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J. Mater. Chem. B, 2020, DOI: 10.1039/C9TB02474C.
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Journal of Materials Chemistry B Accepted Manuscript

Wearable Biochemical Sensors for Human Health Monitoring:
Sensing Materials and Manufacturing Technologies
Received 00th XX 2019, Guanglei Li and Dan Wen
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Accepted 00th XX 2019

Wearable biochemical sensors are of great interest nowadays with for their powerful potential in personalized medicine and
DOI: 10.1039/x0xx00000x
continuous monitoring of the human health. Thus, a great deal of effort have been put into the development of such sensors
to enable the real-time and non-invasive quantification of various chemical constituents in the human body from sweat,
saliva, tears, etc. Thanks to the advances of materials science and mechanical engineering, wearable biochemical sensors
have been developed to probe various biomarkers and subsequently considered as wearable electronic devices for practical
application. In this review, we present a broad overview on the recent advances of electrochemical wearable sensors
towards various organic components and ions closely linked to human health. With an emphasis on materials and
manufacturing technologies of the sensing electrodes, the research status is summarized and the challenges and
opportunities in this growing field are prospected.

monitoring and long-term information collection [4-8]. Wearable

1. lntroduction biophysical sensors can be contacted with the skin to real-time
measure the biophysical parameters of the human body such as
Wearable devices are a kind of portable electronic equipment
blood pressure, heart rate, and skin temperature, which are of
that integrate sensors to the human body in the forms of
great values in medical applications. Wearable biochemical
clothing, ornaments, tattoos and internal implants, realizing in
sensors deal with trace samples and parallel processing of
vivo sensing, data storage, and mobile calculation. With the
different samples with a sensing chip through the lab-on-a-chip
increasing innovation of wearable sensing technologies, as well
technologies. Biomarkers in sweat, saliva, blood, urine, tears as
as the development of microelectronics and wireless
well as respiratory gases can be precisely measured by wearable
communication technologies, the majority of consumer
biochemical sensors [9-14], thus monitoring the metabolism and
electronics companies in the world have launched their own
health condition of the human body. In addition, some
wearable products such as Apple Watch [1], Microsoft Band [2],
wearable biochemical sensors can detect harmful substances
and Huawei Watch . The big data signals collected by wearable
[3]
(such as phosphide and sulphide) and various environmental
devices, which are processed and analysed synchronously, will
conditions [15-20], enhancing the safety and quality of the normal
be used in precision medical service to improve the level of
life.
health care management and the accuracy of nursing diagnostic.
Among these three kinds of wearable sensors, the motion
Since an aging population, the environment pollution, the food
state sensors and the biophysical sensors are launched into
safety and the disease outbreaks, the market scale of the
the market for a long time and widely used by consumers.
wearable devices will be further largely expanded for their easy
However, wearable biochemical sensors are still not completely
operation and in-situ monitoring of the human health.
commercialized because the components in the body fluids are
The key component of a wearable device is wearable sensors.
very complex and thus the biochemical parameters are
These wearable sensors with different functions provide
relatively more difficult to detect than the biophysical
important tools for solving sensor measurement problems in
counterparts [21]. In recent years, a great deal of efforts has been
the fields of health, medical, sports, industrial and military.
devoted to this kind of wearable sensors since more and more
According to different measurement parameters, wearable
people recognize the importance of health which is affected by
sensors can be classified into motion state sensors, biophysical
various biomarkers [22]. Therefore, this review will focus on the
sensors, and biochemical sensors. Motion state sensors mainly
wearable biochemical sensors for detecting chemical
measure the dynamic physical parameters of human body such
components in the human body or from the environment.
as gait, tremor, dyskinesia, and sleep quality to realize real-time
The integration of different sensors and the diversification of
the detection biomarkers are the future development trends of
State Key Laboratory of Solidification Processing, Center for Nano Energy the wearable biochemical sensors, which demands continuous
Materials, School of Materials Science and Engineering, Northwestern breakthroughs in sensing methods to support. Among different
Polytechnical University and Shaanxi Joint Laboratory of Graphene (NPU), Xi’an,
kinds of sensing methods, the electrochemical means shows
710072, P. R. China
Email: dan.wen@nwpu.edu.cn
remarkable advantages such as its simple structure, high

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sensitivity, fast response, and relatively low consumption of
power [23]. It is well known that the sensing electrodes play
dominated roles in wearable biochemical sensors based on the
electrochemical method [24]. However, two critical issues
concerning the functional materials and the manufacturing
technologies of sensing electrodes still need to be addressed to
realize the high performance of wearable biochemical sensors
[25].
Conventional sensing electrodes of wearable biochemical
sensors are based on the precious metals film-electrodes (such
as gold or platinum). In recent years, more and more new
materials such as metal nanoparticles, carbon materials and
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polymers are used as the electrode materials in wearable
biochemical sensors since the rapid development of materials
science and technologies, promoting the performances of
sensors [26-31]. At the same time, the introduction of different
micro-manufacturing technologies provides strong technical
support for the structure design and parameter optimization of
the sensing electrodes of sensors [25]. Unlike several excellent
reviews which describe wearable biosensors from different
perspectives [32-35], the prime objective of this review is about
the research status of the electrode materials and
manufacturing technologies of different kinds of wearable
biochemical sensors. Examples of biochemical wearable
systems of organic components and inorganic ions are
discussed. Following this a range of manufacturing techniques
of the biochemical sensing are presented along with integration
issues. A concluding part prospects future opportunities and
challenges in these wearable biochemical sensing platforms.
