micromachines
Article
A Reduced Graphene Oxide Based Radio
Frequency Glucose Sensing Device Using
Multi-Dimensional Parameters
Byeongho Park 1 , Hyung Goo Park 1 , Jae-hoon Ji 1 , Jinsoo Cho 2 and Seong Chan Jun 1, *
1
2
*
School of Mechanical Engineering, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749, Korea;
enggis@naver.com (B.P.); zeustg@naver.com (H.G.P.); jupitersun@naver.com (J.J.)
Department of Computer Engineering, Gachon University, Gyeonggi-do 461-701, Korea; jscho@gachon.ac.kr
Correspondence: scj@yonsei.ac.kr; Tel: +82-2-2123-5817
Academic Editor: Hiroshi Mizuta
Received: 30 May 2016; Accepted: 1 August 2016; Published: 5 August 2016
Abstract: A reduced graphene oxide (RGO) based glucose sensor using a radio frequency (RF)
signal is demonstrated. An RGO with outstanding electrical property was employed as the
interconnector material between signal electrodes in an RF electric circuit, and it was functionalized
with phenylbutyric acid (PBA) as a linker molecule to bind glucoses. By adding glucose solution,
the fabricated sensor with RGO and PBA showed detecting characteristics in RF signal transmission
and reflection. Frequency dependent electrical parameters such as resistance, inductance, shunt
conductance and shunt capacitance were extracted from the RF results under the equivalent
circuit model. These parameters also provided sensing characteristics of glucose with different
concentrations. Using these multi-dimensional parameters, the RF sensor device detected glucose
levels in the range of 1–4 mM, which ordinarily covers the testing range for diabetes or medical
examination. The RGO based RF sensor, which fits well to a linear curve with fine stability, holds
considerable promise for biomaterials detection, including glucose.
Keywords: glucose biosensor; multi-dimensional parameters; radio frequency; reduced
graphene oxide
1. Introduction
Glucose sensing from blood and urine is the usual diagnosis method for diabetes, and it is
also used in the food industry, such as in fermentation for quality checking [1]. Various sensing
techniques for glucose have been developed, such as fluorescence detection [2], electrochemistry [3],
and surface-enhanced Raman scattering [4]. However, such techniques needed a mediator including
enzymes or antibodies, which result in signal loss with electron- or photon-scattering [5,6]. To overcome
this limitation, a single wall carbon nanotube with a high electrical property was employed as an
interconnector in the sensor, which detected glucose with pico-molar sensitivity [7,8].
Similarly, reduced graphene oxide (RGO) with two-dimensional structure has also provided
significant potential for biosensors, owing to its small signal loss under high electrical property and
fine selectivity with specific binding affinity [9–11]. RGO has been applied to biosensors in several
research areas, such as glucose sensors [12,13], gas sensors [14–16], and electrochemical bacteria
sensors [17]. Aromatic ring structure and functional groups in RGO assist in connecting with the target
material by π–π* stacking on its basal planes and chemical interaction [18]. Phenylboronic acid (PBA),
which also has an aromatic ring structure, is a highly affinitive molecule with RGO, and it also makes
the binding with glucose easily because of the diol group [19,20].
On the basis of the above considerations, we report here a development of the glucose sensor
composed of RGO and PBA interconnector in a radio frequency (RF) system. In the RF measurement,
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On the basis of the above considerations, we report here a development of the glucose sensor
composed of RGO and PBA interconnector in a radio frequency (RF) system. In the RF measurement,
scattering parameter
parameter(S-parameter),
(S-parameter),
ratio
of output
to for
input
for RFtransmission
signal transmission
and
scattering
thethe
ratio
of output
to input
RF signal
and reflection
reflectionthe
through
the interconnector,
obtained
thekHz
range
of GHz.
500 kHz
4.5 GHz. Such
through
interconnector,
was obtainedwas
in the
range ofin500
to 4.5
Suchto
measurement
has
measurement
has exceptional
characteristics
forsensing
simple by
anddropping
rapid sensing
dropping
small volume
exceptional
characteristics
for simple
and rapid
small by
volume
of solution
sample
of solution
sample
and continuous
test with a wireless
platform inmicrowave
the ultraand
continuous
real-time
test with a real-time
wireless examination
platformexamination
in the ultra-broadband
broadbandIn
microwave
In particular,
RF results
in highremarkable
frequencies and
provide
remarkable
spectrum.
particular,spectrum.
the RF results
in high the
frequencies
provide
sensitive
signal
and sensitive
signal
changefeature
with the
resonance
feature
[21].
can
also be regarded
as a
change
with the
resonance
[21].
