Electrochemical Science Adv - 2022 - Cao - ISFET‐based sensors for bio chemical applications A review

Review
1 of 25 Electrochemical Science Advances doi.org/10.1002/elsa.202100207
Received: 30 November 2021

Revised: 23 February 2022
Accepted: 24 February 2022
ISFET-based sensors for (bio)chemical applications: A

review
Shengli Cao1,# Peng Sun1,# Gang Xiao1 Qiang Tang2 Xinyue Sun1
Hongyu Zhao2 Shuang Zhao2 Huibin Lu2 Zhao Yue1,3
1 Department of Microelectronics, Nankai University, Tianjin, P. R. China
2 School of Information Science and Engineering, Yanshan University, Qinhuangdao, P. R. China
3 Tianjin Key Laboratory of Optoelectronic Sensor and Sensing Network Technology, Nankai University, Tianjin, P. R. China
Correspondence
Zhao Yue, Department of Abstract
Microelectronics, Nankai University, Ion-sensitive field effect transistor (ISFET) sensor is a hot topic these years, play-
Tianjin, P. R. China.
Email: yuezhao@nankai.edu.cn ing the combined roles of signal recognizer and converter for (bio)chemical ana-
Huibin Lu, School of Information Science lytes. In this review article, the basic concept, origination, and history of the
and Engineering, Yanshan University,
ISFET sensor are presented. In addition, the common fabrication processes, the
Qinhuangdao, P. R. China.
Email: yjsbl@ysu.edu.cn most-used working principle (potentiometric, amperometric, and impedance-
metric), and the techniques of gate functionality (physical, chemical, and bio-
# ShengliCao and Peng Sun1 share equally
logical) are discussed introducing the afterward signal transfer processes from
contribution.
ISFET to the terminals through different types of circuits. At last, the develop-
Funding information ment and recent progress (until 2021) of ions and biomolecules (DNA molecules,
National Natural Science Foundation,
Grant/Award Numbers: 61871240,
antibodies, enzymatic substrates, and cell-related secretions or metabolism) were
61471207; Opening Project of Key introduced together with the outlook and facing obstacles (Debye screening, the
Laboratory of Microelectronic Devices & wearability of ISFET, the multiplexed detections) before the commercialization
Integrated Technology; Institute of
Microelectronics; Chinese Academy of of ISFET. This review article emphasizes the advantages of the developed ISFET
Sciences; Natural Science Foundation of sensors as miniaturization, low-cost, all-solid, highly sensitive, and easy opera-
Hebei, Grant/Award Numbers:
tion for portable and multiplexed detections.
F2021203102, C20210324
KEYWORDS
Biosensors, ISFET, Multiplexed detection, Portable sensor, Sensing arrays
1 INTRODUCTION
Abbreviations: CNTs, Carbon nanotubes; CV, Cyclic voltammetry;
DG, Double gate; EG, Extended gate; EIS, Electrochemical impedance 1.1 The ISFET-based electrochemical
spectroscopy; FET, Field effect transistor; GOD, Glucose oxidase; IG, sensor
In-plane control gate; ISFET, Ion sensitive field effect transistor; JFET,
Junction field effect transistor; MESFET, Metal-semiconductor field
effect transistor; M-O-S, Metal-oxide-semiconductor; PEI, Nowadays, the monitoring of electrochemical reactions
Polyethyleneimine; QCM, Quartz crystal microbalance; RE, Reference has been used in many fields such as human health
electrode care, waste-water treatment, air pollutant monitoring,
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the
original work is properly cited.
© 2022 The Authors. Electrochemical Science Advances published by Wiley-VCH GmbH.
Electrochem. Sci. Adv. 2023;3:e2100207. wileyonlinelibrary.com/journal/elsa 1 of 25

