REVIEW

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Bio-Multifunctional Smart Wearable Sensors for Medical

Devices
Lili Wang, Zheng Lou, Kai Jiang,* and Guozhen Shen*

Usually, wireless electronic devices are

Advances in digital health care have driven innovations in high-performance loosely coupled onto some parts of the
wearable and smart sensors. One requirement in this field is establishing healthy, human body, especially the wrist or chest,
secure, and reliable medical devices for precisely monitoring vital signs of the in the form of small or rigid blocks that can
detect or record some important physiolog-
human body or the surrounding environment through flexible sensors with not
ical indexes in real time without requiring
only high-sensing performance but also excellent biofunctionality. Smart wear- the heavy-wired hardware present in clini-
able sensors with excellent biofunctionality furnish medical devices with various cal systems. This important and continu-
smart functions such as biocompatibility, biodegradability, and self-healing, ous human indicator information can
which have attracted widespread interest from device engineers and materials alert users of abnormal health, allowing
them to take preventive measures to protect
scientists. Herein, a comprehensive review of the latest progress concerning
their health and avoid serious medical con-
these smart wearable sensors is presented with a focus on bio-multifunctional ditions.[3] Continuous extension of smart
(biocompatible, biodegradable, and self-healing) device designs. The medical wearable sensors in the scope and scale
applications of bio-multifunctional smart wearable sensors are also briefly cov- of their applications has driven the develop-
ered, and to conclude, a discussion of the challenges, opportunities, and future ment of wearable devices to a new high.
perspectives is provided. Five years from now, the worldwide reve-
nue from wearable devices looks likely to
reach $97.8 billion.[4] Although the contin-
ued need for smart wearable sensors in
1. Introduction medical applications is growing, many sensors for practical appli-
cations have limited potential for qualitative improvements in
Over the past several decades, electronics have become central to biofunctionality.
many aspects of biomedicine.[1] The boosting desire for real-time The failure of flexible sensors without biofunctionality to
fitness tracking, health monitoring, and disease forecasting has provide a safe and reliable biological interface is a fundamental
created a fast-growing market for flexible and wearable sensors.[2] limitation in practical applications. For nonstandard health mon-
itoring, these limitations may not affect the simple use of wear-
Prof. L. Wang, Prof. Z. Lou, Prof. G. Shen able devices to monitor daily pulse and heart rate changes.[5]
State Key Laboratory for Superlattices and Microstructures For example, traditional wearable devices can provide acceptable
Institution of Semiconductors performance in heart rate monitoring for entertainment applica-
Chinese Academy of Sciences tions. However, in real clinical applications or specific environ-
Beijing 100083, China
E-mail: gzshen@semi.ac.cn ments, even precise wearable devices cannot provide safe and
Prof. L. Wang
reliable daily movement performance parameters, mainly due
State Key Laboratory of Integrated Optoelectronics to the lack of specific biological functions in wearable devices.
College of Electronic Science and Engineering Thus, with constant innovations in device designs and manu-
Jilin University facturing methods, the market demand for bio-multifunctional
Changchun 130012, China smart wearable sensors has increased. This increased market
Prof. K. Jiang demand requires that sensors have the characteristics of biocom-
Institute & Hospital of Hepatobiliary Surgery
Key Laboratory of Digital Hepatobiliary Surgery of Chinese PLA
patibility, biodegradability, bioabsorbability, self-healing, and
Chinese PLA Medical School safe integrability with human and tissue surfaces.[6,7] The bio-
Chinese PLA General Hospital functionality of these devices is significant in terms of both vari-
Beijing 100853, China ous practical applications and the accuracy/reliability of the
E-mail: jiangk301@126.com resulting data. For example, from a medical perspective, the
The ORCID identification number(s) for the author(s) of this article biocompatibility and biodegradability of devices significantly
can be found under https://doi.org/10.1002/aisy.201900040. improve their intimacy and secure integration with the skin
© 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, interface, whereas self-healing and water-proof wearable devices
Weinheim. This is an open access article under the terms of the Creative can reduce vulnerability and sensitivity to moisture, thereby
Commons Attribution License, which permits use, distribution and enhancing the durability, reliability, and safety of devices.
reproduction in any medium, provided the original work is properly cited.
These biofunctions follow naturally from the flexible character-
DOI: 10.1002/aisy.201900040 istics and requirements of wearable sensors for biophysical and

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biochemical measurements in medical applications, such as
safety, robustness, and lack of irritation at interfaces. Combin-
ed with the recent development of personalized diagnosis and
treatment technology, the improvement in postoperative tracking
technology, and the objective of the early prevention of diseases,
these kinds of bio-multifunctional smart wearable sensors are at
a turning point in realizing widespread applications and have sig-
nificant potential social benefits.[5]
In this review, we highlight the latest advances and provide crit-
ical insights into bio-multifunctional smart wearable sensors for
medical applications (Figure 1). First, the recent successful dem-
onstrations of bio-multifunctional wearable sensors, including
biocompatible, biodegradable, bioabsorbable, and self-healing
wearable sensors, are briefly overviewed. The subsequent
content highlights the most advanced medical applications of
bio-multifunctional wearable sensors, classified into three main
subfields: 1) biophysical monitoring (heart rate/pulse, human
motion, and temperature); 2) biochemical tracking (biomolecule,
blood glucose, and pH); and 3) real-time environmental informa-
tion detection (gas molecules and humidity). Finally, this work
concludes with an overview of key challenges and a summary
of opportunities, ultimately determining that advances in smart
wearable sensors are critical to their continuing progress.
2. Bio-Multifunctional Smart Wearable Sensors
The design concept of a multifunctional biosensor has many ideal
characteristics, such as self-healing, biocompatibility and biode-
gradability, which will be highlighted in this section. To mimic
biofunctions, the selection of nanomaterials with mechanical com-
patibility is an important factor for wearable sensors. The human
body provides a variety of biological signals, including electrophys-
iological signals, physical signs, and habitual physical activity,
which can indicate the existence of fatal diseases. Wearable health
monitoring devices can detect these biological signals for the early
diagnosis of diseases.[16,17] Proper materials can improve the per-
formance and wear resistance of wearable equipment, thereby
expanding its applications. In this section, we discuss current
developments in the materials and techniques for obtaining bio-
functional sensors with optimal properties.
2.1. Biocompatible Wearable Sensors
Because they are directly exposed to the human body, wearable
medical devices are expected not to pose additional health risks
and avoid restrictions on daily activities.[18–20] The biocompatibility
of wearable sensors with the human body is essential to avoid,
causing an immune response.[21] Therefore, biocompatible mate-
rials are the preferred materials for wearable smart sensors with
bio-multifunctional properties. Recently, a silicon-based multi-
functional brain sensor has been proposed by Rogers and cow-
orkers.[22] The sensor for medical monitoring is completely
bioabsorbable. The authors also confirmed that no glial cell
response to the device was found 2, 4, and 8 weeks after implan-
tation, indicating that the silicon circuit has acceptable biocompat-
ibility. This traditional semiconductor is biocompatible and may
be suitable for biomedical implants and health monitoring.
More importantly, this sensor can also be manufactured using
Adv. Intell. Syst. 2019, 1, 1900040 1900040 (2 of 22)
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Lili Wang is an Associate professor in
the College of Electronic Science and
Engineering at Jilin University, China.
She obtained her B.S. in 2010 in
Chemistry and Ph.D. in Micro-
electronics and Solid State Electronics
from Jilin University in 2014. She
successively became a Lecturer at Jilin
University in 2014. Her current
research interests focus on the flexible
and wearable sensor based on biological materials, 2D
materials, and metal-oxide semiconductor.
Kai Jiang received his M.B./B.S.
degree from Second Military Medical
College, Shanghai, China, in 1991, and
M.D./Ph.D. degrees from Chinese PLA
Postgraduate Medical College, Beijing,
China, in 1998. He further studied at
the Queen Mary Hospital of University
of Hong Kong in 2002 and Universitat
de Barcelona, Spain, in 2008. He has
been with the Department of
Hepatobiliary Surgery, Chinese PLA General Hospital, since
1991, where he is currently a professor of surgery and vice
dean of the department. His current research interests
focus on surgical operations and applications of
nanotechnology in clinical medicine.
Guozhen Shen received his B.S.
degree (1999) in chemistry from
Anhui Normal University and Ph.D.
degree (2003) in chemistry from
University of Science and Technology
of China. He joined the Institute of
Semiconductors, Chinese Academy of
Sciences, as a professor in 2013. His
current research is focused on flexible
electronics and printable electronics,
including transistors, photodetectors, sensors, and flexible
energy storage and conversion devices.
traditional microelectronics technology. In addition to traditional
semiconductors, some conductive polymers have been assessed by
in vitro cytotoxicity assessments. An implantable pressure-strain
sensor made entirely of biocompatible conductive polymers was
reported by Bao and coworkers (Figure 2a).[23] The sensor can test
pressure and strain individually using two vertically isolated devi-
ces (Figure 2a). The two devices can also recognize the pressure
exerted by a salt (12 Pa) and a strain of 0.4% without interfering
with each other. Because of this unique feature, the medical sen-
sor proposed here can be used to evaluate real-time tissue healing,
thereby realizing the personalization of rehabilitation pro-
grammers. The biocompatibility of this device was also investi-
gated by the authors. In vivo studies have shown that the
device has good functionality and biocompatibility in rat models,
indicating the potential applicability of the device to real-time
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Figure 1. Different types of bio-multifunctional smart wearable sensors. 1) Biocompatible flexible sensors: “Conformal and biocompatible sensor.”
Reproduced with permission.[8] Copyright 2010, Nature Publishing Group. “Compatible device.” Reproduced with permission.[9] Copyright 2019,
Nature Publishing Group. 2) Biodegradable flexible sensors: “Bioresorbale pressure sensor.” Reproduced with permission.[10] Copyright 2019,
Nature Publishing Group. “Biodegradable biosensor.” Reproduced with permission.[11] Copyright 2018, Wiley-VCH. “Bioresorbale device.”
Reproduced with permission.[12] Copyright 2012, Science. 3) Self-healing flexible sensors: “Self-healing strain sensor.” Reproduced with permission.[13]
Copyright 2018, Wiley-VCH. “Self-healing electronic skin.” Reproduced with permission.[14] Copyright 2018, Nature Publishing Group. “Self-healing pres-
sure sensor.” Reproduced with permission.[15] Copyright 2019, Nature Publishing Group.

