.
[5] L.X. Chen, J. Choo, B. Yan, Microfabricated electrokinetic ow pump and its
related techniques: a potential promising drug delivery technique, Expert Opinion on Drug Delivery 4 (2007) 119129.
[6] L.X. Chen, S. Lee, J. Choo, E.K. Lee, Continuous dynamic ow micropumps for
microuid manipulation, Journal of Micromechanics and Microengineering 18
(2008) 013001.
[7] J. Jung, L.X. Chen, S. Lee, S. Kim, G.H. Seong, J. Choo, E.K. Lee, C.H. Oh, S. Lee,
Fast and sensitive DNA analysis using changes in the FRET signals of molecular
beacons in a PDMS microuidic channel, Analytical and Bioanalytical Chemistry
387 (2007) 26092615.
274
[8] M.A. Unger, H.P. Chou, T. Thorsen, A. Scherer, S.R. Quake, Monolithic microfabricated valves and pumps by multilayer soft lithography, Science 288 (2000)
113116.
[9] J.W. Munyan, H.V. Fuentes, M. Draper, R.T. Kelly, A.T. Woolley, Electrically actuated, pressure-driven microuidic pumps, Lab on a Chip 3 (2003)
217220.
[10] S. Kar, S. McWhorter, S.M. Ford, S.A. Soper, Piezoelectric mechanical pump with
nanoliter per minute pulse-free ow delivery for pressure pumping in microchannels, Analyst 123 (1998) 14351441.
[11] J. Atencia, D.J. Beebe, Magnetically-driven biomimetic micro pumping using,
Lab on a Chip 4 (2004) 598602.
[12] L.X. Chen, J.P. Ma, F. Tan, Y.F. Guan, Generating high-pressure sub-microliter ow
rate in packed microchannel by electroosmotic force: potential application in
microuidic systems, Sensors and Actuators B 88 (2003) 260265.
[13] L.X. Chen, H.L. Wang, J.P. Ma, C.X. Wang, Y.F. Guan, Fabrication and characterization of a multi-stage electroosmotic pump for liquid delivery, Sensors and
Actuators B 104 (2005) 117123.
[14] B. Anders, S. Detlef, P.K. Jrg, B. Henrik, AC electroosmotic pump with bubblefree palladium electrodes and rectifying polymer membrane valves, Lab on a
Chip 6 (2006) 280288.
[15] P. Woias, Micropumpspast, progress and future prospects, Sensors and Actuators B 105 (2005) 2838.
[16] E.S. Roddy, H.W. Xu, A.G. Ewing, Sample introduction techniques for microfabricated separation devices, Electrophoresis 25 (2004) 229242.
[17] C.D. Garca, Y. Liu, A. Paul, C.S. Henry, Versatile 3-channel high-voltage
power supply for microchip capillary electrophoresis, Lab on a Chip 3 (2003)
324328.
[18] P.D.I. Fletcher, S.J. Haswell, X.L. Zhang, Electrokinetic control of a chemical
reaction in a lab-on-a-chip micro-reactor: measurement and quantitative modeling, Lab on a Chip 2 (2002) 102112.
[19] Z.Y. Wu, N. Xanthopoulos, F. Reymond, J.S. Rossier, H.H. Girault, Polymer microchips bonded by O2 -plasma activation, Electrophoresis 23 (2002)
782790.
[20] Q.L. Li, B. Tang, H.X. Tian, Chinese Patent 200510104343.3, 2005.
[21] X.M. Zhou, D.Y. Liu, Y.T. Zhong, Z.P. Dai1, D.P. Wu, H. Wang, Y.G. Du, Z.A. Xia, L.P.
Zhang, X.D. Mei, B.C. Lin, Determination of SARS-coronavirus by microuidic
chip system, Electrophoresis 25 (2004) 30323039.
[22] Y.C. Sun, Application of AT89 Catena Single Chip Microcomputer, Tsinghua University Press, Beijing, 2005.
[23] D.S. Malik, Data Structures Using C++, Tsinghua University Press, Beijing, 2003.