2. Wearable Biochemical Sensors for Organic
Compounds Detection
Organic components in body fluids are important reactants and
products of metabolism. It is very necessary to measure the
content of these organic components, which reflects the
metabolic level of the human body [36-41]. Wearable biochemical
sensors for detecting glucose [42-48], lactate [49-51], uric acid (UA)
[52-63] and alcohol [64-69] have been studied by the majority of
researchers since they are commonly existing in various body
fluids. Additionally, wearable biochemical sensors for dopamine
(DA) [70-72] and ascorbic acid (AA) [73, 74] have gradually become
the focus of research in recent years for their great impacts on
human health. In this section, wearable biochemical sensors for
detecting organic compounds based on different electrode
materials will be described in detail.
2.1 Wearable Glucose Sensors
Abnormal glucose metabolism is an important reason of
diabetes, pancreatitis, hyperglycaemia and many other
complications [75-82]. More than 3 million people around the
world die from diseases caused by abnormal glucose
metabolism every year [83-85]. However, most people do not
know whether the levels of glucose are normal in daily life,
leading to the delay in the detection and treatment of such
diseases. Therefore, it is very essential to realize the real-time
monitoring of the glucose content in the human body for
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significantly improving the physical health and life View quality of
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patients. DOI: 10.1039/C9TB02474C
Wearable glucose sensors can be classified into enzymatic
and non-enzymatic ones, according to the recognition
elements. Due to the high catalytic efficiency and high
Journal of Materials Chemistry B Accepted Manuscript
specificity of the enzyme, the enzymatic sensors would have the
advantages of high sensitivity and excellent selectivity.
Wearable glucose sensors based on the enzymatic electrodes
have been extensively investigated all over the world, whether
they are focused by researchers or commercialized by
companies. Glucose oxidase (GOD) is generally modified on
enzyme immobilization matrix with good electrical conductivity
to reduce the distortion of electrical signals. The enzymatic
electrode sensor put forward by Updick firstly in 1967 was
based on platinum film electrode modified by glucose oxidase
[86]. The oxygen was used as the electronic mediator between
the oxidase and the electrode, realizing the glucose sensing by
detecting the reduction of the oxygen. Then Clark improved the
sensing electrode, which could realize the quantitative
measurement of glucose by detecting the concentration of
produced hydrogen peroxide, avoiding the interference of
oxygen in the air. The first wearable glucose sensors based on
Clark electrode was proposed by Cygnus Inc. in 2001 [87, 88]. Pt/C
composite ink integrated with GOD was used to fabricate the
sensing electrode of the wrist-watch device for detecting the
glucose content in interstitial fluid. The proposed sensor
featured a good sensitivity and selectivity to glucose detection,
opening up the possibility of real-time monitoring of the human
health.
Afterwards, considerable effort has been devoted to develop
wearable sensors that can monitor glucose concentration for
human body in real time. Wang’s group has done deeply
research on wearable sensors [26, 89, 90], especially on the
enzymatic glucose sensors. As shown in Fig. 1, carbon graphite
ink, glucose oxidase and Prussian blue were used to compose
the enzyme electrode of the wearable sensor [73]. The glucose
was oxidized and converted to glucolactone as well as hydrogen
peroxide by the glucose oxidase under the condition of oxygen.
And then the glucose in tears was quantitative determined via
the produced hydrogen peroxide, which was proportional to
the target biomarker. The proposed sensor featured a
favourable response to the glucose in tear, carrying out the
possibility of the non-invasive and real-time glucose detection.
The carbon graphite ink is often used as the sensing
electrodes of wearable glucose sensors as well as the
immobilization matrix of enzymes due to its porous structure
after annealing (Fig. 2A). In addition, some three-dimensional
electrodes fabricated with porous materials such as graphene,
carbon nanotubes (CNTs) and conductive polymer are chosen
to construct the enzymatic sensors. Three-dimensional
electrodes with porous structure, good conductivity and large
specific surface area are more suitable candidates as good
immobilization matrix of enzymes (Fig. 2B-F). For example, Kim
et al. proposed a wearable patch for the sweat-based diabetes
monitoring and feedback therapy (as shown in Fig. 3A). The
gold-doped CVD graphene with electrochemically active
materials was employed to establish a wearable sensor with
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enhanced electrochemical activity and biochemical selectivity,
while maintaining the intrinsic softness of graphene. In recent
years, researchers have also made use of fibrous materials as
the immobilization matrix of enzymes to prepare wearable
glucose sensors (Fig. 3B and C), which features a better
biocompatibility on the basis of good performances.
