See discussions, stats, and author profiles for this publication at: https://www.researchgate.

net/publication/320062439

Interdigitated electrodes as impedance and capacitance biosensors: A review

Conference Paper in AIP Conference Proceedings · September 2017

DOI: 10.1063/1.5002470

CITATIONS READS
19 4,089

8 authors, including:

Muhammad M. Ramli Mohd Mustafa Al Bakri Abdullah

Universiti Malaysia Perlis Universiti Malaysia Perlis
114 PUBLICATIONS 146 CITATIONS 758 PUBLICATIONS 5,554 CITATIONS

SEE PROFILE SEE PROFILE

Dewi Suriyani Che Halin Siti Salwa Mat Isa

Universiti Malaysia Perlis Universiti Malaysia Perlis
83 PUBLICATIONS 181 CITATIONS 73 PUBLICATIONS 105 CITATIONS

SEE PROFILE SEE PROFILE

Some of the authors of this publication are also working on these related projects:

NEW TECHNIQUE FOR SOIL STABILIZATION USING GEOPOLYMERIZATION METHOD View project

Ag/TiO2 thin film View project

All content following this page was uploaded by Dewi Suriyani Che Halin on 09 October 2017.

The user has requested enhancement of the downloaded file.

Interdigitated electrodes as impedance and capacitance biosensors: A review
N. S. Mazlan, M. M. Ramli, M. M. A. B. Abdullah, D. S. C. Halin, S. S. M. Isa, L. F. A. Talip, N. S. Danial, and S.
A. Z. Murad

Citation: AIP Conference Proceedings 1885, 020276 (2017); doi: 10.1063/1.5002470

View online: http://dx.doi.org/10.1063/1.5002470
View Table of Contents: http://aip.scitation.org/toc/apc/1885/1
Published by the American Institute of Physics

Articles you may be interested in

The production of Malaysia bamboo charcoal (Gigantochloa albociliata) as the potential absorbent
AIP Conference Proceedings 1885, 020258 (2017); 10.1063/1.5002452

Single wall carbon nanotubes dispersion study of different dye molecules and chitosan
AIP Conference Proceedings 1885, 020259 (2017); 10.1063/1.5002453

Design of aquaponics water monitoring system using Arduino microcontroller

AIP Conference Proceedings 1885, 020248 (2017); 10.1063/1.5002442
 Interdigitated electrodes as impedance and capacitance
biosensors: A Review
N S Mazlan1,a), M M Ramli1, M M A B Abdullah2, D S C Halin3, S S M Isa1, L F A
Talip1, N S Danial1, and S A Z Murad1
1
School of Microelectronic Engineering, University Malaysia Perlis, Pauh, Perlis.
2
Center of Excellence Geopolymer and Green Technology (CEGeoGTech), School of Materials Engineering,
University Malaysia Perlis, Perlis.
3
School of Materials Engineering, University Malaysia Perlis (UniMAP).
a)
Corresponding author: syafiqahmazlan810@gmail.com

Abstract.Interdigitated electrodes (IDEs) are made of two individually addressable interdigitated comb-like
electrode structures. IDEs are one of the most favored transducers, widely utilized in technological applications
especially in the field of biological and chemical sensors due to their inexpensive, ease of fabrication process and
high sensitivity. In order to detect and analyze a biochemical molecule or analyte, the impedance and capacitance
signal need to be obtained. This paper investigates the working principle and influencer of the impedance and
capacitance biosensors. The impedance biosensor depends on the resistance and capacitance while the capacitance
biosensor influenced by the dielectric permittivity. However, the geometry and structures of the interdigitated
electrodes affect both impedance and capacitance biosensor. The details have been discussed in this paper.

INTRODUCTION
Nowadays, expanding demand for speedy and precise diagnostic approaches has prompted tendency in the
evolution of biomedical sensing devices. Biomedical devices are recommendable to use as a medical diagnostics as
its ability to operate and inspected within a small volumes of biological materials. There has been a rising
attentiveness for the evolution of biosensor which combine label-free with high sensitivity detection especially in
healthcare applications.

