Silicon

https://doi.org/10.1007/s12633-020-00937-w

REVIEW PAPER

A Comprehensive Review on High Electron Mobility Transistor

(HEMT) Based Biosensors: Recent Advances and Future Prospects
and its Comparison with Si-Based Biosensor
V. Hemaja 1 & D. K. Panda 1

Received: 19 November 2020 / Accepted: 30 December 2020

# Springer Nature B.V. 2021

Abstract
In this paper, we focus on recent advances of the high-electron-mobility transistor (HEMT)-based biosensors for the detection of
various biomolecules. The vital utilization of biosensors in various domains leads to standard, accurate and powerful biosensors
as it possesses a huge potential to attain information in a faster and simple manner in comparison to conventional assays.
Amongst various biosensors, high electron mobility transistors (HEMTs) proved more potential and immense advantages due
to their inherent material properties such as higher electron mobility, two-dimensional electron gas (2DEG), chemically inert,
stable at high temperature and high speed. This review paper features the basic related concepts of HEMT based biosensors in
terms of structure-oriented, different methodologies, the significance of various biomarker and biomolecules. This review also
describes the crucial factors which influence the various performance matrices of a biosensor such as sensitivity, selectivity,
specificity, reliability, repeatability, and stability. A comparison of different HEMT based biosensors with Si-based biosensor is
also analyzed. This review will help researchers to get all the information regarding HEMT based biosensors at one place to work
further for developing next-generation biosensors.

Keywords Biosensor . High electron mobility transistors . Sensitivity . Selectivity . Reliability . Stability

1 Introduction cations in terms of high sensitivity, low sample values, cost-ef-

fectiveness, and high throughput [2]. The construction of biosen-
As the potential threat of bioterrorism increases, there is an urgent sor is categorized into three sub-units such as (1)Detection or
need for a highly efficient biosensor device that acts as a diag- recognization of biological molecules,(2)Characterization of
nostic tool to serves as low cost, fast, reliable, accurate, detects novel molecular interactions between various biomolecules and
and avoids the contamination of bioagents in the atmosphere. required enzymes and, (3)quick identification of a component
Biosensors have gained much attention in this fast-growing tech- with a target analyte to determine more or fewer molecules of
nological world for a wide range of applications such as environ- interest. Utilization of biosensors has gained huge interest such as
ment monitoring, medical diagnostics, forensic industries, and food pathogen, environmental monitoring, medical diagnostic,
national security. The basic concept of a biosensor is based on crime detection, drug development, agriculture, sports surveil-
the following three elements: a detector (the bio element) which lance, marine sector, genetic screening, adulterant detection,
recognizes the specific analyte of interest, a transducer for the and internet of thing based applications [3, 4]. Applications in
conversion of the biological signal into a measurable signal, plus the field of biological and medical sensing, diagnosis of disease
a system to amplify the signal and visualize it in a suitable format are being detected by specific biomarkers (functional or structural
correspondingly.[1] Biosensors should possess desirable specifi- abnormal enzymes, low molecular weight proteins or antigens)
in blood, urine, saliva, or tissue samples which have been devel-
oped using various approaches including Enzyme-linked
* D. K. Panda
[email protected]
Immunosorbent assay(ELISA) states that only one analyte could
be measured at a time leads to major drawback, Particle-based
1
Microelectronics and VLSI Design Group, School of Electronics, flow cytometric assays allow for multiple detections using mul-
VIT-AP University, Amaravati, Andhra Pradesh 522237, India tiple beads but the whole detections process generally takes more
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than two hours, which is not practically applicable for in the sample preparation for the detection of target biomolecules in
office or bedside detection, Electrochemical devices gained at- the device.
traction because of low cost and simplicity but still, there is a Optical biosensors collaborate optical fields with target
need of significant improvements in their sensitivities for use analytes for biomolecule detection such as tumor biomarkers,
with clinical samples. Microcantilevers capable of detecting cells, and toxins.
low concentrations, still suffer from an unwanted resonant fre- The mass-based sensors imply the response to the effect of
quency change due to the medium viscosity and cantilever variation in mass. These sensors take a significant role in
damping in the environmental solution [5, 6]. MEMS devices, especially in piezoelectric-based sensors.
The piezoelectric and acoustic wave sensor comes under the
subclasses category of these sensors that find a competitive
application for the detection of glucose, DNA, and living
2 Types of Biosensors organism.
Basically, for the development of an accurate and reliable
Generally, biosensors are categorized depending upon their biosensor, four main parameters should be taken into accounts
detection mechanism (which includes usage of biological el- such as sensitivity, specificity, stability, and ease of fabrica-
ements such as antibodies, enzymes, biological tissues, drugs, tion. Among various kinds of biosensor electrochemical and
proteins, microorganisms, etc.) and transduction method optical biosensors has attained more attention due to their high
(which performs the conversion of a biological signal into specificity and lower detection limit. The design process of
required measurable signal) [8]. Depending upon the trans- mass-based and calorimetric biosensors offers highly compli-
duction method there occurs 4 classes and subclasses as men- cated and lower response time [7]. In the electrochemical bio-
tioned in (Fig. 1). sensors potentiometric type transducer has become more pop-
Various types of biosensors mentioned in (Fig. 1) provide ular after the introduction of FET type biosensor because of
the technique for a wide detection of biomolecules in the de- their higher performance and less cost of fabrication.
vice. The working principle of an electrochemical biosensor
that it experiences the transformation in the electrical proper-
ties of the sensor caused by the chemical reaction. The trans-
formation is used as a measuring parameter is classified into 3 3 FET Based Biosensors
types such as conductometric, potentiometric, and ampero-
metric. These biosensors are widely used for the detection of Among various types of biosensors Field-effect transistors
DNA, glucose, and haemoglobin, etc. (FET) are appropriate candidates for biosensing applications
An optical biosensor is a strong alternate for the conven- because of their high signal-to-noise ratio, ease of integration,
tional analytical type of biosensor as it needs less amount of and low cost. Field-effect transistor-based sensors have