https://doi.org/10.1002/elsa.202100207
26985977, 2023, 4, Downloaded from https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/elsa.202100207 by Readcube (Labtiva Inc.), Wiley Online Library on [19/11/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Review
F I G U R E 1 (a) The classification of typical electrochemical sensors. Reproduced with permission.[11] Copyright 2018 Springer. (b) The
ISFET arrays for multiplexed detections. Reproduced with permission.[12] Copyright 2020 ACS. (c) The miniaturized ISFET for fabricating
portable device. Reproduced with permission.[13] Copyright 2019 Elsevier. (d) The wearable sensor based on the ISFET technique Reproduced
with permission.[14] Copyright 2018 Nature. (e) The graphic scheme of the ISFET-sensing applications for different analytes
and food safety industry.[1] According to different out- as it does not have a unified manufacturing standard.[6]
put signals, traditional electrochemical reaction monitor- To solve these problems, ion-sensitive field effect tran-
ing methods can be divided into optical system[2] and clas- sistor (ISFET) attracted much attention since it was pro-
sic three-electrode system.[3] The optical method, such duced in 1970 (Figure 1a).[7] ISFET has many advantages
as electrochemiluminescence, is based on fluorescence in monitoring electrochemical reactions. First, it is based
change during electrochemical reactions (Figure 1a).[4] on standard complementary metal-oxide-semiconductor
Although achieving high sensitivity, optical systems technique, ISFET can be mass produced and further inte-
need costly, large-size and sophisticated instruments, grated into other sensing systems.[8] Second, compared to
thereby being hard to promote or integrate into portable the three-electrode system, the ISFET requires only one
devices.[5] Classic three-electrode system refers to poten- reference electrode (RE) to achieve biochemical measure-
tiostat using potentiometric and amperometric methods, ments, giving the ISFET a greater advantage in size. Then,
owning advantages such as high sensitivity and low cost ISFET is an all-solid-state sensor without fragile material
(Figure 1a). However, three-electrode system is difficult involved, thereby being acid-alkali resistant, water repel-
to be mass produced and integrated into other systems lent, and crash resistant in practical use.[9] At last, the
Review
ISFET is easily operated and its working principle can be feld in 1925. There are different types of FET depending
stated as follows. The whole sensing system is composed on the gate structure, such as junction FET (JFET), metal-
of the ISFET and RE. ISFET is consisted of three termi- semiconductor FET (MESFET), and insulated gate FET.
nals: source, drain, and gate (Figure 1e). The bias on the The initial JFET was proposed by W. Shockley in 1952.[15]
electrolyte and the insulated gate is provided by the RE. JFET is fabricated by two highly doped p-type regions on
Meanwhile, the switching of the conduction channel can an n-type semiconductor. The electrode drawn from the p-
be adjusted by applying a voltage on the RE. Then, the type region is called gate. Two electrodes are drawn from
drain voltage can influence the channel current. Specif- both ends of the n-type semiconductor, which are called
ically, when a positive voltage is applied to the RE, the drain and source. The JFET is a double p-n junction, which
positive charges close to the gate substrate move down- realizes the control of the depletion layer and the conduc-
ward, leaving negative charges. At the same time, the negative channel through the gate voltage and the drain voltage.
tive charges of the substrate are attracted to move upward. Therefore, the conductivity of the channel will change,
Owing to this charge accumulation under the gate, a con- which is reflected by the external circuit. And also based on
ductive channel can be formed between the source and a semiconductor process, MESFET was realized by using a
drain (Figure 1e). When the channel is formed, the corre- metal-semiconductor junction to replace the p-n junction
sponding voltage is the threshold voltage. Then, when the of JFET to achieve easier fabrication processes and higher
low voltage is applied between the source and the drain, working speed.[16] Compared with MESFET, the represen-
the negative charges will form a drain current (IDS ) in the tative insulated gate FET, using a metal with an insulated
direction of the voltage. The internal electric field formed layer (such as SiO2 ) below to fabricate the gate, was initially
by the voltage on the RE controls the amount of charges invented by Mohamed M. Atalla and Dawan Kahng at Bell
in the channel, which in turn determines the conductiv- Lab in 1960 to solve the problem of “surface state” which
ity of the channel. It can be seen that the IDS can be eas- can be reduced by a sandwich structure of metal (M)-
ily modulated by the gate bias during the turn-on phase. oxide (O)-semiconductor (S), namely the widely known
When the ISFET is placed in the electrolyte, the sensitive MOS structure.[17] However, because this early MOSFET
film on the gate surface will combine with specific ions and worked slowly and damaged easily, until a few years later,
molecules in the electrolyte. Then, the potential distribu- its value as signal transducer with advantages of low cost,
tion on the gate surface will change, thereby affecting the easy fabrication, and easy integrated in large-scale circuit
depletion or accumulation of carriers in the channel. The was finally realized.[18] Considering the maturity of MOS-
process can be reflected by the change of the ISFET elec- FET technology, Piet Bergveld from Dutch retained the
trical output.[10] Thus, the electrochemical reactions in the structure of MOSFET transducer and further developed
electrolyte can be monitored by electric signals. For exam- the ion-sensing application. By removing the metal gate
ple, when Si3 N4 was used as a gate of the ISFET, it can of M-O-S structure, it leads to direct contact between the
absorb H+ because the surface hydroxyl groups can react solution and the oxide to achieve linear detection of ions.
with H+ , resulting in a charge redistribution on the ISFET In 1970, the quantify detection of Na+ was realized by
gate. This change of charge distribution will influence the drain-source current (IDS ) output, which is the world’s first
threshold voltage of ISFET, leading to a change of the cur- ISFET sensor.[19] When the metal gate is removed from
rent IDS , which can be reflected by an electrical output oxide-semiconductor structure, a further sensitive film can
of the ISFET through the external circuits. In conclusion, be immobilized on the oxide layer to detect other type of
ISFET is a newly designed electrochemical sensor with ions and molecules. Finally, the sensing film-O-S structure
advantages of miniaturization, low cost, all-solid, high sen- was formed as the classic ISFET structure widely known
sitivity, and easy operation. Thus, ISFET has become one of nowadays. The sensing film is usually defined as the gate
the main branches of modern sensor today and its prosper- of ISFET. The gate materials on the sensing film determine
ity is from the mutual endeavors of research groups glob- the sensing performance of the ISFET. For example, for the
ally which is presented in the next section in details. detection of H+ ions, by depositing various sensitive films
(such as Si3 N4 , Al2 O3 , Ta2 O5 ) on the insulating oxide layer,
the sensitivity of H+ can be changed from 25 to 55 mV/pH,
1.2 The history of ISFET showing a wide range.[20] This can be explained success-
fully by the site dissociation model mentioned by Bousse
The ISFET sensor consists of a transducer and a sens- et al. in 1983.[21] Later, by replacing sensitive films materi-
ing element. Compared with the sensing unit, the devel- als of the gates, the detection of ions other than H+ can be
opment history of the transducer is more traceable. The expanded.
ISFET is originated from the field effect transistor (FET) Based on the well-studied ionic detections using ISFET,
devices which were first presented by Julius Edgar Lilien- the detection of other types of analytes, such as gas and
Review
biomolecules, was further achieved by the flexible design and the required gate voltage change is about 20 mV.[32]
of the ISFET gate. In 1975, to detect gas for the first time, For the substrate material, for example, Li-Te Yin opti-
the ISFET was successfully fabricated with a gate prepared mized the ISFET gate by replacing the classic Si substrate
by noble metal.[22] Afterward, Steve Caras and Jiri Janata with a glass substrate to simplify the fabrication process,
first reported that ISFET can identify biomolecule of peni- lower the cost of production, improve the sensitivity, solve
cillin through the enzymatic reactions in 1980.[23] Since the ISFET drift when detecting H+ (drift reduced by about
then, many ISFET-based biosensors began to be estab- 10 times), and it has a linear sensitivity of approximately
lished. For example, since 1983, urea can be detected by 58 mV/pH in the pH concentration range 2–12.[8a] The
different functionalities, such as acetylcellulose, polyvinyl structure study refers to the redesigning of the gate struc-
alcohol, and albumin, immobilized on the ISFET gate.[20] ture. For example, representative new designs of extended
Afterward, the size of the sensor was further optimized gate (EG) and Fin gate can effectively overcome the limita-
that Jun-ichi Anzai et al. produced a miniature urea sen- tions of ISFET in terms of applicability, drift and threshold
sor through the enzymatic functionalities on the ISFET voltage, and current-on-off ratio. With the current tech-
gate in 1984.[24] Also, the practicality of the sensor was nology, the EG structure can achieve a small drift rate
studied by the urea detection in human serum based on of 0.4 mV/h, which is 10 times lower than that of ordi-
improvements of enzymatic modification techniques on nary gates. The Fin-gate structure can achieve 176.65 and
the gate.[25] The anti-interference performance of sen- 295.89% of the current switching ratio and threshold volt-
sor was improved by Yuji Miyahara et al. in 1985, so age. Moreover, compared with ordinary gates, the Fin-gate
that urea and glucose can be detected at the same time structure provides more than six times the living space for
with less interference.[26] Thus, the initial application of biomolecules, thus, providing better sensitivity.[34] Also,
ISFET for gas and biomolecules can be verified success- stacking layers of ISFET gate is another type of new struc-
fully. The subsequent development of the ISFET sensor is ture. For example, the reasonable coupling of stacking
based on the clinical applications focusing on the detec- SiO2 /HfO2 /Al2 O3 layers improves the stability and sensi-
tions of glucose, DNA, antibody, and cells.[27] For exam- tivity of the ISFET device greatly.[35] The stacking struc-
ple, Vjacheslav Volotovsky et al. expanded the dynamic ture exhibits a low drift rate of 0.23 mV/h, a low hys-
detection range of glucose by enzymatic modification of teresis width of 1.85 mV, and a high pH sensing level of
ISFET gate in 1996.[28] Maya Zayats et al. developed a new 57.1 mV/pH. The functionality study mainly refers to the
immunosensor after forming an antigen-antibody complex introduction of new materials on the gate of ISFET sen-
on the ISFET device in 2002.[29] Sunil Purushothaman sor. For example, by designing a microstructure on ISFET
et al. reported a new method for identifying nucleotide gate, fast response and ultrasensitive detection of protein
polymorphisms using ISFET sensor in 2006.[30] Gonçalves can be realized, with a linear detection region of 10 nM to
et al. used amorphous silicon-based ISFET in 2008 for the 1 μM for proteins in human plasma.[36] Inspired by that,
label-free detection of DNA hybridization.[31] These works nanomaterials can also be functionalized on the ISFET
verified that the ISFET senor can be expanded from ionic gate to improve the performance of the sensor. For exam-
sensor to the biochemical sensor and used for the clinical ple, by amine-modified polystyrene nanobeads, the detec-
study in practical use. tion of antibodies using ISFET can be improved success-
Nowadays, after the possibilities of clinical detection fully. The calculated limit of detection for the antibody is
were verified, the research emphasis was shifted to the 1.0152 μg/mL and the sensitivity was 4.43 V mL/μg, which
technique to improve the performance of the ISFET is more sensitive than the oxide gate, and the results are
biosensors. The related studies mainly include the mate- very stable even after vigorous washing.[11] Thus, based on
rial, structure, and functionality of the ISFET gate.[32] The the efforts mentioned above, the performance of the ISFET
material study can be summarized as two aspects, namely sensor has been greatly improved preparing for the future
the gate material and the substrate material. For the gate development for better practicality.
material, the performance of six high-k gate materials In the past 30 years, ISFETs developed rapidly and
(Si3 N4 , Al2 O3 , ZrO2 , Ta2 O5 , HfO2 , and TiO2 ) used in the became one of the most popular biochemical sensors with
pH ISFET sensors have been studied, revealing that TiO2 hundreds of top articles published each year.[7a] Nowa-
has the best current sensitivity of 95 μA/pH, while Al2 O3 days, the ISFET-sensing technique has been mature to
has the best voltage sensitivity of 59.37 mV/pH.[33] And some extent. The application was not satisfied with sin-
recently, it should be noticed that there is a new concept gle detection. Multiplexed detection with single chip can
called negative capacitance FET using ferroelectric materi- also be realized by the usage of ISFET arrays due to
als as the ISFET gate to achieve enhanced current sensitiv- the easy integration of ISFET (Figure 1b). When many
ity of the pH ISFET sensors. The corresponding subthresh- ISFETs were integrated on one sensing chip, the on-off of
old slope changes one decade of the source-drain current each ISFET can be controlled electrically. With different
Review
F I G U R E 2 The basic modules of the ISFET-based sensing system to recognize the analytes and then transfer the biochemical signals to
the electrical signals which can be finally output and collected by terminal of PC, smartphone, or other integrated system
functionalities on the gate, only the ISFET under “on” state 2.1 The fabrication of ISFET
is working and transferring the biochemical signals from
the corresponding analytes as electrical signals. When Since the main difference between ISFET and MOSFET
the ISFETs with different functionalities were operated is the gate structure, ISFET can be mass produced using
one by one, different analytes can be detected with sin- similar techniques with simple procedures, which is very
gle chip at same time. Moreover, when the ISFET is fab- promising for the future commercialization.[37] In details,
ricated as small size (Figure 1c) with high performance, the related fabrication processes can be concluded as fol-
portable and wearable device can be realized by ISFET- lows. As shown in Figure 3a, the first step is the selection of
sensing system (Figure 1d). Based on that, the ISFET sen- the substrate material. The most-used substrate materials
sors have been used to detect different analytes including are elemental (such as silicon, germanium) and compound
ions, DNA molecules, antibodies, enzymatic substrates, (such as gallium arsenide) semiconductors.[38] The first
and cell-related secretions or metabolism (Figure 1e). The study of semiconductor is based on germanium and sili-
realization of these aspects not only depends on the study con accumulating mature techniques to fabricate smooth
of ISFET, but also relies on the well-developed sensing sys- and thin layer, also considering the cost of production, so
tem which can be checked in the next section. that they are usually the most appropriate and represen-
tative ones. Also, for a better selection, there are two key
points needed to be noticed including the crystal orienta-
