biosensors

Review
Self-Powered Biosensors for Monitoring Human
Physiological Changes
Ziao Xue 1,2 , Li Wu 1,2 , Junlin Yuan 1,2 , Guodong Xu 1, * and Yuxiang Wu 1,2, *

1 Department of Health and Physical Education, Jianghan University, Wuhan 430056, China
2 Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing 101400, China
* Correspondence: [email protected] (G.X.); [email protected] (Y.W.)

Abstract: Human physiological signals have an important role in the guidance of human health or
exercise training and can usually be divided into physical signals (electrical signals, blood pressure,
temperature, etc.) and chemical signals (saliva, blood, tears, sweat). With the development and
upgrading of biosensors, many sensors for monitoring human signals have appeared. These sensors
are characterized by softness and stretching and are self-powered. This article summarizes the
progress in self-powered biosensors in the past five years. Most of these biosensors are used as
nanogenerators and biofuel batteries to obtain energy. A nanogenerator is a kind of generator that
collects energy at the nanoscale. Due to its characteristics, it is very suitable for bioenergy harvesting
and sensing of the human body. With the development of biological sensing devices, the combination
of nanogenerators and classical sensors so that they can more accurately monitor the physiological
state of the human body and provide energy for biosensor devices has played a great role in long-
range medical care and sports health. A biofuel cell has a small volume and good biocompatibility. It
is a device in which electrochemical reactions convert chemical energy into electrical energy and is
mostly used for monitoring chemical signals. This review analyzes different classifications of human
signals and different forms of biosensors (implanted and wearable) and summarizes the sources of
self-powered biosensor devices. Self-powered biosensor devices based on nanogenerators and biofuel
cells are also summarized and presented. Finally, some representative applications of self-powered
biosensors based on nanogenerators are introduced.

Keywords: nanogenerator; self-powered; biosensor; health monitoring

Citation: Xue, Z.; Wu, L.; Yuan, J.; Xu,

G.; Wu, Y. Self-Powered Biosensors
for Monitoring Human Physiological 1. Introduction
Changes. Biosensors 2023, 13, 236.
The human body is metabolizing all day long, and some of the body’s signals can
https://doi.org/10.3390/
reflect the body’s vital signs and predict its physical state. The monitoring of these body
bios13020236
signals plays an important role in disease diagnosis and the health monitoring of the human
Received: 30 December 2022 body [1,2]. Currently, a few instruments are used in the clinical setting to monitor these
Revised: 30 January 2023 signals: blood pressure meter, oximeter, electrocardiograph, electromyography, electroen-
Accepted: 2 February 2023 cephalograph, thermometer, etc. The disadvantage of such products is that they are large
Published: 7 February 2023 and not easy to carry. Some smart wearable devices are also available on the market, and
these devices also have the function of monitoring human signals, such as smart bracelets,
smart watches, etc. However, the monitoring accuracy of such products is not good and
cannot be used for the diagnosis and auxiliary treatment of diseases.
Copyright: © 2023 by the authors.
In order to address the shortcomings and development needs of existing products, re-
Licensee MDPI, Basel, Switzerland.
searchers have begun to experiment with combining sensors with wearable and implantable
This article is an open access article
technologies and integrating other electronic devices [3]. Supported by the Internet of
distributed under the terms and
conditions of the Creative Commons
Things, sensors become nodes that realize a variety of functions, such as in-body sensing,
Attribution (CC BY) license (https://
measurement, and data processing and analysis. Due to the characteristics of wearable
creativecommons.org/licenses/by/ sensors and implantable sensors, they have the advantages of small size, light weight, func-
4.0/). tional integration, and good biocompatibility. They can be useful in telemedicine, health

Biosensors 2023, 13, 236. https://doi.org/10.3390/bios13020236 https://www.mdpi.com/journal/biosensors