In addition,
it can
alsoInbeaddition,
regardeditas
a valuable
system since
valuable
system multi–parameters,
since the decomposed
multi–parameters,
(R), inductance
the
decomposed
resistance
(R), inductanceresistance
(L), shunt conductance
(G) (L),
and shunt
conductance(C)
(G)allow
and shunt
capacitance
(C) allow
usprecisely
to analyze
the results more precisely [22].
capacitance
us to analyze
the results
more
[22].
2.
ExperimentalSection
Section
2. Experimental
D´(+)
glucose(C(C
purchased
from
Sigma
Aldrich
Korea
(Yongin,
Korea),
andused
we
6H
126O
6 ) was
D−(+) glucose
6H
12O
) was
purchased
from
Sigma
Aldrich
Korea
(Yongin,
Korea),
and we
used
several
concentrations
of glucose
solution
100 µM
4 mM
since
usual
reference
range
several
concentrations
of glucose
solution
fromfrom
100 μM
to 4to
mM
since
the the
usual
reference
range
of
of
concentration
in
blood
is
close
to
2.6
mM.
The
phosphate
buffer
tablets
(10
mM
phosphate,
150
mM
concentration in blood is close to 2.6 mM. The phosphate buffer tablets (10 mM phosphate, 150 mM
sodium
sodium chloride,
chloride, pH
pH 7.3
7.3 to
to 7.5)
7.5) were
were from
from Seoulin
Seoulin bioscience
bioscience (Seoul,
(Seoul, Korea).
Korea). Our
Our interconnector
interconnector
material
prepared by
material composed
composed of
of graphene
graphene oxide
oxide (GO)
(GO) was
was prepared
by the
the modified
modified hummer
hummer method
method [23],
[23], and
and
it
was
reduced
by
annealing,
as
in
a
previous
work
[24–26].
The
high
resistivity
Si
substrate
purchased
it was reduced by annealing, as in a previous work [24–26]. The high resistivity Si substrate purchased
from Woori
Woori Material
Material (Daejeon,
(Daejeon, Korea)
Korea) with
with 500
500 nm
nm dielectric
dielectric layer
layer (SiO
(SiO22) for obtaining the stable
electrical signal in RF was employed (Figure 1a). Gold electrodes (500 nm) were deposited by electron
beam sputtering on the titanium adhesion layer (10 nm). Our
Our electrode
electrode pattern
pattern had
had two
two signal
signal (S)
lines with a 4 μm
µm gap on the center
center of
of the
the pattern
pattern and
and ground
ground (G)
(G) lines,
lines, named
named ground-signal-ground
ground-signal-ground
(GSG).
To
connect
the
signal
line
using
RGO
as
an
interconnector,
the
Dielectrophoresis
(DEP) method
(GSG). To connect the signal line using RGO as an interconnector, the Dielectrophoresis
(DEP)
by
alternating
electric
fields
was
used
to
focus
the
RGO
flakes
on
the
target
position
and
to form
method by alternating electric fields was used to focus the RGO flakes on the target position
andthe
to
channel
a shortin
time
[15].time
For the
RGO suspended
solution (3
µL) was
form thein
channel
a short
[15].dielectrophoresis,
For the dielectrophoresis,
RGO suspended
solution
(3dropped
μL) was
on
the middle
of the
substrate,
an alternating
(AC) current
through(AC)
signalthrough
lines was
applied
under
dropped
on the
middle
of theand
substrate,
and ancurrent
alternating
signal
lines
was
10
V of potential
KHz of frequency
forof2frequency
min.
applied
under 10and
V of10potential
and 10 KHz
for 2 min.
Figure 1. (a) Schematic of radio frequency (RF) measurement system with transmission and reflection
Figure 1. (a) Schematic of radio frequency (RF) measurement system with transmission and reflection
between signal
signal electrodes
electrodes on
on ground-signal-ground
ground-signal-ground (GSG)
pattern (b)
(b) chemical
chemical reaction
reaction between
between
between
(GSG) pattern
phenylbutyric
acid
(PBA)
and
glucose.
phenylbutyric acid (PBA) and glucose.