Fig. 1 Classification of biosensor

[7]
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become one of the major technologies for the detection of structures of different III-V devices for detection of various dis-
ions, DNA, proteins, and in the sensing regime application eases from a higher to lower detection target range and its im-
ranging from environmental monitoring (in macro-scale) to provement in the field of sensitivity, selectivity, stability, spec-
study of biomolecular interactions (in nanoscale). Si-based ificity, reliability, repeatability. There is a lot of work done for
Field Effect transistors biosensors possess high sensitivity be- the early diagnosis of disease to reduce the mortality rate.
cause of the analyte binding site of the receptor close to the Section-6 presents a descriptive analysis of various biomarkers
surface, smaller size, simpler transduction mechanism, com- in comparison with silicon, different biomolecules, and bio-
patibility with Complementary Metal Oxide Semiconductor marker used for different diseases attained a better detection
(CMOS) process technology, lesser cost, reproducibility, and limit. Section 7 deals with the comparative performance of sil-
controllable electrical response have gained the huge focus of icon over GaN material and Section-8 Deals with the study of
research attention. Conventional Si-based field-effect transis- various sensing performance metrics for sensitivity, selectivity,
tor sensor suffers from degradation or shift in electrical re- reliability, specificity, stability, repeatability performance en-
sponse due to the hydrolysis of the oxide layer in aqueous hancement. Finally, the conclusion has been drawn in Section 9.
solutions, being easily attacked and distorted by chemical
and biological agents and intermediate oxide or gate metalli-
zation layers is the increase in the distance which causes 4 Working Mechanism of HEMT Based Sensor
charge analytes binds to the charge carrier channel resulting
in lower sensitivity [9–11]. The working principle operates on the mechanism of biomark-
Group III nitride-based devices eradicate drawback of Si- er and involvement of biomolecules introduced in the device.
based systems in terms of higher thermal and chemical stability These biomarkers (antibody, aptamer, enzymes, molecules,
in aqueous solution, chemically inert, high resistivity to high genes) can bind or link large no of samples. Once it gets into
electron salt environment, high bandgap, sensitivity, low pos- contact with an increase in the concentration of biomolecules
sibility of corrosion, low power consumption, and faster re- there is a huge variation in the electrical characteristic of the
sponses. Due to the formation of two-dimensional electron device in terms of the electron concentration, drain current and
gas(2DEG) at the hetero-interface of AlGaN /GaN high elec- threshold voltage, etc. Finally, these sensors detect how fast a
tron mobility transistor(HEMT) results in promising bio/ device works i.e. sensing speed, selectivity, sensitivity, and
chemical sensing application. These devices possess unique stability.
properties that are ideally suited because of their high electron
sheet concentration induced by spontaneous and piezoelectric
polarization leads to a higher density and mobility of the two- 5 Review on Various HEMT Device Structures
dimensional gas in the interface of the heterostructure since it’s for Detection of Various Diseases
induced between the strained AlGaN and the GaN layer. For and Biomolecules
most of the high electron mobility transistor(HEMT) structures
sensor’s potential on the surface changes the piezoelectric- 5.1 Prostate Cancer
induced carrier density in the channel, which in turn causes a
change in the drain or gate current. Advantages of high electron A fully fabricated high electron mobility transistor biosensor with
mobility transistor(HEMT) based sensors offers higher mobil- Al2O3 as gate dielectric offers a reduction in cost, time, process
ity and formation of two-dimensional electron gas(2DEG) in- overhead, and offered device sensitivity around 0.91 mA/
duce a higher sensitivity and also reduces the possibility of ngmL−1 [14]. AlGaInN based sensors and indium oxide nano-
damage from static electricity [12]. Nanomaterials devices are wires used for prostate-specific antigen detected a range from
strong candidates offering an excellent option towards fast, 1 μg/mL to 10 pg/mL [15]. In gateless transistors by a coating
label-free, sensitive, selective and multiple detections for both of the thin scandium oxide layer over the gate sensing area, has
in the field of clinical and preclinical applications. Integration determined more sensitiveness and reproducible pH sensing. The
of nanomaterials with AlGaN/GaN high electron mobility characteristics of these sensors bear faster responses (in liquid
transistors(HEMT) have gained advantages in increasing sen- phase 5–10 s and gas-phase around milliseconds), digitalized
sitivity detection [13]. output signals, smaller device size (which is less than
This review deals with the various diseases related devices 100*100μm2), chemical and thermal stability. These sensors pro-
focusing on their enhancement results of sensitivity, selectivity, vide a clear vision to use reliable semiconductors sensors for the
specificity, reliability, stability using a variety of sensing metrics, development of handheld exhaled breath, saliva, urine, or blood