monitoring of tendon healing. Immunohistochemistry and
Hematoxylin and eosin (H&E) staining showed that poly(octa-
methylene maleate anhydride citrate) (POMaC) had good biocom-
patibility 8 weeks after implantation. There was no significant
difference between the POMaC and silica gel (control) samples
(Figure 2b).
The interaction between the human body and a single sub-
stance is difficult to predict due to biological reactions in the
human body. The precise design of materials and rational in vivo
testing are very critical to confirm whether a specific material
is biocompatible in a particular application.[21] One plausible
way to improve biocompatibility is to select natural biomaterials,
such as sodium alginate,[24] silk,[25] chitin,[26] cellulose,[27] and
wood [28,29] because of their excellent nontoxicity. In recent
years, biomaterials serving as the active components and sub-
strates of various biocompatible flexible sensors have been widely
reported.[1] Chitosan is one of the most studied materials at pres-
ent.[30,31] The tensile and conductive properties of chitosan are
improved by various methods. For example, Wang and cow-
orkers propose a simplified strategy for designing multifunc-
tional biomaterials by integrating the fascinating structure of
natural chitosan with the high conductivity of graphene.[32]
Compared with other structural materials, biocomposites result-
ing from this material design method have advantages in high
response, rapid response rate, and low detection limits
(20 ppb), and the applicability of this approach to the design
of chemical sensors for real-time diabetes monitoring has been
further confirmed. With the effective adaptation of the core func-
tions and physical and chemical properties of materials, a flexi-
ble, biocompatible, and high-performance sensor has been
developed, thereby showing the prospects of wearable and
implantable sensors. Some other biomaterials were also used

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Figure 2. a) Illustration of the flexible medical sensor that can allow the rehabilitation protocol after a tendon repair to be personalized for each patient.
b) Results of immunohistochemistry from 1 to 8 weeks. Scale bars: 100 μm. a–b) Reproduced with permission.[23] Copyright 2018, Nature Publishing Group.
c) Illustration displaying the hierarchical structures and the fabrication of CSF strain sensors. c) Reproduced with permission.[22] Copyright 2016, Wiley-VCH.
for wearable medical devices. For example, Zhang and coworkers
reported that carbonized silk fabrics (CSF) can be used to fabri-
cate super-deformable and high-performance strain sensors with
excellent pressure-sensing properties for monitoring various
human body movements (Figure 2c).[22] This kind of carbon
material is derived from natural and renewable resources and
has great production capacity and environmental friendliness.
2.2. Biodegradable Flexible Sensors
In recent years, biodegradable devices have shown great potential
in enabling advanced health monitoring and reducing the
amount of electronic waste.[33–35] The benefits of this no-trace
behavior are decreases in the costs and health risks of wearable
medical systems during medical treatment, especially in the con-
text of temporary biomedical implants. For instance, Bao and
coworkers designed and manufactured a high performance wear-
able pressure device based on biodegradable conductive poly-
mers.[36] These sensors have good sensing performance and
can be used as wearable medical devices for continuous cardio-
vascular monitoring, such as collecting blood pulse signals from
human femoral, carotid, and radial arteries. More importantly,
the authors claim that the fabrication of these sensors is the first
step toward more complex biodegradable sensors that may be
used in biomedical applications in humans to avoid further sur-
gical interventions and reduce waste generation. Recently, their
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team also reported the design of a pressure sensor based on edge
field capacitance and biodegradable technology, to measure arte-
rial blood flow in both contact and noncontact modes, as shown
in Figure 3a-c.[37] For real-time monitoring, a mature radio fre-
quency coupling method is used to enable wireless operations. In
addition, because the device is made entirely of biodegradable
materials, it is reabsorbed in a few months, so there is no need
to remove the device. The sensor can be used in a variety of appli-
cations including the heart, blood vessels, during transplantation
and reconstruction, as well as in small and large vessels requiring
vascular anastomosis. This technique is helpful for real-time
monitoring of blood flow after reconstructive surgery.
Rogers’s team has also pioneered in research about implantable
silicon-based transient electronic devices that can be used in wear-
able medical systems (Figure 3d,e).[12] A silicon-based sensor using
silk as a substrate is placed in an aqueous solution and rapid dis-
solution of the device can be observed within 10 min
(Figure 3f). This implantable instantaneous device provides a sys-
tem-level example of a programmable nanoantibiotic fungicide
(Figure 3a). Although these materials do not exist naturally, it is
reported that each material is biocompatible. In addition to silk,
other materials such as natural collagen,[38,39] gelatin,[40,41]
shellac,[42] chitin[26,43], protein,[44] and seminatural/semisynthetic
materials[45] derived from natural materials can be used as biode-
gradable substrates.[46] Due to its lightweight property, seminatural
property, inexpensive structure, environmental friendliness, and
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Figure 3. a) Illustration of exposure maps of double-layer coil structure and cuff-type pulse sensor wound around arteries for wireless data transmission.
Inset shows equivalent electrical circuit. b) Optical image of pulse sensor with the two variable capacitors. c) Optical image of pulse sensor (top image)
with a micro-structured poly(glycerol sebacate) (PGS) layer (middle image) and scanning electron microscope (SEM) image of pyramid structures (bot-
tom image). a–c) Reproduced with permission.[37] Copyright 2019, Nature Publishing Group. d) Optical image and e) schematic diagram of a transient
electronics with silk substrate. f ) Optical image of degradation process of the devices in deionized water. d–f ) Reproduced with permission.[12] Copyright
2012, Science.