Biosensor can be used in order to identify or quantify a biochemical molecule, for an example, protein or DNA
sequence. Many biosensors are affinity-based which means they use an immobilized capture probe to attach the
molecule being detect, thus the select target or analyte will shift the task of sensing a target in solution into detecting
a change at a limit surface. Electrical biosensors depend on the evaluation of currents and/or voltages to detect
binding [1]. Biosensor can be assimilated into portable lab-on-chip devices enable to diagnose within short time.
One of the cost-effective alternatives to detect cancer cells is by using electrical property changes (impedence,
resistance and capacitance) of interdigitated electrode [2].

Interdigitated electrodes (IDEs) are optimized in various sensing devices including surface acoustic wave (SAW)
sensors, chemical sensors and current MEMS biosensors. Operating modalities of biosensors using IDEs can be
either faradaic or non-faradaic. It is crucial to differentiate between faradaic and non-faradaic biosensors. Faradaic
process is a process of a current flow as a result of electronic transfer whereas non-faradaic process is where the
current flow as a result of capacitive nature of an electrode, termed as the double layer capacitance, Cdl. The
biosensors operating in faradaic mode are often based on electrochemical impedance spectroscopy (EIS) by
measuring electron transfer resistance and double layer capacitance within a frequency range [1–3]. In other hand,

3rd Electronic and Green Materials International Conference 2017 (EGM 2017)
AIP Conf. Proc. 1885, 020276-1–020276-8; doi: 10.1063/1.5002470
Published by AIP Publishing. 978-0-7354-1565-2/$30.00

020276-1
for the non-faradaic mode, it is based on changes in capacitance between interdigitated electrodes to indicate
molecular binding events at the electrode surface [2].

The objective of this review paper is to summarize the operating modalities of interdigitated electrode and
distinguish between the impedance and capacitive biosensors in order to detect and analyze a biochemical molecule.
In this paper, the important aspects when designing the biosensors and its efficiency will be highlighted.

Impedance Biosensor
In recent years, most biosensor detection related in biomedical and public health fields rely on dyes or
fluorescent labels by using data readout and imaging. However, fluorescent label-based techniques not only demand
highly accurate and over-costing instrument but also initiate uncertain interference into the sensing system which
induce an inaccurate result [4].
To counteract these drawbacks, interdigitated electrode-based impedance biosensor is used due to its label-free
operation, ease of miniaturization and low cost. In order to monitor the attachment, spreading, growth and death of
the cancer cell, the impedance biosensor or Electric cell-substrate impedance sensing (ECIS) can be used [5]. Cells
deposited on the electrodes form insulating dielectric membranes which impede the flow of current. The number of
cells cultured on the electrode, interaction of cell, changes of cell morphological and cell motility will give the
impedance measurement between the two electrodes.
The illustration of schematic principles of electrochemical impedance spectroscopy (EIS) measurement of the
absent and present of the cells on the measured Bode impedance spectra has been shown in Fig. 1. The circuit model
illustrate the impedance present of the IDE and the cells. The impedance induce only from double layer capacitance
of the electrodes (Cdl) and the resistance of the solution (Rsol) when there is no attachment of cells.
As cells are deposited on the surface of the electrode, the circuit should include the contain of the impedance
contribution from the cells in addition to the Rsol and Cdl. The impedance of the attached cells can be represent as the
resistance (Rcell) and a capacitance (Ccell) in parallel. With cells deposited on the electrodes surface, the interface
impedance increased because of their high insulating of cell membrane which minimize the area of electrode where
the current reaches.
The present of cells also influence the ionic environment around the electrode or solution interface as they
change the Cdl and Rsol which prompt to the rising of the impedance of the electrode. It is stated that capacitance
contributes to the impedance dependent of the frequency and resistance contributes to impedance independent of
frequency as expressed by Eq. (1) and (2),
1
Z (1)
2Sfc