The good selectivity of enzymatic electrodes has made it an
important research direction in the field of wearable glucose
sensors. However, this kind of sensors suffered an unsatisfied
long-time stability due to the variability of the enzyme activity
under different environment conditions such as temperatures,
pH and ionic strength. The enzyme will even lose activity in
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extreme conditions, leading to the abnormal work of the
sensors. Therefore, wearable glucose sensors based on non-
enzymatic electrodes have currently attracted a lot of attention.
Wearable glucose sensors based on non-enzymatic
electrodes mostly utilize sensing materials that have good
electro-catalytic characteristics to glucose. A lot of metal
materials such as gold, platinum, palladium, and metallic oxides
such as nickel oxide, copper oxide, can directly catalyse glucose
[81, 82, 92, 93]. In order to increase the sensitivity of sensors, they
are often made into the form of nanostructures with excellent
electrocatalytic activity. Some groups use metal nanowires or
nanosheets to construct the sensing electrodes, achieving
superior performances than the film electrodes (Fig. 4A and B)
[92, 93]. In addition, carbon nanomaterials can also have good
catalytic characteristics on specific substances after modified
with different functional groups [55]. For instance, a novel
sensing electrode with Cu3(btc)2 nanotubes and flexible amino-
functionalized graphene paper (Fig. 4C) was developed by Wang
et al. This sensing electrode was applied in a non-enzymatic
electrochemical platform to detect glucose in perspiration. The
proposed wearable sensors have a remarkable sensitivity due
to the large specific surface area brought by the porous
structure of the graphene.
Different from the enzymatic counterparts, non-enzymatic
glucose sensors generally use a selective permeable membrane
or optimize the pore size of materials to improve the selectivity.
One of the outstanding advantages of the non-enzymatic
glucose sensors is their superior long-term working stability
since the electrode sensing materials will hardly lose their
electrochemical activities under different environment
conditions or in a long time.
2.2 Wearable Sensors for the other Organic Compounds
Detection
Beyond glucose, some other organic compounds in the body
fluids are closely related to human health as well. For instance,
UA is the final product of purine metabolism. Excessive UA will
be retained in the body if the excretory system of UA is
degraded, which will lead to the change of normal pH of body
fluids and affect the normal function of human cells. Disease
such as the gout will happen if UA content in the body is
neglected for a long term. Lactate and alcohol are also
important metabolites in body fluids to reveal human’s health.
Thus, wearable biochemical sensors for detecting such organic
compounds are often based on corresponding enzymatic
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electrodes which are similarly fabricated to the Viewenzymatic
Article Online
glucose sensors [13, 21, 73]. DOI: 10.1039/C9TB02474C
In addition, other kinds of organic biomarkers, which are
scarce in the body, play important roles in the regulation of
metabolism. For example, dopamine is an important
Journal of Materials Chemistry B Accepted Manuscript
information transmitter of central nervous system in mammals
and human beings [70]. It is widely distributed in many tissues
and plays an important role in increasing cardiac output,
elevating arterial blood pressure and expanding cerebral
vessels. Trace detection of dopamine and its metabolites in
brain tissues or body fluids is of great significance for the study
of the physiological functions of these transmitters, as well as
the diagnosis and drug treatment of diseases related to
abnormal transmitter metabolism [71, 72]. On the other hand,
vitamin is a class of organic compounds which is necessary to
sustain the health of the body [73]. In these cases, there is a need
for continuous monitoring of these biomarkers to assess human
health and wellbeing since adverse effect will be happened to
the human health in the lack of these compounds.
The sensing electrodes of such sensors can provide obvious
output signals without enzymes since these organic substances
such as dopamine and vitamins have good electrochemical
activity and are easy to be directly catalysed. For instance, a
wearable dopamine sensor based on an organic
electrochemical transistor, which is composed of PVA-co-PE
nanofibers and polypyrrole nanofiber network [72], was
proposed by Lu et al. (Fig. 5A). The developed sensor had long-
term stability with a detection region from 1 nM to 1 μM, a rapid
response time to a set of DA concentrations, a remarkable
selectivity in the presence of sodium chloride, UA, AA or glucose,
and a superior reproducibility. The three-dimensional porous
structure of fibrous material and good electrical conductivity of
the polymer provide the electrode a high sensitivity as well as
good biocompatibility, which were suitable for the preparation
of wearable biochemical sensors. In addition, carbon materials
are also used to fabricate the sensing electrode of these kinds
of wearable biochemical sensors. Wang et al. had prepared a
wearable vitamins sensor based on carbon ink sensing
electrodes (see Fig. 5B). On the surface of the carbon electrode,
the oxidation peaks of different kinds of vitamins (B2, C and B6)
occurred at different potentials, realizing the detecting of
multiple vitamins. Wooi et al. achieved quantitative detection
of AA through sensing electrodes prepared by CNTs (Fig. 5C).
Since the excellent intrinsic electrochemical activity of these
biomarkers, non-metallic materials, such as graphene, carbon
nanotubes and conductive polymers, can be directly used as
sensing electrodes in this kind of wearable biochemical sensors.