structures, methods, models, and material. Section 2 deals with monitors with wireless capability to analyze frequently screening
types of biosensors. Section 3 deals with FET-based biosensors. that can diagnose the early development of diseases, which in
Section 4 deals with the working mechanism of HEMT based turn helps in reducing the suffering of patients from late diagno-
sensor. Section-5 deals with comparative analysis of various sis, lowers the medical cost and detected over a wide range of
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concentrations from 1 μg/mL to 10 pg/mL [16]. GaN high elec- of detection and linear range detection for various AlGaN
tron mobility transistor biosensors implemented using label-free based HEMT for various methods.
electrical detection with millimeter grade biomolecule gated pro-
vided superior advantages with a fewer number of steps in the
fabrication process, potentially gained a lower detection limit 5.2 Cardiovascular Disease
because of the chosen target biomarker closer to the two-
dimensional gas, and achieved a sensitivity of 0.027% for AlGaN /GaN high electron mobility transistor biosensor for
0.1 pg/ml to 10.269 ng/mL prostate-specific antigen solution the detection of C-reactive protein using a null balancing cir-
[17]. A biomolecule gated AlGaN/GaN high electron mobility cuit not only measures the change of the gate potential, sensor
transistor using UV/ozone for oxidizing GaN surface and there- output signal without the use of bulky semiconductor param-
after a 3-aminopropyl trimethoxysilane (APTES) self-assembled eter analyzer but also offers a suitable device configuration for
monolayer was bound to its sensing region that can detect the signal processing which detected over a wide range of con-
current in logarithmic scale in relation against prostate-specific centrations from 10 ng/mL to 1000 ng/mL [22]. A Platinum
antigen detection concentration range from 0.1 pg/mL (which gate high electron mobility transistor used in the differential
enhanced sensitivity around 2.15%) to 0.993 ng/mL. This pro- mode circuit reduces 97% of noise signal based biosensor
cess is useful in the field of prostate cancer screening [18]. improves the detection limit in low C-Reactive Protein con-
Ethanolamine modification strategy in molecular gold gated centration from 0.01 ng/mL to 1000 ng/mL [23]. Electric
AlGaN/GaN high electron mobility transistor results instability, Double Gating mechanism using covalently linked antibody
low sensitivity, realized detection of ions, proteins and DNA, immobilization strategy and thiol modified aptamer offered
verified their feasibilities in pH and antigen. To overcome the better charge screening effect and shows high sensitivity,
demerits (i.e. low sensitivity) of the molecular gated device, the specificity which is around 0.006-148 ng/mL. This process
sensor is modified with ethanolamine with InP nanowires which proves rapid, inexpensive, Cardio Vascular disease biomarker
improved both pH and antigen detection. The microscale pH array for point-of-care diagnostics [24].
sensor detected a limit for prostate-specific antigen as 1fgmL−1
in phosphate buffer saline(PBS) buffer and a sensitivity of 2.04%
for 100 ng mL−1 [19]. Disposable gate AlGaN/GaN high elec- 5.3 pH Sensor
tron mobility transistor sensor prevents contamination in the bio-
chemical environment upon implementation of a separate high An extended gate version of AlGaN/GaN high electron mo-
electron mobility transistor containing the sensitive membrane bility transistor pH sensor implemented using a metal-
which helps in Trace-level biological detection and achieved insulator-semiconductor structure(MIS) improves the unsta-
limit to 100 fg/mL for the prostate-specific antigen detection. ble gate leakage, an increase in sensitivity up to 56.39mv/pH
The device also offered stability, linearity, and specificity [20]. and linearity of 98.93% and offered a high electrical signal
Figure 2 reveals that the molecular gate(Using EA for sur- which changed the efficiency of biomaterials, disposable and
face animation) has achieved a higher limit of detection i.e. point-of-care systems over the conventional based metal-
1 fg/mL−1as well as its higher modification efficiency leads to semiconductor high electron mobility transistor(HEMT) pH
more active sites for pH detection. Table 1 represents the limit sensor [25]. Peltier element cooling of ungated AlGaN/GaN
high electron mobility transistors with scandium oxide gate
dielectric functionalized with ZnO nanorods is an effective
method for condensing exhaled breathe offered pH range in
7–8 and achieved a detection limit to 0.5 nM. The integration
of HEMT sensors and a wireless detection system allows for
remote monitoring applications [26]. The use of ungated
AlGaN high electron mobility transistors with scandium oxide
in the gate region and Peltier element mounted on the backside
lowers the temperature to condense the exhaled breath sensors
exhibited a linear range in current between pH 3–10 of 37 μA/
pH [15, 16].
From Fig. 3 it’s clear that in the case of A the drain current
change for exhaled breathe condensate shows the pH values
range between 7.2–7.5 and a better limit of detection i.e.
0.5 nM which is the typical range of Human blood whereas
in the case of B its shows a wide range in pH variation be-
Fig. 2 Limit of detection for various AlGaN based HEMT [17–19, 21] tween 3 and 10.
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Table 1 Limit of detection and