Biosensors 2023, 13, 236 2 of 21

monitoring, sports monitoring, etc. [4,5]. Compared to traditional monitoring technologies,

sensors provide more accurate and direct access to data and can avoid using private and
irrelevant information.
An important research direction for sensors is the improvement and upgrading of
materials [6]. Whether implanted in the body or worn on the body surface, these sensors
need to be in long-term contact with the body. Therefore, the selection of soft and biocom-
patible materials is of great importance for the use of sensors on the human body [7]. In
addition, motion and external impacts may cause damage to the sensor and the loss of its
function. Wearable sensors can be easily replaced, but for sensors implanted in the body,
replacement is more problematic. Some self-healing materials are thus good choices for
sensors to solve this problem. Some materials can not only restore the mechanical structure
after the sensor is cut off but even restore the sensing performance. In order to facilitate a
single surgical intervention for implantation without the need for another one for surgical
removal, some sensors are biodegradable in vivo, while others can be degraded in the
natural environment without polluting it.
With the sustainable development and application of biosensor devices, it has become
important to solve the problem of energy supply. Some wearable sensor devices have huge
battery sizes [8], which greatly reduces user comfort; for some implanted devices, such as
pacemakers, after a few years of use, the power is not high enough for the normal operation
of the device. This results in the need for a second surgery to replace the device. This will
not only affect the patient’s experience using it but also increase the workload of medical
workers. Obviously, the energy supply of the device directly affects the efficiency of the
device and the patient’s experience [9], so the improvement of energy supply technology
becomes very important. To address the need for the device’s energy supply, researchers
have begun to develop self-powered technologies. As the closest toucher of the device, the
human body can generate abundant energy, such as a large amount of mechanical energy
during movement. Therefore, scientists began to experiment with energy harvesting from
the human body and human surroundings. Wang et al. [10] first proposed nanogenerators
in 2006 [11–13], which collect low-frequency mechanical energy [14]; this makes harvesting
energy from the human body and the surrounding environment a reality and has attracted
more researchers to study the use of nanogenerators to harvest energy [15]. In addition
to nanogenerators, biofuel cells [16] can be used for energy harvesting, which can convert
biochemical energy from the human body into electrical energy. In addition to this, there
are technologies such as solar cells [17] and electromagnetic generators [18] that can be
used as the device’s energy supply, and these technologies have greatly broadened the way
in which sensors can be supplied with energy.
This paper first introduces the signal parameters of the human body. Then, it intro-
duces the sensing measurements of wearable and implantable sensors, followed by some
sensors that are flexible, self-healing, biocompatible, and degradable. The principles of
nanogenerators and biofuel cells are presented in terms of energy supply, as well as some
representative work. After that, this paper classifies a large number of sensor devices and
finally selects representative work to introduce the application of sensors in human health
monitoring. Finally, this paper summarizes the current development status of sensors in
the field of human health monitoring and looks at future development directions.

2. Human Body Signals

The human body is rich in physiological signals, and the heartbeat and respiration are
continuous even when not in motion. The monitoring of these signals is of great importance
for the health monitoring of the human body [19]. Wearable sensors are “eyes” that are
developed and manufactured to recognize the various signals that need to be utilized.
Sensors made on the basis of different principles can distinguish between different signals.
Some sensors are even made to recognize certain signals. Thus, it is particularly important
to understand the classification of the types of body signals. Based on the nature of body
signals, they can be divided into two categories: physical and chemical signals (Figure 1).
 Biosensors 2023, 12, x FOR PEER REVIEW 3

important to understand the classification of the types of body signals. Based on the
Biosensors 2023, 13, 236 3 of 21
ture of body signals, they can be divided into two categories: physical and chemical
nals (Figure 1).

Figure
Figure 1. Physical 1. (electrical,
signals Physical signals (electrical,
blood pressure, blood pressure,
temperature) temperature)
and chemical and
signals chemical
(saliva, signals (sa
blood,
blood,
tears, sweat) that tears,
can be sweat)from
collected thatthe
canhuman
be collected
body.from the 1human
(Figure body.
made by Figdraw).