These wearable biochemical sensors not only feature a high
sensitivity due to characteristics of the nanostructured
materials, but also further decrease the cost of materials rather
than those sensors based on metal electrode materials.
3. Wearable Biochemical Sensors for Ions
Detection
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Besides the organic compounds, ions such as inorganic salt ion
and hydrogen ion play important roles in the body fluids.
Inorganic salt ions in body fluids, such as K+, Na+, Ca2+, Cl-, NH4+
and so on, have functions of regulating cell membrane
permeability, controlling water content, maintaining normal
osmotic pressure, transporting elements, participating in nerve
activities, and muscle contraction [37, 94-104]. Hydrogen ions are
important for maintaining the pH balance of the human body
[105-111]. Therefore, the real-time detection of various ions in
body fluids can also achieve the aim of monitoring human
health. In this section, the development status of sensing
electrode materials for several inorganic salt ion and pH sensors
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will be presented.
3.1 Wearable Inorganic Salt Ions Sensors
Potassium ion participates in cell metabolism and provides
suitable conditions for the normal activities of certain enzymes.
The most prominent role of potassium ions is to maintain the
normal excitability, self-discipline, and conductivity of
cardiomyocytes. Sodium can enhance the excitability of nerve
muscle. The body will show the symptoms such as appetite
decreasing, nausea or blood pressure decreasing when the
body lacks sodium. Potassium and sodium also play very
important roles in regulating acid-base balance, maintaining
osmotic pressure and water balance. Chloride ion and ammonia
ion also play decisive roles on the physiological regulation of the
human body. In addition, calcium and zinc ion and the other
inorganic salt ions are also essential elements in human body.
Therefore, the development of strategies for monitoring the
content of these ions in the body fluid is essential.
According to the different structure of electrodes, the
inorganic salt ions sensors can be classified into two types. One
kind of ions sensors is based on ion selection electrode (ISE),
which is composed of an ion selective membrane and an ion
exchange membrane. The membrane potential related to the
concentration of ions on the phase interface of the ISE will be
obtained when the ISE contact with the solution containing ions
to be measured. As the sensing unit of the electrode, ISE have
responses to specific ions, making this kind of sensor has the
characteristics of good selectivity. At the same time, the
relationship between the membrane potential and the content
of measured ions conforms to the Nernst formula, providing the
sensor a short equilibrium time. Materials with porous structure
are often used to increase the specific surface area of the
electrode in order to enhance the sensitivity. This approach was
employed by Hanein et al. to develop a wearable sensor based
on CNTs sensing electrode for detecting Na+ in human sweat (Fig.
6A). CNTs with highly porous structure was filled with the ion
selective membrane, forming an attachment that was stronger
than that achieved with flat Au, Pt film electrode [95]. Gao et al.
prepared similar wearable ion sensors to detect the potassium
and sodium in sweat (Fig. 6B). Poly (3, 4-
ethylenedioxythiophene) was deposited onto the sensing
electrode by galvanostatic electrochemical polymerization to
fabricate the ion-electron transducer since its high conductivity
and stability in the redox reaction [101]. In addition, carbon ink
and graphene have also been used to prepared similar ion
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sensors electrodes (Fig. 6C and D) to detect the potassium,
View Article Online
sodium and chloride ion in real time. DOI: Since the membrane
10.1039/C9TB02474C
electrode can directly interact with the measured ions to
generate electrochemical signals, the only need for the sensing
electrode materials is to meet the requirements of electrical
Journal of Materials Chemistry B Accepted Manuscript
conductivity and large specific surface area in order to obtain
high sensitivity. Some porous conductive materials are more
favourable for the preparation of such wearable biochemical
sensors.
Unlike the ions sensor based on the ISE, another type of ion
sensor is based on the principle of the field effect transistor
(FET). Sensitive materials are often modified on one channel of
the FET, which are fabricated with semiconductor materials.
The resistance of the channel will change when the measured
ions contact with sensitive materials. Then the concentration of
the ions can be evaluated by measuring the variation of the
output electrical signals of the FET. Based on this working
principle, Bao et al. prepared a wearable ion selective sensor on
silicon materials. The mixture of sliver nanoparticles,
polyurethane, N, N-dimethylformamide and tetrahydrofuran
was used to fabricate the sensing electrode. The prepared
wearable sensor could not only detect the concentration of
potassium and calcium ions in saliva, but also detect ammonia
ions, realizing the effective integration of multiple sensors (Fig.
7A and B) [98]. Some flexible sensing materials, such as
molybdenum disulphide (MoS2), are attractive semiconductor
analogues that can be directly fabricated to the FET. For
example, Wu et al. made use of the MoS2 to design the sensing
electrode of the ion sensor due to its outstanding electrical and
mechanical properties (Fig. 7C and D). In addition, the natural
band gap in MoS2 (1.2 eV) results in a strong modulation on
current produced by molecule adsorption, fundamentally
improving its sensitivity. The flexible integrated MoS2 ion sensor
realized simultaneous and trace detection of Na+, Cd2+, Hg2+ and
Pb2+with excellent selectivity.