2 THE SENSING SYSTEM OF THE tion and electrical conductivity.[39] For example, when sil-
ISFET DEVICE icon is selected, a 100-crystal orientation and p-type sub-
strate is usually adopted because of the highly efficient
When the ISFET is used as sensors, several modules should mobility of charged carriers, large drain current, strong
be used to support the ISFET as a whole sensing system. inversion region, and large electrical output for a better
The sensing processes can be presented briefly as follows. performance of ISFET.[40] Afterward, when the substrate
In Figure 2, the ISFET is the analyte recognizer in the is selected, the second step is called etching to prepare
electrolyte for the purpose of signal collection and trans- the source and drain electrodes of ISFET (Figure 3a).[41]
fer. This is finished with the help of the flexible design of The etching processes are essential because pits can be
the gate material and structure together with the diverse formed on the substrate to load electrodes by diffusion
functional techniques of the ISFET gate. Finally, the bio- technique and ISFET size can be thinner compared with
chemical signal from analytes can be transferred to elec- the case without pits. With the current process, the thick-
trical ones by the ISFET transducer successfully based on ness of ISFET can be controlled below 500 μm. For exam-
the potential, current, or impedance output of the ISFET. ple, Anastasios Vilouras et al. used a series of processes,
The electrical signals will be transmitted to the terminals, such as chemical vapor deposition (CVD), ion implanta-
such as PC, smartphone, or other integrated system, for tion, plasma etching, and chemical mechanical thinning,
further analysis with the help of the external circuits. In to prepare ultra-thin ISFET chips with enhanced bend-
this section, the ISFET-based sensing system will be pre- ing induction performance. The overall thickness of the
sented including the fabrication of ISFET, the working chip is approximately 100 μm.[42] Most importantly, it is
principles of ISFET, the most-used measurement circuits beneficial to control the size and shape of the electrodes
of the ISFET-based sensing system, and the common tech- and adjust the width-to-length ratio of the ISFET chan-
niques of ISFET gate functionality. nel to optimize sensing performance. Bigger ratio value
Review
F I G U R E 3 (a) The fabrication process, (b) the lateral view, and (c) the top view of a common ISFET. Reproduced with
permission.[39,41,47–49] Copyright 1997 Elsevier. Copyright 2017 Elsevier. Copyright 2002 Elsevier. Copyright 2018 Elsevier. Copyright 2006
Springer. (d) The formation of conducting channel when the ISFET is working with the help of the gate potential (VGS ) applied. Reproduced
with permission.[50] Copyright 2006 APS
contributes to larger saturation current and better conduc- insulating layer also realizes the separation of the channel
tivity of the ISFET, thereby improving the ionic sensitiv- and the sensing film. Second, the surface passivation of the
ity of ISFET sensor.[43] However, this also increases the insulating layer can prevent oxidation of the substrate and
power consumption and drift of the ISFET sensor induc- reduce the influence of the interface state, thereby improv-
ing limited stand-by time and stability. Thus, an appro- ing and stabilizing the performance of the ISFET. Third,
priate aspect ratio is very important for an ISFET fabrica- the insulating layer also can realize a waterproof control
tion. After that, in the third step an ion-implantation tech- and prevent the migration and penetration of ions from
nique is used to fabricate two highly doped n-type regions, electrolyte to the substrate for ISFET’s stability. Finally, the
and two metal electrodes are drawn out as the source and sensing film should have the ability to recognize ions in the
drain, respectively.[44] Afterward, an insulating layer (such electrolytes to offer good sensitivity and selectivity of the
as SiO2 ) and a sensing film are deposited on the two elec- ISFET sensor. In practical use, single type of sensing film
trodes by techniques such as CVD, magnetron sputtering cannot meet the three requirements at the same time, so
or radio frequency sputtering.[45] Their function in the that stacking layers with different materials in each layer
ISFET can be concluded as follows. First, the insulating is needed.[35,46] For example, Wang Lei et al. fabricated
layer serves as a dielectric between the sensing film and the an highly sensitive ISFET pH sensor with multiple layers
substrate, and the three form a capacitor. Furthermore, the of AlGaN/GaN/Al2 O3 coated realizing stable detection.[47]
gate voltage can be controlled to form a conductive chan- Based on that, the ISFET fabricated needs further packag-
nel near the substrate of the insulating layer, so that the ing because ISFET mainly works in the aqueous medium,
Review
the packaging of the entire device is particularly important per unit area; and w/l is the channel width-to-length ratio.
to further improve the water-proof properties.[48] The rep- Thus, by selecting parts of the parameters of Equation (2)
resentative method is using epoxy resin to seal the whole as fixed values, the VT can be output indirectly by other
ISFET and only leave the ion-sensitive gate exposing to the parameters such as IDS , VGS , and VDS , the related sensor
electrolyte.[38] The fabricated ISFET in Figure 3b and c and can be defined as potentiometric or amperometric sen-
the detailed working processes can be seen in the next sec- sors. Based on this, impedance can be further used as an
tion. output which can be defined as impedancemetric sensor.
The details can be found as follows. For the potentiomet-
ric principle, when the IDS and VDS are set as fixed val-
2.2 The working principle of ISFET ues, the VT change affected by the ion concentration in the
sensor electrolyte can be reflected by the VGS output; when the
[ ] IDS and VGS are set as fixed values, the VT is reflected by
( ) 𝑄𝑜𝑥 ∅
𝑉𝑇 = 𝐸𝑟𝑒𝑓 + 𝜑 + 𝑥 − 𝜑𝑒𝑜 − − 2∅𝑓 + 𝑠𝑖 , (1) the VDS output. The VGS output is the most used method
𝐶𝑜𝑥 𝑞 comparing with the VDS output. For example, an ISFET-
based sweat microsensor was built based on the potentio-
[ ]
𝑤 1 2 metric principle by monitor the VGS , when the VDS and
𝐼𝐷𝑆 = 𝑢𝐶𝑜𝑥 (𝑉𝐺𝑆 − 𝑉𝑇 ) 𝑉𝐷𝑆 − 𝑉𝐷𝑆 . (2)
𝑙 2 IDS are fixed.[51] For the amperometric principle, when the
VGS and VDS are kept as constant values, the VT change
The ISFET fabricated can be used for transferring can be reflected by the IDS change. For example, based on
biochemical signal to electrical signal for further col- the IDS output, Ibrahim Fakih et al. developed an ISFET
lection, analysis, and study. The structure of ISFET is sensor realizing the real-time and simultaneous measure-
similar to the MOSFET by replacing metal gate by ment of K+ , Na+ , NH4 + , NO3 − , SO4 2− , HPO4 2− , and Cl−
RE/electrolyte/insulating gate as a whole. Thus, the signal to study the mineral uptake by aquatic organisms.[52] For
transfer mechanism is similar and the basic principle can the impedancemetric principle, when the VDS is fixed,
be concluded as follows. In details, when ISFET is work- the VT changes can also be reflected by the transconduc-
ing for ion detection, a gate voltage (VGS ) is applied by a tance (gm = ΔIDS /ΔVGS ) output or impedance Z output of
RE through electrolyte (Figure 3d). When the VGS scan- ISFET. For example, Jingbo Chang et al. built an ISFET
ning from small to big value, the holes of ISFET substrate sensor using gm as output, realizing the ultra-highly sen-
are pushed down and the generation of electrons accumu- sitive detection of Pb2+ with a low LOD of 1 nM.[53] On
lated begins to form a channel connecting the source and the basis of the three principles above, ISFET sensors have
drain electrodes (Figure 3d). When the VGS increases to a been developed from laboratory to practicality and more
certain level (threshold voltage, VT ), the amounts of elec- ionic sensing applications based on the three working prin-
tron in the channel can be enough to make the channel ciples can be found in Table 1. It can be seen that the ISFET-
conductive with current (IDS ) and voltage (VDS ) generated sensing applications for ions using different working prin-
between the source and drain electrodes. Thus, the con- ciples are mature.
centration of ions in the analytes can be quantified by VT Based on the potentiometric, amperometric, and
directly which can be explained by Equation (1). Where impedancemetric principles mentioned above, ions
Eref is the potential of RE; φ is the potential between the could be detected directly by the ISFET. However, for
RE and electrolyte; 𝑥, 𝜑𝑒𝑜 , 𝐶𝑜𝑥 , and Qox are the polariza- the nonlabeled analytes, such as biomolecules, it is not
tion potential, surface potential, capacitance per area, and possible to detect them with bare ISFET gate directly,
charge density of the gate; ∅𝑓 and ∅𝑠𝑖 are the Fermi poten- because they cannot be captured to affect the gate sur-
tial and work function of silicon substrate; q is the unit face charge distribution. To solve this, the most-used
charge.[50] Thus, VT is only affected by 𝜑𝑒𝑜 which is deter- method is the functionalities of the ISFET gate using
mined by ion concentration. biochemical probes to specifically recognize and detect
VT plays two roles, namely controlling the on-off of biomolecules.[54] When the recognition processes affect
the ISFET and determining the ion concentration to real- the charge distribution or resistance of the ISFET gate,
ize the signal transfer from chemical to electrical ones. the concentration of the biomolecules can be reflected by
However, in practical, the VT cannot be collected directly the ISFET electrical output similar to the ionic detection.
and only can be reflected by other parameters of voltage For example, Maya Zayats et al. developed a new type of
(VGS or VDS ), current (IDS ), or impedance. There is a rela- immunosensor using an antigen layer fixed on the gate to
tionship among IDS , VGS , VT , and VDS based on Equa- detect anti-dinitrophenyl antibodies based on the Z output
tion (2), where u represents the electron mobility of the of the ISFET gate.[29] More examples of the biomolecule
ISFET at room temperature; 𝐶𝑜𝑥 is the gate capacitance detection using ISFET can be seen in Table 1 and section 3.
Review
TA B L E 1 The conclusion of different principles for ISFET sensors (LOD means the limit of detection; n.s. means not specified)
Principle Output Fixed Configuration Performance Application Year References
Potentiometric VGS IDS VDS High aspect ratio Fin-gate 30-35 mV/pH pH 2018 [55]
Ta2 O5 /SiO2 film gate 2.3 μM protein 2019 [56]
Sol–gel TiO2 film for an 61.44 mV/pH pH 2019 [57]
extended-gate
one-dimensional 3–5 fM cell 2020 [58]
nanoISFET arrays of
silicon
Enzyme/Si3 N4 film gate n.s. Enterobacteria 2021 [59]
EG-ISFET with 63.15 mV/pH pH 2021 [60]
Mesoporous
Multimetallic Oxide
Amperometric IDS VGS VDS electrically-floating n.s. real-time DNA 2018 [61]
electrode
DG HfO2 gate 0-23.16 μA /pH pH 2019 [62]
0-27.68 μA
/mW
horseradish peroxidase gate ≥106 cfu/mL peroxidase 2019 [63]
activity
Si3 N4 -gate -4.22 μA/pH pH and blood 2019 [64]
gases
ISFET-based multi-sensor 4.23 μA/pH uric acid 2020 [65]
readout system on chip
DG handheld ISFET 0.3 pg/mL cardiac troponin 2021 [66]
I
Impedancemetric gm VDS IDS Extended gate ISFET based 0.033 mV/kLux optical effect 2014 [67]
on SnO2 /ITO
gm p-channel, open-gate n.s. cellular 2015 [68]
adhesion and
detachment
processes
gm/ Si nanowires ISFET <1 cell/Ml ultrarare 2019 [69]
circulating
tumor cells
Z Anticocaine aptamer 1 × 10−6 M analysis of 2019 [70]
fragments gate cocaine
Z The lead ion selective 10−11 - 10−10 M Pb2+ detection 2020 [71]
membrane EG-ISFET
Z Impedance-modulated 10−11 - 10−10 M Lead ion 2020 [71]
ISFET detection in
human blood
Z Polyaniline gate 1 pM-1 μM DNA/RNA 2021 [72]
biomarker
Z Si-nanowire ISFET n.s. biomolecule 2021 [73]
binding
2.3 The technique of gate functionality and long lasting for stable detection. Third, the coverage of
the probes on the gate should be high to ensure the sens-
There are several mature techniques of the gate function- ing performance. The most-used techniques of ISFET gate
ality that meet three requirements. First, the processes functionality can be concluded as three types using dif-
should be simple and easy to operate. Second, after the ferent probes (Figure 4a). First, the physical probe refers
functionality, the activities of the probes should be high to the functionality using noncovalent forces, such as van
Review
F I G U R E 4 The diagram of gate functionality based on (a) physical probes, chemicals probes using (b) covalent bond and (c)
cross-linking and (d) biological probes. Reproduced with permission.[54] Copyright 2019 Springe
der Waal’s force and electrostatic forces, to absorb analytes. 2.4 The measuring circuit of ISFET
Its advantage is easily operated and less damages to the
ISFET gate surface, while the disadvantages are the sta- The processing of ISFET output, such as the potential,
bility which can be affected by pH.[54] Also, the analytes current, and impendence, can be realized with the help
should be charged species, resulting in limited sensing of external measuring circuits. In the past, because of
types. The chemical probe refers to the using of covalent the poor compatibility between ISFET and measuring cir-
bond to bind analytes to the gate (Figure 4b). Comparing cuits, the performance ISFET sensor was not completely
with the physical one, although the covalent bond needs explored.[76] However, with the continuous development
more complicated processes involving poisonous chemi- of the integrated circuit technology these years, the com-
cals, it is more stable with stronger binding force result- patibility has been improved greatly. Different types of
ing in an improved stability of the sensor. For example, the measurement circuits have been developed and the
based on the covalent functionality of silanization on the most used ones can be concluded as follows depending
gate, urea, glucose, and acetylcholine can be detected by on the ISFET working principles. The measuring circuits
ISFET successfully.[74] Also, the binding method of cross- of the potentiometric ISFET sensors mainly include three
linking cannot be neglected which is also using the chem- basic types: (i) As mentioned above, VT changes can be
ical probes and refers to the linking of analytes as short affected by the analyte concentration and indirectly out-
chains or sequences bond on the ISFET gate (Figure 4b). put by VGS when IDS and VDS are fixed. However, there
In details, the cross-linking can be realized based on chem- is always difference between the VGS value and the real
icals with two or multiple functional groups that can con- VT value in practical use. To solve this, as shown in
nect to analytes and gate surface at the same time.[54] Figure 5a, a circuit with MOSFET-based differential ampli-
Moreover, biological probes can be immobilized on the fier and two symmetry load-resistances was introduced.
ISFET gate to further detect biomolecules (Figure 4c). For The closer value between the two resistances, the more
example, Bruno Veigas et al. immobilized DNA probes on accurate VT value can be obtained from the VGS (Vout ).
the ISFET gate for relative mismatch detection.[75] Thus, However, limited by the resistance manufacturing tech-
based on the mature working principles and diverse func- nique with inevitable deviations, the value of the two resis-
tionality techniques mentioned above, different types of tances cannot be totally same.[77] Thus, other types of mea-
analytes can be recognized by ISFET converting biochem- suring circuit were studied to output accurate VT values.
ical signal to electrical signal. Afterward, external circuits (ii) As shown in Figure 5b, without using the symme-
should be further used for the signal transmission and pro- try resistances, this type of circuit using MOSFET-based
cessing which can be seen in the next section. complementary amplifier can output the VT precisely by
Review
The transconductance (gm = ΔIDS /ΔVGS ) is measured by