flexibility, paper has become an attractive solution for the fabrica-
tion of flexible and wearable sensors.[47,48] A high-performance
wearable electronic device based on cellulose nanofibers was dem-
onstrated by Jung et al.[27] They successfully fabricated key elec-
tronic components on flexible cellulose nanofiber paper, whose
properties are comparable with those of rigid cellulose paper,
and they clearly demonstrated the fungal biodegradation of the cel-
lulose nanofiber-based electronic components. As a result, the
fabrication of biodegradable flexible electronic devices with envi-
ronmental-friendly materials is feasible. In addition, Chen’s
group[49] used fine rice paper that consisted of tortuous bam-
boo-derived cellulose fibers with diameters of 5–40 μm to produce
mesoporous membranes with thicknesses of approximately
110 μm. Compared with commercial polypropylene/polyethyl-
ene/polypropylene separator membranes, rice paper membranes
exhibit low resistance at the same thickness due to less cost, good

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flexibility, and a porous structure. As a result, rice paper mem-
branes will offer attractive building blocks for applications in green
electronics.
2.3. Self-Healing Flexible Sensors
At present, wearable medical devices are often limited by robust-
ness because their components are easily scratched and dam-
aged, which may damage their functions and reduce their
sensing performance. These events may also severely limit
their lifetime and affect their electronic properties. Ideal bio-
multifunctional wearable and intelligent sensors not only
retain their electronic functions, but also repair themselves by
maintaining their electrical and mechanical properties after mild
micromechanical damage.[50] Wearable electronic skin devices
need to self-repair automatically without external stimulation
(e.g., heat) to restore the original mechanical and electrical con-
nections.[13,51–53] These properties can extend the life of the
equipment and reduce maintenance costs. Some self-healing
flexible sensors based on conductors and polymers have been
investigated. Despite the rapid development of self-healing mate-
rials, only a few self-healing polymers have been used in the field
of flexible electronics. Composite materials filled with healing
agent-loaded capsules or conductive particles are commonly used
to achieve self-healing ability. For example, Wang and coworkers
make electronic devices via incorporating ionic liquids into self-
healing polymer channels.[54] Bandodkar et al. reported the intro-
duction of a conductive ink, which contained 45% carbon and 5%
capsules in an acrylic varnish binder, into a self-heating
device.[55] For self-healing medical devices, Bao and coworkers
reported an intrinsically self-healing conductive composite.[56]
They presented a rubber-like bulk conductive composite based
on inorganic micronickel (μNi) particles and organic supramolec-
ular polymers, in which self-repair is driven via the recombina-
tion of hydrogen bonds between cut surfaces (Figure 4a). In
addition, when the material undergoes mechanical damage,
90% conductivity can be restored within 15 s, indicating that
the material has inherent self-healing abilities (Figure 4b).
The unique nanostructure of μNi particles contributes to the
self-healing properties of the composites, and similar composites
made of smooth μNi particles have low conductivity (10 to
6 s cm
1). Moreover, by keeping the volume loading of μNi par-
ticles below the osmotic threshold (15% volume loading), the
composite exhibits good pressure-sensing performance. The
bending and/or compressive stresses produced by tactile stimu-
lation bring μNi particles closer to each other and produce an
inductive response. In addition, the piezoresistive effect is
restored by the bending force and tactile force exerted by reverse
direction sensing. The good self-healing ability obtained by a
simple contact fracture interface may prolong the service life
of tactile sensors and expand the application range of the existing
tactile-sensing systems (Figure 4c). However, more work needs
to be done to improve the stability and sensitivity of these
materials.
Dynamic polymer materials are another kind of self-healing
materials based on reversible bonds and dynamic interactions.
Recently, Tee and his team reported on a bio-inspired skin-like
material that is transparent, conductive, and self-healing in dry
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and humid environments.[15] Amorphous polymers are com-
bined with chemically compatible ions to form gelatinous, aque-
ous, stretchable, and self-healing electronic skin (Figure 4d). As
the emitter content increases from 10 to 30 wt%, the material
exhibits a higher strain failure point, a lower Young’s modulus,
and a lower maximum tensile stress. As shown in Figure 4e, the
material then heals under normal environmental conditions
without adding foreign solvents or materials. After 24 h at room
temperature, the material recovery rate is approximately 43.9%,
and after 24 h of curing at 50  C, the material recovery rate is
99.1%. Interestingly, this material can heal even in various water
environments, such as in deionized aqueous, seawater or
extremely acidic and alkaline solutions. More importantly, the
high optical transparency of these materials indicates that they
can be used in autonomous underwater explorations and in
emerging optoelectronic man–machine and communication
interfaces (Figure 4f).
3. Promising Applications of Smart Wearable
Sensors in Health Monitoring
Wearable sensors are very flexible. They can be placed not only at
any position on or inside the human body, such as the human
head, throat, chest, arm, wrist, finger, and organ, but also on any
object, such as clothes, shoes, watches, glass, masks, and
gloves.[57] In the last few years, flexible and wearable sensors have
displayed great prospects in all fields due to their flexibility and
versatility. In this section, we will focus on the applications of
bio-multifunctional smart wearable sensors in biophysical mon-
itoring, biochemical tracking, and real-time environmental infor-
mation detection.
3.1. Biophysical Monitoring
The monitoring of biophysical signals has attracted widespread
attention.[58,59] As an important branch of health monitoring,
monitoring the heart rate/pulse,[60,61] human motion,[62,63]
and temperature[64] is essential for health assessments.[65]
Different types of physiological information can be quantified
from body movements or body fluids. High-sensitivity wearable
sensors have been used to continuously record pulse and heart
rate to collect basic health information.[66,67] The following sub-
sections will critically assess the main progress in measuring
these signals, which are roughly divided into pulse and heart rate,
exercise, and temperature regulation.
3.1.1. Heart Rate and Pulse Monitoring
In clinical practice, arterial pulse is an important index of arterial
blood pressure, heart rate, and old or stiff blood vessels.[68] It also
provides useful information on possible cardiovascular diseases,
which are diagnosed by noninvasive medicine and are one of the
most serious causes of death in humans.[69] Wearable pressure
sensors, including radial artery pressure sensors for cardiovascu-
lar diagnosis, accurately monitor cardiovascular pulse pressure
waveforms.[70] For instance, using carbon nanotube (CNT)-
polydimethylsiloxane (PDMS) composite materials, Lee and
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Figure 4. a) Illustration of a rubber-like μNi particles-based oligomer chains. b) The resistance response of the self-healing composite during self-healing
process within 15 s. The inset is microscope image of the self-healing composite under break state and healed state. c) Demonstration of the healing
process for a conductive composite with an LED in series with a self-healing electrical conductor. a–c) Reproduced with permission.[56] Copyright 2012,
Nature Publishing Group. d) Schematic illustration of principal component of the self-healing conductive polymer. e) Functionality of a gel-like, aquatic,
stretchable, and self-healing electronic skin (GLASSES) dipped in water for 3 h. f ) Transmittance spectrum of 30 wt% 1-ethyl-3-methylimidazolium
bis(trifuoromethylsulfonyl)imide (EMITFSI) film. d–f) Reproduced with permission.[15] Copyright 2019, Nature Publishing Group.