For planting PBA on the RGO surface, 4-phenylbutyric acid (C6H5(CH2)3COOH, Sigma Aldrich,
For planting PBA on the RGO surface, 4-phenylbutyric acid (C6 H5 (CH2 )3 COOH, Sigma Aldrich,
St. Louis, MO, USA) and 3-aminophenylboronic acid (C6H8BNO2, Sigma
Aldrich, St. Louis, MO, USA)
St. Louis, MO, USA) and 3-aminophenylboronic acid (C6 H8 BNO2 , Sigma Aldrich, St. Louis, MO, USA)
were dissolved in N,N-dimethylmethanamide (C3H7NO, DMF, Sigma Aldrich, St. Louis, MO, USA),
were dissolved in N,N-dimethylmethanamide (C3 H7 NO, DMF, Sigma Aldrich, St. Louis, MO, USA),
and then N-(3-Dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride (C8H17N3·HCl, EDAC,
and then N-(3-Dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride (C8 H17 N3 ¨HCl, EDAC,
Sigma Aldrich, St. Louis, MO, USA) was continuously added. We dropped this solution (10 μL) onto
Sigma Aldrich, St. Louis, MO, USA) was continuously added. We dropped this solution (10 µL) onto
the RGO surface in the sensing device, and kept it for 2 h at room temperature. The functional groups
the RGO surface in the sensing device, and kept it for 2 h at room temperature. The functional groups
of RGO assisted in attaching PBA on it with chemical interactions. After that, it was rinsed twice with
of RGO assisted in attaching PBA on it with chemical interactions. After that, it was rinsed twice
pure DMF and distilled water to remove the reagents. Then, using a sensor device with PBA on RGO
with pure DMF and distilled water to remove the reagents. Then, using a sensor device with PBA on
(PBA/RGO), we measured the S-parameter, which is the ratio of output to input signal between
RGO (PBA/RGO), we measured the S-parameter, which is the ratio of output to input signal between
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connected
connected ports,
ports, by
by GSG
GSG probe
probe with
with network
network analyzer
analyzer (E5071C,
(E5071C, Agilent,
Agilent, Santa
Santa Clara,
Clara, CA, USA) after
dropping
onon
thethe
device
surface.
TheThe
network
analyzer
generated
the microwave
signal
droppingglucose
glucosesolution
solution
device
surface.
network
analyzer
generated
the microwave
and
detected
the returning
signalsignal
from the
sensor
device
with with
GSG GSG
pattern.
As shown
in Figure
1a, the
signal
and detected
the returning
from
the sensor
device
pattern.
As shown
in Figure
1a,
reflected
S-parameter
(S11)(S11)
was was
obtained
fromfrom
port 1port
to 11again,
and the
S-parameter
(S21)
the reflected
S-parameter
obtained
to 1 again,
andtransmitted
the transmitted
S-parameter
was
to 2.1 By
the
between
PBAPBA
and and
glucose
molecule
described
in Figure
1b,
(S21)from
was port
from1port
to 2.
Byinteraction
the interaction
between
glucose
molecule
described
in Figure
glucose
molecules
werewere
caught
on the
interconnector.
1b, glucose
molecules
caught
on PBA/RGO
the PBA/RGO
interconnector.
For
For monitoring
monitoring the structure
structure of
of RGO
RGO on
on the substrate, we measured
measured the field
field emission
emission scanning
scanning
electron
(SEM)
(JSM-6701F,
JEOLJEOL
Ltd., Tokyo,
Japan) and
transmission
electron microscope
electron microscope
microscope
(SEM)
(JSM-6701F,
Ltd., Tokyo,
Japan)
and transmission
electron
(TEM)
(JEM-2010,
Ltd., Tokyo,
Japan)
images,
and
atomicand
force
microscope
(AFM) (XE-BiO,
microscope
(TEM) JEOL
(JEM-2010,
JEOL Ltd.,
Tokyo,
Japan)
images,
atomic
force microscope
(AFM)
Park
Systems,
X-ray
photoelectron
spectroscopy
(K-alpha, Thermo
Scientific,
(XE-BiO,
Park Suwon,
Systems,Korea).
Suwon,
Korea).
X-ray photoelectron
spectroscopy
(K-alpha,Fisher
Thermo
Fisher
Waltham,
USA) was
characterize
the graphene
sample.
Scientific, MA
Waltham,
MA used
USA)towas
used to characterize
thebased
graphene
based sample.
3.