Z R (2)

Cell attachment affect the ionic solution at the area of electrode which influence to the rising of Cdl and Rsol. In
addition, cell attachment generated new impedance which included the Ccell and Rcell. The impedance generated by
the attachment of the cell was measured according to the Eq. (3) [6, 7],

2 1
z R 
(2Sf
(3)
cell cell
c cell
)2

020276-2
 (a) (b)

(c) (d)

FIGURE 1. The figure of schematic principles of EIS measurement without redox probe along with their circuits when (a) absent
of cell and (b) present of cell on the electrodes, and the respective Bode impedance spectra and fitting spectra when (c) absent of
cell and (d) present of cell on the electrodes [6].
Based on the impedance measurements, phase of the cellular activities can be analyzed. When there is no cell
deposited on the electrode, only the values of Rsol and Cdl are obtained. After attached the cell on the electrodes, the
two resistance components, Rsol and Rcell increased with time. However, Rsol seems higher than Rcell since the cell
growth is relatively slow. This is the phase where cell adhesion takes place and capacitive value is high as it did not
allow any current to pass through.
During cell spreading, Rcell increased greater than Rsol due to the high insulating cell membrane which increased
the binding of cell on the interdigitated microelectrodes (IMEs). The small rising in Rsol is due to the change in the
solution environment of the electrode. During this stage, Ccell starts to decrease.
Finally, as the cell proliferation happened, the Rcell reached it maximum value while Ccell is at its minimum. The
results proved that the declining of the capacitance value due to the spreading and proliferating of cells affected to
the increasing of the impedance as capacitance is inversely related with impedance[6–10].
According to A. Han et. al. [11], four types of breast cancer cell lines which consist of normal human breast
tissue cell line (MCF-10A), early-stage breast cancer cell line (MCF-7), invasive human breast cancer cell line
(MDA-MB-231) and metastasized human breast cancer cell line (MDA-MB-435) are measured its electrical
impedance by using frequency between 100 Hz to 3 MHz. The capacitance and resistance membrane of each cell
line is calculated by modeling a cell as series of parallel RC circuits [6, 8]. The result shows the declining in
capacitance of all cancer cell lines, MCF-7, MDA-MB-231 and MDA-MB-435 compared with the normal cell line
which are 4.1%, 16.0% and 19.1%, respectively. At 100 kHz, the membrane capacitance of MDA-MB-435 is the
lowest while it resistance is the highest compared to the other cell lines. It can be deduce that capacitance decreased
due to the increased of pathologically progressed cancer cell lines which influenced by it rising of permeability of
the cell membrane. The result proves that this method can be used not only to discern between a normal or
cancerous cell line but also to differentiate from early to late-stage cancer models.
An impedance spectrum is one of the methods to identify the changes of the capacitance and resistance due to
the binding of cell to the surface of IDEs in cell growth medium. As stated by J. Mamouni et. al. [6], cell proliferate
reduce the capacitance value and increase the resistance. Impedance change at frequency range of 10 kHz to 100
kHz. It has been found that the impedance is increased linearly with increased of cell number of cancerous oral cell
(CAL 27) on the IMEs. In collation between non-cancer oral epithelial cells (Het-1A) with similar amount of CAL
27, cancerous cells regularly triggered greater impedance compared to non-cancerous cells. This has been proved by

020276-3
T. Anh-Nguyen et. al. [8] , where the cell spreading of breast cancer cell MCF-7 generate an inclining of membrane
resistance to 57% and declining of membrane capacitance by 2%.

Capacitance Biosensor
Capacitance measurement could be a useful tool to detect or measure specific proteins or biomolecule
substances. In some cases, it can detect the biomolecules through the properties of antigens or antibodies and it is
called as affinity-based capacitive sensors. The analyte can be regulate directly in a sample by using this capacitive
sensor. The three main measuring concept of these sensors are based on the adjustment of the properties of
dielectric, charge distribution, and the change of the conductivity when analyte formed on the surface of the
electrode [12].