linear range for various AlGaN Method Linear range Limit of Detection
based HEMT
Au-gated AlGaN /GaN HEMTs 10 pg/mL-10 ng/mL 10 pg/mL [21]
Bimolecule gated AlGaN/GaN HEMTs 0.1 pg/mL-10.269 ng/mL 0.1 pg/mL [17]
Molecular gate(using APTES for surface amination) 100 fg/mL−1 to 1 ng/mL−1 100 fg/mL−1[18]
Molecular gate (using EA for surface animation) 1 fg/mL−1 to 100 ng/mL−1 1 fg/mL−1[19]

5.4 Glucose Detection a mismatched deoxyribonucleic acid (DNA) was used as a control
showed that nonspecific binding was also absent [15, 16].
From Table 2 we conclude that glucose biosensor APTES Figure 4 depicts that AlGaN based sensor results in a de-
based HEMT delivers a suitable environment to sustain the crease of 115 μA for AlGaN sensor whereas a decrease of
GOX activity due to its higher sensitivity limit. 69 μA for AlInN sensor and 38 μA for AlGaN sensor proves
strong evidence that AlInN sensor acts as more sensitive for
DNA hybridization in comparison with AlGaN HEMT.
5.5 DNA Detection
5.6 Kidney Injury Molecule Detection
AlInN/GaN high electron mobility transistor (HEMT) possessing
a thin barrier thickness results in negligible stress and piezoelectric
Kidney injury molecule-I (KIM-I) used as a biomarker for the
effect potentially improving the stability and higher sensitivity i.e.
early detection of Acute Kidney Injury or renal failure in the
at VDS = 0.5 V it decreases the value to 69 μA and upon further
urinary antigen is generally carried out with an Enzyme-linked
introducing 1μmolL−1 complementary deoxyribonucleic
Immunosorbent assay (ELISA) technique. These biosensors
acid(DNA) at sensor area reduces to 38 μA which shows a greater
have achieved a target detection limit of 1 ng/mL over a gated
potential in the medical field detection [33]. The advantage of
area of 20*50 μm2 [15, 16].
using gold nanoparticles provides a well-established system for
the detection of analyte-receptor interaction used for the detection
of various biomolecules including DNA, proteins, and cell surface 5.7 Uricase Detection
receptors. The way to bind receptors nanostructures patterned at
the gate is to achieve a higher receptor density. In sensors with ZnO nanotetrapods (T-ZnO) used in High electron mobility
arrays of biochemical sensing transducers, incorporation of statis- transistor(HEMT) composes a special structure with four legs
tical analysis method on-chip could help in the reduction of false- which extend out of the surrounding surface in different directions
positive and negatives when the device-to-device variability exists had attained better electron transportation and immobilization
[34]. Both the structures showed a linear decrease of 115 μA and over other low IEP organic molecule to be made suitable for the

Fig. 3 Drain current variation of

pH sensor(for Peltier element
cooling ungated HEMT and
Sc2O3 capped HEMT)versus time
[15, 16, 26]
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Table 2 Comparison of APTES AlGaN based HEMT glucose performance in the field of biomedical and clinical diagnosis ap-
biosensors with previously reported biosensors [27–32]
plications [36].
BIOSENSOR LINEAR SENSITIVITY Figure 5 revealed that in the case of curve A during the first
RANGE (μA mM−1 cm−2) 250 s there is no current change that offers better stability and
reliability and after the addition of 0.2 nM solution to the gate
Nafion/GOX/ZnO nanorods/ITO 0.05–1.00 mM 48.75
[27] 1.00–20.00 mM 3.87
area of HEMT, there is an immediate change in the current
Nf/PdNPs/rGO 3 μm-4.57 mM 234.1
signal with the increasing concentration of UA whereas in
APTES/GOX/GCE [28] case of curve B it shows a linear response and the device
PET/QCS-MOX-OD/GOx 1-111 mM 176 achieved a lower detection limit of 0.2 nm and a faster re-
electrode [29] sponse time of ~1 s was observed and the device offers good
CoWO4/CNT/CNT-AuNS [30] 0–0.3 mM 10.89
repeatability.
CQDs-AuNPs-GOX [31] 0.16–4.32 mM 626.06
APTES/GOX/AlGaN/GaNHEMT 0.1–10 μM 9.4*105
[32] 10 μM–100 μM 3.15*104
1-9 mM 1.95*105 5.8 Breast Cancer Detection