coworkers demonstrated a flexible, biocompatible electrode,
which showed excellent long-term stability in wearable electro-
cardiogram (ECG) monitoring after being connected with tradi-
tional ECG equipment.[71] Cho and his team produced a bionic
layered graphene/PDMS array for medical and health applica-
tions.[72] They demonstrated a highly sensitive piezoresistive
pressure sensor, which responds linearly to applied pressure
and uses a new layered structure capable of accurately monitor-
ing wrist pulses. To date, various materials have been used to
fabricate bendable/connectable devices for detecting wrist
pulses, including metal–organic frameworks, polyvinylidene
fluoride (PVDF) films, semiconducting polymers, CNT/PDMS
composites, and ZnO-based flexible fibers.
To avoid the waste associated with wearable and point-of-care
diagnostics, Bao and coworkers reported the application of a dis-
posable and biodegradable pressure sensor patch in cardiovascular
monitoring.[36] As shown in Figure 5a, they fixed the biodegrad-
able pressure sensor on the human wrist above the radial artery,
which is typical of an arterial sphygmomanometer. Real-time test-
ing of several pulse cycles and an enlarged view of pulses with

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Figure 5. a) Dynamic response of flexible sensors to pulse at the radial artery. b) Comparison of carotid artery pulse wave/femoral artery pulse wave.
Optical image of flexible pressure sensors c) before in vitro degradation and d) after 7 weeks of incubation. a–d) Reproduced with permission.[37]
Copyright 2015, Wiley-VCH. e) Schematic diagram of the preparation step for raw fish skin (FSK)-based device. f ) Optical image of the FSK-based
device exhibiting the flexibility. g) Pressure response of the FSK-based device to natural butterfly with the weight of 58 mg. Current response of
the FSK-based device to (h) radial artery and (i) carotid artery pulses. e–i) Reproduced with permission.[73] Copyright 2017, American Chemical
Society.

characteristic peaks, usually measured at the radial artery, were
shown. Additionally, pulse wave velocity measurement using
the same recording settings as those described earlier is success-
ful. The pressure sensor is first connected above the adult carotid
artery, and it recorded the arterial pulse wave, as displayed in
Figure 5b. ECG was recorded as a time reference. Then the pres-
sure sensor was attached to the femoral artery, and the pulse wave
and ECG were recorded again. In addition, in vitro biodegradation
tests were carried out to further study the adsorption characteris-
tics of the equipment (Figure 5c,d). The results showed that the
elastomer still had small hysteresis and viscoelastic behavior after
7 weeks of incubation in the phosphate-buffered saline (PBS) solu-
tion and that there was no obvious change. The authors envisage
that their work will contribute to the biomedical application of
completely biodegradable sensors in vivo.
Recently, human pulse and heart rate monitoring systems
based on other biological functional materials (such as collagen
and silk) have also been studied.[74,75] Bio-multifunctional
flexible/wearable systems based on natural silk and electronic
skin based on fish skin composed of collagen nanofibers are
other significant developments in personalized medical monitor-
ing systems.[73] Mandall and coworkers developed a wearable
sensor for sustainable energy production based on fish skin
(Figure 5e,f).[73] The sensor interacts with various parts of the
human body and monitors physiological signals in real time,
as illustrated in Figure 5g-i. Figure 5h displays that the wearable
pressure sensor is connected to the upper radial artery of the
human wrist because this artery is usually used for arterial sphyg-
momanometers and blood pressure meters. The characteristic
pulse pressure shape (PPS) is formed by the superposition of
the left ventricular systolic and lower limb reflex blood flow.
The synchronous monitoring of wrist impulse pressure provides
a new approach for wearable electronics with low power con-
sumption. In addition, as shown in Figure 5i, the pressure sensor

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also tests the real-time arterial pulse wave at the site where it is
attached to the carotid artery of the neck.
Because photoelectric devices can monitor human physiolog-
ical characteristics in real time and provide corresponding clin-
ical information, they are widely used in medical diagnosis and
treatment.[76–84] Recently, many researchers have used photode-
tectors to achieve photoelectronic skin, showing super-flexible
and integrated tricolor, high-efficiency polymer light-emitting
diodes (PLEDs), and organic light detectors (OPDs), introduc-
ing a variety of electronic functions for the human skin sur-
face.[76] Someya and coworkers recently reported on a new
ultra-flexible reflective pulse sensor. The device combines red
OPD with green light-emitting diode (LED) to detect oxygen
concentration in blood on human fingers. In addition, seven-
segment color and digital displays can display data directly
on the human skin. For another report, LEDs and photovoltaics
form flexible light sensors on thin films. The sensor can be
closely attached to the human skin surface and has broad appli-
cation prospects.[85,86]
3.1.2. Human Motion Monitoring
Tracking physical activity and habitual movements provide use-
ful information to ensure good health and correct posture.
Periodic analyses of body movements can detect abnormal gait
patterns and sudden tremors in the hands, which are the precur-
sors of fatal diseases such as Parkinson’s disease, Alzheimer’s
disease, and diabetes, and contribute to the early diagnosis
and treatment of such diseases[18]. The development of motion
detection mechanical sensors also opens up potential applica-
tions in human–machine interfaces, rehabilitation, prosthesis,
and sports training. In recent years, bio-multifunctional wearable
sensors have been widely used for motion detection in our daily
lives, including assisted living, rehabilitation, and monitoring.[87]
Motion monitoring can be roughly divided into two categories:
monitoring large-scale movements, such as finger, hand, and
knee bending, and monitoring small-scale movements, such
as subtle throat and chest movements during swallowing and
breathing. [58,88,89]
To date, efforts have been made to exploit multifunctional
wearable sensors for tracking human motion through real-time
continuous signals.[89] Recently, consumer devices such as Fitbit
One and Fitbit Flex have been tested and checked to monitor
patient steps, energy consumption, and activity levels. The
results of reliability and validity tests show that wearable activity
monitoring has broad prospects in many clinical environments,
such as the postoperative recovery of heart disease patients, lung
rehabilitation, activity counseling of diabetic patients, and assess-
ment of patients undergoing chemotherapy. Wang et al. demon-
strated the fabrication of a biocompatible flexible pressure sensor
based on the incorporation of sunflower pollen microcapsules
into bionic structures (Figure 6a,b).[46] This design represents
a new biotechnology for the design of flexible motion sensors
(Figure 6c). Complex deglutition behavior can be reliably and
repeatedly identified through versatile biological wearable devi-
ces (when connected to a person’s throat). During the swallowing
process, the relative changes in the current are divided into two
steps that correspond to the movement of the laryngeal muscles.
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Figure 6d,e shows the simultaneous detection of pressure and
strain when the biocompatible, flexible pressure sensor is con-
nected to a finger for continuous finger movement monitoring.
According to the finger motion angles corresponding to motion
I, motion II, and motion III, the relative current gradually
increases. To demonstrate the characteristics important for elec-
tronic skin and wearable sensor applications, fast-tension release
motion was detected and measured, displaying a fast response in
four repetitive cycles. Looking ahead, this study opens up a new
direction for incorporating stimuli–responsive microcapsules
into the designs of wearable sensors and emphasizes the poten-
tial of using natural materials to enhance the function and per-
formance of flexible sensors.
Similarly, Zhang and coworkers prepared smart multiwalled
CNT/thermoplastic elastomer (MWCNT/TPE)-based flexible
sensors with high tensile, bending, and torsional-sensing capa-
bilities (Figure 6f).[21] As shown in Figure 6g, smart gloves can be
easily obtained by applying multifunctional MWCNT/TPE films
to monitor finger movements. Figure 6h shows real-time bend-
ing motion detection of an index finger of a person wearing
smart gloves. With the slow and repeated bending and relaxation
of the index finger, the normalized relative resistance increases
and decreases gradually and periodically, achieving real-time
detection of the movement of the index finger (the small differ-
ence between each cycle is caused by the small difference
between each bending motion). In addition, there is no obvious
change in the sensing performance of the MWCNT/TPE-based
flexible sensor under intermittent droplets, because the droplets
almost immediately roll down from the superhydrophobic sur-
face, which indicates that the device can work in wet or rainy
environments.
3.1.3. Temperature Monitoring
Body temperature provides insight into a person’s physical
state.[88] Although body temperature may vary slightly with envi-
ronmental temperature or physical activity, irregular and abnor-
mal changes in body temperature are indicators of some diseases
that can be accompanied by acute fever and hypothermia.[91]
Because heat transfer between the environment and biological
organs may cause spatial and temporal changes, it is necessary
to monitor body temperature in real time with high sensitivity
and accuracy.[92,93] Moreover, changes in a human body’s normal
temperature are very small, and health-monitoring temperature
sensors require not only high resolution, high precision, high
sensitivity, and wide detection range, but also biocompatibility
and mechanical flexibility.[94,95] At present, wearable temperature
sensors also use a variety of nanomaterials, including conduc-
tive polymers,[96,97] graphene,[89,98] CNTs,[46,99] nickel,[100]
silver,[101,102] and copper metal nanoparticles and nanowires[103]
as thermal-sensing elements.
Recently, Rogers and coworkers suggested using a wearable
temperature sensor to monitor blood perfusion and generate
local heat in tissues for medical care and medical applica-
tions.[104] Salvatore et al. prepared highly deformable tempera-
ture sensors on Eco-Flex thin films using SiO2, Si3N4, and Mg
as biodegradable materials.[105] An ultra-thin temperature sensor
can endure multiaxis deformation and maintain a dynamic
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Figure 6. a) SEM images of sunflower pollen microcapsules (left) and MWCNT/sunflower pollen composite (right), respectively. b) SEM and c) optical
images (15  10 cm2) of sunflower pollen-based composite film. d) Optical images of flexible pressure sensor attached on finger with different finger
motions. e) Sensitivity of flexible pressure sensor to different finger motions. a–e) Reproduced with permission.[46] Copyright 2017, Elsevier. f ) Optical
image of flexibility and water repellency of as-prepared-coated cloth. g) Sensitivity of flexible sensors under dry and dropping water state. h) Dynamic
response curve of device on the cloth for different human motion. f–h) Reproduced with permission.[90] Copyright 2017, Wiley-VCH.