Resultsand
andDiscussion
Discussion
3. Results
Figure
present SEM
SEM images
images ofofstretched
stretchedtwo
twosignal
signallines
linesand
and
GSG
electrode
pattern.
Figure 2a,b
2a,b present
GSG
electrode
pattern.
A
A
PBA/RGO
interconnector
connectedbetween
betweentwo
twosignal
signalelectrodes
electrodesand
andPBA
PBA built
built up
up the
the entangled
PBA/RGO
interconnector
connected
entangled
structure
interconnector was
structure on
on the
the RGO
RGO sheet.
sheet. The
The thickness
thickness of
of the
the PBA/RGO
PBA/RGO interconnector
was 110
110 nm,
nm, as
as described
described
in
in Figure
Figure 2c.
2c.
Figure 2.
2. SEM
image of
of (a)
(a) biosensor
biosensor device
device with
with GSG
GSG pattern,
pattern,(inset)
(inset)signal
signalline,
line,and
and(b)
(b)PBA/reduced
PBA/reduced
Figure
SEM image
graphene
oxide
(RGO)
interconnector
part
(c)
AFM
image
of
PBA/RGO
interconnector.
graphene oxide (RGO) interconnector part (c) AFM image of PBA/RGO interconnector.
With C 1s, N 1s, and B 1s orbitals, Figure 3 represented the X-ray photoelectron spectra (XPS)
With C 1s, N 1s, and B 1s orbitals, Figure 3 represented the X-ray photoelectron spectra (XPS)
results, which provides the information of chemical interaction, of PBA/RGO and glucose combined
results, which provides the information of chemical interaction,
of PBA/RGO and glucose combined
PBA/RGO. The C 1s results completely match with sp22 C–C bonding corresponding to 284.8 eV,
PBA/RGO. The C 1s results completely match with sp C–C 2bonding corresponding to 284.8 eV,
C–OH/O–C–O, and COOH near 286 eV [27]; the intensity of sp at 284.8 eV was the most dominant
C–OH/O–C–O, and COOH near 286 eV [27]; the intensity of sp2 at 284.8 eV was the most dominant
in all features of the carbon based sample. PBA/RGO was reduced by adding glucose solution, and
in all features of the carbon based sample. PBA/RGO was reduced by adding glucose solution,
its shoulder peak at 286.7 eV decreased owing to new binding between PBA and glucose in the
and its shoulder peak at 286.7 eV decreased owing to new binding between PBA and glucose in the
replacement of PBA/RGO functional groups [28,29]. The N 1s features consisted of three individual
replacement of PBA/RGO functional groups [28,29]. The N 1s features consisted of three+ individual
peaks appearing at 398.2 eV for =N–, at 399.7 eV for –NH–, and at 401.1 eV for NH3 . PBA/RGO
peaks appearing at 398.2 eV for =N–, at 399.7 eV for –NH–, and at 401.1 eV for NH3 + . PBA/RGO
exhibited mainly =N– feature at 398.2 eV from PBA before adding glucose. After glucose treatment,
exhibited mainly =N– feature at 398.2 eV from PBA before adding glucose. After glucose treatment,
PBA/RGO showed decrement in =N– binding, and small –NH– features remain in the N 1s orbital of
PBA/RGO showed decrement in =N– binding, and small –NH– features remain in the N 1s orbital of
XPS characterization. In the B 1s, PBA/RGO with glucose presented –C–B(OH)2 feature at 191.6 eV
XPS characterization. In the B 1s, PBA/RGO with glucose presented –C–B(OH)2 feature at 191.6 eV [30].
[30]. In PBA/RGO, 3–aminophenylboronic acid that is able to interact chemically with glucose
In PBA/RGO, 3–aminophenylboronic acid that is able to interact chemically with glucose molecule
molecule has the nitrogen in amino and boron in boronic acid. The XPS features of these two atoms
has the nitrogen in amino and boron in boronic acid. The XPS features of these two atoms remarkably
remarkably showed the existence of a functional group on PBA/RGO and interaction with glucose
showed the existence of a functional group on PBA/RGO and interaction with glucose [31].
[31].