Gold NPs were functionalized with PP58 over AlGaN/GaN

high electron mobility transistor(HEMT) as PP58 retains its
fabrication of a reliable and stable biosensor. These biosensor has actual activity when attached to solid substrates which serve
achieved a wide target detection range over 0.2 nM to 0.2 mM as a receptor to trap SRC kinase chosen as model analyte
and average time response of one second [35]. To perform uricase electrically detected 1 pM SRC kinase in an ionic solution.
immobilization which enhances sensitivity performance by the A clinically based application example is triple-negative
distribution of synthesized T-ZnOs bearing advanced electron breast cancer (TNBC) drug screening study [37].
transportation over other low isoelectric points (IEP) immobilized
organic molecules using chemical vapor deposition (CVD) meth-
od on the gate areas of high electron mobility transistor(HEMT) 5.9 Ovarian, Lung, and Gastric Cancer
which detected fast response toward UA at ~1 s and linear range
from 0.2 nm to 0.2 mm. These devices offered excellent transport An electronic microsensor designed with unique sensing struc-
property of T-ZnO producing outstanding results in sensitivity ture by using nanoparticle tracking analysis and flow cytome-
and good repeatability made this biosensor suitable for detecting try is implemented in the high field operation of GaN high
ultra-low concentration environments. The results obtained point- electron mobility transistor (HEMT) which is composed of
ed out the access to design electronic device as miniaturized lab electric double layer gated with extracellular vesicles offered
on chip device due to its high sensitivity and specificity wide concentration range from 107 to 108 Evs/ML that facili-
tated detection of subcellular components, existed possibility
for risk assessment of cardiovascular coronary artery disease
and early diagnosis of ovarian, lung and gastric cancer which
potentially improved the point-of-care diagnostic for the dis-
eases that caused the largest mortality over worldwide [38].

Fig. 4 The variation of drain current versus time depending upon

exposure to thiol-modified and matched DNA for AlGaN and AlInN Fig. 5 Variation of drain current signal of T-ZnO HEMT to a series
sensor [15, 16, 33] concentration of UA [35, 36]
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5.10 Lactic Acid Detection 5.11.2 Disposable Gate HEMT Sensor

Si-doped GaAs cap layer over Si-doped AlGaAs layer The schematic view of the proposed device is shown in Fig. 7.
high electron mobility transistor (HEMT) biosensor not determines potential development problem of ungated HEMT
only enhances chemical stability of the gate but also im- structures as the sensors get contaminated in the biological en-
proves transport property of the carrier in cap layer could vironment as their structures modify with a different HEMT and
detect lactic acid concentration range from 0.03 nM to sensing structure [20].
300 nM, whereas comparative analysis has been per-
formed to the combination of ZnO nanowires-gated 5.11.3 Dielectric Modulated HEMT Based Sensor
AlGaAs/GaAs high electron mobility transistor (HEMT)
with an excellent enzymatic lactic acid biosensor delivers From Fig. 8 it observed that devices operate when current
the fast response, excellent sensitivity, long term stability flows between the source and drain electrodes when the gate
and wide detection range in the field of medical applica- to source voltage is greater than the threshold voltage that can
tions in measuring lactic acid levels(exhaled breathe con- be modulated by varying its dielectric material cavity. The
densate as a surrogate for blood-based lactate measure- nanogap cavity layer present on both sides of the oxide under
ments) [39]. the gate acts as a sensing site for immobilization of target
biomolecules [42].
Finally, this Section 5 deals with a discussion of various
5.11 Different Structures HEMT Based Biosensor types of diseases in terms of superior sensitivity, selectivity
performance due to the change in structure, biomolecules,
The main factors which influence the performance of devices biomarker, biosensor, and different structure- related perfor-
in terms of current, frequency, power performance, immobili- mance analysis in terms of frequency, power, current, and
zation of biomolecules, throughput has been described in threshold voltage.
these various devices [40, 41].

6 Review on Various Biomarkers

5.11.1 AlGaN/AlN/GaN-Based BIO-HEMT Sensor for the Detection of Biomolecules

AlGaN/GaN high electron mobility transistor(HEMT) incor- Silicon-based sensors are still the abundant, dominant, and
porated using AlN interlayer in their epi layer design maxi- widely available material of the semiconductor segment be-
mizes device performance such as device on current over the cause of their less cost, reproducible and controllable electronic
conventional high electron mobility transistor, frequency, and response. The main drawback of these sensors is not suitable
power performance [11] (Fig. 6). for operation in a harsh environment, for instance, high