response (10 ms), 41 mK resolution, high thermal sensitivity,
and a stable sensing performance.
For bio-multifunctional wearable temperature sensors, Zhang
and coworkers reported a biocompatible flexible pressure–
temperature sensors based on a sensing layer comprising silk
nanofiber-derived carbon fiber films.[106] Figure 7a displays a
schematic diagram of the preparation steps of the silk nanofiber-
derived carbon fiber flexible pressure–temperature sensor. The
device can detect temperature changes by using the temperature
dependence of the film resistance caused by thermal resistance
effects (Figure 7b). The flexible pressure temperature sensor can
detect not only sensations encountered by the human body in
daily life, such as finger pressing and breathing frequency,
but also the spatial distribution of external stimuli. This work
shows great application potentials in human–machine interfaces
and temperature detection. In addition, due to low cost and good
biocompatibility of natural silk materials, flexible pressure and
temperature sensors made of silk-driven carbon fibers possess

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Figure 7. a) Schematic diagram of the preparation steps of the silk-based flexible pressure-temperature sensor. b) I
V curves of the temperature sensor with
the temperature range from 25 to 80  C. a–b) Reproduced with permission.[106] Copyright 2017, American Chemical Society. c) Schematic diagram of gas
permeability and water repellency of the device. Optical image showing the biocompatibility of the device: d) device attached on human skin for 24 h with two
times of shower and e) device attached on human skin after 24 h. c–e) Reproduced with permission.[94] Copyright 2015, Nature Publishing Group.

obvious advantages and improvements over other temperature
sensors. Wearable temperature sensors attached to the skin
for medical care must be biocompatible and able to adapt to spe-
cific skin environments in terms of breathing and sweating.
Recently, Feng and coworkers reported a strategy of developing
a biocompatible temperature sensor inspired by skin with a
porous semipermeable membrane that has good permeability
and is highly waterproof as the base (Figure 7c).[107] As shown
in Figure 7d,e, the authors connect these temperature sensors
to the armpit and forearm to test the temperature of the armpit
and the body surface, respectively. Volunteers used the sensor for
24 h and took two showers. In vitro tests showed no signs of irri-
tation. Moreover, falling water and blowing tests show that the
device can cope with the tiny temperature changes triggered
by the ambient environment, indicating that the device may
be applied to the construction of an intelligent artificial skin sys-
tem. Huang and coworkers also developed a biocompatible flexi-
ble temperature sensor using a 3D polylactic-co-glycolic acid and
polylactide (PLA) composite as the dielectric and substrate
layers.[108] These bio-multifunctional devices have comprehen-
sive advantages such as biocompatibility, degradability, temper-
ature sensitivity, transparency, and flexibility. They also have
wide application prospects such as environmental protection,
electronics, implantable medical devices, and artificial skin.
3.2. Biochemical Tracking
Wearable electrochemical sensors have been widely used in med-
ical, fitness, safety, sports, and forensic monitoring fields.[109]
Skin-mounted sensors can continuously monitor biochemical sub-
stances in body fluids (e.g., glucose/lactate, biomolecules, and pH)
and alert users of fatigue, dehydration, and early disease symp-
toms. This application requires devices to maintain their biocom-
patibility, comfort, flexibility, and conformability when they are in
contact with the human body.[109,110] In addition, wearable electro-
chemical sensors must also overcome the challenges associated
with all analytical devices’ reliability, accuracy, calibration, and life-
time. Combining the advantages of wearable and electrochemical
technology opens the door for a large number of applications.
3.2.1. Blood Glucose Recording
According to World Health Organization statistics, 9% of adults
worldwide currently suffer from diabetes.[2,111] Glucose monitor-
ing is an important technique for assessing the health conditions
of people with diabetes and must be performed frequently every
day. Thus, glucose monitoring may require devices that are nat-
urally conformable, biocompatible, flexible, stretchable, and non-
toxic to adhere to the skin surface to minimize user awareness,
while providing accurate data for the real-time detection of glu-
cose oxidase (e.g., glucose values for a healthy person and a per-
son with diabetes are 70–100 and 80–130 mg dL
1,
respectively).[4] In particular, biocompatible and biodegradable
wearable glucose sensors have been widely used in human health
monitoring and biomedical diagnostics because of their excellent
biological functions. In addition, compared with traditional glu-
cose sensors, bio-multifunctional wearable glucose sensors can
improve the safety of devices and reduce electronic waste.