2.1. Physical Signals

2.1. Physical Signals
Physical signals are the physical media used to load information and represent
Physical signals are the physical media used to load information and represent the
symbols, states, and signs of the information. The human body is rich in physical si
symbols, states, and signs of the information. The human body is rich in physical sig-
parameters that can reflect a person’s current state and can even be risk-predictive. Th
nal parameters that can reflect a person’s current state and can even be risk-predictive.
signals mainly include physiological electrical signals [20], blood pressure [21,22], t
These signals mainly include physiological electrical signals [20], blood pressure [21,22],
perature [22,23], respiration [24], and acceleration [25].
temperature [22,23], respiration [24], and acceleration [25].
Physiological electrical signals. Physiological electrical signals are regular elect
Physiological electrical signals. Physiological electrical signals are regular electrical
signals closely related to the physiological state of the body during activity or in the r
signals closely related to the physiological state of the body during activity or in the resting
ing state [20,26]. These signals are electroencephalographic signals (EEG) [27], electro
state [20,26]. These signals are electroencephalographic signals (EEG) [27], electrocardio-
diographic signals (ECG) [28], electromyographic signals (EMG) [29], etc. EEG signal
graphic signals (ECG) [28], electromyographic signals (EMG) [29], etc. EEG signals reflect
flect changes in brain activity [30]; ECG signals reflect changes in the activity gener
changes in brain activity [30]; ECG signals reflect changes in the activity generated by each
by each heartbeat cycle, which is important for heart health monitoring [31]; and E
heartbeat cycle, which is important for heart health monitoring [31]; and EMG signals
signals reflect the changes that occur during muscle movement and are often used
reflect the changes that occur during muscle movement and are often used as a guide
guide during exercise training [32].
during exercise training [32].
Blood pressure. Blood pressure is the pressure per unit area of blood vessel wall
Blood pressure. Blood pressure is the pressure per unit area of blood vessel wall that
blood exerts as it flows through the blood vessels. For patients suffering from hyper
blood exerts as it flows through the blood vessels. For patients suffering from hypertension,
sion, monitoring blood pressure changes at all times is beneficial. Wearable devices al
monitoring blood pressure changes at all times is beneficial. Wearable devices allow for
convenient 24/7 blood pressure monitoring [33], increasing the health security of the user.
Temperature. Body temperature reflects, to a large extent, the physical condition of
the human body. The temperature of a normal human body is between 36 ◦ C and 37 ◦ C,
independent of the surrounding environment. A normal body temperature is necessary for
Biosensors 2023, 13, 236 4 of 21

normal metabolism and vital activities. Usually, we feel cold or hot, but the body tempera-
ture hardly fluctuates at all. When the body is infected with a disease, the body temperature
rises due to the body’s immune system; when the body is exposed to an extremely cold
environment, the core body temperature drops and can cause hypothermia [34].
Respiration. Respiration is the process of gas exchange between the organism and
the external environment. Respiration can be used as a means of noninvasive health
monitoring, and the amplitude and frequency of breathing play an important role in health
analysis [4,35]. Wearable sensors can easily and quickly acquire these signals for subsequent
monitoring and analysis. By wearing or attaching sensors to the surface of the human
body [36], the breathing amplitude and frequency of the human body can be monitored.
Acceleration. Acceleration sensors are mainly used to monitor the speed of human
spatial displacement and the speed of movement or changes in human posture. In motion,
the speed at which the human body moves is called the displacement speed; the speed
at which the human body completes the movement action is called the action speed.
Acceleration sensors can monitor the displacement velocity and movement velocity of
the human body and identify the posture or state of the human body by changes in
acceleration; they can warn of a fall before it is recognized [37] or send a distress signal
after it is recognized [38].
Future wearable devices will integrate multiple sensors that can monitor more than
one signal [39], and these monitored signals will be used synergistically with each other as
an analysis of the user’s health status.

2.2. Chemical Signals

Chemical signals, also called biochemical signals, are biochemical molecules that
communicate with each other between cells. The human body is also rich in biochemical
signals, which can be obtained from body fluids such as blood, saliva, tears, sweat, and
urine [40]. Biochemical parameters that can be measured by wearable sensors include pH,
lactate, blood glucose, electrolytes, oxygen saturation, etc.
In contrast, saliva, tears, sweat, and urine can be collected in a noninvasive manner,
and the biochemical parameters of these fluids can be analyzed to determine the health
status of the human body [41,42] and, in some cases, can be used to power the device. In
the future, noninvasive collection and monitoring will be the development trend of sensor
devices, and electrochemical sensors are particularly suitable for body fluid detection
due to their high performance, inherent miniaturization, and low cost. In addition, the
fusion of different chemical sensors will allow noninvasive sensors to achieve multi-analyte
detection [19,43,44].