Fig. 6 Two-dimensional cross-

sectional AlGaN/AlN/GaN
HEMT biosensor for detection of
various biomolecules [11]
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isoelectric point at 9.5 and offer advantages in the field of

nanotechnology such as biocompatibility, relative chemical sta-
bility, electrochemical activity high specific surface area and
high electron communication feature, non-toxicity, vast sur-
face–to-bulk ratio, low fabrication cost, and are an attractive
matrix for LOX immobilization [45–47].
Table 3 represents the various types of biomolecules,
biomarker, serum marker used for the diagnosis of dis-
eases. Here we can observe that a lot of work has been
performed on various types of diseases amongst which
Prostate cancer has achieved much better results in few
fg/mL−1.
Fig. 7 Schematic view MgZnO/ZnO Disposable gate HEMT
Section 6 deals with the comparative performance of
different material HEMT based sensors and their prior ad-
vantage over another and different types of serum marker,
temperatures, high pressure, or corrosive ambient. To over- biomarker use in disease diagnosis with their detection
come the demerits of these Silicon-based sensors, Wide limit.
bandgap group III nitride compound semiconductors are alter-
nate options due to their chemical resistance, high temperature
or high power capability, high electron saturation velocity.
AlGaN /GaN materials are most widely used as high sensitivity 7 COMPARISON PERFORMANCE OF SILICON
gas, chemical and biological sensors as it bears unique material BAsed BIOSENSORWITH HEMT BASED
properties such as chemical inertness, non-toxicity, biocompat- BIOSENSORS
ibility, high transconductance, chemical stability in solution,
electrical stability in an ionic solution, stable at high tempera- Table 4 represents the superior comparison performance of
tures, good chemical resistivity, high electron mobility, lower silicon over GaN HEMT Biosensor in terms of bandwidth,
power consumption, faster response, and higher bandgap [43, fast witching, thermal conductivity, operates at a higher tem-
44]. ZnO nanomaterials are an ideal choice due to their high perature, efficiency [54–56].

Fig. 8 Schematic view of

Dielectric modulated normally-
off HEMT based biosensor
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Table 3 Review on various biomolecules and biomarkers 8 Review on Various Performance Matrics
MARKER DETECTION LIMIT/ of HEMT Biosensor
DISEASE RANGE
8.1 Sensitivity
Serum marker-prostate-specific antigen 100 fg/ml [20]
Prostrate cancer
Biomarker-1)prostate-specific antigen, 1)1 μg/ml-10 pg/ml [16]
The main performance metrics which affect the sensitivity of
2)kidney injury molecule-1 2)1 ng/ml [16] the device are conductance, current gain, nanogap cavity, gate
1)prostate cancer length, threshold voltage shift for detection of biomolecules,
2)acute kidney injury or acute renal failure on current, transconductance, channel conductance, channel
Cardiac Maker Fibrinogen 0-5 g/L [9]
Coronary Artery Disease and Thrombosis
potential, thin barrier. The sensitivity of the device could be
Biomarker-RNA 1 fm [48] enhanced by optimizing parameters such as nanogap cavity,
Cardiovascular disease length, width, and gate length. A lot of authors proposed var-
Biomarker-c-reactive protein 0.01 ng/ml-1000 ng/ml ious methods or techniques which increases the sensitivity of
Acute phase infection [23]
the device are as follows:-.
Biomarker-prostate specific antigen 0.1 pg/ml [17]
Prostate cancer
Xiang et al. proposed an AlInN/GaN high electron mobility
Biomarker-prostate specific antigen 0.1 pg/ml −0.993 ng/ml transistors(HEMT) sensors possess thin barriers attained higher
Prostate cancer [18] sensitivity in comparison to traditional AlGaN/GaN high elec-
Serum marker-prostate specific antigen 1 fg/ml−1[19] tron mobility transistors [33]. Kia et al. has developed an
Prostate cancer Optimized Surface Functionalization method using AlGaN
Biomarker-c-reactive protein 10 ng/ml-1000 ng/ml
/GaN high electron mobility transistor (HEMT) which not only
Cardiovascular disease [22]
improved the sensitivity but also has achieved a concentration
Biomarker-Troponin1 concentration in serum 2.62 pg/ml [24]
Cardiotoxicity, Unstable angina, Cardiac level of 4.73pM [43] Ju-Young Pyo et al. fabricated metal-
muscle injury, and Renal failure Analysis insulator-semiconductor structures using tin dioxide as sensing
Bio marker-alpha fetoprotein 20 pg/ml [49] membrane material, high mobility ALD Al2O3 thin layer and
Colorectal,breast,lung cancer
high electron concentration that predicts possible outcomes
Biomarker- Monokine induced by 5-500 ng/ml [50]
interferon-gamma such as high output characteristic, the concentration of electro-
Transplant Rejection lyte accurately and stably [25]. Zhixin Wang et al. developed a
Biomarker-NT-pro BNP 80.54mv/decade novel TAS2R14-functionalized high electron mobility
Heart failure [51]
transistor(HEMT) sensor modified using membrane protein
Biomarker- Nucleic Acid, Protein 10fgmL−1-10ngmL−1[52]
without over-expressed TAS2R14 was used as negative control
Cancer
Biomarker-Organokine 1.53pgmL−1[53] which detected a sensitivity range from 0.1pM to 1 mM was
Diabetes applied to detect and fish out the potential TAS2R14 agonists
from P.grandiflorum extracts [57]. Hee Ho Lee et al. proposed
a Bio-high electron mobility transistor(HEMT)/Ref-high