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For example, Pak and coworkers reported a glucose oxidase/
silk/graphene (GOx-silk/graphene) composite-based flexible
field-effect transistor (FET) glucose sensor (Figure 8a).[112]
This work mainly uses natural silk as a flexible, transparent
substrate and enzyme immobilization matrix to detect glucose
(Figure 8b). The flexible FET glucose sensor is mainly composed
of a graphene/silk substrate, a silk/GOx sensitive layer, gold/tita-
nium (Au/Ti) source/drain contacts at both ends, and a top-gate
electrode (Figure 8c). The optical image in Figure 8d shows that
the prepared GOx-silk/graphene FET glucose sensor is flexible
and can be closely attached to the skin surface. Because GOx
can react with glucose, the conductivity of the flexible FET
glucose sensor channel increases with increasing glucose concen-
tration. At the same time, the Dirac point of graphene has also
been transferred, showing a p-doping effect (Figure 8e). The
drain/source current of the flexible FET glucose sensor exhibited
a high sensitivity of 2.5 μA mM
1 to 0.1
10 mM glucose at
Vds ¼ 100 mV and Vg ¼ 0 V (Figure 8f ). This work also implies
that this biocompatible, flexible, and reliable silk-based FET
glucose sensor has broad application prospects in implantable,
portable, and wearable electronic devices in future.
It has been reported that glucose in sweat is also directly related
to blood sugar metabolism.[114] Therefore, effective monitoring and
collection of glucose in sweat or tears can also be used as an indi-
cator for the diagnosis and treatment of diabetes.[115–117]
Recently, Gao and coworkers developed a fully flexible biosensor
array based on biocompatible chitosan/CNT-sensing materials
capable of detecting glucose and lactate in sweat for multichannel
in situ sweat analysis (Figure 8g).[113] In addition, these biocompat-
ible flexible sensors can detect skin temperature and sodium and
potassium ions. The biosensor uses mechanically flexible PET as
the substrate, which can make the device conform well to the skin
surface. Figure 8h shows a structural diagram of the multichannel
sensor array for sweat detection. Glucose oxidase immobilization
on chitosan-based sensitive membranes can cause current
changes, thus realizing the detection of glucose. Figure 8i presents
the dynamic sensing response curve of the biosensor to 0–200 μM
glucose solutions, and the glucose sensitivity of this biosensor is
2.35 nA μM
1 (inset of Figure 8i). Because of the good biocompat-
ibility and flexibility of chitosan devices, this wearable biosensor
can be comfortably attached to all positions of the human body
for a long time, such as the arms, wrists, and forehead.
Figure 8j shows the wearable biosensor attached to the human
wrist and forehead for real-time monitoring and analysis of human
sweat during continuous exercise. Obviously, the concentration of
glucose decreases gradually with continued perspiration during
exercise, which may be due to the glucose dilution effect of glucose
caused by the increase in sweat rate. The accuracy of the in situ
wearable sensor is verified by comparing the sweat sample analysis
data with the sweat sample analysis data collected by the body
forehead sensor. (Figure 8k). Thus, the development of bio-
multifunctional smart wearable sensors is highly anticipated.
3.2.2. Biomolecule Recording
Biochemical sensors, unlike most flexible sensors intended to
obtain vital signs, provide a more convenient platform for non-
invasive personal health monitoring at the molecular level.[118] In
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recent years, many flexible biochemical sensors have been
applied to real-time and in situ monitoring of human cancer
molecules and protein markers. For instance, a biocompatible
silk/graphene-based saliva sensor was reported by McAlpine
and coworkers (Figure 9a).[119] The flexible saliva sensor not only
recognizes Helicobacter pylori cells in human saliva but also
exhibits a low limit of detection (LOD) of approximately 100 cells
when this device is transferred to the surface of the tooth enamel
(Figure 9b). Although the flexible saliva sensor exhibits high sen-
sitivity to H. pylori cells, it is often affected by dietary habits,
which limits its ability to accurately monitor health. Therefore,
the design of a new flexible saliva sensor with high performance
and resistance to environmental interference is very important.
In addition to the monitoring of protein molecules, the serum
samples of patients contain abundant target molecules, so the
detection of cancer biomolecules by flexible biochemical sensors
provides an effective means of health and safety screening.
Recently, Wang et al. demonstrated a biocompatible, flexible bio-
sensor based on natural sunflower pollen surrounded by a gra-
phene conducting layer (Figure 9c).[120] This biosensor not only
provides a completely nontoxic and biocompatible sensing plat-
form, but also permits intimate integration on the curvilinear
surfaces of objects. Through the self-assembly of antibodies
on the surface of biomaterials, we reported bio-selective detection
of vital biomarker proteins for prostate cancer at ultra-low con-
centration levels in real time. Specific chemical treatment and
antibody immobilization on rGO@SFP-based flexible biosensors
facilitated pathogenic prostrate-specific antigen (PSA) cancer
marker detection in real time with ultra-high sensitivity, a fast
response time (4 s), LOD (1.7 fM), excellent reproducibility,
and good bio-selectivity (Figure 9d). This combination of flexible
biosensor features and nontoxic biomaterials holds considerable
promise for creating an attractive class of biosensors with highly
flexible contacts, good detection performance, and high biocom-
patibility that satisfy the requirements of diverse health care and
point-of-care applications.
In addition to material biocompatibility, device design toward
biodegradation is a challenging yet mandatory goal, particularly
for implantable diagnostic applications. For flexible sensors used
in clinical applications, their characteristics must be determined
according to their biocompatibility, which should include biosafety
(no cytotoxicity, mutagenesis, or carcinogenesis) and biofunction-
ality (biocompatibility, biodegradability, and self-healing).[122]
Unfortunately, implanted biosensors often lose their function over
time, mainly due to foreign body reactions caused by biofouling
around biosensors. Thus, the development of biodegradable
implantable biosensors to detect cancer molecules is necessary.
Yadavalli and coworkers develop a biodegradable, flexible biosen-
sor for the detection of vascular endothelial growth factors
(VEGFs) (Figure 9e).[121] This flexible device was fabricated via
a conducting ink with a photolithographic pattern consisting of
a conductive polymer coupled with photoreactive silk sericin.
This design enables the sensor to suitably match with human soft
tissue to ensure the accuracy of data for the in situ detection of
protein markers (Figure 9f,g). As a result, the device is highly sen-
sitive to and selective for the target protein, even in human serum
(Figure 9h). In addition, this flexible device exhibits biocompati-
bility and biodegradability, which can effectively reduce damage to
human organs. This work demonstrates the clinical medicine
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Figure 8. a) Optical image of bombyx mori silk cocoons. b) Optical image of transparent silk fibroin film. c) Schematic diagram of graphene/silk
(GOx-silk)-based glucose sensors. d) Optical image of silk/graphene-based glucose sensors attached onto the human skin. Inset shows the SEM image
of biosensor channel. e) Charge transfer and (f ) response curves of silk/graphene-based biosensors to different glucose concentrations. a–f ) Reproduced
with permission.[112] Copyright 2014, Elsevier. g) Optical image of flexible biosensor array attached onto human wrist. h) Illustration of the biosensor
array. i) Dynamic response of biosensor to different glucose concentration. j) Optical image of smart sensors attached on the human head.
k) Comparison of sweat samples of ex situ and on-body data of glucose sensors during the stationary cycling exercise. g–k) Reproduced with
permission.[113] Copyright 2016, Nature Publishing Group.

