IBE Annual Meeting, March IBE Annual Meeting, March 6 6 - - 9, 2008. Chapel Hill, NC 9, 2008. Chapel Hill, NC 1 1 Microfabricated Microfabricated Interdigitated Interdigitated Microelectrodes Microelectrodes - - Based Based Electrical/Electrochemical Impedance for Electrical/Electrochemical Impedance for Biological Detection Biological Detection Liju Liju Yang Yang Biomanufacturing Biomanufacturing Research Institute & Research Institute & Technology Enterprise (BRITE), Technology Enterprise (BRITE), Department of Pharmaceutical Science, Department of Pharmaceutical Science, North Carolina Central University, Durham, NC North Carolina Central University, Durham, NC 27707 27707
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IBE Annual Meeting, March IBE Annual Meeting, March 66--9, 2008. Chapel Hill, NC9, 2008. Chapel Hill, NC 11
MicrofabricatedMicrofabricated InterdigitatedInterdigitatedMicroelectrodesMicroelectrodes--Based Based
Electrical/Electrochemical Impedance for Electrical/Electrochemical Impedance for Biological Detection Biological Detection
LijuLiju YangYang
BiomanufacturingBiomanufacturing Research Institute & Research Institute & Technology Enterprise (BRITE), Technology Enterprise (BRITE),
Department of Pharmaceutical Science, Department of Pharmaceutical Science, North Carolina Central University, Durham, NC North Carolina Central University, Durham, NC
2770727707
IBE Annual Meeting, March IBE Annual Meeting, March 66--9, 2008. Chapel Hill, NC9, 2008. Chapel Hill, NC 22
Impedance is a measurement of the ability of a circuit or electrical element to resist the flow of AC electrical current.
Solution
Impedance analyzer
Electrode
IBE Annual Meeting, March IBE Annual Meeting, March 66--9, 2008. Chapel Hill, NC9, 2008. Chapel Hill, NC 33
Conductive property change in the solution
Conductive property change at the interface of the electrodes
Impedance Change
1. Biological events occur in the solution.
2. Biological events occur at the interface of the electrodes
IBE Annual Meeting, March IBE Annual Meeting, March 66--9, 2008. Chapel Hill, NC9, 2008. Chapel Hill, NC 44
Interdigitated Array (IDA) Microelectrodes
Two-electrode systemMultiple electrode pairsProgressively shorter electrode distanceLarge electrode surface area
IBE Annual Meeting, March IBE Annual Meeting, March 66--9, 2008. Chapel Hill, NC9, 2008. Chapel Hill, NC 55
Chamber (50 µl)
Interdigitatedmicroelectrodes
Silicone rubber
Contact pads
Silicon substrate
AC signal generator
(a)
(b)
Van Gerwen P, et al. Sens. Actuators B, 1998; 49, 73-80
IBE Annual Meeting, March IBE Annual Meeting, March 66--9, 2008. Chapel Hill, NC9, 2008. Chapel Hill, NC 66
Impedance of biological cells
The cell membrane consists of a lipid bilayercontaining many proteins. It is highly insulating. The conductivity is around 10 -7 S/m.
The inside of a cell contains many dissolved charged molecules. The conductivity of the interior of a cell can be as high as 1 S/m.
IBE Annual Meeting, March IBE Annual Meeting, March 66--9, 2008. Chapel Hill, NC9, 2008. Chapel Hill, NC 77
(i) Making use of the metabolic activity of biological cells. This is represented by impedance microbiology, which is based on the measurements of the change in electric impedance in a medium or a reactant solution resulting from the bacterial metabolism.
Mechanisms for impedance detection of biological cells
(ii) Making use of the insulating properties of the cell membrane. –Label free biosensor.
(iii) Making use of the highly ionic cytoplasmof the cells. – cell lysis or ion release
IBE Annual Meeting, March IBE Annual Meeting, March 66--9, 2008. Chapel Hill, NC9, 2008. Chapel Hill, NC 88
180
200
220
240
260
280
0 2 4 6 8 10 12 14 16 18 20Time / h
Med
ium
Res
ista
nce
/ Ω No cell
9.3 x 103 CFU/ml 6.5 x 105 CFU/ml
7.6 x 101 CFU/ml
Conventional E at 1MHz
16
20
24
28
32
36
0 2 4 6 8 10 12 14 16 18
Growth time / h
Impe
danc
e / kΩ
0
104 103
102
101100105
IDA E at 10 Hz
0
2
4
6
8
10
12
14
16
1.0E+0 1.0E+1 1.0E+2 1.0E+3 1.0E+4 1.0E+5 1.0E+6
Concentration of Salmonella ( Log cfu/ml)
Det
ectio
n tim
e (h
)
Interdigitatedmicroelectrode
ConventionalElectrode
(i) Impedance detection based on bacterial metabolism
IBE Annual Meeting, March IBE Annual Meeting, March 66--9, 2008. Chapel Hill, NC9, 2008. Chapel Hill, NC 99
IBE Annual Meeting, March IBE Annual Meeting, March 66--9, 2008. Chapel Hill, NC9, 2008. Chapel Hill, NC 1616
1.0E+3
1.0E+4
1.0E+5
0 20 40 60 80 100Time (min)
Impe
danc
e ( Ω
)
109
103106
107105 104 102
108
water
y = -2.06 Log (x) + 5.23R2 = 0.98
0
5
10
15
20
25
30
35
40
1.0E+01.0E+21.0E+41.0E+61.0E+81.0E+10
Bacterial Concentration (cells/20µl)
Impe
danc
e at
1 k
Hz
(kΩ
)
Water
-25
-20
-15
-10
-5
0
5
0 5 10 15 20 25 30 35Time (h)
perc
enta
ge o
f im
peda
nce
chan
ge
(%)
PBS
PBS w ith cells
Water
Water w ith cells
IBE Annual Meeting, March IBE Annual Meeting, March 66--9, 2008. Chapel Hill, NC9, 2008. Chapel Hill, NC 1717
Acknowledgement Funding from Golden LEAF Foundation and the State of North Carolina through the Biomanufacturing Research Institute & Technology Enterprise (BRITE) Center for Excellence at North Carolina Central University.