3. Biosensors in Different Forms and Additional Characteristics

Biosensors can be classified according to different criteria, including their principle,
purpose, and function. According to the principle and measurement method of sensors,
sensors can be divided into those that monitor physical signals and those that monitor
chemical signals; according to the form of sensor contact with the human body, they can
be divided into invasive (in vivo) and noninvasive (in vitro), which can also be called
wearable sensors and implantable sensors (Table 1).
Biosensors 2023, 13, 236 5 of 21

Table 1. Summary of the different forms of biosensors parameters.

Placement
Sort Target Range Sensitivity Ref.
Sites
Muscle
Skin 0.5–2.0 V 0.1 V [45]
deformation
Wearable Volleyball
Arm 6.65–19.21 kPa 0.3086 V kPa−1 [46]
reception
Wrist Gesture \ 92.6% accuracy [47]
Aorta (pig) Blood pressure 0–200 mmHg 14.32 mV/mmHg [48]
Left ventricle (pig)/ Endocardial 1.195 mV
Implantable 0–350 mmHg [49]
left atrium (pig) pressure mmHg−1
Ligament Ligament strain 0–600% 25% strain rate [50]

3.1. Wearable and Implantable Biosensors

3.1.1. Wearable Biosensors
Wearable biosensors are noninvasive sensors that acquire signal parameters from the
body when attached to the human epidermis. Such sensors are noninvasive to the human
body and do not require signal parameters to be acquired through their implantation into
the body. Examples include wristbands, belts, watches, bracelets, etc.
Wearable biosensors can be applied to detect changes in body surface muscle mor-
phology. Wang et al. proposed a stretchable, skin-friendly, and noninvasive wearable
sensor for implementing human motion monitoring (Figure 2a) [45]. The deformation of
the double-layer silicone rubber structure (DS-TENG) causes friction between the layers
due to uneven strain, generating a frictional charge that can be induced in the electrodes
as a voltage signal in response to deformation. A 3D muscle sensor made according to
this principle can monitor the degree of deformation in different muscle regions based
on the change in the output voltage of the DS-TENG. Wearable sensors can be attached
to the body surface to monitor stress changes. Wang et al. reported a soft, breathable
wearable e-skin (Figure 2b) [46]. This e-skin provided excellent thermal and wet comfort
and showed significant antibacterial effects against E. coli and S. aureus. A pressure sensi-
tivity of 0.3086 V kPa−1 was measured in the sensing range of 6.65–19.21 kPa. In addition,
a 2 × 3 e-skin array-based statistical analysis system for volleyball catching was further
developed. This work confirms the practical application of wearable biosensors in the field
of sports. Wearable biosensors are also often used for hand posture analysis. Tan et al.
developed a gesture recognition wristband with a full keyboard and multiple command
inputs (Figure 2c) [47]. A hybrid generator consisting of TENG and PENG was integrated
into a small box of 0.4 cm × 0.8 cm × 1 cm. The bracelet monitors hand movements to
recognize gestures and can be easily worn on the wrist without interfering with the daily
activities of the hand. The bracelet can recognize a variety of gestures with an accuracy of
92.6%. This gesture recognition function can be used for human–computer interaction, for
disability assistance, or in special environments and scenarios where verbal communication
is not convenient.

3.1.2. Implantable Biosensors

An implantable biosensor is a type of sensor that is implanted in the body to monitor
human signal parameters. Due to the characteristics of implantable biosensors, it contacts
the body more directly and thoroughly, so it is able to obtain more direct and accurate
physiological and biochemical signals. Chen et al. designed a piezoelectric thin film (PETF)-
based pressure sensor (Figure 2d) that can be wrapped around the aorta to monitor changes
in blood pressure [48]. It was implanted around the ascending aorta of pigs with excellent
stability, linearity, and sensitivity (R2 = 0.97, sensitivity 14.32 mV/mmHg).
Biosensors 2023, 13, 236 6 of 21