observing the ratio of the drain current change to the gate-
source voltage change when a DC signal is applied to
the gate. The transconductance reflects the amplification
capability of ISFET, and the better the amplification capa-
bility, the higher the current sensitivity of the ISFET sen-
sor. This enables detection of weak signal changes with
higher amplification capabilities to optimize minimum
detection limits. In addition, the impedance method can
be implemented by applying an AC signal. Impedance Z
can be measured by the circuit of Figure 5d and e. Specif-
ically, when VDS is fixed, the impedance Z can be suc-
cessfully calculated and output by an AC signal applied
on the gate. Analyte’s concentration is quantified by out-
put impedance.[81] This method is suitable for the situ-
ation where the corresponding information of the mea-
sured object is characterized by the phase when the voltage
amplitude change is weak. Hence, the biochemical quan-
tity can be characterized by applying a DC signal to mea-
sure the transconductance gm or applying an AC signal
to measure the impedance Z. Thus, under the joint efforts
of ISFET and external circuits for signal transmission, the
ISFET-sensing system can be used to detect different ana-
lytes and the latest progresses can be found in the next sec-
tion.
F I G U R E 5 Measuring circuits of ISFET using potentiometric

methods containing (a) differential amplifier, (b) complementary 3 SENSING APPLICATIONS OF THE
amplifier, (c) double amplifier and amperometric methods (d) with ISFET
and (e) without temperature compensation circuit. Reproduced
with permission.[77–81] Copyright 2000 Elibrary. Copyright 2004
ISFET have strong response directly to specific ions due
IEEE. Copyright 2004 Elsevier. Copyright 2007 Elsevier. Copyright
to the inherent properties of the gate materials. Also,
2015 RSC
the interactions between biomolecule and ISFET gate
will affect the ISFET electrical output. Thus, ions and
VGS (Vout ). However, to fulfill this, the selection of work- biomolecules can be detected by ISFET successfully such
ing points should be in the saturation region, introducing as DNA molecules, antibodies/antigens, enzymatic sub-
troubles to the ISFET practical operations.[78] (iii) To solve strates, and cell-related substances.[82] Their recent devel-
this, as shown in Figure 5c, another type of measuring cir- opments are presented in the following sections with more
cuit could be used based on double amplifiers containing details.
a current source and a buffer amplifier to output the VT
precisely by VGS (Vout ) and avoid the selection of work-
ing point because this circuit only have one fixed working 3.1 Ion detection
point.[79]
Considering that the measuring circuit using poten- The successful and stable detection of ions using ISFET
tiometric method responds slowly to high-frequency sig- is a very important topic nowadays, because it is a foun-
nal, the circuits using amperometric method are studied. dation to further detect other biomolecules. The initial
Figure 5d is a typical one, using a current mirror and a study of ISFET ionic sensor can be traced back to 1970
source follower (M1) to obtain the IDS of ISFET.[80] Based that Piet Bergveld fabricated the first ISFET using SiO2
on this, considering the external factors, such as temper- gate to detect Na+ and Cl− around nerves.[19] This ISFET
ature, a classic temperature compensation circuit can be replaced the metal gate of the classic MOSFET by a
introduced as a support as in Figure 5e.[80] Also, based combination module of ion-selective film/electrolyte/RE
on the circuits of amperometric method, the measure- as a whole, realizing the ionic sensitivity. Since that,
ment of transconductance method can be further realized. ISFET ionic sensor was introduced to the publics with a
Review
TA B L E 2 The most-used pH sensor using ISFET and other methods in recent years (n.s. means not specified)
Methods Configuration Sensitivity Linear range Year References
ISFET Ta2 O5 /Y2 O3 gate carbon nanotube 454 mV/pH 4-9 2019 [46a]
ISFET HfO2 and ZnO 943 mV/pH 5-9 2019 [88]
ISFET In2 O3 nano gate 88.125 mV/pH 6-10 2020 [89]
ISFET SiNW gate 720.7 mV/pH 4-10 2020 [90]
ISFET Y2 O3 gate 847 mV/pH 4-9 2020 [46c]
ISFET TiO2 and ultrathin body 1250 mV/pH 1-12 2020 [91]
ISFET SiO2 /Ta2 O5 gate 2364 mV/pH 3-10 2020 [84]
ISFET AlGaN/GaN gate 84.39 μA/pH 4-9 2021 [92]
ISFET Sn O2 gate 167.71 mV/pH 3.02-9.98 2021 [93]
ISFET In-Ga-Zn-O nanofiber 998 mV/pH 3-10 2021 [94]
ISFET SiNW gate 1438.8 mV/pH 3.07-9.87 2021 [95]
popularization to study the performance. For example, ions existed together.[52,61] In summary, the development
Vladan Janković and Jane P. Chang investigated the ionic of ionic ISFET sensor is relatively mature which can be
sensing performance from different gate materials and verified by the recent developments of the last 3 years in
fabrication techniques based on the thermally grown SiO2 Table 2. Based on this, more types of biological analytes
gate, the plasma-enhanced chemical vapor deposition of can be further detected based on the specific functionali-
ZrO2 gate, and plasma-enhanced atomic layer deposition ties of the ISFET gate, which can be found in the following
of HfO2 gate.[19] It can be verified that both of the material sections with details.
and technique can affect the ionic performances. Also,
the thickness of the gate was investigated by precise
controlling to obtain excellent sensitivity of 425.89 mV/pH 3.2 DNA detection
overcoming the Nernst limit as well, and it can be verified
that thicker gate shows better performance.[83] In addi- Accurate detection of DNA is very important in many
tion, the performance was further improved by the flexible fields such as the diagnosis of genetic diseases, the
design of gate structures. For example, an EG ISFET was screening of the cancer genome, and the discovery of
studied by Jin-Hyeok Jeon and Won-Ju Cho to obtain new medicines.[96] Many sensing methods been devel-
enhanced ionic sensing performance overcoming the oped including enzymatic, magnetic, optical (such as flu-
Nernst limit (59 mV/pH) to 379.2 mV/pH. And based on orescent and radiochemical labels), and electrochemical
this, an in-plane control gate (IG) was further proposed, (such as electrochemical impedance spectroscopy [EIS]
achieving a pH sensitivity of 2364 mV/pH.[84] and cyclic voltammetry [CV]) ones.[97] However, although
In addition, the practicality of the ISFET is also stud- these methods exhibit high sensitivity and low detection
ied. The short life span and poor reliability of ISFETs were limits, their shortcomings of complex measurement cir-
overcome by introducing graphene due to the high car- cuits, large and expensive instruments, time-consuming
rier mobility of atomically thin layers.[85] And the reusabil- preparation, and radioactive or poisonous labels cannot be
ity was also investigated by designing an easily replaced neglected.[75] To solve this, ISFET method can be the excel-
gate.[84] In addition, the durability of the ISFET ionic lent candidate due to the simple measurement circuit, the
sensor was investigated based on the bending strain of small size of the sensing system, the easily fabricated and
ISFET.[42] Nowadays, the ISFET ionic sensor can be finally easily operated sensing processes.[98] Currently, there are
fabricated as a flexible and wearable sensor with a good mainly two sensing mechanisms of the ISFET-based DNA
practicality.[84,86] And nanosized ISFET (50 nm × 10 μm) sensor. One is the usage of enzymic reactions based on
can be successfully achieved based on nanowires and a DNA polymerase to generate H+ ions which affect the sur-
large number of nano-ISFETs were integrated on single face charge distribution of the ISFET gate, thereby induc-
chip realizing low-cost, high signal-to-noise ratio, low- ing the change of gate surface potential output by elec-
power, low-noise, and higher sensitivity.[87] In addition, trical signal to detect DNA.[96] Similar to that, the other
ISFET-sensing arrays can be fabricated and multiple types one is based on the DNA strand hybridization which gen-
of ions can be detected at the same time with high res- erates negative charges and influences the surface charge
olution, which is very promising for clinical applications distribution of ISFET gate and then induces the change
of human body where there are always different types of of ISFET electrical output.[40] The combination of DNA
Review
and ISFET shows more advantages of fast detection speed,