The ion sensor based on FET owns very good selectivity since
the sensing electrode material can only react with ions to be
measured. In addition, the FET sensor has the advantage of high
sensitivity due to the amplification effect of the FET, which is
suitable for trace detection of metal element ions in the body
fluid. However, compared with the ion sensors based on
membrane electrodes, the structure of the ion sensor based on
FET is more complex, as well as the manufacturing process.
3.2 Wearable pH Sensors
Measurement of the hydrogen ion can provide an important
assessment to determine individual health conditions.
Hydrogen ion sensor is also called pH sensor because it
determines the pH value of body fluids. Since many materials
(such as carbon materials, metals and their oxides, biological
enzymes, etc.) are capable of chemical reactions with hydrogen
ions, the materials of sensing electrodes that can be used in pH
sensors are more abundant, making pH sensors attract more
attention.
Carbon ink mixed with metal ink is often used to prepare the
sensing electrode of the pH sensor in order to overcome
challenges such as the drift of the sensors and the delamination
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of the electrode layers under the mechanical strains. As shown
in Fig. 8A, electrodes ink was formulated with carbon ink and
silver ink. The proposed sensor could detect pH in sweat with a
good long-time stability [25]. A lot of metals (gold, silver,
palladium, etc.) and metal oxides (lead oxide, indium oxide,
etc.) can also be used to fabricate bio-FETs as the sensing
electrode of wearable pH sensors (Fig. 8B and C). The pH
sensors fabricated with these metal materials are more
sensitive [108-110]. What is more, since wearable biochemical
sensors such as glucose and lactate sensor are also sensitive to
pH, the pH sensor can be combined with these wearable
biochemical sensors for more accurate detection of human
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physiological indicators. For example, a wearable biochemical
sensor based on the MXene material modified with oxidases for
detecting glucose and lactate in sweat (Fig. 8D) was prepared by
Lei et al [105]. For this wearable sensor, enzymes were used as a
kind of sensing materials for detecting the value of pH, so as to
calibrate the glucose sensor and the lactate sensor. The only fly
in the ointment is the detecting range of the pH was relatively
narrow due to the issue of the maintaining of the enzymatic
activity. The pH sensor will be an important part of wearable
biochemical sensor, since it can not only monitor human
physiological indicators in real time, but also improve the
accuracy of wearable biochemical sensor.
4. Wearable Biochemical Sensors for other
Harmful Agents Detection
The majority of wearable biochemical sensors are used to
detect the biomarkers which are generally existing in the body.
However, some chemicals do not normally present in healthy
people, but appear in the body when people fall ill or suffer
health damage. For example, antigens are often distributed in
the body fluids or tissue cells of patients or injured people [112-
114]. In addition, some harmful chemicals in the environment
such as phosphates [115-118], toxic sulphides [119], cocaine and
nerve gas [18-20] may be exposed to people through air or food,
causing harm to health. Wearable biochemical sensors that
detect such substances can be used to monitor the recovery of
disease and the safety detection of the environment for human
body.
The sensing electrodes of the antigen sensors are usually
fabricated with three-dimensional conductive materials
modified with antibodies. The large specific surface area makes
the three-dimensional conductive materials an excellent
immobilization matrix for antibodies, which are similar to
enzyme immobilization strategy. For example, the mixture of
photoresist and conductive polymer modified with the antibody
was used to construct the sensing electrode which can detect
specific antigens [113]. Lee et al. used gold to prepare a sensing
electrode with three-dimensional structure. The proposed
wearable sensor can also be used to detect tumour cells in
patients after attaching antibodies (Fig. 9A) [112].
Similarly, sensors that detect phosphates, sulphides, and
other substances typically use materials such as the conductive
polymers, conductive carbon materials to combine with the
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substances that can react with biomarkers as View theArticle
sensing
Online
electrodes. Hall et al. described a wearable
DOI:glove-based sensor
10.1039/C9TB02474C
which consists of carbon electrodes modified with a mixture of
multi-walled CNTs and 4-(3-butyl-1-imidazolio)-1-
butanesulfonate. The glove-based sensor could directly oxidize
Journal of Materials Chemistry B Accepted Manuscript
fentanyl in both liquid and powder forms with a detection limit
of 10 μM via the method of square-wave voltammetry (Fig. 9B)
[18]. Zhao et al. proposed a fully integrated portable nano-
sensing system based on graphene to detect cytokine
biomarkers in saliva, the entire size of the proposed sensor was
smaller than a smart-phone and could be handheld (Fig. 9C) [114].
The three-dimensional structures were formed from either the
material itself or micro-manufacturing process. In general, it is
more economical to use the conductive porous materials rather
than through the complex manufacturing technologies.
5. Manufacturing Technologies
The development of the wearable biochemical sensors has close
relationship with the manufacturing technologies of the sensing
electrodes. Many approaches are proposed to fabricate the
sensing electrodes of wearable biochemical sensors. Some
simple and convenient methods such as textile technologies (Fig.
10A) [72], inkjet printing (Fig. 10B) [109], 3D printing [97], are often
used to prepare sensing electrodes in laboratory conditions.