Table 4 A comparative analysis

of silicon with GaN HEMT based SILICON BIOSENSOR GaN HEMT BIOSENSOR
sensors
Higher gate charge Lower gate charge which reduces driving loss and enables faster switching.
High bias gate Low bias gate voltage(5-6 V) to get on state source-drain resistance.
voltage(10-12 V)
Performance is Better for high bandwidth control applications such as the ability of fast
comparatively poor. switching due to low gate charge, low output capacitance.
A lower critical electric field A higher critical electric field
A higher intrinsic carrier A lower intrinsic carrier concentration
concentration
Lower thermal conductivity Higher thermal conductivity
Low saturation velocity High saturation velocity leads to low loss for power devices.
Operates at a lower Offers higher temperature withstanding capability and switching speeds.
temperature
Provides comparatively Higher efficiency
lesser efficiency.
 Silicon

electron mobility transistor(HEMT)/QRE in low C-Reactive

Protein enhanced sensitivity factor by more than 100 owing
to the rejection of the common-mode noise signal [23].
The authors of [11, 14, 18, 19] reported that by the application
of Charge deduction based sensitivity method analysis to a GaN
MOSHEMT for Cerb-2, it produces the breast cancer biomarker
about 9 times higher sensitivity than the existing device i.e.
around 0.054 mA/μgmL−1 (because it modifies device epi de-
sign and MOS gate)and similarly by gate bias or interface charge
deduced biomarkers such as prostate-specific antigen(PSA) -
0.91 mA/μgmL−1, MIG −0.254 mA/μgmL−1 and glucose oxi-
dase enzyme −0.48 mA/ngmL−1, 2.0691 mA/mmolL−1These
results have been obtained by using sensing metrics i.e. for the
glucose oxidase enzyme is Δg I ds (variation in channel conductance
ds

divided by current), MIG from serum is ΔE(x) (channel conduc-

tion current), CerB-2 from saliva is the ΔID (drain current), KIM-
I from urine is Δchpot (variation in channel potential), prostate- Fig. 9 Sensitivity variation to target PSA concentration
specific antigen from serum is Δgd (variation in channel
conductance).On using biomolecule gated AlGaN/GaN high albumin blocking technique avoids the non-specific binding
electron mobility transistor (HEMT) and by oxidizing UV/ and has offered a detection limit of few pg/mL [49]. Hee Ho
ozone to the GaN surface, APTES bounded to the sensing region Lee et al. proposed a unique method modified by Ni/Au gate
detected the current in logarithmic scale in relation against region with C-Reactive Protein antibody immobilization and
prostate-specific antigen(PSA) concentration from 0.1 pg/mL with the usage of Troponin T, the target C-Reactive Protein
(which showed sensitivity around 2.15%) to 0.993 ng/mL which could be selectively detected through the immune reaction
made this process useful in the field of prostate cancer screening [22]. Authors of [58] used different coats (platinum, gold)in
[50]. Ethanolamine surface functionalization technique provides a droplet or solid forms which are suggested for selective
more active sites and opportunities for bonding of biomolecular adsorption of biological molecules in the gate region.
results in sensitivity gain of the biosensor where the detection From Fig. 10 it is revealed that in the case of B, the output
limit for prostrate-specific antigen (PSA) is 1fgmL−1 in phos- voltage variations occurred because of specific binding of
phate buffer saline buffer and sensitivity reaching 2.04% for CRP to CRP antibody and not by the non-specific binding
100 ng mL−1 [19]. Arathy et al. use Charge control based sensor of other biomolecules to CRP-antibody whereas in the case
model and device conductance as sensing performance metric of A, CRP reacted only with CRP antibody and not by non-
for CerB-2 detection of AlGaN/AlN/GaN-based high electron specific binding of other biomolecules to CRP antibody and
mobility transistor (HEMT) sensor by varying gate length for CRP was greater than about 8–12 times than output voltage
1 μm to 5 μm reduction in sensitivity value is observed for
1 μm gate length around 2.5 mA/mgL−1 and similarly for
5 μm gate length around 0.72 mA/mgL−1 [11].
The authors of [24] reported that High sensitivity Troponin-I
assays are made very sensitive to closely monitor damages to the
myocardial tissue. Change in current gain used as sensing metric
that predicts high sensitivity and an extremely low troponin-I
detection limit to 250fM when measured using purified physio-
logical buffer solution and 0.006 ng/mL in human serum.
From Fig. 9. it is observed that curve A has gained higher
sensitivity performance because of using molecular gate(using
ethanolamine for surface animation) and all the curve(A-D)
show logarithmic dependence as target PSA concentrations.

8.2 Selectivity

Kia ding et al. reported that Alpha Fetoprotein using AlGaAs Fig. 10 Output voltage characteristics of HEMT based sensor for a
/GaAs high electron mobility transistor based on Bovin serum selectivity test with Troponin T
Silicon

variation for Troponin T which detected a wide range of con-

centration from 10 to 1000 ng/mL.