high sensitivity, low detection limit, good specificity, sim-
ple manufacturing process, and low cost. Based on the
advantages, many studies of the ISFET-based DNA sensors
have been developed these years. For example, by using 3-
aminopropyltriethoxysilane (APTES) to silanize the ISFET
gate and immobilize DNA probes on the gate, M. Mahdavi
et al. prepared a highly sensitive DNA sensor. When the
sensor is in contact with a DNA solution at a concentration
of 10 pM, an output signal of about 500 mV is produced.
For this sensor, it is observed that the minimum readout
resolution is 50 μV, and the LOD of DNA can be calcu-
lated to be 1 fM, and the corresponding DNA sensitivity is
50 μV/fM.[99] Similar immobilization method of the DNA
probes using silane on the ISFET gate can also be seen in
Figure 6a.[96] However, this aminopropyltriethoxysilane-
based ISFET sensor using chemical functionalities is with
complicated processes and contains poisonous materials.
Thus, Nang Mo Hom et al. developed an simple and green
method using protein to immobilize the DNA probes on
the ISFET gate.[99] However, this method also has down-
sides that the LOD is not good enough as it is approxi-
mately 0.08 μM. Several efforts can be made to improve the
performance such as the introduction of nanomaterial on
the gate. For example, based on the single-layer graphene
introduced to ISFET, Rui Campos et al. not only monitored
the DNA hybridization processes at a very low concen-
tration with relative green methods, but also successfully
recognized the nucleotide polymorphisms (Figure 6b).[100]
Also, the performance of the DNA sensor was further
improved by a crumpled graphene on the gate realizing
an excellent LOD of 8 × 10−21 M because of the higher
surface area (Figure 6c).[85] Nowadays, the technique and
performance of the ISFET-based DNA sensor is becoming F I G U R E 6 (a) Schematic diagram of ISFET surface
mature and the recent ISFET-based DNA sensor can be modification by silane-based method to immobilize the DNA
seen in Table 3. Based on that, integrated sensing device for probes. Reproduced with permission.[96] Copyright 2021 ACS. (b)
further commercialization can be realized that a new type Schematic diagram of the ISFET-based DNA sensor using graphene
of bioelectronic nose was realized by Alexander Kuznetsov on the gate. Reproduced with permission.[100] Copyright 2019 ACS.
(c) Schematic diagram of ISFET sensor based on the crumpled
et al. using ISFET and DNA as the sensing elements
graphene on the gate with higher surface area. Reproduced with
(Figure 6d).[101]
permission.[85] Copyright 2020 Wiley. (d) General structure of the
bioelectronic nose newly developed. Reproduced with
permission.[101] Copyright 2019 Elsevier
3.3 Enzymatic detection
Enzyme-based ISFETs, namely ENFETs, are new types of Caras and Jiri Janata first reported an enzyme-coupled
biosensors constructed by immobilizing enzymes on the FET constructed by depositing a cross-linked penicillinase-
ISFET gate surface to detect the enzymatic substrates.[113] albumin layer on the gate, these years ENFET has been
Enzymatic reactions occur at the gate or electrolyte inter- improved in both theory and practice.[23] Due to the high
face affecting the charge distribution of the gate sur- selectivity and rapid response of enzymatic reactions, in
face which can be monitored by the electrical output addition to the small size of ISFETs, ENFET is highly sen-
changes. Based on this, ENFETs can be developed to detect sitive and only requires small volume of samples.
many biological analytes such as penicillin, glucose, urea, However, there are still drawbacks that limit the further
cholesterol, and dopamine.[96,114] Since 1980, when Steve developments of ENFET. First, the sensitivity of ENFET
Review
TA B L E 3 The most-used DNA sensor using ISFET and other methods in recent years (LOD means the limit of detection ; n.s. means not
specified)
Method Material Linear range LOD Year References
SPR biotinylated reporter and streptavidin 0-3 nM 1.0 nM 2020 [102]
QCM miR-21-DNA and pyrene 2.5 pM-2.5 μM 3.6 pM 2019 [103]
EIS AuNTs 0.01pM-1μM 1 fM 2019 [104]
CV WS2 QD 1 nM-100 μM 1 nM 2020 [105]
ISFET 20-mer DNA 10 nM-1 μM 50 pM 2018 [106]
ISFET molecular-charge-contact 1.8-180 μM 2.3 μM 2019 [57]
ISFET graphene 40 × 10−15 - 40 × 10−18 M 10 × 10−18 M 2020 [85]
−18 −6
ISFET hepatitis B virus DNA 10 -10 M 10 fM-1 μM 2020 [107]
ISFET diameters 1-1000 ng/mL 1.8 ng/mL 2020 [108]
ISFET single-stranded DNA probe 1 nM-1 μM 10 nM 2020 [109]
ISFET SiO2 1 fM-10 μM 103 2020 [110]
7 3
ISFET Si3 N4 10 -10 n.s. 2020 [111]
ISFET hepatitis B virus DNA 10 pM-1 nM 10 pM 2021 [112]
needs to be further improved. To solve this, continuous have been made by scientific groups. For example, an ultra-
improvements on the gate immobilization technique can thin Al2 O3 gate can be used to achieve uniform and inten-
be studied. For example, Alexandre Kisner et al. prepared sive penicillinase immobilization for better stability, and
an ISFET with a gate of high-density nanoporous Al2 O3 a wheatstone layout can be used to decrease the tempera-
immobilized. As the large surface area of the nanoporous ture drift of the ENFET sensor (Figure 7e).[120] Also, silk
structure enables more tyrosinase immobilized to oxidize fibroin film was used to immobilize GOD on the gate for
dopamine, higher sensitivity of dopamine was achieved sensitive detection of glucose with high temperature resis-
(Figure 7a).[115] Similar work also has been done by Ching- tance and excellent stability in more than 30 days.[121]
Ting Lee et al. realizing a high-sensitive glucose biosen- Moreover, layer-by-layer method was used to construct a
sor with the help of ZnO-based nanorod arrays on the gate PEI-urease multilayer structure for highly stable detection
to increase the amounts of glucose oxidase (GOD) immo- of urea (Figure 7f).[122] Catalytic materials, such as silver
bilized (Figure 7b).[116] Furthermore, the shape of nanos- nanoparticles, with rich free electrons on the surface can
tructures used was further studied verifying that the nano- also be used to improve the stability of ISFET.[114a] Also,
material with curved surface will load more enzymes per the activity of the enzyme on the gate will be changed over
area to enhance the ENFET performance. For example, the time, which undoubtedly affects the stability of the sen-
carbon nanotube (CNT) with curved surface is very suit- sor. To solve this, as shown in Figure 7g, Xueqiu You et al.
able for the immobilization of spherical biomolecules like used silk fibroin to immobilize and maintain GOD activ-
enzymes. (Figure 7c).[117] Also, it was verified that electron- ity on the gate for a long time at room temperature, which
rich materials introduced on the gate can help to improve successfully enhances the stability of the sensor.[113] All in
the ENFET performance. For example, Gaurav Kesh- all, although there are disadvantages of the ENFET, great
wani and Jiten Chandra Dutta prepared polyethyleneimine advances have been made to detect many types of analytes
(PEI) doped gate with high density of electron-rich amines shown in Table 4.
inside to build an ENFET sensor with excellent sensing
sensitivity.[118] Also, nanocomposites were used to improve
the sensitivity of ENFET because of the higher density 3.4 Antigen-antibody-related detection
of electrons inside. For example, Abdul Barik et al. pre-
pared a new type of ENFET using nanocomposite of The antigen-antibody-related immune detection is very
kalium/polypyrrole/CNT to achieve high performance of important for detecting and preventing diseases of tuber-
cholesterol detection (Figure 7d). The metal of kalium culosis, influenza, immune disease, and cancer.[11,108,132]
doped increases the sensitivity of the ENFET sensor by The basic sensing principle is that the antigen-antibody
larger amounts of free-charge carriers inside.[119] The sec- binding processes can affect the charge distribution or
ond disadvantage of ENFET which cannot be neglected is resistance of the gate to be reflected by the electrical output
the stability affected by the environmental changes such of ISFETs. As a classic low power device, ISFET only needs
as pH and temperature. To improve this, diverse efforts very small working potential and is harmless to the binding
Review
F I G U R E 7 (a) Diagram of ISFET with nanoporous Al2 O3 gate. Reproduced with permission.[115] Copyright 2012 Elsevier. (b) Schematic
diagram of AlGaN/GaN ISFET sensor using ZnO nanorods on the gate with enzyme immobilized. Reproduced with permission.[116]
Copyright 2015 Elsevier. (c) Schematic diagram of ISFET biosensor based on single-walled carbon nanotubes (CNTs) and aligned multi-walled
CNTs. Reproduced with permission.[117] Copyright 2020 IEEE. (d) Schematic diagram of ENFET composed of kalium/polypyrrole/CNT and
ZrO2 . Reproduced with permission.[119] Copyright 2014 Springer. (e) A schematic diagram of a ISFET with ultra-thin Al2 O3 gate and
wheatstone layout. Reproduced with permission.[120] Copyright 2018 Elsevier. (f) Diagram of ISFET with PEI-urease multilayer structure.
Reproduced with permission.[122] Copyright 2017 Elsevier. (g) Schematic diagram of the glucose sensor based on the silk fibroin functionalized
ISFET. Reproduced with permission.[113] Copyright 2014 Elsevier
of antigen-antibody. Currently, the efforts made for the human serum for the prediction of inflammation in vivo
popularization are mainly focused on the sensitivity and and the diagnosis of acute diseases.[133] Second, the inven-
reusability. First, stacked multilayer structure of the gate tion of ISFET gate with different structures was also the
can be seen as the most used method to improve the common way. For example, based on the double-gate (DG)
sensitivity. For example, Haoyue Yang and Toshiya Sakata structure, an improved performance to detect antigen
used stacked Ta2 O5 /SiO2 gate to obtain higher sensing (HBsAg) from the hepatitis B surface can be realized with
sensitivity for streptavidin antibodies based on the antigen- an excellent detection limit of 22.5 fg/mL.[134] Third, nano-
antibody reaction, which is important for understanding materials can be introduced on the ISFET gate to increase
the processes of protein purification and chemotherapeu- the sensitivity because of the high surface-to-volume ratio.
tic drugs delivery.[56] Similar to that, Oksana Kutova et al. For example, polystyrene nanospheres were used on the
constructed a multilayer gate of CeO2 /SiO2 for highly ISFET gate to detect antibodies of immunoglobulin G ENV
sensitive C-reactive protein antigen detections. The sensor mAB with high sensitivity.[11] Also, nanoribbons were
can also achieve great practicability in both PBS and used to support the detection of prostate-specific antigen
Review
TA B L E 4 The most-used enzyme-based ISFETs in recent 2 years (LOD means the limit of detection; n.s. means not specified; Ref. means
references)
Gate enzyme Detection substance Sensitivity LOD Linear range Year References
glucose oxidase glucose n.s. 0.001 mg/mL 0.1-1 mg/mL 2020 [123]
laccase 2, 2-azino-bis 3.66 A 3 μM 300 μM 2020 [117]
3-ethylbenzothiazoline- M -1 cm −2
6-sulphonic
acid
carbapenemases imipenem hydrolysis n.s. 100 nM n.s. 2021 [124]
cholesterol oxidase cholesterol 60 mV/dec 0.23 mM 0.5-25 mM 2021 [118]
uricase uric acid 8.63 mV/(mg/dL) 2 mg/dL n.s. 2021 [125]
uricase uric acid 12.69 mV/(mg/dL) 0.082 mg/dL 2-7 mg/dL 2021 [126]
tyrosinase dopamine 3.16 mA/M 3.3 nM 1-120 μM 2021 [127]
glucose oxidase glucose 26.05 μA/cm2 /mM 0.51 μM 1 μM-20 mM 2021 [128]
urease urea 3632.1 mV/pUrea n.s. 10 μM-316 mM 2021 [129]
uricase uric acid n.s. n.s. 1-30 mg/dL 2021 [130]
lactate L-lactic acid n.s. 7.5 mM 0-7.5 mM 2021 [131]
dehydrogenase
enzyme
TA B L E 5 The recent ISFET-based antibody-antigen sensor (LOD means the limit of detection; n.s. means not specified)
Configuration Detection substance Sensitivity LOD Detection range Year References
ISFET/nanobeads/ IgG1 antibody −4.43 V mL/μg 1.0152 μg/mL n.s. 2018 [11]
peptides
DG-ISFET/GOx C-reactive protein and n.s. 12.5 and 125 pg/mL n.s. 2018 [135]
immunoglobulin E
ISFET/SiO2 - C-reactive protein 290 mV/(mg/L) 0.1 mg/L n.s. 2019 [133]
CeO2 /antibody
ISFET/rGO N-terminal pro-brain n.s. 10 pg/mL 1-10 pg/mL 2019 [136]
natriuretic peptide
antigen
ISFET/mouse antibodies influenza A and B virus n.s. 1.8 and 2.1 ng/mL n.s. 2020 [108]
ISFET/NWs/antibodies cytokines n.s. 3-5 fM 25 fg/mL- 2.5 μg/mL 2020 [58]
FET/Si NWs/antibody Human cardiac n.s. n.s. 1 pg/mL- 1 mg/mL 2020 [137]
anti-troponin I antigen
ISFET/PBLs/antibody prostate cancer biomarker n.s. 1 fg/mL 1 fg/mL- 100 ng/ml 2020 [138]
(PSMA)
ISFET/anti-TNF-α Tumor necrosis factor-α n.s. 5 pg/mL 5-20 pg/mL 2020 [139]
antibodies
DG- ISFET/enzyme cardiac troponin I 132 pA/(pg⋅mL) 0.3 pg/mL 1-1000 pg/mL 2021 [66]
with a good detection limit of 0.4 pg/mL.[101] In addition to further realized such as to greatly shorten the time and
that, the reusability of the ISFET-based antigen-antibody complexity of tuberculosis diagnosis,[132b] to detect the
sensor was also studied. For example, Yen-Heng Lin influenza A virus samples,[108] and to early warn the acute
et al. prepared a high-performance antigen-antibody myocardial infarction.[60] Recently, with a portable and
sensor using magnetic beads to capture the apolipoprotein packaged sensing system, ISFET-based antibody-antigen
A1 and successful introducing reusability to the ISFET sensor has been successfully realized for the detection
sensor.[100] After years’ optimization, the ISFET based of cardiac troponin I and potential diagnosis of acute
antibody-antigen sensor has been greatly improved and myocardial infarction (Figure 8).[66] In the future, the
the recent work to detect different analytes can be found ISFET-based antibody-antigen sensor should be further
in Table 5. Based on this, clinical applications can be improved in the durability, repeatability, and portability,
Review
F I G U R E 8 The graphic illustration of the ISFET based antibody-antigen sensor and a packaged and portable device for handheld
use.[66] Reproduced with permission.[66] Copyright 2021 Elsevier
which can be realized based on the study of gate materials, duced by cartilage cells adhered on the ISFET gate, which
gate structure, and the sensing film. realizes the monitoring of the cartilage cell quality and is
of great significance for the recovery of damaged tissues in
the human body (Figure 9c).[143] Similar to that, Toshiya
3.5 Cell-related detection Sakata et al. cultured cells on the surface of the ISFET
Ta2 O5 gate and monitored cell respiration in real time. By
The processes of cell metabolism can produce secretions, comparing cancer cells and healthy cells, the pH values of
such as H+ , OH− , K+ , which can be detected by the ISFET the two extracellular microenvironments can be accurately
ionic sensor to monitor the cell life activities. Comparing distinguished.[144] In addition, this sensing device has very
with the most-used methods, such as the fluorescent stain- good stability, after immersing the device in the cell culture
ing and microscopic observation for the cell-related detec- medium for a week, the pH sensitivity is almost unchanged
tion, the ISFET-sensing method is cheaper, easy to oper- as 58 mV/pH.
ate, better biocompatible, and highly sensitive.[140] Many Furthermore, with the continuous development of
cell-related sensing applications have been realized using ISFET-sensing technology, ISFET arrays can be fabricated
ISFET-based sensing system. For example, Kenneth B. by complementary metal-oxide-semiconductor technique
Walsh et al. used ISFET achieving intercellular ion screen- for better sensitivity and higher sensing efficiency of the
ing to monitor human physiological activities such as cell-related detection. For example, Hongmei Li et al. pre-
muscle contraction and neurotransmitter transmission. In pared graphene-based ISFET arrays containing 25 devices
details, the K+ produced by cell metabolism was accurately which is more sensitive to K+ flowing out of neuronal cells
measured by inserting the ISFET into epithelial cells or comparing with single device. This lays the foundation
glioma cells to quickly and noninvasively obtain K+ efflux for further monitoring physiological activities of neuronal
data (Figure 9a).[141] Also, Diputi Raney et al. used ISFET signal transduction, cell secretion, and large-area live-cell
with antibody proteins (αIL-4 and αIL-2) immobilized on analysis.[145] Ghazal Nabovati et al. proposed a multiplexed
the gate to screen the cytokines secreted by mouse T-helper biosensor based on the 8 × 8 ISFET arrays for simultane-
cells, which enables real-time and accurate monitoring ous measurement of extracellular pH and cell growth rate
of cell growth, differentiation, and immunity.[58] Daniel with a single chip, achieving highly efficient detections
Schaffhauser et al. developed a new pH-sensitive ISFET (Figure 9d).[146] Yu Jiang et al. produced 512 × 576 ISFET
sensor that can effectively measure the rapid changes of arrays on a 5 × 5 mm chip to realize distributed detection
pH near the cell membrane (Figure 9b), which has a sig- of E. coli and the detection time is shortened six times.
nificant contribution to the pH adjustment of tissues and This method greatly improves the detection efficiency of
also the maintenance of cell volume.[142] Hiroto Satake bacteria in food to prevent the poisoning incidents caused
and Toshiya Sakata constructed a ISFET sensor for label- by food-borne bacteria.[147] Thus, based on the discussion
free and noninvasive detection of extracellular matrix pro- above, the cell-related biological detections using ISFET
Review
working principles and gate functionality methods are