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Figure 9. a) Biotransferrable graphene wireless nanosensor. b) Response curve of tooth sensors to 100 cells (H. Pylori) in human saliva. a–b) Reproduced
with permission.[119] Copyright 2012, Nature Publishing Group. c) Schematic diagram of fabrication of natural sunflower pollen/graphene-based flexible
biosensor. d) Sensitivity of flexible biosensor to different PSA concentrations in PBS buffer and both bull serum albumin (BSA) and PBS buffer.
c–d) Reproduced with permission.[120] Copyright 2017, Elsevier. e) Optical image of silk-based flexible biosensor. Inset shows the SEM image of
the flexible sensor electrode under a rolled-up state. f–g) Optical image of flexible biosensor attached on human soft tissue. h) Response curves of
flexible biosensor to artificial urine with (red line) and without albumin (blue line). e–h) Reproduced with permission.[121] Copyright 2019,
American Chemical Society.

applications of biodegradation and biocompatible biosensors that
are capable of monitoring cancer or target molecules in patient
serum samples.
3.2.3. pH Recording
As another important property of bio-fluids, the solution pH
value is also closely related to human health. Specifically, rapid,
real-time, and accurate monitoring of the solution’s pH value
can effectively ensure early diagnosis of related diseases.[123]
At present, the research emphasis regarding flexible pH sen-
sors is on developing high-performance and sensitive sensing
systems and effective sweat sampling methods. Various wear-
able pH sensors have been reported, such as flexible FETs or
sensors.[124,125] A recent impressive biodegradable pH sensor
was reported by Rogers and coworkers (Figure 10a-c).[126]
By incorporating single-crystalline silicon nanomembranes into
a biodegradable elastomer (poly(1,8-octanediol-co-citrate),
POC), they obtained a biodegradable flexible pH sensor that
exhibited high strain capacity (strain up to 30%) and high
sensitivity (0.3  0.02 and 0.1  0.01 μS pH
1 for boron-
doped Si nanoribbons (NRs) and phosphorus, respectively)
(Figure 10d,e). In addition, the pH sensor exhibited excellent
biodegradation, and all components completely disappeared
after several weeks (Figure 10f).
In addition, the ability to simultaneously monitor physical and
chemical characteristics is very important to obtain effective,
high-value, and complementary reference data for the diagnosis
and prediction of human health. For example, dehydration
caused by exercise can be effectively predicted by monitoring
the pH value concurrently in skin temperature and sweat.
Some studies on detecting physical and chemical characteristics
have been reported. For example, Takei and coworkers recently
reported a new flexible pH chemical sensor, consisting mainly of
temperature sensors and ion-sensitive field-effect transistors
(ISFETs), that can detect pH and human body temperature in
real time (Figure 11a-d).[127] The advantage of combining a tem-
perature sensor with a flexible ISFET-based pH chemical sensor
is that the resulting sensor is able to compensate for the temper-
ature effect on the flexible ISFET-based pH chemical sensor

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Figure 10. a,c) Schematic diagram and b) optical images of biodegradable flexible biosensor arrays. d) Micrographs and computed results image of
flexible biosensors under 0–30% strain state. e) Conductance change of flexible biosensor under PBS solution with pH value from 4 to 10 at 37  C.
f ) Optical image of degradation processes of flexible biosensor in PBS solution at room temperature. a–f ) Reproduced with permission.[126] Copyright
2015, American Chemical Society.

(Figure 11b). The ISFET is composed of a pH-sensing mem-
brane, Al2O3, and InGaZnO (Figure 11c). As a result, the newly
designed flexible sensor can detect temperature and pH
simultaneously.
The sensor can also compensate for the potential displace-
ment caused by temperature and pH, thus achieving accurate
pH measurement in a wide temperature range. Figure 11e shows
that the current (IDS) increases when the sensor temperature
changes from 24.2 to 47.2  C, which may be because the
InGaZnO transistors are more sensitive to temperature changes
than to pH changes. By comparing the results of temperature
compensation experiments, we can find that after the compen-
sation test, the pH value (pH ¼ 7.2) of the solution remains stable
as the temperature increases (from 29 to 44 C), whereas without
the compensation test, the measured pH value of the same solu-
tion still decreases as the temperature increases (Figure 11f).
Therefore, we can see that by compensating for a temperature
of 43.4 C in ISFET-based sensors, the detection error of the
pH value decreases from 7.64% to 0.97%. In addition, the
device exhibits excellent mechanical flexibility (Figure 11g).
3.3. Real-Time Detection of Environmental Information
Wearable environmental sensors, which mainly monitor environ-
mental parameters, such as various environmental gases,[128–134]
breathing gases,[32,135,136] and humidity,[137–139] have received
extensive attention. This information can not only protect people
from adverse environments, enhancing awareness of the impact
of the environment on health care, but also the interaction
between people and the environment, improving human–
computer interactions. Although traditional sensors allow rapid

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Figure 11. a) Top view and cross-sectional illustration and b) optical images of a flexible pH and temperature sensors. Magnified optical image of c) pH
sensor and d) temperature sensor. e) I–V curve of flexible ISFET-based device under different temperatures for a pH 7.2 solution. f ) pH values of flexible
ISFET-based device with (blue) and without (red) temperature compensation. g) Optical image of flexible ISFET-based device attached on the curved tube.
a–g) Reproduced with permission.[127] Copyright 2015, American Chemical Society.

field analysis,[140–142] in most cases, their structure, size, weight,
and biofunctional factors hinder their direct integration with the
human body and limit their application in certain fields. In this
context, improving a biosensor’s biofunctions and flexibility to
improve its ability to adapt to the skin or human tissue can make
real-time and accurate detection of environmental hazards possi-
ble. The following subsections mainly review the development of
wearable environmental-sensing platforms designed for collecting
signals from the environment.
3.3.1. Gas Detection
Flexible gas sensors have been widely used to detect ambient
gases in our daily lives.[128,143,144] These devices are the basis
of realizing unmanned control and automatic detection for
advanced electronic technology. For example, a wire-based
printable flexible gas sensor with a polycrystalline Zn2GeO4
(pZGO) sensing layer can effectively detect 20 ppm of NH3
gas molecules compared with single-crystalline Zn2GeO4
(sZGO) (Figure 12a,b and Figure 12d).[128] In this regard, inte-
grating grain boundaries into polycrystalline materials has been
displayed to result in rich new mechanical properties, catalytic
activities, and electronic structures for flexible sensors
(Figure 12a,b). The adsorption of gas molecules at a grain bound-
ary dramatically changes the resistivity of pZGO (Figure 12c).
Moreover, after two cycles of mechanical bending (60 ), the
pZGO-based flexible device still exhibits high sensitivity for
200 ppm ammonia molecules, a fast recovery time, and good
mechanical properties (Figure 12e).
In fact, most flexible gas sensors are used in special environ-
ments, such as settings where they are often moved, shocked,

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Figure 12. a) Schematic diagram of printed pZGO microwire arrays-based flexible gas sensors. b) Illustration of flexible gas sensor structure. c) The
charge density difference image for ammonia gas molecule adsorbed on printed pZGO microwires arrays-based flexible gas sensor. d) Sensitivity
curves of pZGO microwires and sZGO microwires-based flexible gas sensors to 200 ppm ammonia gas molecules. e) Dynamic response of pZGO
microwires-based flexible gas sensor to 200 ppm ammonia gas molecules under bent state (60 ). a–e) Reproduced with permission.[128] Copyright
2019, Wiley-VCH. f ) Schematic diagram of the fabrication processes of the CNT-based healable flexible gas sensor. g) Optical image of flexible gas
sensor. h) Dynamic response of flexible gas sensor to 5–100 ppm NH3 gas. i) Sensitivity of flexible gas sensor to 25 ppm NH3 under different bending
cycles (0–500 cycles). j) Sensitivity of flexible gas sensor to 25 ppm NH3 after healing for different times. f–j) Reproduced with permission.[145]
Copyright 2015, Wiley-VCH.