(a) (b)

FIGURE 2. (a) Interdigitated electrode affinity biosensor. (b) Capacitive affinity sensor based on two metal plates. Changes in
the properties of the dielectric between the electrodes by binding or releasing an analyte in or out of the field between the
electrodes will induce a capacitance change [13].

Capacitive affinity biosensors can be assembled by using immobilizing recognition elements (e.g. antibodies) in
fine layers on the electrode. For providing higher surface area of the sensor, conductors can be made as a pattern of
interdigitated fingers [12, 13]. The basic capacitance equation is shown in Eq. (4) [13],

A
C HH r $
d
(4)

where εₒ is the vacuum permittivity, εr is the relative permittivity of the material connecting the plates, A is the
electrode plate’s surface area and d is the distance of the plate. It can be proved from Eq. (4) that a change in the
capacitance can be cause by adjusting the distance between the two plates, adjusting the overlapping area between
the two plates and by amend dielectric permittivity between the plates.

The main principle sensing of interdigital capacitive sensors is based on the change of the dielectric constant of
the interdigitated capacitor. It has been proved by A. Quershi et. al. [12] and V. Tsouti et. al. [13], where the
changed of the capacitance occurred when the properties of the dielectric of the material between the plates changed.
The capacitance of the IDE sensor is stated in Eq. (5),

lt
C sensor
KH (5)
d

where η is the number of fingers, ε is the permittivity of the sensitive coating film, l is the length of interdigital
electrodes, t is the thickness of interdigital electrodes and d is the distance between the electrodes. However this
calculation of capacitance cannot be applied when nanoscale electrodes are used [13].

020276-4
 According to L. Zhang et. al. [14], five cell lines obtained from different state human colorectal tumors were
measured its cell dielectric permittivity under frequencies range from 5 GHz to 14 GHz using microwave
biosensors. In order to design this sensor, a microwave coplanar waveguide which is implemented with a set of
parallel twisted inductor and two interdigitated comb (IDC) capacitors is used. The resonance frequency is changed
when cells deposited on the IDC capacitors. As absent of the cell, the resonant frequencies of the biosensor are
lower in the range of 5 to 12 GHz. As one, two, three and four SW620 cells are loaded on the IDC capacitors, the
measured frequency inclined to 75 MHz, 40 MHz, 89 MHz and 112 MHz, respectively. Hence, it can be stated that
the relative dielectric permittivity of cells decreased as the frequency increased. This can be proved by Eq. (6) and
(7),

2
C .W
H r _ cell
H .V . N
cell IDC
(6)
$ cell cell

f
f )( f f
2
W (   )
H
IDC 0 1 0 1
(7)
f H .V . N
r _ cell 2

1 $ cell cell

where Ccell is the capacitors with the present of the cells on the electrodes, W IDC is the width of the air gap which
linked the two IDC fingers, εₒ is the vacuum permittivity, Vcell is the volume of the cell, Ncell is the amount of cells
attached on the sensor, ƒₒ is the unloaded sensor resonant frequency and ƒ1 is the loaded sensor resonant frequency.
In addition, the ideal capacitance behavior of a sensing probe has to be stable, sensitive and highly specific. As
reported by S. Carrara et. al. [15], an immunosensor is successfully developed by using capacitance detection. An
accurate immobilize probe is used to gain valid capacitance measurements. For an example, alkanethiols for proteins
immobilization do not provide adequately stable capacitance measurements. Thus, in order to produce more stable
lab-on-chip device for cancer markers detection, the new ethylene-glycol is used to functionalized alkanethiols
which act as a protein immobilization of the device [15].
Bare capacitor surface is weakly charged. Thus, by immobilized the aptamer, it will increased the charged
surface. According to A. Qureshi et. al. [16], the alternative method is used in order to develop a stable biosensor
which is by using synthetic biorecognition elements such as aptamers. Aptamers consists of DNA or RNA can
complete the spaces related with biomolecules derived of cells and attach to their targets which assist them as a new
biorecognition elements for biosensing. For an example, the label-free capacitive aptasensor was evolved by using
anti-HER2 ssDNA aptamers functionalized on IMEs as biorecognition elements with attachment of human
epidermal growth factor receptor 2 (HER2) proteins. It can be proved that the capacitance can be used to measure
any reaction between the ligands immobilized with target captured on the sensor surface.