listed in this review article, which could offer a guide-
line for groups to build the ISFET-sensing platform. Due
to the excellent properties of water-proof, all solid and
high sensitivity of ISFET, the ISFET-based system offers
a promising means for the fabrication of sensors for
ions, DNA molecules, antibody-antigen proteins, enzy-
matic substrates, and cell-related secretions. These types
of analytes have been achieved with very good practicality
and excellent detection limit, such as picomolar or even
femtomolar level, which are enough for the practical use
of real-time, continuous and reusable detections. Based
on this, benefited from the mature fabrication process of
ISFET, packaged and portable sensing device can be real-
ized for the commercialization to monitor clinical diseases
and cell metabolism processes. Also, the outlook and fac-
ing obstacles of the ISFET-sensing system can be found in
the following paragraphs, including the Debye screening
problem, in the high ionic solutions, the miniaturization of
the ISFET system especially for the fabrication of the RE,
and the multiplexed detections for different analytes with
single chip at the same time.
4.2 Outlook
4.2.1 Debye screening
Nowadays, the main issue limiting the ISFETs’ further

development is the Debye screening in the high concen-
F I G U R E 9 (a) Development of ISFET sensor for intercellular tration of ionic solutions, which will shield the contact of
ion screening to monitor human physiological activities. analytes to ISFET gate, especially for the analytes of small
Reproduced with permission.[141] Copyright 2021 Elsevier. (b) ISFET
molecules whose sizes are comparable and smaller than
sensor with Ta2 O5 gate that can measure the changes of pH near the
the Debye length (λ).[13] On the gate-electrolyte interface,
cell membrane. Reproduced with permission.[142] Copyright 2014
within the distance smaller than the λ, there is a high
Elsevier. (c) Schematic diagram of ISFET sensing device to detect
extracellular matrix produced by cartilage cells adhered on the ionic strength which limits the contact of analytes to the
ISFET gate. Reproduced with permission.[143] Copyright 2016 MDPI. ISFET gate.[144] Thus, these analytes cannot induce the
(d) The diagram and micrograph of the 64-pixel ISFET sensing surface potential change of the ISFET gate and are failed
arrays to detect extracellular pH and cell growth rate at the same to be detected. Especially, in the complex environment
time. Reproduced with permission.[146] Copyright 2020 RSC with high ionic concentration which cannot be diluted
such as the intracellular and in vivo environment, the
effect of Debye screening cannot be neglected.[154] To solve
have been realized in biological field and more selected this, instead of direct affecting the gate surface potential
examples with biological applications in the recent 3 years by the analytes, probes are usually used on the gate to
can be found in Table 6. bind analytes and affect the gate surface potential. First,
biological probes have been tried. For example, Anne M.
Andrews et al. using deoxyribonucleotide aptamers as
4 SUMMARY AND OUTLOOK probes modified on ISFET gate successfully overcame
the Debye screening on detecting small molecules of
4.1 Summary glucose.[154] Also, by enzyme-linked immunosorbent
assay, Hyun-June Jang et al. used alkaline phosphatase as
In summary, the ISFET sensors are widely developed with probes on the ISFET gate to overcome the Debye screen-
long history and sophisticated techniques. The most- used ing effect.[114a] Shuang Zhao et al. used Con A protein as
Review
TA B L E 6 The recent ISFET-based sensor for the cell-related detection for different biological applications (n.s. means not specified)
Configuration Cell type Application Medium Sensitivity Year References
ISFET Cancer Cells Live and label-free pH 58 mV/pH 2018 [144]
monitoring of cellular
functions such as
metabolism and
extracellular acidosis of
cancer cells
ISFET Bovine chondrocytes Cellular respiration pH n.s. 2018 [144]
+
ISFET Live human Caucasian Molecularly sized pH and NH4 -55.4 ± 2019 [148]
hepatocyte transmembrane pores 1.8 mV/pH
carcinoma (HepG2 )
cells
ISFET Autologous Label-free, noninvasive, pH 59 mV/pH 2019 [143]
chondrocytes and real-time
Graphene ISFET Neuronal cells Muscle contraction and K+ 41 μA/dec 2020 [145]
neurotransmitter
transmission
ISFET/light Human hepatoma cells Cell metabolism in a pH, glucose, and 335.5 nA/pH 2020 [149]
addressable real-time doxorubicin
potentiometric
sensor (LAPS)
ISFET Live human Caucasian Penetration phenomenon pH and NH4 + n.s. 2020 [150]
hepatocyte of
carcinoma (HepG2 ) phospholipid-mimicking
cells amphiphilic polymers
ISFET Array Escherichis coli Long-term bacterial pH n.s. 2020 [151]
metabolism monitoring
ISFET Array Escherichis coli Bacterial viability and pH 221 mV/pH 2021 [152]
concentration
ISFET Array ESR1 Multiple breast cancer pH n.s. 2021 [153]
ESR1 mutations
probes modified on the ISFET gate to overcome the limit 4.2.2 The wearability of ISFET
of Debye screening.[13] Second, chemical probes, such as
nanomaterials, are also tried. By introducing nanoscale Nowadays, with the development of sensing techniques,
thin layers or nanoparticles as probes immobilized on the new requests were put forward, such as flexible and wear-
gate, the Debye shielding effect can also be overcome. able ISFET sensing devices, for timely and continuous
For example, Mahnaz Mahdavi et al. used nanoscale health monitoring. The simplest pH value in the human
porous polysilicon as probes on the gate to overcome the body can provide important information about human
Debye shielding effect.[99] Also, Galina Presnova et al. metabolism, and the monitoring of the pH value of sweat
constructed a highly sensitive ISFET sensor based on the on the body surface has become a reliable candidate for
silicon nanowires and gold nanoparticles to overcome noninvasive diagnosis. For example, Jin-Hyeok Jeon and
Debye screening and achieve low-concentration detection Won-Ju Cho developed a wearable ISFET sensor based
of prostate-specific antigen.[155] Also, other methods can on a flexible transparent substrate (Figure 10a). Through
be seen from scientific articles such as the blocking agent the IG-sensing mode, a sensitivity of 2364 mV/pH was
method, the prefiltered method, the on-chip separation achieved at room temperature, which can detect the pH
method, and the external stimuli to disturb the double of the human body extremely sensitively.[84] To solve the
layer.[140] In the future, more effective methods overcom- nonideal effect of ISFET sensors when realizing weara-
ing the Debye screening should be investigated to build bility, researchers have introduced a series of nanomate-
the sensors with higher sensitivity, better stability, and rials to optimize the gate channel. For example, Eun-Ki
easier fabricated processes for small molecules. Hong and Won-Ju Cho prepared a DG-ISFET sensor with
Review
F I G U R E 1 0 (a) Schematic diagram of IG-ISFET sensor for wearable pH detection. Reproduced with permission.[84] Copyright 2020
Taylor & Francis. (b) Structural diagram of DG-ISFET flexible sensor with nanofiber channels. Reproduced with permission.[94] Copyright
2021 Elsevier. (c) ISFET sensor with a newly designed RE in a system-on-chip. Reproduced with permission.[157] Copyright 2017 IEEE. (d) The
manufacturing process of Ag/AgCl RE array on a plastic substrate. Reproduced with permission.[158] Copyright 2018 RSC. (e) Schematic
illustration of the integrated ISFET sensor for pH detection in sweat and skin surface temperature monitoring. Reproduced with
permission.[159] Copyright 2017 ACS. (f) The schematic diagram of an integrated ISFET miniature sensor for multi-ion detection with small
RE and sensing area of a few square microns. Reproduced with permission.[160] Copyright 2017 Elsevier
excellent performance by preparing transparent and flexi- many parts including metal tip, anion pool, and ion selec-
ble nanofiber channels on a Si substrate (Figure 10b). Com- tive permeation membrane, which inevitably becomes the
pared to the ISFET with thin film channel, the ISFET with bottleneck of ISFET wearable development.[156] To solve
nanofiber channel has higher pH sensitivity, lower drift this, research groups studied the new design of RE to
rate, and hysteresis voltage. Thus, it greatly suppresses the realize the integration of RE and ISFET on one small
nonideal effects of the device, and can achieve accurate chip. For example, Sang-Chan Park et al. integrated an
detection of human pH value.[94] For a wearable ISFET- Ag/AgCl RE into a system-on-chip of ISFET sensor real-
sensing system, the key point is the design of RE which izing a miniaturization of the entire system with real-
need to be small with excellent performance. To provide time, continuous, and wearable monitoring of sodium ions
a stable potential applied on the ISFET gate, the tradi- in human sweat (Figure 10c).[157] After years’of optimiza-
tional RE, such as Ag/AgCl electrode, usually consists of tion, the size of RE can be fabricated much smaller. Based
Review
on this, when the sizes of ISFET and RE were fabri- ference from different analytes can improve the sensing
cated as small as possible, attention should also be paid efficiency greatly to detect different analytes at the same
to obtain excellent performance. To obtain excellent pH- time. This can be realized by integrating several ISFETs
sensing performance based on hand-held ISFET sensors, on single chip to fabricate arrays based on the excellent
the RE array (2 × 10 mm, 42 × 4) designed by Shi Qiu performance, miniaturization, and easy integration of sin-
et al. has attracted the attention of the scientific groups gle ISFET sensor. The basic principle is that each ISFET
(Figure 10d).[158] In addition to integrating a RE on a flexi- can be used to recognize one type of analyte and, with
ble substrate to make a small sensor for human pH mea- the joint work of many ISFET, different types of analytes
surement, the development of a multifunctional ISFET can be detected at the same time when the ISFETs work
sensor for analyzing multiple information is essential for in turns. To achieve this, for the moment the facing prob-
realizing personal health monitoring. Therefore, scholars lems can be concluded as follows. First, each ISFET of the
have developed a multiparameter ISFET wearable sensor arrays needs wires to realize the on-off controlling that, for
that can characterize human health indicators. For exam- example, when a n × n ISFET array is used, at least n2
ple, Shogo Nakata et al. integrated a flexible temperature wires are needed, which brings high cost of the integra-
sensor and an ISFET sensor based on a flexible polymer tion technique and limits the commercialization. To solve
film to construct a wearable temperature sensor and a this, related studies have been started using light address-
sweat pH value sensor (Figure 10e).[159] The pH values able system. Instead of using wires, a light beam moving
of sweat and skin temperature were real-time measured over the ISFET arrays was used to control the on-off to
through skin contact. Erick Garcia-Cordero et al. inte- overcome the difficulties of integration. Second, for the
grated an ultra-thin ISFET sensors and microfluidic sys- moment, several ISFET arrays are used to increase the
tems on a single silicon chip to prepare wearable sensors sensitivity comparing to single ISFET, instead of multiple
to realize real-time monitoring of health information from detections. For example, Mirko Lehmann et al. developed
the sweat on the skin surface such as pH, Na+ and K+ con- a biocompatible ISFET array with higher sensitivity com-
centrations (Figure 10f). The whole sensing device is less paring to single ISFET to detect pH in the cell microen-
than 1 cm2 with complete modules of ISFET, microfluidic vironment to indicate the overall extracellular acidifica-
interface, measuring circuit, and miniature RE.[160] For tion rate.[162–165] Yuji Kagohashi et al. reported 32 × 32
healthcare applications, obtaining more parameter infor- ISFET arrays for pH detection realizing an increased pH
mation of the skin surface condition has become the cur- sensitivity. Third, limited by the functionality technique of
rent research focus. Meritxell Rovira et al. used hybrid ISFET gate, the spatial resolution of the multiplexed sens-
integration technology to integrate flexible ISFETs and ing system still needs improvements to increase the num-
gold film microelectrodes to prepare a multisensing wear- ber of analytes that can be detected at the same time.[52]
able platform. The platform can continuously measure For the moment, as shown in Figure 10e, Nicolas Moser
the composition of sweat and realize the rapid detection et al. described an array with 1024 ISFETs and realized four
of five substances (pH, potassium, sodium, chlorine, and types of ions detected at the same time.[12] Thus, as the
lactic acid).[161] The way forward for future development practical analytes is complicated, such as in the body fluid,
is to build the ideal ISFET with characteristics of flexi- foods and pollutants, the development of ISFET-based
ble, robustness, reusability, excellent sensing performance, multiplexed sensor in the healthcare, food safety and envi-
and good stability. Although efforts have been made, for ronmental protection fields still needs further efforts, and
the moment, the ISFET-based sensing system existed can- a greater number of analytes detected one time with high
not fulfill these requirements at the same time and in the efficiency, good stability, and excellent LOD are expected
near future more investigations should be carried out to in the future.
achieve this.
AC K N OW L E D G M E N T S
This work was supported by the National Natural Science
4.2.3 Multiplexed detection Foundation (Grant Nos. 61871240, 61471207) and the Open-
ing Project of Key Laboratory of Microelectronic Devices &
In addition to the portable sensing application, high- Integrated Technology, Institute of Microelectronics, Chi-
efficiency detection should be another hot trend of the nese Academy of Sciences. This work was also supported
ISFET sensor development in the future. To solve this, mul- by the Natural Science Foundation of Hebei (Grant Nos.
tiplexed detection is the most used method these years as F2021203102, C20210324).
in practical use there are usually many analytes existed
together to form a complicated environment such as blood. CONFLICT OF INTEREST
The multiplexed detection technique excluding the inter- The authors declare no conflict of interest.
Review
D A T A AVA I L A B I L I T Y S T A T E M E N T 24. J. I. Anzai, T. Kusano, T. Osa, H. Nakajima, T. Matsuo, Bunseki