or touched. As a result, they are very fragile, so accidental
scratching and dropping can cause sensor failures. If bio-
multifunctional (biocompatible or self-repairing) sensors are
used, we can effectively prolong the lifetime of such devices,
especially in both their sensing performance and their func-
tional aspects. Chen and coworkers reported the introduction
of functional CNTs on a flexible and healable substrate to
fabricate a novel transparent room-temperature gas sensor
(Figure 12f,g).[145] The special feature of this device is that it
has self-healing properties. If the device is cut off, the device
can heal automatically after 30 min in the presence of water.
This healing is mainly due to the high interdiffusion and fluid-
ity of the polyelectrolyte multilayer (PEM) film. The transparent,
healable, and flexible sensing device exhibited high selectivity
for ammonia (NH3) gas molecules over other gas molecules
(water, ethanol, acetone, dichloromethane, and toluene)
(Figure 12h). In addition, mechanical stability (Figure 12i)
and repeated healability (Figure 12j) of the flexible sensing
device, which can detect down to 25 ppm ammonia gas mole-
cules, were studied. Overall, the flexible device exhibits good
mechanical stability and self-healing.
In addition to the detection of environmental gases, monitor-
ing gases in exhaled breath, specifically volatile organic com-
pounds (VOCs), is of growing scientific and clinical interest.
Wang et al. demonstrated a biocompatible flexible butterfly
wing-based gas sensor that could record current changes in real
time under bending and exposure due to their high sensing
response to acetone gas in exhaled breath (Figure 13a,b).[32]

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Figure 13. a) Illustration of butterfly wing-based flexible gas sensor to detect acetone gas for the early diagnosis of diabetes. b) Optical image of butterfly
wing-based flexible gas sensor. c) Selectivity of butterfly wing-based flexible gas sensor to various target gases in simulated exhale breath. d) Sensitivity of
butterfly wing-based flexible gas sensor to 0.05–0.5 ppm acetone gases under flat and bent state. e) Optical image of flexible gas sensor attached on
human wrist. f ) Sensitivity of flexible gas sensor attached on human wrist to 2 ppm acetone gases. a–f ) Reproduced with permission.[32] Copyright 2017,
Royal Society of Chemistry.

This sensor enables the detection of acetone gas in breath for the
early diagnosis of diabetes. Sensing analysis shows a histogram
response to exhaled breath exposure (Figure 13c). Butterfly wing/
graphene composite films exhibit the highest sensitivity for ace-
tone gas molecules over water and other gas molecules. In addi-
tion, no significant decrease in the sensor sensitivity was
observed when the device was suddenly bent (Figure 13d). As
a result, the sensor demonstrates ultrahigh sensitivity and selec-
tivity and features real-time monitoring capabilities, making it a
highly desirable platform for portable and wearable sensor appli-
cations (Figure 13e).
3.3.2. Humidity Detection
Humidity is one of the common contact parameters used to
monitor tactile behavior in an artificial medical-sensing sys-
tem.[146] Relative humidity (RH), the basic physical quantity of
humidity, refers to the ratio of water vapor’s partial pressure
to saturated vapor pressure at a certain temperature and is used
in daily life. Currently, the reports on humidity sensors are
mainly focused on capacitive and resistive sensors.[147–149] For
example, the existence of ionic conductivity and proton transfer
on the surface functional groups of graphene oxide is affected by
humidity, as the capacitance increases with increasing humidity.
Borini and coworkers demonstrated a wearable breath humidity
sensor with a thin graphene oxide–sensing film and measured
the performance of the sensor using a controllable humidity gen-
erator (Figure 14a).[150] Significantly, sensors can distinguish dif-
ferent human behavior patterns (such as different whistles,
breathing frequencies, and different languages) by responding
to different humidities, which may be of great significance for
identifying different users by breath monitoring (Figure 14b,c).
In addition, Kulkarni and coworkers also used humidity as an
index of expiration. Resistance changes of graphene oxide were
measured, and respiratory activity was monitored in real
time.[151] To achieve sustainable development, electronic bioma-
terials with good biological properties have attracted extensive
attention from researchers. To date, a large number of bio-based
humidity sensors have been reported. Rolandi and coworkers
reported the first demonstration of a proton FET with proton-
transparent PdHx contacts (Figure 14d).[152] As shown in
Figure 14e, when a bias voltage is introduced between contacts,
the current increases with an increase in RH (and the hydration
level of the polysaccharides).
In addition, the same trend is also observed in the hysteresis
curve, which is mainly due to the increase in charge accumulation/
loss at the contact point. Zhang and coworkers reported a bright
color humidity-sensitive submicron film prepared by using a
natural silk fibroin solution.[153] The silk fibroin-based device
shows a rapid response and obvious color change within 5 s
due to the excellent hydrophilicity of silk fibroin. With a peak
redshift of more than 130 nm, the film is better than many other
multilayer or photonic crystal humidity sensors. A strategy of
manufacturing humidity sensors by host–guest interaction-
coupled polymer networks and conductive single-walled carbon
nanotubes (SWCNTs) has also been demonstrated.[154] The
polymer-based humidity sensor has high humidity sensitivity
due to the large resistance variation of the polymer in a humid
environment. Specifically, the resistance of the sample in dry air
(10% RH) is 8.62 kW, which is two and six times higher than
that in 30% RH and 60% RH, respectively. In addition, the

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Figure 14. a) Schematic diagram of humidity respiration rate detection and optical image of the flexible humidity sensor. b) Humidity response of the
flexible GO-based sensor. c) Responses of the flexible GO-based sensor to tune whistled. a–c) Reproduced with permission.[150] Copyright 2013,
American Chemical Society. d) Schematic of the biocompatible maleic–chitosan nanofiber-based FET humidity sensor and atomic force microscope
(AFM) image of the biocompatible maleic–chitosan nanofiber. e) The biocompatible maleic–chitosan nanofiber-based FET humidity sensor under dif-
ferent humidities (50–75% RH). d–e) Reproduced with permission.[152] Copyright 2011, Nature Publishing Group.

obtained materials have the advantages of humidity sensitivity,
volume conductivity, and rapid self-healing without external
stimulation.
4. Challenges and Future Outlook
Considering that most laboratory-on-a-chip testing tools, health-
care monitoring devices, and wearable electronics can be
expected to come into contact with the human skin, organ,
and tissue interfaces, the biofunctionality of flexible sensors is
very important for improving man–machine interactions and
enhancing the safety, reliability, and stability of tests. In this
review paper, we detailed and discussed smart wearable sensors,
focusing on biofunctionality, such as biocompatibility, biode-
gradable, and self-healing. In particular, different wearable sen-
sors for vital sign monitoring (biophysical, biochemical, and
environmental signals) were discussed, whereas the advantages
of bio-multifunctional sensors for use in wearable medical
devices are presented. These applications are in fields where
there is a demand for biocompatibility, safety, accuracy, mechan-
ical flexibility, high sensitivity, reproducibility, and stability. As
the range of functionalities of flexible and wearable sensors is
continuously growing, the identification of novel wearable sen-
sors that can fulfill the demands of medical applications is highly
desired.
Although multifunctional wearable sensors have made tre-
mendous progress, they still respond to multiple stimuli at
the same time, which makes the device very sure of the intensity
and type of each stimulus. Therefore, the study of wearable sen-
sors with low cross sensitivity and high recognition is a direction
of the future development of flexible electronics. Another chal-
lenge is fabricating smart multifunctional sensors by developing
new material to provide a robust sensing platform, such as the
development of wearable devices with biofunctionality to copy
the characteristics of the human skin and make smart devices
work in harsh environments. We hope that this work will con-
vince readers that with the further development of smart

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www.advancedsciencenews.com
wearable sensors coupled with bio-functionalities, the promise of
bioelectronic devices and their applications in medical diagnosis
and treatment is limitless.
Acknowledgements
L.L.W. and Z.L. contributed equally to this work. The authors sincerely
acknowledge financial support from the National Natural Science
Foundation of China (NSFC Grant No. 61874111, 61625404, 21571080,
61888102), the Science and Technology Development Plan of Jilin
Province (20190103135JH), and Young Elite Scientists Sponsorship
Program by CAST (2018QNRC001).
Conflict of Interest
The authors declare no conflict of interest.
Keywords
biofunctionality, health monitoring, medical devices, multifunctional
sensors, wearable sensors
Received: June 10, 2019
Revised: June 28, 2019
Published online: August 15, 2019
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