020276-5
 FIGURE 3. a) Image of the IDE capacitor array chip, (b) Image of a representative capacitor, (c) Image of functionalized anti-
HER2 aptamer with a gold IDE which phosphodiester backbone consists of negative charged, (d) Interaction of aptamer–target
protein (HER2)complex generate the distribution of charge and (e) IDC sensor equivalent circuit [16].

Based on Fig. 3, Rf1 and Rf2 represent the resistances between the fingers of the electrode. L1 and L2 represent
self-inductances of magnetic coupling between the fingers while C is the passage between the insulated electrodes
through SiO2 layer and Silicon substrate. The insulating layers on the electrodes is connected with the capacitance
Cg. The change of the thickness of film surface on electrodes is influenced by the probe immobilization and target
binding on sensor surface. This effect to the adjustment of the capacitive responses and surface conductivity of the
sensors.

TABLE 1. Example of biosensor types with their different target molecule.

Biosensor type Target molecule Limit of detection Sensitivity Reference
Capacitive biosensor DNA fragment 1.5aM >70nF 2.
(gold microIDE) (down to 20 DNA
molucule)
Capacitor biosensor C-reactive protein, 0.025-0.8mg/l 12.
(gold electrode) CRP
Capacitive biochip Cancer marker 2.43μg/ml (6.27 x 10-8M) 15.
Capacitive biosensor
(serpentine electrode, (5±0.2) fF/%RH 17.
interdigitated electrode) (4.2±0.2)fF/%RH
Impedance biosensor E Coli O157
(aluminium
interdigitated comb 10² CFU/ml 11% 18.
finger-like electrode)

Optimization of The IDE

One of the most important factors to be considered in order to analyze the impedance and capacitance biosensor
of the IDE is its electrode geometry. The output of the impedance and capacitance can be adjusted by selectively
design the width, spacing and active area of the interdigitated electrode. According to H. Pandya et. al. [10], the
percentage of the difference impedance of benign group and cancerous breast tissue is significantly ~69 % higher by

020276-6
using 10 μm compared to 30 μm spacing of IDEs. The increase of the gaps between IDE fingers lead to the rising of
it impedance. As the impedance is inversely proportional to the capacitance, the impedance decline as the
capacitance incline on the increasing of the surface area. This result is proved by the Eq. (4) that the surface area of
the electrodes and the distance between finger electrodes play important role for impedance or capacitance
measurement. Hence, by reducing the electrode spacing, it will increased the effective electrode area, thereby
increasing the sensitivity of the device to the existence of cells due to the concentrated perforation depth [10, 12].

(a) (b)

FIGURE 4. Illustration of (a) microchip with IDEs having 10 μm width and 10 μm spacing and (b) 10 μm width and 30 μm
spacing [10].

According to A. Rivadeneyra et. al. [17], instead of using interdigitated electrodes, another novel electrode
structure has been study which is by combine the twisted and interdigitated electrodes (known as serpentine) in
single structures. The serpentine electrode structure shows a greater geometrical capacitance factor compared to the
interdigitated capacitor. However, one finger interrupted in serpentine electrodes lead to the sensor uselessness
while failed fingers in IDE only results in lower sensor performance.

(a)

(b)

FIGURE 5. (a) Serpentine electrode (SRE) and (b) interdigitated electrode (IDE) structures [17].