Data sharing is not applicable to this article as no new data Kagaku 1984, 33, E131–E136.
were created or analyzed in this study. 25. O. A. Boubriak, A. P. Soldatkin, N. F. Starodub, A. K.
Sandrovsky, A. K. El’skaya, Sens. Actuators B 1995, 27, 429.
26. Y. Miyahara, T. Moriizumi, K. Ichimura, Sensors & Actuators
REFERENCES 1985, 7, 1.
1. (a) B. J. Privett, J. H. Shin, M. H. Schoenfisch, Anal. Chem. 2010, 27. P. B. Luppa, L. J. Sokoll, D. W. Chan, Clin. Chim. Acta 2001, 314,
82, 4723; (b) E. Bakker, M. Telting-Diaz, Anal. Chem. 2002, 74, 1.
2781; (c) X. Wang, X. Zhang, Electrochim. Acta 2013, 112, 774; 28. V. Volotovsky, A. P. Soldatkin, A. A. Shul’ga, V. K. Rossokhaty,
(d) C. Chen, J. F. Khosrowabadi Kotyk, S. W. Sheehan, Chem V. I. Strikha, A. V. El’skaya, Anal. Chim. Acta 1996, 322, 77.
2018, 4, 2571; (e) Y. Wang, H. Xu, J. Zhang, G. Li, Sensors 2008, 29. M. Zayats, O. A. Raitman, V. I. Chegel, A. B. Kharitonov, I.
8, 2043. Willner, Anal. Chem. 2002, 74, 4763.
2. R. Shiwaku, H. Matsui, K. Nagamine, M. Uematsu, T. Mano, Y. 30. S. Purushothaman, C. Toumazou, C.-P. Ou, Sens. Actuators B
Maruyama, A. Nomura, K. Tsuchiya, K. Hayasaka, Y. Takeda, 2006, 114, 964.
T. Fukuda, D. Kumaki, S. Tokito, Sci. Rep. 2018, 8, 3922. 31. D. Gonçalves, D. M. F. Prazeres, V. Chu, J. P. Conde, Biosens.
3. T. Kuno, K. Niitsu, K. Nakazato, Japan. J. Appl. Phys. 2014, 53, Bioelectron. 2008, 24, 545.
04EL01. 32. F. Bellando, C. K. Dabhi, A. Saeidi, C. Gastaldi, Y. S. Chauhan,
4. P. Bertoncello, R. J. Forster, Biosens. Bioelectron. 2009, 24, 3191. A. M. Ionescu, Appl. Phys. Lett. 2020, 116, 173503.
5. B. A. Prabowo, A. Purwidyantri, K. C. Liu, Biosensors 2018, 8, 33. T. M. Abdolkader, A. G. Alahdal, Sens. Actuators B 2018, 259,
80. 36.
6. (a) R. De Marco, G. Clarke, B. Pejcic, Electroanalysis 2007, 19, 34. (a) M. L. Chen, X. Sun, H. Liu, H. Wang, Q. Zhu, S. Wang, H.
1987; (b) S. Komaba, J. Arakawa, M. Seyama, T. Osaka, I. Satoh, Du, B. Dong, J. Zhang, Y. Sun, Nat. Commun. 2020, 11, 1; (b) Z.
S. Nakamura, Talanta 1998, 46, 1293. Zeng, W. Wei, B. Li, M. Gao, Z. G. Yu, W. K. Chim, C. Zhu, J.
7. (a) P. Bergveld, Sens. Actuators B 2003, 88, 1; (b) A. Loi, I. Electrochem. Soc. 2021, 168, 126507; (c) A. Dixit, D. P. Samajdar,
Manunza, A. Bonfiglio, Appl. Phys. Lett. 2005, 86, 103512; (c) V. Chauhan, IEEE Trans. Electron Devices 2021, 68, 5204.
C.-S. Lee, S. K. Kim, M. Kim, Sensors 2009, 9, 7111. 35. H. J. Jang, W. J. Cho, Appl. Phys. Lett. 2011, 99, 043703.
8. (a) L. T. Yin, J. C. Chou, W. Y. Chung, T. P. Sun, S. K. Hsiung, 36. S. Ma, X. Li, Y. K. Lee, A. Zhang, Biosens. Bioelectron. 2018, 117,
Sens. Actuators B 2000, 71, 106; (b) B. Zhao, T. Sai, A. Rahman, 276.
K. Levon, MRS Proc. 2011, 828, A7.8. 37. Y. L. Chin, J. C. Chou, T. P. Sun, H. K. Liao, W. Y. Chung, S. K.
9. (a) Z. Yue, W. Niu, W. Zhang, G. Liu, W. J. Parak, J. Colloid Inter- Hsiung, Sens. Actuators B 2001, 75, 36.
face Sci. 2010, 348, 227; (b) X. Yuan, X. Zhang, Y. Huang, J. Jie, 38. V. Khanna, Indian J. Pure Appl. Phys. 2012, 50, 199.
Q. Wei, M. Tan, Y. Yu, Int. J. Electrochem. Sci. 2021,16, 150911; (c) 39. H. Li, Y. Zhu, M. S. Islam, M. A. Rahman, K. B. Walsh, G. Koley,
P. J. Bresnahan, Y. Takeshita, T. Wirth, T. R. Martz, T. Cyronak, Sens. Actuators B 2017, 253, 759.
R. Albright, K. Wolfe, J. K. Warren, K. Mertz, Limnol. Oceano- 40. C. S. Lee, S. K. Kim, M. Kim, Sensors 2009, 9, 7111.
graph.: Methods 2021, 19, 132. 41. C. Cane, I. Gracia, A. Merlos, Microelectron. J. 1997, 28, 389.
10. J. Artigas, A. Beltran, C. Jiménez, A. Baldi, R. Mas, C. 42. A. Vilouras, A. Christou, L. Manjakkal, R. Dahiya, ACS Appl.
Domıńguez, J. Alonso, Comput. Electron. Agric. 2001, 31, 281. Electronic Material. 2020, 2, 2601.
11. M. Hosseini, M. Fathollahzadeh, M. Kolahdouz, A. Rostamian, 43. F. Ren, S. J. Pearton, S. Pearton, F. Ren, Semiconductor Device-
M. Mahmoodian, A. Samaeian, H. H. Radamson, J. Solid State Based Sensors for Gas, Chemical, and Biomedical Applications,
Electrochem. 2018, 22, 3161. CRC Press Boca, Raton, FL 2011.
12. N. Moser, C. L. Leong, Y. Hu, C. Cicatiello, S. Gowers, M. 44. K. B. Parizi, X. Xu, A. Pal, X. Hu, H. P. Wong, Sci. Rep. 2017, 7,
Boutelle, P. Georgiou, Anal. Chem. 2020, 92, 5276. 1.
13. S. Zhao, C. Shi, H. Hu, Z. Li, G. Xiao, Q. Yang, P. Sun, L. 45. M. Vila, C. Prieto, P. Miranzo, M. Osendi, R. J. S. Ramırez, C.
Cheng, W. Niu, J. Bi, Z. Yue, Biosens. Bioelectron. 2020, 151, Technology, 2002, 151, 67.
111962. 46. (a) D. Bhatt, N. Kumar, S. Panda, ACS Appl. Electron. Material.
14. (a) C. Bao, W. S. Kim, Adv. Eng. Mater. 2020, 22, 2000116; (b) 2019, 1, 1465; (b) T. N. Lee, H. J. Chen, K. C. Hsieh, in 2015
S. Nakata, M. Shiomi, Y. Fujita, T. Arie, S. Akita, K. Takei, Nat. IEEE International Conference on Electron Devices and Solid-
Electron. 2018, 1, 596. State Circuits (EDSSC), IEEE 2015, pp. 808; (c) D. Bhatt, S.
15. W. Shockley, Proc. IRE 1952, 40, 1365. Panda, ACS Appl. Electron Material. 2020, 2, 2699.
16. H. Umezawa, T. Matsumoto, S. Shikata, IEEE Electron Device 47. L. Wang, L. Li, T. Zhang, X. Liu, J.-P. Ao, Appl. Surf. Sci. 2018,
Lett. 2014, 35, 1112. 427, 1199.
17. D. Kahng, IRE Solid State Device Res. Conf 1960, 4. 48. C. Bartic, G. Borghs, Anal. Bioanal.Chem. 2006, 384, 354.
18. L. C. Clark Jr, C. Lyons, Ann. N.Y. Acad. Sci. 1962, 102, 29. 49. M. Vila, C. Prieto, P. Miranzo, M. Osendi, R. Ramırez, Surf.
19. P. Bergveld, IEEE Trans. Biomed. Eng. 1970, BME-17, 70. Coat. Technol. 2002, 151-152, 67.
20. B. H. van der Schoot, P. Bergveld, Biosensors 1987, 3, 161. 50. K. S. Song, G. J. Zhang, Y. Nakamura, K. Furukawa, T. Hiraki,
21. L. Bousse, N. Rooij, P. Bergveld, IEEE Trans. Electron Devices J.-H. Yang, T. Funatsu, I. Ohdomari, H. Kawarada, Phys. Rev. E
1983, 30, 1263. 2006, 74, 041919.
22. K. I. Lundström, M. S. Shivaraman, C. M. Svensson, J. Appl. 51. A. Cazalé, W. Sant, F. Ginot, J. C. Launay, G. Savourey, F. Revol-
Phys. 1975, 46, 3876. Cavalier, J. M. Lagarde, D. Heinry, J. Launay, P. Temple-Boyer,
23. S. Caras, J. Janata, Anal. Chem. 1980, 52, 1935. Sens. Actuators B 2016, 225, 1.
Review
52. I. Fakih, O. Durnan, F. Mahvash, I. Napal, A. Centeno, A. 87. S. Kim, T. Rim, K. Kim, U. Lee, E. Baek, H. Lee, C. K. Baek, M.
Zurutuza, V. Yargeau, T. Szkopek, Nat. Commun. 2020, 11, 3226. Meyyappan, M. J. Deen, J. S. Lee, Analyst 2011, 136, 5012.
53. J. Chang, A. Maity, H. Pu, X. Sui, G. Zhou, R. Ren, G. Lu, J. 88. J. C. Dutta, H. R. Thakur, G. Keshwani, IEEE Sensors J. 2019,
Chen, Nanotechnology 2018, 29, 375501. 19, 5692–5699.
54. T. Wadhera, D. Kakkar, G. Wadhwa, B. Raj, J. Electron. Mater. 89. Y. Wang, M. Yang, C. Wu, Sensors 2020, 20, 6921.
2019, 48, 7635. 90. K. Zhou, Z. Zhao, P. Yu, Z. Wang, Sens. Actuators B 2020, 320,
55. W. J. Cho, C. M. Lim, Solid State Electron. 2018, 140, 96. 128403.
56. S. Rollo, D. Rani, R. Leturcq, W. Olthuis, C. Pascual García, 91. A. Zain, A. M. Dinar, F. Salehuddin, H. Hazura, A. Hanim, S.
Nano Lett. 2019, 19, 2879. Idris, A. M. A. Hamid, in Journal of Physics: Conference Series,
57. H. Yang, T. Sakata, Sensors 2019, 19, 3393. 1502, IOP Publishing 2020, 1502, 012048.
58. D. Rani, Y. Singh, M. Salker, X. T. Vu, S. Ingebrandt, V. Pachauri, 92. Y. He, X. Wang, J. Y. Zhou, T. T. Wang, M. K. Ren, G. Q. Chen,
Anal. Bioanal.Chem. 2020, 412, 6777. T. F. Pu, X. B. Li, M. Jia, Y. Y. Bu, IEEE Trans. Electron Devices
59. S. D. Kotsakis, G. Miliotis, E. Tzelepi, L. S. Tzouvelekis, V. 2021, 68, 1250.
Miriagou, Sci. Rep. 2021, 11, 12061. 93. S. K. Cho, W. J. Cho, Chemosensors 2021, 9, 42.
60. T. Rao, J. Li, W. Cai, M. Wu, J. Jiang, P. Yang, Y. Zhou, W. Liao, 94. E. K. Hong, W. J. Cho, Sens. Actuators B 2021, 326, 128827.
ACS Omega 2021, 6, 32297. 95. S. K. Cho, W. J. Cho, Sens. Actuators B 2021, 326, 128835.
61. N. Miscourides, P. Georgiou, IEEE Sensors J. 2018, 19, 1224. 96. S. Santermans, F. Schanovsky, M. Gupta, G. Hellings, M. Heyns,
62. W. E. Hsu, Y. H. Chang, C. T. Lin, IEEE Sensors J. 2019, 19, 9983. W. Van Roy, K. Martens, ACS Sensors 2021, 6, 1049.
63. N. Tomari, K. Sasamoto, H. Sakai, T. Tani, Y. Yamamoto, Y. 97. C. A. Vu, W. Y. Chen, Sensors 2019, 19, 4214.
Nishiya, Anal. Biochem. 2019, 584, 113353. 98. N. Moser, J. Rodriguez-Manzano, T. S. Lande, P. Georgiou, IEEE
64. S. Jamasb, Biosensors 2019, 9, 44. Trans. Biomed. Circuits Syst. 2018, 12, 390.
65. A. A. Silverio, W. Y. Chung, V. F. Tsai, C. Cheng, Microelectron. 99. M. Mahdavi, A. Samaeian, M. Hajmirzaheydarali, M.
J. 2020, 100, 104769. Shahmohammadi, S. Mohajerzadeh, M. A. Malboobi, RSC Adv.
66. Y. Wang, T. Liu, M. Yang, C. Wu, W. Zhang, Z. Chu, W. Jin, 2014, 4, 36854.
Biosens. Bioelectron. 2021, 193, 113554. 100. R. Campos, J. Borme, J. R. Guerreiro, G. Machado, M. F.
67. P. Y. Chen, L. T. Yin, T. H. Cho, Life Sci. J. 2014, 11, 871. Cerqueira, D. Y. Petrovykh, P. Alpuim, ACS Sensors 2019, 4, 286.
68. A. Susloparova, D. Koppenhöfer, J. Law, X. Vu, S. Ingebrandt, 101. A. E. Kuznetsov, N. V. Komarova, E. V. Kuznetsov, M. S.
Lab Chip 2015, 15, 668. Andrianova, V. P. Grudtsov, E. N. Rybachek, K. V. Puchnin, D.
69. D. P. Tran, M. Winter, C. T. Yang, R. Stockmann, A. V. Ryazantsev, A. N. Saurov, Biosens. Bioelectron. 2019, 129, 29.
Offenhäusser, B. Thierry, Anal. Chem. 2019, 91, 12568. 102. M. Mansouri, F. Fathi, R. Jalili, S. Shoeibie, S. Dastmalchi, A.
70. E. Sharon, R. Freeman, R. Tel Vered, I. Willner, Electroanalysis Khataee, M. R. Rashidi, Food Chemist. 2020, 331, 127163.
2009, 21, 1291. 103. H. J. Park, S. S. Lee, Analyst 2019, 144, 6936.
71. S. L. Wang, C. Y. Hsieh, R. Sukesan, J. C. Chen, Y. L. Wang, ECS 104. M. Shariati, M. Ghorbani, P. Sasanpour, A. Karimizefreh, Anal.
J. Solid State Sci. Technol. 2020, 9, 055020. Chim. Acta 2019, 1048, 31.
72. H. J. N. P. D. Mello, B. Bachour Junior, M. Mulato, Sens. Actua- 105. R. Gupta, M. O. Valappil, A. Sakthivel, A. Mathur, C. S. Pundir,
tors A 2021, 318, 112481. K. Murugavel, J. Narang, S. Alwarappan, J. Electrochem. Soc.
73. A. Bhattacharjee, T. C. Nguyen, V. Pachauri, S. Ingebrandt, X. 2020, 167, 107501.
T. Vu, Micromachines 2021, 12, 39. 106. S. Ma, Y. K. Lee, A. Zhang, X. Li, Sens. Actuators B 2018, 264,
74. A. B. Kharitonov, M. Zayats, A. Lichtenstein, E. Katz, I. Willner, 344.
Sens. Actuators B 2000, 70, 222. 107. C. F. Chang, M. S. C. Lu, IEEE Sensors J. 2020, 20, 8930.
75. B. Veigas, E. Fortunato, P. V. Baptista, Sensors 2015, 15, 10380. 108. J. H. Bong, H. R. Kim, J. W. Yoo, M. J. Kang, M. G. Shin, J. S. Lee,
76. N. Moser, T. S. Lande, C. Toumazou, P. Georgiou, IEEE Sensors W. B. Shim, S. D. Lee, J. C. Pyun, Biosens. Bioelectron. 2020, 165,
J. 2016, 16, 6496. 112341.
77. S. Casans, D. Ramirez, A. Navarro, Edn 2000, 45, 164. 109. Y. Xu, H. Tavakkoli, J. Xu, Y. K. Lee, in 2020 IEEE 15th Inter-
78. P. A. Hammond, D. Ali, D. R. S. Cumming, IEEE Sensors J. national Conference on Nano/Micro Engineered and Molecular
2004, 4, 706. System (NEMS), IEEE 2020, pp. 398.
79. A. Morgenshtein, L. Sudakov-Boreysha, U. Dinnar, C. G. 110. C. Lee, M. S. C. Lu, in 2020 IEEE 33rd International Conference
Jakobson, Y. Nemirovsky, Sens. Actuators B 2004, 97, 122. on Micro Electro Mechanical Systems (MEMS), IEEE 2020, pp.
80. B. Premanode, C. Toumazou, Sens. Actuators B 2007, 120, 732. 299.
81. A. Susloparova, D. Koppenhöfer, J. Law, X. T. Vu, S. Ingebrandt, 111. M. Kalofonou, K. Malpartida Cardenas, G. Alexandrou, J.
Lab Chip 2015, 15, 668. Rodriguez Manzano, L. S. Yu, N. Miscourides, R. Allsopp, K.
82. V. Pachauri, S. Ingebrandt, Essays Biochem. 2016, 60, 81. L. Gleason, K. Goddard, D. Fernandez Garcia, Sci. Rep. 2020,
83. C. C. Chen, H. I. Chen, H. Y. Liu, P. C. Chou, J. K. Liou, W. C. 10, 1.