However, the large-scale production of sensing electrodes
prepared by these methods is limited and the consistency
between each electrode is not high enough. Therefore, these
manufacturing methods are only suitable for laboratory
research, hindering the widespread utilization of wearable
biochemical sensors. The development of micro-manufacturing
technologies has solved this problem. The screen printing and
micro-electromechanical system (MEMS) technologies are two
mainly methods for preparing sensing electrodes of wearable
biochemical sensors. These two conventional manufacturing
technologies are introduced to the field of wearable
biochemical sensor, promoting the development of sensor
technology and application.
Screen-printing technologies are one of the important
methods to fabricate the sensing electrodes with the use of
screen-printing plate. The image to be printed is
photographically transferred to a very fine fabric (the screen) so
that the non-printing areas are blocked off and the fabric serves
as a stencil. With the screen-printing technologies, different
biosensors can be integrated on the same sensing electrode to
achieve simultaneous detection of multiple quantities. For
example, Fig. 11A shows the screen-printed three-electrodes of
a wearable lactate sensor and an electrocardiogram sensor [21],
realizing multimodal monitoring of biochemical parameter as
well as biophysical parameter. The prepared wearable
biochemical sensors manufactured with this method not only
featured good consistency but also reduced production cost of
the electrode since a batch of devices will be produced at the
same time.
MEMS technologies are mostly used in chip manufacturing
based on the silicon wafer. In recent years, flexible sensing
electrodes of the wearable biochemical sensor fabricated by
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MEMS technologies have also been widely investigated due to
the good properties of the flexible materials. As shown in Fig.
11B, the lithography and development technologies were used
to fabricate the sensing electrode of the wearable antigen
sensor [113]. The photoresist mixed with conductive polymer was
washed off after developing, thus obtaining a porous structure,
which could enhance the sensitivity of the sensor. In addition of
preparing electrodes on the flexible substrate, MEMS
technologies can also make the sensing electrode with different
structure characteristics on the substrates by means of
lithography, deep etching and oxygen ion etching technologies
[111].
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Both screen-printing and MEMS technologies have the
advantage of mass-produced sensing electrodes for wearable
biochemical sensors. It is worth to notice that screen-printing
technologies requires fewer equipment and simpler production
lines, making it more suitable for most laboratories; while
MEMS technologies make the control of the thickness of the
film on the sensing electrodes several nanometres feasible.
Generally speaking, these two technologies not only realize the
mass production of sensing electrodes for wearable
biochemical sensors, but also make it easier to realize the
structures design, electrodes integration, and parameter
optimization of the sensing electrodes.
6. Conclusions: prospects and challenges
In this review, the sensing materials and manufacturing
technologies of the sensing electrodes of wearable biochemical
sensors for detecting different biomarkers are described. The
development and application of new materials have greatly
improved the sensitivity, selectivity and stability of sensors. At
the same time, the introduction of the different manufacturing
technologies of sensing electrodes makes the preparation of
sensing electrodes more simple, convenient and diversified,
laying a technical foundation for the development of wearable
biochemical sensors. In spite of the extensive progress, there
remain numerous challenges to overcome for the successful
implementation of wearable biosensors.
As we know, though various biosensors which could detect
different biomarkers have been developed by researchers, only
a few biosensors were transformed to wearable sensors. One of
the key issues is the non-specific adsorption of interfering
substances on the sensing electrode, leading to the electrode
fouling. Many methods have been proposed to solve such
problem. For instance, Nafion is often used on a glucose sensor
as a semi-permeable membrane to prevent the interfering
substances with negative charge [26, 30]. Ion selective
membranes can also enhance the antifouling performance of
ions sensors [96, 101, 104]. In addition, some porous materials with
particular size can also realize similar function [92]. Nevertheless,
these methods are not suitable for all the biosensors especially
the ones which detect the biomarkers with large molecular
weight (such as proteins, RNA and DNA) since they are suffered
more severely from the co-existed non-specific bio-
macromolecules. Meanwhile, some interfering substances with
small molecular weight may also foul the electrodes. Therefore,
6|
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Journal of Materials Chemistry B
more new approaches should be proposed to View enhance the
Article Online
antifouling performance of biomoleculesDOI: sensors for wearable
10.1039/C9TB02474C
application in actual systems.
For a wearable biosensor which will be coupled onto the skin
or the closes of human body, bending is a common mechanical
Journal of Materials Chemistry B Accepted Manuscript
stress expected during daily wear. Therefore, the sensing
electrodes of the wearable biosensors should be flexible and
stretchable in order to meet the demands for wearable
applications. The challenge could be overcome by using
stretchable substrates or designing special structure of the
electrodes. For example, flexible materials such as textiles,
tattoos and polymers are often used as the flexible substrates
of wearable biosensors to enhance their stretchability [21, 30, 62].
Additionally, some sensing electrodes (carbon ink, hydrogels
and conductive polymers, etc.) were designed into wrinkled or
serpentine structures to achieve the stretchability [92, 94, 112].
With these strategies, the wearable biosensors remain robust
sensing performances while the sensing electrodes are being
stretched. In spite of these approaches, future efforts should
also aim at developing the intrinsic stretchability of the sensing
materials, further improving the stretchability of the wearable
biosensors.