However, implantable sensors also have disadvantages. For people who are afraid
of pain, implantable sensors will undoubtedly lead to a bad wearing experience and even
aggravate their psychological shadow; for people who are exercising, an invasive method
of obtaining physiological and biochemical parameters not only will be inconvenient but
also may cause inaccurate data collection because of sweat, the sports environment, dust,
and other factors and even cause additional damage. Another drawback of implantable
sensors is the energy problem. When using batteries to power the sensor, there is a
thermal effect of electrical energy conversion; the batteries also need to be removed for
replacement when they run out of power. This is detrimental to the patient experience
and expensive. Nanogenerators are a solution to the energy supply of implantable devices.
Li et al. reported a miniaturized, flexible, and self-powered endocardial pressure sensor
(SEPS) based on the friction nanogenerator (TENG) (Figure 2e) [49]. It can be integrated
with a surgical catheter for minimally invasive implantation. The SEPS was implanted
in the left ventricle and left atrium of pigs. The SEPS achieved ultra-sensitive real-time
monitoring and mechanical stability in pigs, obtaining excellent linearity (R2 = 0.997) with
a sensitivity of 1.195 mV mmHg−1 . In addition, the SEPS can detect heart rate arrhythmias,
such as ventricular fibrillation and premature ventricular beats, and has an important
role in monitoring and diagnosing cardiovascular diseases. The sensitivity of SEPS is
1.195 mV mmHg−1 . Wang et al. proposed a TENG (OFS-TENG)-based organogel/silica
fiber helical sensor with stability and stretchability (Figure 2f) [50]. This sensor can be
implanted to monitor real-time strain in ligaments. In vitro and in vivo tests have shown
the OFS-TENG to be biocompatible. In the case of the OFS-TENG, it was successfully
implanted in the patellar ligament of the rabbit’s knee. When the rabbit flexes its knee, the
output is continuously monitored at different frequencies and bending angles. With its
good sensitivity and stability, the OFS-TENG offers a broad platform and holds promise
for implantable self-powered sensors, wearable devices, and health monitoring.

3.2. Biosensors with Additional Characteristics

With the progress in technology and the development of biosensors, they have become
smaller and smaller, and their detection accuracy has been greatly improved. In addi-
tion, some biosensors have unique properties with the upgrade of materials, for example,
flexibility, self-healing, high biocompatibility, and degradability.
The good adaptability of flexible wearable and implantable biosensors to the shape
of human tissues or organs will improve the performance of the biosensor itself. Wang
et al. fabricated a stretchable and fully enclosed self-powered power system by combining
a stretchable TENG and a stretchable energy storage system and encapsulating them with
flexible materials (Figure 3b) [51]. It is flexible enough to withstand external forces such as
stretching and twisting and derives energy from them. The energy obtained from human
action when mounted on the human body can drive an electronic watch.
Some wearable biosensors are inevitably bumped and damaged in daily life. It is well
known that most organisms in nature have the ability to heal themselves. Some researchers
have developed self-healing biosensors that have the ability to heal themselves not only
structurally but also functionally. Usually, devices with self-healing capabilities also have
soft and stretchable characteristics. The soft, stretchable and self-healing properties of
hydrogels can be used to develop new biosensors. Wan et al. prepared a hydrogel with
covalent cross-linking and CNCs-Fe3+ ligands as binding units in a synergistic soft and hard
network structure (Figure 3a) [52]. This hydrogel is robust, stretchable, strain-sensitive, and
self-healing. When the hydrogel is cut, the gap can automatically repair itself within 5 min.
Based on the properties of the hydrogel, a wearable flexible strain sensor was fabricated
that can quickly and accurately monitor changes in finger joints and breathing patterns and
also monitor slight pulses in different states of motion. Li et al. produced a self-healing
PAA-Gel-NaCl hydrogel, and a repairable single-electrode TENG was fabricated on the
basis of the hydrogel for use as an energy-harvesting electronic skin (Figure 3c) [53]. The
PAA-Gel-NaCl hydrogel (polyacrylic acid–gelatin–sodium chloride hydrogel) was sliced in
 effect of electrical energy conversion; the batteries also need to be removed for replace
ment when they run out of power. This is detrimental to the patient experience and ex
pensive. Nanogenerators are a solution to the energy supply of implantable devices. Li e
al. reported a miniaturized, flexible, and self-powered endocardial pressure sensor (SEPS
Biosensors 2023, 13, 236 based on the friction nanogenerator (TENG) (Figure 2e) [49]. It can be integrated 7 of 21 with
surgical catheter for minimally invasive implantation. The SEPS was implanted in the le
ventricle and left atrium of pigs. The SEPS achieved ultra-sensitive real-time monitorin
and mechanical stability in pigs, obtaining excellent linearity (R2 = 0.997) with a sensitivit
half and could of
self-heal
1.195 mV within
mmHg 2.5 −1min
. Inataddition,
room temperature.
the SEPS can The resistance
detect heart of thearrhythmias,
rate hydrogel such a
before slicing ventricular Ω. After and
was 359.28fibrillation 2.5 premature
min of self-healing, the resistance returned
ventricular beats, and has an important to role
a in mon
stable 363.3 Ω,itoring
with only a slight increase over the original state. The hydrogel-based
and diagnosing cardiovascular diseases. The sensitivity of SEPS is 1.195 m
SH-TENG can mmHglight up−1. six
Wangredet light-emitting
al. proposed adiodes
TENG(LEDs). It also has good
(OFS-TENG)-based sensitivity to
organogel/silica fiber helica
low-frequencysensor
touch with
and can be used as an electronic skin for touch and pressure
stability and stretchability (Figure 2f) [50]. This sensor can sensing.
be implanted t
Wang et al. proposed
monitorareal-time
TENG that caninbe
strain shape-adapted
ligaments. In vitro and self-healing
and in (Figure
vivo tests have 3d) the
shown [54].
OFS-TEN
Using a viscoelastic polymer as the In
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substrate, SS-TENG
patellarisligament
endowed of with the ability
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the output is con
and the instantaneous
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at different frequencies and bendingcan angles.
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and stability, flexion and conforming
OFS-TENG to wrist
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holds automatically
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heal after 1 min of severance.
self-powered sensors, wearable devices, and health monitoring.