From two signal electrodes or ports on the RF device, a network analyzer can produce the input
From two signal electrodes or ports on the RF device, a network analyzer can produce the input
electrical power and receive the output power. The magnitude is determined by the ratio of output
electrical power and receive the output power. The magnitude is determined by the ratio of output
to input signal power. Each port, i and j, can provide four types of S-parameters such as S11 , S12 , S21 ,
to input signal power. Each port, i and j, can provide four types of S-parameters such as S11, S12, S21,
and S22 . These parameters are the reflection (i = j) and the transmission (i ‰ j). S11 and S21 can be
and S22. These parameters are the reflection (i = j) and the transmission (i ≠ j). S11 and S21 can be
considered as a representative parameter individually to demonstrate all components in S parameters
considered as a representative parameter individually to demonstrate all components in S parameters
of the RF device. Figure 4 presents S-parameters of RGO and PBA/RGO devices with increasing
of the RF device. Figure 4 presents S-parameters of RGO and PBA/RGO devices with increasing
glucose solution from 0 to 4 mM. According to the property of interconnector material, S-parameters
glucose solution from 0 to 4 mM. According to the property of interconnector material, S-parameters
were changed; intrinsic GO had similar characteristics to the open circuit, RGO and PBA/RGO showed
were changed; intrinsic GO had similar characteristics to the open circuit, RGO and PBA/RGO
showed RGO dominant S11 and S21 results (Figure S1). RGO based devices provided better signal
transmission with higher conductivity.
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RGO dominant S11 and S21 results (Figure S1). RGO based devices provided better signal transmission
with
higher2016,
conductivity.
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Figure
Figure 3.
3. XPS
XPS results
results of
of PBA/RGO
PBA/RGOinterconnector
interconnectorbefore
before and
and after
after adding
adding glucose
glucose in
in (a,b)
(a,b) C
C 1s,
1s; (c)
(c) N
N
1s,
and
(d)
B
1s
orbital.
1s;
and
(d)
B
1s
orbital.
Figure 3. XPS results of PBA/RGO interconnector before and after adding glucose in (a,b) C 1s, (c) N
1s, and (d) B 1s orbital.
Figure 4. Up to 4.5 GHz, RF measurement result of RGO and PBA/RGO RF device. (a) Signal reflection
(signal from
port 1 to port 1, S11) and (b)result
transmission
(signal
from port
1 to port
2, S21).reflection
Glucose
of RGO
RGO and
and
PBA/RGO
RF device.
(a)
Figure 4. Up to 4.5 GHz, RF measurement result
of
PBA/RGO
(a) Signal
Signal
solution
(3
μL)
from
1
to
4
mM
was
dropped
on
the
central
position
of
the
PBA/RGO
device.
(signal from port 1 to
to port
port 1,
1, S11)
S11) and
and (b)
(b) transmission
transmission (signal
(signal from
from port
port 11 to
to port
port 2,
2, S21).
S21). Glucose
Glucose
solution (3 µL)
μL) from
from 11 to
to 44 mM
mM was
was dropped
dropped on
on the
the central
central position
position of
ofthe
thePBA/RGO
PBA/RGO device.
After adding glucose solution, the transmission was significantly increased through the whole
frequency
reflection
parameter
in Figure 4a
showed
that theincreased
reflectionthrough
property
not
After range.
addingThe
glucose
solution,
the transmission
was
significantly
thedid
whole
After adding glucose solution, the transmission was significantly increased through the whole
considerably
change
under
1
GHz,
and
over
2
GHz
the
reflection
magnitudes
of
glucose
solutions
frequency range. The reflection parameter in Figure 4a showed that the reflection property did not
frequency range. The reflection parameter in Figure 4a showed that the reflection property did not
were
substantially
decreased
that2ofGHz
the bare
PBA/RGOmagnitudes
line. PBA/RGO
device provided
considerably
change
under 1compared
GHz, andtoover
the reflection
of glucose
solutions
considerably change under 1 GHz, and over 2 GHz the reflection magnitudes of glucose solutions
considerable
change
in
the
S11
and
S21
result
after
dropping
glucose
solution.
Such
S-parameter
were substantially decreased compared to that of the bare PBA/RGO line. PBA/RGO device
provided
were substantially decreased compared to that of the bare PBA/RGO line. PBA/RGO device provided
change
indicates
that the
transmission
increased
decrement
of signal
loss in the
interconnector.
considerable
change
in the
S11 and S21
result with
after adropping
glucose
solution.
Such
S-parameter
considerable change in the S11 and S21 result after dropping glucose solution. Such S-parameter
The
interaction
between
PBA
and
glucose
assisted
in
reducing
the
signal
loss
and
the
signal
reflection
change indicates that the transmission increased with a decrement of signal loss in the interconnector.
change indicates that the transmission increased with a decrement of signal loss in the interconnector.
in
the
PBA/RGO
interconnector
[32,33].