CONCLUSIONS

Interdigitated electrodes implemented in various sensing devices promise many benefits in biosensing field such
as ease of miniaturization, label-free operation and low cost device. In this review, it can be concluded that the
impedance biosensor is depend on the resistance and capacitance. The volume or number of cells play an important
role since increasing the volume or number of cell can affect the value of resistance and capacitance which influence
the value of impedance. The value of the resistance component, Rcell increased and the value of the capacitance
component, Ccell decreased as the number of the cancer cell rose. Thus, the value of the impedance will be increased.
As the impedance biosensor can discern the pathologic states from different stage cancer models, the impedance will

020276-7
 be increased as the stage increased. In other hand, the main influence in capacitance signal is the dielectric
permittivity. This include of the distribution of charge upon attachment of target aptamer probe, concentration of
target analyte (proteins or cells), applied AC electrical frequency and the pattern of the interdigitated electrode
structures. However, the geometry and structures of the interdigitated electrodes influence both impedance and
capacitance biosensor.

ACKNOWLEDGMENT

This work was supported by Fundamental Research Grant (FRGS) (No.: 9003-00532) funded by Ministry of
Education Malaysia.

REFERENCES
1. J.S. Daniels and N. Pourmand, Electroanalysis 19, 1239 (2007).
2. L. Wang, M. Veselinovic, L. Yang, B.J. Geiss, D.S. Dandy, and T. Chen, Biosens. Bioelectron. 87, 646
(2017).
3. G. Chornokur, S.K. Arya, C. Phelan, R. Tanner, and S. Bhansali, J. Sensors 2011, (2011).
4. H. Ma, R.W.R. Wallbank, R. Chaji, J. Li, Y. Suzuki, C. Jiggins, and A. Nathan, Sci. Rep. 3, 2730 (2013).
5. J. Wang, C. Wu, N. Hu, J. Zhou, L. Du, and P. Wang, Biosensors 2, 127 (2012).
6. J. Mamouni and L. Yang, Biomed. Microdevices 13, 1075 (2011).
7. D. Seidel, J. Obendorf, B. Englich, H.G. Jahnke, V. Semkova, S. Haupt, M. Girard, M. Peschanski, O.
Br??stle, and A.A. Robitzki, Biosens. Bioelectron. 86, 277 (2016).
8. T. Anh-Nguyen, B. Tiberius, U. Pliquett, and G.A. Urban, Sensors Actuators, A Phys. (2015).
9. Y. Qiu, R. Liao, and X. Zhang, Biophys. J. 96, 1985 (2009).
10. H.J. Pandya, H.T. Kim, R. Roy, W. Chen, L. Cong, H. Zhong, D.J. Foran, and J.P. Desai, Sensors Actuators, B
Chem. 199, 259 (2014).
11. A. Han, L. Yang, and A.B. Frazier, Clin. Cancer Res. 13, 139 (2007).
12. A. Quershi, Y. Gurbuz, W.P. Kang, and J.L. Davidson, Biosens. Bioelectron. 25, 877 (2009).
13. V. Tsouti, C. Boutopoulos, I. Zergioti, and S. Chatzandroulis, Biosens. Bioelectron. 27, 1 (2011).
14. L.Y. Zhang, C.B.M. du Puch, C. Dalmay, A. Lacroix, A. Landoulsi, J. Leroy, C. Mélin, F. Lalloué, S. Battu,
C. Lautrette, S. Giraud, A. Bessaudou, P. Blondy, M.O. Jauberteau, and A. Pothier, Sensors Actuators A Phys.
12 (2014).
15. S. Carrara, V. Bhalla, C. Stagni, L. Benini, A. Ferretti, F. Valle, A. Gallotta, B. Riccò, and B. Samorì, Sensors
Actuators, B Chem. 136, 163 (2009).
16. A. Qureshi, Y. Gurbuz, and J.H. Niazi, Sensors Actuators, B Chem. 220, 1145 (2015).
17. A. Rivadeneyra, J. Fernández-Salmerón, J. Banqueri, J.A. López-Villanueva, L.F. Capitan-Vallvey, and A.J.
Palma, Sensors Actuators, B Chem. 204, 552 (2014).

020276-8
View publication stats