Thanks to the manufacturing technologies mentioned in this
review, many researchers have developed wearable biosensors
which can detect different biomarkers such as glucose, lactate,
and various ions at the same time [73, 96, 97]. In addition, some
sensing materials can detect biochemical parameters as well as
biophysical parameters (such as strain, electrocardiogram and
temperature) [21, 111, 120] to achieve multimodal monitoring.
Therefore, the integration of different kinds of sensors on single
chip will be the future development trend of wearable
biosensors.
Carbon ink and metal film are traditional electrode materials
to fabricate the wearable sensing platform. For sensors with low
requirements on sensitivity, they are not only simple to
fabricate, but also relatively reliable. With the growing
requirement for high performance sensing devices in human
health monitoring, new nanostructured materials (i.e.,
graphene, CNTs and porous metals) and conducting polymers
would be more suitable candidates to achieve high-sensitivity,
fast-response, and high-selectivity determination. This is
because they are not only excellent matrices for biorecognitions
in sensing devices, but also sometimes high-efficient
electrocatalysts of the interest targets. In addition, the porous
materials with hollow structure are often used as the
immobilization matrix for enzymes, antibodies and other
sensitive materials in enzymatic sensors and the other wearable
biochemical sensors. In the future, the multifunctional
materials with three-dimensional porous structure, good
electrical conductivity, and catalytic ability may attract more
attention. This kind of materials will have a wide range of
applications in the fields of enzymatic sensors as well as non-
enzymatic sensors.
The progress of manufacturing technologies promotes the
development of wearable sensing devices. The screen-printing
technologies and MEMS technologies are introduced into the
sensing electrode production of wearable sensors since a good
This journal is © The Royal Society of Chemistry 2019
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consistency and a low production cost are important
parameters for wearable biochemical sensors. These mature
technologies have simple operation methods, and the prepared
sensing electrodes have the advantages of small error, high
consistency, and low cost, which provide a strong guarantee for
7 J. Q. Zhao, Y. J. Lin, J. B. Wu, H. Y. Y. Nyein, M. ViewBariya, L. Tai,
Article Online
M. H. Chao, W. B. Ji, G. Zhang, Z. Y. Fan, DOI:A. Javey, ACS Sens.,
10.1039/C9TB02474C
2019. doi.org/10.1002/adma.201902083.
8 S. Xia, S. X. Song, F. Jia and G. H Gao, J. Mater. Chem. B, 2019,
7, 4638-4648.
9 X. P. Zeng, Y. Z. Zhang, X. L. Du, Y. F. Li and W. W. Tang, New J.

Journal of Materials Chemistry B Accepted Manuscript

the commercialization of wearable biochemical sensors. On the
other hand, newer and simpler manufacturing techniques such 10
11
as textile technologies, inkjet printing, and 3D printing are also
developed and exploited since not all research labs can build a 12
production line due to some equipment for MEMS technologies
are expensive. These technologies have significant potential to 13
be the main candidate manufacturing technologies as long as
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Chem., 2018, 42, 11944-11953.
X. Li, C. Zhao and X. Y. Liu, Microsyst. Nanoeng., 2015, 15014.
E. Cho, M. Mohammadifar, S. Choi, MEMS 2017, DOI:
10.1109/MEMSYS.2017.7863417
I. Jeerapan, J. R. Sempionatto, A. Pavinatto, J. You and J. Wang,
J. Mater. Chem. A, 2016, 4, 18342-18353.
J. Kim, S. Imani, W. R. Araujo, J. Warchall, G. V. Ramírez, T. R.
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2015, 74, 1061-1068.

the realization of the batch production of sensing electrodes.
Sensing electrodes are the core of wearable biochemical
sensors. The development of the wearable sensor is in fact the
developments of sensing materials and the manufacturing
technologies. Although significant developments of wearable
biochemical sensors have been reported in the past several
years, it is still required a substantial amount of effort to further
advance the commercialization of such devices in order to
realize the promise of truly innocuous sensing in a broad range
of healthcare, fitness, and military applications.
Conflicts of Interest
There are no conflicts to declare.
ORCID
Dan Wen: 0000-0001-6879-7982
Guanglei Li: 0000-0002-5038-5039
Acknowledgements
This work is supported by the National Natural Science
Foundation of China (61901389, 21804108), the Natural Science
Foundation of Shaanxi (2019JM-239), the Fundamental
Research Funds for the Central Universities (3102019PY008,
3102019JC005), and the 1000 Youth Talent Program of China.
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Figure 1 (A) Scheme of the procedure used for on-body glucose sensing experiments. (B)
Monitoring of glucose levels during the entire day: breakfast, lunch, and dinner. Note: Tear
stimulation (arrows) and meal (M). Bottom, correlation between blood glucose measurements
with a glucometer (red) and the current response of the wearable tear sensor (black). Reprinted
with permission from ref. [73] (copyright 2019, Elsevier)
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Figure 2 (A) The SEM images of carbon graphite ink. Reprinted with permission from ref. [49]
(copyright 2019, Elsevier). (B) The SEM images of CNTs. Reprinted with permission from ref. [26]
(copyright 2017, Royal Society of Chemistry). (C) The SEM images of graphene. Reprinted with
permission from ref. [28] (copyright 2018, Elsevier). (D) The SEM images of nano-porous metal.