Many
hydroxyl
groups
of
the
diol,
which
significantly
reduce
The interaction between PBA and glucose assisted in reducing the signal loss and the signal reflection
The interaction between PBA and glucose assisted in reducing the signal loss and the signal reflection
the
conductivity
of graphene and
interfere
transmission,
in PBA/RGO
removed
with
in the
PBA/RGO interconnector
[32,33].
Manysignal
hydroxyl
groups of the
diol, whichwere
significantly
reduce
in the PBA/RGO interconnector [32,33]. Many hydroxyl groups of the diol, which significantly reduce
condensation
reaction
of
PBA
and
glucose
[34].
As
the
concentration
of
glucose
increases
from
1
to 4
the conductivity of graphene and interfere signal transmission, in PBA/RGO were removed with
the conductivity of graphene and interfere signal transmission, in PBA/RGO were removed with
mM,
S11
magnitude
of
PBA/RGO
device
was
decreased.
Although
variations
also
occurred
in
the
S214
condensation reaction of PBA and glucose [34]. As the concentration of glucose increases from 1 to
condensation reaction of PBA and glucose [34]. As the concentration of glucose increases from 1 to
result,
it ismagnitude
too small of
to PBA/RGO
conceive asdevice
a sensor
mM, S11
wascharacteristic.
decreased. Although variations also occurred in the S21
4 mM, S11 magnitude of PBA/RGO device was decreased. Although variations also occurred in the
result, it is too small to conceive as a sensor characteristic.
S21
result, it Signal
is too small
to conceive as a sensor characteristic.
4.
Electrical
of RLGC
4. Electrical
Signal
of RLGC
Since the
S11 and
S21 results provided too little variation to be used for sensor application, R, L,
G, and
C were
extracted
toresults
investigate
the specific
sensor
characteristics
PBA/RGO
RF device.
Since
the S11
and S21
provided
too little
variation
to be used of
forthe
sensor
application,
R, L,
From
results,
those four
parameters
were characteristics
calculated withofthe
G, andthe
C S-parameter
were extracted
to investigate
the
specific sensor
thefollowing
PBA/RGOequation
RF device.
From the S-parameter results, those four parameters
the
following equation
2
2were calculated2 with
2
2
 (1 − S11 + S21 )
Z0 ((1 + S11 ) − S21 
A B
1 

2
2
=
 1 (1 − S + S )
Z0 ((1 + S2 112 )2 −
S2 
CA D
(1 − S11 + S212 ) 21
B 2S121  ((1 − S1111 )2 −21S212 )


C D  = 2S  Z10 ((1 − S )2 − S 2 )
(1 − S112 + S212 ) 
11
21


21
Z

(1)
(1)
Micromachines 2016, 7, 136
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4. Electrical Signal of RLGC
Since the S11 and S21 results provided too little variation to be used for sensor application, R, L,
G, and C were extracted to investigate the specific sensor characteristics of the PBA/RGO RF device.
From the S-parameter results, those four parameters were calculated with the following equation
«
A
C
Micromachines 2016, 7, 136
B
D
ff
1
“
2S21
«
2 ` S2 q
p1 ´ S11
21
2
1
2
Z0 pp1 ´ S11 q ´ S21 q
2
2 q ´ S2
Z0 pp1 ` S11
21
2 ` S2 q
p1 ´ S11
21
ff
(1)
5 of 8
where
Then the
theimpedance
impedance ZZ and
where ZZ00 indicate
indicatethe
theinitial
initialload
load50
50Ω
Ω for
for GSG
GSG probing
probing [35–37].