8.3 Specificity

Indu Sarangadharan et al. implemented an Electric Double

Gating mechanism which provides a better charge screening
effect, high sensitivity, specificity which is around 0.006-
148 ng/mL. This process proves rapid, inexpensive, Cardio
Vascular disease biomarker array for point-of-care diagnostics
[24].
From Fig. 11 it is revealed that the test samples carried out
using purified protein treatment and clinical serum samples
depict high specificity and a wider range of concentration
from (0.006-148 ng/mL) as the unique gating mechanism im-
plemented here overcomes the drawback of charge screening
and allows detection without sample processing steps [20]. Fig. 12 Drain current versus change on the pH value [58]

8.4 Reliability
8.5 Repeatability
Studies reported in [14, 25, 58] proposed some method which
Byung Hwan Chu et al. modeled Ungated AlGaN/GaN
confirms the reliability of the device (1)By the implementa-
high electron mobility transistor(HEMT) using scandium
tion of a mathematical model based AlGaN/GaN HEMT bio-
oxide as a gate dielectric are sensitive for exposure to ex-
sensor detected a drain current around μA/pH which in turn
haled breathe condensate and similarly, functionalization
confirms the reliability of the model, (2)Real-time response
method used with ZnO nanorods and glucose oxidase are
method of observing real-time signals which are being detect-
seen responsive to the glucose. These detection approaches
ed by different conditions such as electrolyte concentration
provide rapid response and good repeatability which
and (3)Gate to the source is less than the gate to the drain
gained potentiality for investigation of airway pathology
spacing designed to lower the effective source resistance and
[26].
maximizes the reliability of the device.
From Fig. 13 it is observed that good repeatability was
Figure 12 represents the dependence of drain current with
obtained as the author here combined well biocompatible T-
change on the pH value which predicted the sensitivity of the
ZnO and high sensitivity HEMTs to meet the needs of UA
biosensor 80μA/pH which was being confirmed by the exper-
detection in real samples [36].
imental data [58].

Fig. 11 Drain current versus time for aptamer-troponin I [24] Fig. 13 Current versus time for testing repeatability [36]
 Silicon

8.6 Stability AlGaAs/ GaAs, AlInN/ AlN/, InGaAs, ZnO based high elec-
tron mobility transistor. The selection of these materials has
Studies reported in [9, 17, 25, 39] attained stability(1) No vari- attained potential in various fields due to its overspread prop-
ation in current change is observed with the addition of PBS at erties:-higher sensitivity, good selectivity, specificity, reliabil-
approx.. 150 s, which provides good stability(which exclude ity, stability, good repeatability, linearity, chemical and ther-
possible noise arising with the change of lactic acid solution) mal stability, high electron mobility, and small device size.
and specificity of the device, (2) Metal-insulator-semiconductor This significant biosensor technology offers various applica-
(MIS) structure consisting of Schottky junctions can be stabi- tions in the field of biomedical engineering such as detection
lized by lowering the gate leakage due to the high barrier height of pathogens and toxins, transplant rejection, troponin I, cell
of the insulator,(3)Diagnosis of fibrinogen in human plasma differentiation, early disease diagnosis and prognosis, drug
using aptamer functionalized has achieved better stability, which development, medicine, and study of cellular dynamics.
made it suitable for point of care or home care diagnostic for HEMT based biosensors show promising results for cardio-
easy assessment of cardiovascular disease risk,(4)GaN high vascular disease, protein, DNA, kidney injury, glucose in ex-
electron mobility transistor(HEMT) biosensor for prostate- haled breathe condensate, acute phase infections, pH values of
specific antigen(PSA) by using label-free electrical detection solutions, and antigen detection. This technology offers a re-
with millimeter grade biomolecule gated offers good stability duction in the cost, time, easy to integrate into portable sys-
and sensitivity around 0.027% for 0.1 pg/ml PSA solution. tems, and shows signs of future excellence as point-of-care
From Fig. 14 it is observed that after heating treatment, the diagnostics. A comprehensive review on performance com-
water contact angle of the sensing surface is 48°for both curve parison of HEMT based biosensor with Si FET based biosen-
A and B, and after immersion into 0.01*PBS, it raises to 49° sors is also presented. From this review it is concluded that Si
for curve A whereas it decreases to 37° for curve B and almost based FET is suitable for low power application whereas
does not vary with the increasing immersion time which HEMT based biosensor can be applicable in harsh environ-
shows that the APTES self –assembled monolayer has good ments. This review will help researchers to get all the infor-
stability in buffer solution over 24 h. mation regarding HEMT based biosensors at one place to
Section 8 deals with sensitivity, selectivity, stability, reli- work further for developing next-generation biosensors.
ability, and repeatability performance. There is good sensitiv-
ity and stability report obtained from prostate cancer, selectiv- Acknowledgments The authors acknowledge VIT-AP university for pro-
viding the necessary facilities for carrying out the research work.
ity performance for cardiovascular disease.
Authors’ Contributions Mrs. Hemaja has done the compressive review.
Dr. Deepak has done the necessary editing.

9 Conclusion Data Availability Not applicable.

This review paper demonstrates different types of biosensors Compliance with Ethical Standards The manuscript is pre-
based on different heterostructures such as AlGaN/ GaN, pared as per the ethical standard of the journal.

Conflict of Interest The authors declare that they have no conflict of

interest.

Consent to Participate Not applicable.

Consent for Publication The authors have given Consent for

Publication as per the journal policy.

Code Availability Not applicable.

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