Liu, Sens. Actuators B 2015, 209, 658. 112. C. Lee, Y. W. Chen, M. S. C. Lu, IEEE Sensors J. 2020, 21, 4135.
84. J. H. Jeon, W. J. Cho, Sci. Technol. Adv. Mater. 2020, 21, 371. 113. X. You, J. J. Pak, Sens. Actuators B 2014, 202, 1357.
85. A. Ganguli, V. Faramarzi, A. Mostafa, M. T. Hwang, S. You, R. 114. (a) H. J. Jang, J. Ahn, M. G. Kim, Y. B. Shin, M. Jeun, W.
Bashir, Adv. Funct. Mater. 2020, 30, 2001031. J. Cho, K. H. Lee, Biosens. Bioelectron. 2015, 64, 318; (b) Y.
86. M. Douthwaite, E. Koutsos, D. C. Yates, P. D. Mitcheson, P. Rayanasukha, S. Pratontep, S. Porntheeraphat, W. Bunjongpru,
Georgiou, IEEE Trans. Biomed. Circuits Syst. 2017, 11, 1324. J. Nukeaw, Surf. Coat. Technol. 2016, 306, 147.
Review
115. A. Kisner, R. Stockmann, M. Jansen, U. Yegin, A. Offenhäusser, 141. K. B. Walsh, N. DeRoller, Y. Zhu, G. Koley, Biosens. Bioelectron.
L. T. Kubota, Y. Mourzina, Biosens. Bioelectron. 2012, 31, 157– 2014, 54, 448.
163. 142. D. Schaffhauser, M. Fine, M. Tabata, T. Goda, Y. Miyahara,
116. C. T. Lee, Y. S. Chiu, Sens. Actuators B 2015, 210, 756. Biosensors 2016, 6, 11.
117. S. Ebrahimi, Z. E. Nataj, S. Khodaverdian, A. Khamsavi, Y. 143. H. Satake, T. Sakata, Anal. Chem. 2019, 91, 16017.
Abdi, K. Khajeh, IEEE Sensors J. 2020, 20, 14590. 144. T. Sakata, H. Sugimoto, A. Saito, Anal. Chem. 2018, 90, 12731.
118. G. Keshwani, J. C. Dutta, Curr. Trends Biotechnol. Pharmacy 145. H. Li, K. B. Walsh, F. Bayram, G. Koley, RSC Adv. 2020, 10,
2021, 15, 182. 37728.
119. M. A. Barik, M. K. Sarma, C. R. Sarkar, J. C. Dutta, Appl. 146. G. Nabovati, E. Ghafar Zadeh, M. Sawan, in 2016 IEEE Interna-
Biochem. Biotechnol. 2014, 174, 1104. tional Symposium on Circuits and Systems (ISCAS), IEEE 2016,
120. D. Stock, G. M. Müntze, S. Figge, M. Eickhoff, Sens. Actuators pp. 2855.
B 2018, 263, 20. 147. Y. Jiang, X. Liu, T. C. Dang, X. Huang, H. Feng, Q. Zhang, H.
121. K. Koike, T. Sasaki, K. Hiraki, K. Ike, M. Yano, Biosensors 2020, Yu, IEEE Trans. Biomed. Circuits Syst. 2018, 12, 402.
10, 57. 148. T. Goda, Y. Imaizumi, H. Hatano, A. Matsumoto, K. Ishihara,
122. E. Piccinini, C. Bliem, C. Reiner Rozman, F. Battaglini, O. Y. Miyahara, Langmuir 2019, 35, 8167.
Azzaroni, W. Knoll, Biosens. Bioelectron. 2017, 92, 661. 149. T. Liang, C. Gu, Y. Gan, Q. Wu, C. He, J. Tu, Y. Pan, Y. Qiu, L.
123. K. Koike, T. Sasaki, K. Hiraki, K. Ike, Y. Hirofuji, M. Yano, Kong, H. Wan, P. Wang, Sens. Actuators B 2019, 301, 127004.
Biosensors 2020, 10, 57. 150. T. Goda, Y. Miyahara, K. Ishihara, J. Materials Chemist. B 2020,
124. S. D. Kotsakis, G. Miliotis, E. Tzelepi, L. S. Tzouvelekis, V. 8, 7633.
Miriagou, Sci. Rep. 2021, 11, 1. 151. M. Duan, X. Zhong, J. Xu, Y. K. Lee, A. Bermak, IEEE Trans.
125. P. Y. Kuo, Y. Y. Chen, W. H. Lai, C. H. Chang, IEEE J Electron Biomed. Circuits Syst. 2020, 14, 463.
Devices Soc. 2021, 1502, 012048. 152. M. Duan, X. Zhong, X. Zhao, O. M. El-Agnaf, Y. K. Lee, A.
126. P. Y. Kuo, Y. Y. Chen, W. H. Lai, C. H. Chang, IEEE Sensors J. Bermak, IEEE Trans. Biomed. Circuits Syst. 2021, 15, 497.
2021, 21, 20229. 153. G. Alexandrou, N. Moser, K. T. Mantikas, J. Rodriguez-
127. N. Liu, X. Xiang, L. Fu, Q. Cao, R. Huang, H. Liu, G. Han, L. Manzano, S. Ali, R. C. Coombes, J. Shaw, P. Georgiou, C.
Wu, Biosens. Bioelectron. 2021, 188, 113340. Toumazou, M. Kalofonou, IEEE Trans. Biomed. Circuits Syst.
128. B. Wang, Y. Luo, L. Gao, B. Liu, G. Duan, Biosens. Bioelectron. 2021, 15, 380.
2021, 171, 112736. 154. N. Nakatsuka, K. A. Yang, J. M. Abendroth, K. M. Cheung, X.
129. S. K. Cho, W. J. Cho, Sensors 2021, 21, 4748. Xu, H. Yang, C. Zhao, B. Zhu, Y. S. Rim, Y. Yang, Science 2018,
130. T. M. Pan, C. H. Lin, J. Electrochem. Soc. 2021, 168, 017511. 362, 319.
131. A. Schuck, H. E. Kim, J. K. Moreira, P. S. Lora, Y.-S. Kim, Sensors 155. G. Presnova, D. Presnov, V. Krupenin, V. Grigorenko, A.
2021, 21, 1852. Trifonov, I. Andreeva, O. Ignatenko, A. Egorov, M. Rubtsova,
132. (a) S. Hideshima, R. Sato, S. Kuroiwa, T. Osaka, Biosens. Bio- Biosens. Bioelectron. 2017, 88, 283.
electron. 2011, 26, 2419; (b) P. Saengdee, W. Chaisriratanakul, 156. (a) K.-M. Chang, C.-T. Chang, K.-M. Chan, Sensors 2010, 10,
W. Bunjongpru, W. Sripumkhai, A. Srisuwan, C. Hruanun, A. 6115; (b) Q. Li, W. Tang, Y. Su, Y. Huang, S. Peng, B. Zhuo, S.
Poyai, P. Phunpae, S. Pata, W. Jeamsaksiri, Analyst 2016, 141, Qiu, L. Ding, Y. Li, X. Guo, IEEE Electron Device Lett. 2017, 38,
5767. 1469; (c) W. Poetter, C. Dumschat, K. Cammann, Anal. Chem.
133. O. Kutova, M. Dusheiko, N. I. Klyui, V. A. Skryshevsky, Micro- 1995, 67, 4586.
electron. Eng. 2019, 215, 110993. 157. S. C. Park, H. J. Jeong, M. Heo, J. H. Shin, J. H. Ahn, ACS Appl.
134. I. K. Lee, M. Jeun, H. J. Jang, W. J. Cho, K. Lee, Nanoscale 2015, Electronic Materials 2021, 3, 2580.
7, 16789. 158. S. Qiu, W. Tang, X. Xi, W. Sun, Y. Huang, R. Liu, Y. Su, L. Jiang,
135. D. S. Juang, C. H. Lin, Y. R. Huo, C. Y. Tang, C. R. Cheng, H. Q. Wei, Y. Yu, X. Guo, IEEE Sensors Lett. 2018, 2, 1.
S. Wu, S. F. Huang, A. Kalnitsky, C. C. Lin, Biosens. Bioelectron. 159. S. Nakata, T. Arie, S. Akita, K. Takei, ACS Sensors 2017, 2, 443.
2018, 117, 175. 160. E. Garcia Cordero, F. Bellando, J. Zhang, F. Wildhaber, J. Longo,
136. W. M. Munief, X. Lu, T. Teucke, J. Wilhelm, A. Britz, F. H. Guérin, A. M. Ionescu, ACS Nano 2018, 12, 12646.
Hempel, R. Lanche, M. Schwartz, J. K. Y. Law, S. Grandthyll, 161. M. Rovira, C. Fernández-Sánchez, S. Demuru, P. K. Brince, D.
F. Müller, J. U. Neurohr, K. Jacobs, M. Schmitt, V. Pachauri, Briand, C. Jimenez-Jorquera, Engineering Proc. 2021, 6, 78.
R. Hempelmann, S. Ingebrandt, Biosens. Bioelectron. 2019, 126, 162. Y. Kagohashi, H. Ozawa, S. Uno, K. Nakazato, K. Ohdaira, H.
136. Matsumura, Japan. J. Appl. Phys. 2010, 49, 01.
137. Y. Kutovyi, J. Li, I. Zadorozhnyi, H. Hlukhova, N. Boichuk, 163. Z. Yue, W. Khalid, M. Zanella, A. Z. Abbasi, A. Pfreundt,
D. Yehorov, M. Menger, S. Vitusevich, MRS Advances 2020, 5, P. Rivera Gil, K. Schubert, F. Lisdat, W. J. Parak, Anal.
835. Bioanal.Chem. 2010, 396, 1095.
138. S. Park, M. Kim, D. Kim, S. H. Kang, K. H. Lee, Y. Jeong, Biosens. 164. (a) T. Yoshinobu, M. J. Schöning, Curr. Opinion Electrochemist.
Bioelectron. 2020, 147, 111737. 2021, 28, 100727; (b) T. Liang, N. Jiang, S. Zhou, X. Wang, Y. Xu,
139. D. Vozgirdaite, H. Ben Halima, F. G. Bellagambi, A. Alcacer, F. C. Wu, D. Kirsanov, A. Legin, H. Wan, P. Wang, Anal. Chim.
Palacio, N. Jaffrezic Renault, N. Zine, J. Bausells, A. Elaissari, Acta 2021, 1179, 338603.
A. Errachid, Chemosensors 2021, 9, 26. 165. M. Lehmann, W. Baumann, M. Brischwein, R. Ehret, M. Kraus,
140. A. Poghossian, M. J. Schöning, Curr. Opinion Electrochemist. A. Schwinde, M. Bitzenhofer, I. Freund, B. Wolf, Biosens. Bio-
2021, 29, 100811. electron. 2000, 15, 117.
Review
AU T H O R B I O G R A P H I E S
sensing system based on the combination of physical
and chemical methods.
Shengli Cao received the Master
degree of Electronics and Com- Xinyue Sun is currently a mas-
munication Engineering from ter student majoring in Electronic
Taiyuan University of Technology, Science and Technology at Nankai
China, in 2020. He is currently University, Tianjin, China. Her
pursuing his PhD degree in Nankai research interests are inertial sen-
University, Tianjin, China. During sors and embedded sensing sys-
Master’s degree, his researches tems.
included the self-powered sensing systems and energy
harvesting. Currently, he majors in Electronic Science Hongyu Zhao received the Bach-
and Technology focusing on the nanomaterial-based elor degree in Microelectronics
photoelectrochemical biological sensors. from Xi’an Polytechnic University
in 2020. She is studying as a mas-
Peng Sun is currently a master
ter student in Yanshan University,
student majoring in the integrated
Qinhuangdao, China, majoring in
circuit engineering at Nankai
Electronic Science and Technology
University, Tianjin, China. His
with a research interest of network
researches are mainly based on the
and intelligent hardware of sensing system.
biosensors and intelligent circuit
systems, such as the biochemical Shuang Zhao obtained his PhD
detection using ISFET and GFET, in the Physics Department from
from 2020 to 2022. Hamburg University, Germany, in
Gang Xiao received the Master 2020. He is currently a lecturer in
degree of Electronic Science and the School of Information Science
Technology from Nankai Uni- and Engineering of Yanshan Uni-
versity, Tianjin, China, in 2021. versity in Qinhuangdao, China. He
He majored in the nanomaterial- is mainly engaged in the study
based photoelectrochemical of semiconductor nanomaterial-based photoelectro-
sensor and the development of chemical sensor for light-addressable biological detec-
embedded systems. He focused tions and ion-sensitive field-effect transistor (ISFET)-
on reusable photoelectrochemical sensor based on based portable sensing platform for wirelessly real-time
Fe3 O4 nanoparticles for real-time glucose detection detections.
with high sensitivity. Besides, he was interested in a Huibin Lu was born in Jiaohe,
dual-sensing system based on photoelectrochemistry Jilin Province, China, in 1965.
and surface plasmon resonance for the detection of he received the Bachelor degree
small molecules and macromolecules. from Northeast Heavy Machinery
Qiang Tang graduated from Institute, Qiqihaer, Heilongjiang
Chongqing University of Tech- Province, China, in 1986. Then, he
nology in 2020, majoring in new finished the Master degree in 1994
energy science and engineering. and the PhD degree in circuits
He is studying as a master student and systems in 2004, from Yanshan University, Hebei
and majoring in Electronic Sci- Province, China. He is now a professor in the School of
ence and Technology at Yanshan Information Science Engineering, Yanshan University.
University, Qinhuangdao, China. His research interests include computer network
His research interests are nanomaterial-based sensors security, signal processing and communication, and
and mechanism analysis of the photoelectrochemical the related applications to build software and hardware
system.
Review
Zhao Yue is a full professor in the How to cite this article: S. Cao, P. Sun, G. Xiao,
Department of Microelectronics, Q. Tang, X. Sun, H. Zhao, S. Zhao, H. Lu, Z. Yue.
Nankai University. His research Electrochem Sci Adv. 2023, 3, e2100207.
interests include nanosensors, https://doi.org/10.1002/elsa.202100207
photoelectrochemical sensors,
FET sensors, and smart sensing
system.

Electrochemical Science Adv - 2022 - Cao - ISFET‐based sensors for bio chemical applications A review

Uploaded by

Copyright:

Available Formats

Electrochemical Science Adv - 2022 - Cao - ISFET‐based sensors for bio chemical applications A review

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Electrochemical Science Adv - 2022 - Cao - ISFET‐based sensors for bio chemical applications A review

Uploaded by

Copyright:

Available Formats

Review

1 of 25 Electrochemical Science Advances doi.org/10.1002/elsa.202100207

Received: 30 November 2021

ISFET-based sensors for (bio)chemical applications: A

Electrochem. Sci. Adv. 2023;3:e2100207. wileyonlinelibrary.com/journal/elsa 1 of 25

The transconductance (gm = ΔIDS /ΔVGS ) is measured by

F I G U R E 5 Measuring circuits of ISFET using potentiometric

and ISFET shows more advantages of fast detection speed,

working principles and gate functionality methods are

4.2.1 Debye screening

Nowadays, the main issue limiting the ISFETs’ further

D A T A AVA I L A B I L I T Y S T A T E M E N T 24. J. I. Anzai, T. Kusano, T. Osa, H. Nakajima, T. Matsuo, Bunseki

You might also like