[35–37]. Then
and RF
RF
propagation constant γ was computed by,
γ
was computed by,
propagation constant
c
B
´−11
γγ “
(2)
= cos
co s A,
A ,Z Z“= B
(2)
C
C
From
telegraphermodel,
model,
the properties
of RF electronic
were
obtained by
From telegrapher
the properties
of RF electronic
circuit werecircuit
obtained
by de-embedding,
de-embedding,
removing
the
fixed
effect
and
taking
meaningful
values
from
the
measured
results.
removing the fixed effect and taking meaningful
avalues from the measured results. The relationship
pR ` jωLq { pG ` jωCq and propagation constant,
The
relationship between impedance, Z “
between
a impedance, Z = ( R + jωL) / ( G + jωC) and propagation constant, γ = ( R + jωL)( G + jωC ) is
γ “ pR ` jωLq pG ` jωCq is composed of the standard electronic features of R, L, G and C.
composed of the standard electronic features of R, L, G and C. These features were extracted as
These features were extracted as follows,
follows,
Im{tγZu
RR =“RRe
e{tγZu
γ Z },,LL =“Im
γ Z } /{ω,
ω,
tγ{Zu
,
C
“
Im
tγ{Zu
G
“
Re
G = R e{γ / Z }, C = Im {γ / Z }{ω
/ω
(3)
(3)
R
considerably
related
withwith
the interconnector’s
electrical
properties,
G and G
C values
R and
andLLvalues
valueswere
were
considerably
related
the interconnector’s
electrical
properties,
and C
were
obtained
from thefrom
interaction
between interconnector
and substrate.
values
are represented
values
were obtained
the interaction
between interconnector
andThese
substrate.
These
values are
in
Figure 5. in Figure 5.
represented
Figure 5.
5. (a)
(a) Resistance,
Resistance, R;
R;(b)
(b)inductance,
inductance,L;L;(c)
(c)shunt
shuntconductance,
conductance,G;G;
and
shunt
capacitance,
Figure
and
(d)(d)
shunt
capacitance,
C, C,
of
of
PBA/RGO
device
according
to
adding
glucose
with
different
concentrations
from
0
to
4
mM.
PBA/RGO device according to adding glucose with different concentrations from 0 to 4 mM.
According to increasing frequency, the resistances were decreased since the electron
According to increasing frequency, the resistances were decreased since the electron transmission
transmission was significantly enhanced at high frequency, as shown in Figure 5a. Near the 2.75 GHz
was significantly enhanced at high frequency, as shown in Figure 5a. Near the 2.75 GHz measurement
measurement frequency, the inductance result of PBA/RGO device showed a specific dip which
originated from the resonance characteristic.
As the concentration of glucose increased, the resistance (Figure 5a) generally decreased and the
conductance (Figure 5c) and capacitance (Figure 5d) increased owing to the enhancement of
conductivity with the RGO reduction, which resulted from the condensation reaction (Figure 1b)
between PBA and glucose molecules. In particular, in Figure 5b, the inductance provided a resonance
Micromachines 2016, 7, 136
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frequency, the inductance result of PBA/RGO device showed a specific dip which originated from the
resonance characteristic.
As the concentration of glucose increased, the resistance (Figure 5a) generally decreased and
the conductance (Figure 5c) and capacitance (Figure 5d) increased owing to the enhancement of
conductivity with the RGO reduction, which resulted from the condensation reaction (Figure 1b)
between PBA and glucose molecules. In particular, in Figure 5b, the inductance provided a resonance
dip shifting according to glucose concentration. The dip shift to a lower frequency can be demonstrated
through the relation between the resonance features and the viscosity of glucose solution [38,39].
Adding glucose on the PBA/RGO interconnector surface results in the enhancement of viscosity and
acts
as a damper,
especially in the condition with the boronic acid [40]. Under the RF system,6the
Micromachines
2016, 7, 136
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conduction transferring the carrier to the opposite port was interfered with by the inductance and took
a longer
time when
inductance
of the biosensor
device hadwas
a high
magnitude.
Linearity
of thethe
PBA/RGO
glucose
investigated
with the R-square between the
Linearity
of
the
PBA/RGO
glucose
biosensor
was
investigated
with
R-square
between
the
fitted results and experimental data according to glucose concentration. Thethe
linearity
of the
resistance
fitted
data according
to glucose
linearity
of the resistance
resultresults
(Figureand
6a)experimental
showed the highest
linear response
forconcentration.
glucose with The
95.45%
of R-square,
and that
result
(Figure
6a)
showed
the
highest
linear
response
for
glucose
with
95.45%
of
R-square,
and
that
of
of the inductance result (Figure 6b) corresponded to 93.23%. Shunt conductance
shunt
the
inductance
result (Figure
6b) interaction
corresponded
to 93.23%.
Shunt conductance
and shunt
capacitance,
capacitance,
determined
by the
between
interconnector
and substrate,
provided
worse
determined
linearity. by the interaction between interconnector and substrate, provided worse linearity.
Figure 6.