[24] L.M. Fu, C.H. Lin, Numerical analysis and experimental estimation of a lowleakage injection technique for capillary electrophoresis, Analytical Chemistry
75 (2003) 57905796.
[25] L.M. Fu, R.J. Yang, G.B. Lee, Electrokinetic focusing injection methods on
microuidic devices, Analytical Chemistry 75 (2003) 19051910.
[26] P.D.I. Fletcher, S.J. Haswell, X. Zhang, Electrical currents and liquid ow rates in
micro-reactors, Lab on a Chip 1 (2001) 115121.
[27] M.B. Christopher, H.D. Robert, Electroosmotic ow in channels with step
changes in zeta potential and cross section, Journal of colloid and Interface
Science 270 (2004) 242246.
[28] L.X. Chen, G.A. Luo, K.H. Liu, J.P. Ma, B. Yao, Y.C. Yan, Y.M. Wang, Bonding of glassbased microuidic chips at low- or room-temperature in routine laboratory,
Sensors and Actuators B 119 (2006) 335344.
[29] P.J.A. Kenis, R.F. Ismagilov, G.M. Whitesides, Microfabrication inside capillaries
using multiphase laminar ow patterning, Science 285 (1999) 8385.
[30] B.H. Weigl, P. Yager, Microuidicsmicrouidic diffusion-based separation and
detection, Science 283 (1999) 346347.
[31] B. Ma, X.M. Zhou, G. Wang, H.Q. Huang, Z.P. Dai, J.H. Qin, B.C. Lin, Integrated
isotachophoretic preconcentration with zone electrophoresis separation on
a quartz microchip for UV detection of avonoids, Electrophoresis 27 (2006)
49044909.
[32] W. Wang, X.Q. Xu, Q. Bin, J.M. Ling, G.N. Chen, A new method for fabrication of
an integrated indium tin oxide electrode on electrophoresis microchips with
amperometric detection and its application for determination of synephrine
and hesperidin in pericarpium citri reticulatae, Electrophoresis 27 (2006)
41744181.
[33] B. Ma, X.M. Zhou, G. Wang, Z.P. Dai, J.H. Qin, B.C. Lin, A hybrid microdevice with
a thin PDMS membrane on the detection window for UV absorbance detection,
Electrophoresis 28 (2007) 24742477.
Biographies
Qingling Li received his B.Sc. in electrical engineering from Shandong Industrial
University in 1984. From 1984 to 2005, he was an engineer and senior engineer in
Shandong Chemical Engineering Institute. Since 2005, he has been a senior engineer in College of Chemistry at Shandong Normal University. His research interests
include capillary electrophoresis, microuids delivery & control and microuidic
detection.
Hui Zhang received her B.Sc. in chemistry education from Shandong Normal University in 2001, and a M.Sc. in analytical chemistry from Shandong Normal University
in 2004. Now, she is a Ph.D. candidate in Shandong Chemical Engineering Institute.
Her research interest is focused on ow injection analysis.
Yan Wang received her B.Sc. and M.Sc. in optical analytical chemistry from Shandong
University in 1990 and in 1993, respectively. Since 1993, she is an associate professor
in College of Chemistry at Shandong Normal University. Her research interest is
focused on capillary electrophoresis.
Bo Tang received his B.Sc. degree in Applied Chemistry from China University of
Geosciences in 1988, and a M.Sc. and a Ph.D. in optical analytical chemistry from
Nankai University in 1991 and in 1994, respectively. Since 1994, he is an associate
professor and professor in College of Chemistry at Shandong Normal University. His
research interests include optical analysis, uorescence nanoprobe and molecular
identication.
Xin Liu received her B.Sc. in Environment Engineering from North University of
China in 2006. Since 2006, she is a Ph.D. candidate in College of Chemistry at Shandong Normal University. Her research interests include microchip electrophoresis
and microuidic detection.
Xiaocong Gong received her B.Sc. in chemistry education from Linyi Normal University in 2006. Since 2006, she is a graduate student in College of Chemistry at
Shandong Normal University. Her research interest is focused on micrototal analysis.