Figure 2. WearableFigure 2. Wearable

biosensors biosensors and
and implantable implantable
biosensors. (a) Abiosensors.
stretchable(a)wearable
A stretchable
sensorwearable
for mo- sensor fo
motion monitoring [45]. Copyright 2019 American Chemical Society. (b) A soft and breathab
tion monitoring [45]. Copyright 2019 American Chemical Society. (b) A soft and breathable electronic
skin that can be worn on the arm for volleyball catch statistics [46]. Copyright 2021 American Chemi-
cal Society. (c) A wristband for gesture recognition and full keyboard letter input [47]. Copyright 2022
Wiley Online Library. (d) An implantable pressure sensor based on a piezoelectric film to monitor
blood pressure changes [48]. Copyright 2016, Elsevier. (e) An implantable endocardial pressure
sensor for monitoring heart rate arrhythmias, ventricular fibrillation, and premature ventricular
contractions [49]. Copyright 2019, Wiley Online Library. (f) A spiral organogel sensor implanted in
the patellar ligament to monitor knee flexion frequency and angle [50]. Copyright 2022 American
Chemical Society.

Generally, implantable biosensors need to be removed after completing their work

in vivo, which can exacerbate the pain of patients and also add to the workload of medical
personnel, and biodegradable devices are a good way to solve this problem. Wang et al.
reported a biodegradable friction nanogenerator (BD-TENG) for short-term in vivo biome-
chanical energy conversion (Figure 3e) [55]. The BD-TENG consists of a multilayer structure
of a biodegradable polymer (BDP) and an absorbable metal. It can be degraded and re-
absorbed in vivo after completing its work without any adverse effects. The open-circuit
voltage (Voc) of the BD-TENG can reach up to ~40 V, and the corresponding short-circuit
current (Isc) can reach ~1 µA.
 Biosensors 2023, 12, x FOR PEER REVIEW 8 of

Biosensors 2023, 13, 236 8 of 21

circuit voltage (Voc) of the BD-TENG can reach up to ~40 V, and the corresponding sho
circuit current (Isc) can reach ~1 μA.
In addition to biodegradation in vivo, thereinare
In addition to biodegradation devices
vivo, therethat can be degraded
are devices that can beindegraded
the in t
natural environment to reduce the impact on the natural environment. Bian et al. fabricated
natural environment to reduce the impact on the natural environment. Bian et al. fab
a water-solublecated
TENG (WS-TENG) using
a water-soluble TENGbiodegradable
(WS-TENG) using recycled paper andrecycled
biodegradable water-soluble
paper and wate
graphite electrodes (Figure 3f) [56]. Cellulose nanocrystals (CNCs) were extracted
soluble graphite electrodes (Figure 3f) [56]. Cellulose nanocrystals (CNCs) from were
the extract
paper and further mixed with methylcellulose (MC) to form CNC/MC films,
from the paper and further mixed with methylcellulose (MC) to form CNC/MC which can be film
used as a positive electric material with ordinary MC films as a negative electric
which can be used as a positive electric material with ordinary MC films as material to a negati
form TENG device materials.
electric material The output
to form TENGvoltage
deviceofmaterials.
the WS-TENG is between
The output voltage 0V of and 2
the WS-TENG
V, which can accurately
between 0distinguish various
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as a real-time it can degrade
signal-monitoring in water
sensor. in 30 min and
Additionally, it canin degrade
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in water in
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and in the natural environment in 30 days.

