volume of 20–125 μL, show a reproducibility of 85–90%. As labels are needed, the
prices for an ELISA kit are quite high. The impedimetric aptasensor developed by
Park et al. cannot compete with the detection limit of the ELISA, but the time for
detection is reduced to 1 h, the price is reduced significantly due to the absence of
labels, and also the required sample volume is lower (5 μL). Further development is
needed on the accuracy, sensitivity, and reproducibility, and several serum samples
from different patients shall be measured to validate reproducibility. Due to the array
structure, 45 IDEs on 1.4 cm
2 , this biosensor could offer a worthy alternative to
ELISA.
In 2015, the same group used the IDE array for the detection of human epidermal
growth factor receptor 2 (HER2), a transmembrane tyrosine kinase receptor [40].
Its overexpression is a marker for breast and other cancers. This time, Qureshi et al.
optimized the amount of immobilized aptamer (2 μM) and used a lower frequency
range of 50–350 MHz, while they chose 242 MHz for the binding curve, reaching
a detection limit of 0.2 ng/mL (2 pM) in diluted serum.
Arya et al. [41] also used IDEs to detect HER2 in undiluted serum samples.
The capacitive measurement was performed with two electrodes in the frequency
range 100 kHz–100 MHz with 200 mV amplitude. They found a minimum in
the phase angle (about À82
) at 2 Hz, concluding that the capacitive fraction
in the imaginary part of the impedance is greatest at this frequency. Compared
to the previous presented system, Arya et al. detected significant higher capacitance
changes (0.12 μF–6.5 pF) with a sensitivity of 35 pF per decade and reached
a detection limit of 0.1 ng/mL (1 pM). Maybe this is contributed by the measurement
in solution and at lower frequencies. They showed a good repeatability on different
electrodes of 95%, and required sample volume is 50 μL. Although Arya et al.
showed in their publication a lower detection limit than [40] and many other
optical and electrochemical biosensors, already in 2013, Chun et al. [42] developed
a simple faradaic impedance sensor for HER2 detection based on gold nanoparticles and reached a detection limit of 10 fg/mL (0.1 fM) in PBS. Besides that,
again there are several commercially available ELISA kits with detection ranges
from 8 pg/mL up to 40 ng/mL, but more prevalent are immunohistochemistry (IHC)
and fluorescence in situ hybridization (FISH).
As the last example, Liao et al. developed a non-faradaic impedance aptasensor
for monitoring of platelet-derived growth factor BB (PDGF-BB) [43]. They modified a silicon electrode with silane and covalently attached the aptamer on the
surface. Optimization was performed by application of an AC potential of 10 mV
amplitude in the frequency range of 300 kHz–0.1 Hz at the stepwise increased DC
potential of À0.4 V to 0.4 V. The DC potential is the baseline on which the
sinusoidal voltage is laid. Online measurements were performed at the optimized
conditions of À0.1 V and 5 kHz. A 2 μM PDGF-BB solution caused a decrease of
total capacitance of about 35 nF. They were able to detect down to 40 nM PDGFBB, low non-specific binding, and high specificity.
The same research group published 1 year later a faradaic impedance biosensor
using the same aptamer on gold electrodes modified with polypyrrole [44]. In this
way, they were able to detect PDGF-BB down to 0.4 nM, thus an increase of
30
P. Reich et al.
prices for an ELISA kit are quite high. The impedimetric aptasensor developed by
Park et al. cannot compete with the detection limit of the ELISA, but the time for
detection is reduced to 1 h, the price is reduced significantly due to the absence of
labels, and also the required sample volume is lower (5 μL). Further development is
needed on the accuracy, sensitivity, and reproducibility, and several serum samples
from different patients shall be measured to validate reproducibility. Due to the array
structure, 45 IDEs on 1.4 cm
2 , this biosensor could offer a worthy alternative to
ELISA.
In 2015, the same group used the IDE array for the detection of human epidermal
growth factor receptor 2 (HER2), a transmembrane tyrosine kinase receptor [40].
Its overexpression is a marker for breast and other cancers. This time, Qureshi et al.
optimized the amount of immobilized aptamer (2 μM) and used a lower frequency
range of 50–350 MHz, while they chose 242 MHz for the binding curve, reaching
a detection limit of 0.2 ng/mL (2 pM) in diluted serum.
Arya et al. [41] also used IDEs to detect HER2 in undiluted serum samples.
The capacitive measurement was performed with two electrodes in the frequency
range 100 kHz–100 MHz with 200 mV amplitude. They found a minimum in
the phase angle (about À82
) at 2 Hz, concluding that the capacitive fraction
in the imaginary part of the impedance is greatest at this frequency. Compared
to the previous presented system, Arya et al. detected significant higher capacitance
changes (0.12 μF–6.5 pF) with a sensitivity of 35 pF per decade and reached
a detection limit of 0.1 ng/mL (1 pM). Maybe this is contributed by the measurement
in solution and at lower frequencies. They showed a good repeatability on different
electrodes of 95%, and required sample volume is 50 μL. Although Arya et al.
showed in their publication a lower detection limit than [40] and many other
optical and electrochemical biosensors, already in 2013, Chun et al. [42] developed
a simple faradaic impedance sensor for HER2 detection based on gold nanoparticles and reached a detection limit of 10 fg/mL (0.1 fM) in PBS. Besides that,
again there are several commercially available ELISA kits with detection ranges
from 8 pg/mL up to 40 ng/mL, but more prevalent are immunohistochemistry (IHC)
and fluorescence in situ hybridization (FISH).
As the last example, Liao et al. developed a non-faradaic impedance aptasensor
for monitoring of platelet-derived growth factor BB (PDGF-BB) [43]. They modified a silicon electrode with silane and covalently attached the aptamer on the
surface. Optimization was performed by application of an AC potential of 10 mV
amplitude in the frequency range of 300 kHz–0.1 Hz at the stepwise increased DC
potential of À0.4 V to 0.4 V. The DC potential is the baseline on which the
sinusoidal voltage is laid. Online measurements were performed at the optimized
conditions of À0.1 V and 5 kHz. A 2 μM PDGF-BB solution caused a decrease of
total capacitance of about 35 nF. They were able to detect down to 40 nM PDGFBB, low non-specific binding, and high specificity.
The same research group published 1 year later a faradaic impedance biosensor
using the same aptamer on gold electrodes modified with polypyrrole [44]. In this
way, they were able to detect PDGF-BB down to 0.4 nM, thus an increase of
30
P. Reich et al.