Reprinted with permission from ref. [61] (copyright 2019, Elsevier). (E) The SEM images of
polyaniline nanorods. Reprinted with permission from ref. [27] (copyright 2019, American
Chemical Society). (F) The SEM images of cellulose / β-CD / GOD nanofibers. Reprinted with
permission from ref. [31] (copyright 2019, Royal Society of Chemistry).
 Journal of Materials Chemistry B Page 12 of 21

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Figure 3 (A) Wearable patch for sweat-based diabetes monitoring and feedback therapy. Reprinted
with permission from ref. [30] (copyright 2016, Springer Nature). (B) Enzymatic wearable glucose
sensor based on AuNWs & SEBS. Reprinted with permission from ref. [91] (copyright 2019,
American Chemical Society). (C) Enzymatic wearable glucose sensor based on CA/β-CD NFs.
Reprinted with permission from ref. [31] (copyright 2019, Royal Society of Chemistry)
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Figure 4 (A) Non-enzymatic wearable biochemical sensor based on nanoporous gold. Reprinted
with permission from ref. [92] (copyright 2019, American Chemical Society). (B) Non-enzymatic
wearable biochemical sensor based on gold nanosheet. Reprinted with permission from ref. [93]
(copyright 2018, American Chemical Society). (C) Non-enzymatic wearable biochemical sensor
based on graphene oxide paper modified with Cu3(btc)2. Reprinted with permission from ref. [55]
(copyright copyright 2018, Royal Society of Chemistry).
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Figure 5 (A) Wearable dopamine sensor based on PVA-co-PE nanofibers and polypyrrole nanofiber
network. Reprinted with permission from ref. [72] (copyright 2019, American Chemical Society).
(B) Wearable vitamins sensor based on carbon ink. Reprinted with permission from ref. [73]
(copyright 2019, Elsevier). (C) Wearable AA sensor based on CNTs. Reprinted with permission from
ref. [74] (copyright 2019, American Chemical Society).
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Figure 6 (A) Wearable sensor based on CNTs electrode for Na+ sensing in human sweat. Reprinted
with permission from ref. [95] (copyright 2017, American Chemical Society). (B) Integrated
wearable K+ and Na+ sensor. Reprinted with permission from ref. [101] (copyright 2016, Springer).
(C) Wearable K+ sensor. Reprinted with permission from ref. [96] (copyright 2017, Royal Society of
Chemistry). (D) Wearable sensor for Cl- sensing in human sweat. Reprinted with permission from
ref. [104] (copyright 2019, Elsevier).
 Journal of Materials Chemistry B Page 16 of 21

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Figure 7 (A-B) The ion-selective FET based on silicon materials. Reprinted with permission from ref.
[98] (copyright 2019, Elsevier). (C-D) The ion sensor based on MoS2 sensing electrode. Reprinted
with permission from ref. [97] (copyright 2019, Elsevier).
 Page 17 of 21 Journal of Materials Chemistry B

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Figure 8 (A) Wearable pH sensor based on carbon ink electrode. Reprinted with permission from
ref. [25] (copyright 2018, American Chemical Society) (B) Wearable pH sensor with high sensitivity
based on a flexible charge-coupled device. Reprinted with permission from ref. [107] (copyright
2017, American Chemical Society). (C) Quasi-Two-Dimensional metal oxide semiconductors based
ultrasensitive potentiometric biosensors. Reprinted with permission from ref. [111] (copyright
2018, Springer Nature). (D) Wearable biochemical sensor based on the enzymatic electrode
modified with MXene material. Reprinted with permission from ref. [105] (copyright 2019, John
Wiley and Sons).
 Journal of Materials Chemistry B Page 18 of 21

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Figure 9 (A) Wearable tumour cells sensor. Reprinted with permission from ref. [112] (copyright
2018, Elsevier). (B) The glove-based fentanyl sensor. Reprinted with permission from ref. [18]
(copyright 2019, Elsevier). (C) A graphene-based fully integrated portable nano-sensing system for
on-line detection of cytokine biomarkers in saliva. Reprinted with permission from ref. [114]
(copyright 2019, Elsevier).
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Figure 10 (A) Wearable biochemical sensor fabricated by textile technologies. Reprinted with
permission from ref. [72] (copyright 2019, American Chemical Society. (B) Inkjet printing
technologies to fabricate the sensing electrodes. Reprinted with permission from ref. [109]
(copyright2016, John Wiley and Sons).
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Figure 11 (A) Screen-printing technologies. Reprinted with permission from ref. [21] (copyright
2016, Springer Nature). (B) Sensing electrodes manufactured with MEMS technologies. Reprinted
with permission from ref. [113] (copyright 2019, American Chemical Society).
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Recent achievements and challenges in materials and manufacturing technologies of sensing

electrodes in wearable biosensors have been highlighted.