6. Linearity
Linearity of
of (a)
(a) resistance,
resistance, R;
R; (b)
(b) resonance
resonance feature
feature of
of inductance,
inductance, L;
L; (c)
(c) shunt
shunt conductance,
conductance,
Figure
G;
and
(d)
shunt
capacitance,
C,
of
PBA/RGO
device
according
to
adding
glucose
with
different
G; and (d) shunt capacitance, C, of PBA/RGO device according to adding glucose with different
concentrations
from
1
to
4
mM.
concentrations from 1 to 4 mM.
Up to 100 μM level of glucose concentration, our PBA/RGO glucose sensor showed insufficient
Up to 100 µM level of glucose concentration, our PBA/RGO glucose sensor showed insufficient
linearity with RF results, as shown in Table 1. Over the milli-molar concentration, the linear
linearity with RF results, as shown in Table 1. Over the milli-molar concentration, the linear relationship
relationship between RF results and glucose concentration was remarkably revealed with high Rbetween RF results and glucose concentration was remarkably revealed with high R-square value in
square value in the resistance and the resonance feature of inductance. Generally, linearity variations
the resistance and the resonance feature of inductance. Generally, linearity variations were increased
were increased under high glucose concentration. While the sensing ability of the resistance was
under high glucose concentration. While the sensing ability of the resistance was balanced with a
balanced with a small range of error and fine linearity, the resonance feature of inductance exhibited
small range of error and fine linearity, the resonance feature of inductance exhibited unstable results
unstable results with high fluctuation. The PBA/RGO glucose sensor showed a detection limit of 3 ×
with high fluctuation. The PBA/RGO glucose sensor showed a detection limit of 3 ˆ 10´5 mol/L,
10−5 mol/L, which is higher than that of the electrochemical glucose sensor composed of a carbon
which is higher than that of the electrochemical glucose sensor composed of a carbon nanotube [41].
nanotube [41].
Table 1: R-square of resistance (R), resonance feature of inductance (L), shunt conductance (G), and
shunt capacitance (C).
Linearity (R-Square, %)
Range of Glucose
Concentration (mM)
R
L
G
C
0.1–0.4
83.15 ± 4.22
69.04 ± 31.41
23.80 ± 2.28
21.51 ± 6.15
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Table 1. R-square of resistance (R), resonance feature of inductance (L), shunt conductance (G), and
shunt capacitance (C).
Linearity (R-Square, %)
Range of Glucose
Concentration (mM)
R
L
G
C
0.1–0.4
1–4
83.15 ˘ 4.22
95.45 ˘ 9.60
69.04 ˘ 31.41
93.23 ˘ 29.37
23.80 ˘ 2.28
69.28 ˘ 42.54
21.51 ˘ 6.15
86.49 ˘ 19.82
5. Conclusions
In the present study, we demonstrated a glucose sensor using an RGO based RF system. RGO as
an interconnector was functionalized with a PBA linker in order to catch the glucose molecules.
The fabricated sensor showed detecting characteristics with fine linearity of the RF signal change as
glucose solution was added. From measurement of the RF signal, several parameters such as R, L, G
and C can be extracted by the equivalent circuit model. Under a high frequency domain, the RGO
based RF sensor could sensitively detect small glucose concentration using multi-dimensional analysis
with the four electrical parameters. The resistance was the most effective parameter for monitoring the
glucose level with stable linearity and small fluctuation. The developed RF sensor can open up new
possibilities in rapid and sensitive detection by applying various interconnector materials with specific
binding affinity.
Supplementary Materials: The following are available online at http://www.mdpi.com/2072-666X/7/8/136/s1,
Figure S1: S-parameter results, (a) S11; (b) S21, of several electrodes with open without interconnector, GO, RGO,
PBA/RGO.
Acknowledgments: This work was partially supported by the Priority Research Centers Program (2009-0093823),
the Korean Government (MSIP) (No. 2015R1A5A1037668) through the National Research Foundation of Korea
(NRF) funded by the Ministry of Education, Science and Technology (MEST), and the ICT R&D program of
MSIP/IITP (R0101-15-0034).
Author Contributions: Byeongho Park wrote and investigated; Hyung Goo Park designed and performed the
experiments; Jae-hoon Ji, Jinsoo Cho and Seong Chan Jun discussed results.
Conflicts of Interest: The authors declare no conflict of interest.
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(CC-BY) license (http://creativecommons.org/licenses/by/4.0/).