Figure
Figure 3. Biosensors 3. Biosensors
with with their characteristics.
their characteristics. (a) A hydrogel(a) A hydrogel
sensor sensor
that can that pulse,
monitor can monitor
with pulse, w
stretchable and
stretchable and self-healing self-healing characteristics,
characteristics, and a notch thatandcana notch that within
self-heal can self-heal
5 minwithin 5 min after bei
after being
cut [52]. Copyright 2017, American Chemical Society. (b) A stretchable TENG and energy stora
cut [52]. Copyright 2017, American Chemical Society. (b) A stretchable TENG and energy storage
composite energy system that can drive an electronic meter with energy derived from the hum
composite energy system
body [51]. that can drive
Copyright 2016an electronic
American meter Society.
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(c) A TENG from
with theadaptation
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body [51]. Copyright
itself 12016
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after being Chemical Society. (c)
cut [53]. Copyright A MDPI.
2021, TENG (d) with shape adaptation
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water-soluble TEN
heals itself 1 minthat degrades
after in water
being cut [53]. and the natural
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2021, MDPI. (d)[54]. Copyright 2019,
A biodegradable American Chemical So
water-soluble
TENG that degrades ety. in
(e)water
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and the natural that completes
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2019, American being cut at roo
Chemical
temperature and can be used as a touch- and pressure-sensing e-skin [55].
Society. (e) A self-healing hydrogel that completes self-healing within 2.5 min after being cut at room Copyright 2016, Scien
(f) A biodegradable TENG that degrades and is reabsorbed in vivo after completing its task [5
temperature and can be used as a touch- and pressure-sensing e-skin [55]. Copyright 2016, Science.
Copyright 2022, Elsevier.
(f) A biodegradable TENG that degrades and is reabsorbed in vivo after completing its task [56].
Copyright 2022, Elsevier.
4. Self-Powered Types of Biosensors
The human body can produce an abundance of energy and is generating energy
4. Self-Powered Types
the of Biosensors
time [57]. Every heartbeat of the human body, every step during movement, and ev
The human thebody
heat can produce
emitted from an
theabundance of energy
skin or organs and is
can be used asgenerating
a source forenergy
energyall
harvesting
the time [57]. Every
supply heartbeat
energy toofsensor
the human body,
devices. The every
currentstep during movement,
technologies and even
for self-powered sensor devic
the heat emittedarefrom
mainly
the based
skin oronorgans
harvesting
can beenergy
used from the human
as a source body and
for energy human surrounding
harvesting to
supply energy toThe technologies
sensor devices.that
Thecan be used
current as self-powered
technologies systems are sensor
for self-powered piezoelectric
devicesnanogener
are mainly basedtors,
ontriboelectric
harvestingnanogenerators,
energy from the pyroelectric
human body nanogenerators,
and human and biofuel cells (Table
surroundings.
The technologies that can be used as self-powered systems are piezoelectric nanogenerators,
triboelectric nanogenerators, pyroelectric nanogenerators, and biofuel cells (Table 2).

4.1. Piezoelectric Nanogenerators

A piezoelectric nanogenerator [58] (PENG) is a kind of nanogenerator that uses the
piezoelectric effect to generate electricity at the nanoscale. The piezoelectric effect is a
phenomenon in which some special materials generate an internal electrical potential by an
Biosensors 2023, 13, 236 9 of 21

applied external mechanical force. These materials are called piezoelectric materials, such
as ZnO. When the piezoelectric material is not subjected to externally applied mechanical
forces, the dielectric inside the piezoelectric material is disordered and does not show
electrical properties externally. When a mechanical force is applied externally to the
piezoelectric material, the dielectric suddenly becomes regular. This process completes the
energy conversion of mechanical energy to electrical energy. A PENG has the advantages of
low power consumption, simple design, flexibility, and mechanical stability, but its output
is relatively low. The output magnitude of a PENG depends mainly on the piezoelectric
coefficient and the strain of the piezoelectric material. Therefore, researchers usually
increase the interface effect through material compounding or improve the structural
design, both of which can increase the piezoelectric performance [59,60].
Due to the working principle of the piezoelectric nanogenerator, it can adhere to the
human skin to collect the energy generated by the deformation of the skin surface. Chou
et al. proposed a high-performance stretchable PENG (Figure 4a) [61]. The use of piezoelec-
tric and conductive particles combined with solid rubber produced a PENG with integrated
and high elasticity, excellent piezoelectric properties, and stretchability. This stretchable
SPENG can be directly attached to a human joint to achieve kinetic energy harvesting, and
the collected energy can drive an electronic meter. Of course, the piezoelectric nanogenera-
tor is also capable of making the device more integrated to achieve simultaneous sensing
and energy supply. Wang et al. proposed a highly compatible electronic skin with a PENG
energy supply (Figure 4b) [62]. Due to the characteristics of the PENG, the electronic skin
can obtain energy while sensing the external world at the same time. Our PENG has a
maximum output current density of 9.704 mA·m−2 and an open-circuit voltage of ~100 V,
capable of powering more than 40 green LEDs or charging a 10 µF commercial capacitor
from ~0 V to 6 V for about 500 s.

4.2. Triboelectric Nanogenerator

A triboelectric nanogenerator [63,64] (TENG) is a nanogenerator designed according to
the frictional electric effect and electrostatic effect. The frictional effect refers to the different
electron capture characteristics of different materials: when the surfaces of two materials
have different electron capture characteristics of friction, contact, or separation due to
external mechanical forces, the two materials will carry different charges, and therefore,
when the two materials are in contact, the potential difference between the two material
surfaces will induce the flow of electrons from high potential to low potential, leading to
the formation of current. Electrostatic induction, also known as electrostatic influence, is
the physical phenomenon that the charge in the conductor redistributes without any actual
contact with a charged body. When one surface electrode is connected to an external circuit
and the two materials are separated by contact, the electrostatic induction phenomenon
creates an electrostatic potential that drives the flow of charge and forms an electric current.
The TENG is available in four different operating modes: vertical Contact-Separation
Mode, Lateral Sliding Mode, Single-Electrode Mode, and Free-Standing Triboelectric-Layer
Mode. The advantages of the vertical Contact-Separation Mode TENG include its simple
design and fabrication, high instantaneous power output, and easy multilayer integration.
The Lateral Sliding Mode TENG has a lower output but has a wide range of applications in
haptics and pressure because one of the friction surfaces does not need to be connected to a
wire [65–67]. The Free-Standing Triboelectric-Layer Mode TENG does not necessarily need
to be in direct contact with the electrode when moving, so there is less wear on the material
surface, and it has high durability.
The nanogenerator can realize sensing and energy supply with a special structure.
Some specially designed TENGs can obtain energy from the human body’s mechanical
energy and obtain human state information from the electrical signal at the same time. This
means that the TENG can not only be used as a power supply but also be used directly as an
active sensor [68]. Liao et al. proposed a nestable kind of arch-shaped flexible tribological
electrical nanogenerator (NA-TENG) (Figure 4c) [69]. It is highly flexible and reproducible
Biosensors 2023, 13, 236 10 of 21

and can be attached to the wrist bend to analyze the electrical signal versus bending angle.
Its highlight is that it can be assembled like a nesting device, which greatly optimizes
the scalability of the NA-TENG’s output performance. They fabricated a three-layer NA-
TENG and found that the electrical output improved with the increasing number of layers
and the expanding distance between two layers. With changes in materials, triboelectric
nanogenerators can find new applications. Yun-Ze Long et al. proposed a multifunctional
wearable TENG (Figure 4d) [70]. By using common fabric polymerized polyaniline as an
electrode, the sensor is softer and more breathable than the conventional frictional electric
structure, so it can be worn for a long time. In the electrical output of the tested TENG,
with an area of 4 cm × 8 cm or 10 cm × 10 cm, the short-circuit current and open-circuit
voltage output can reach 200 µA and 1000 V, respectively. The 10 cm ×10 cm wearable
TENG can drive 944 LEDs.

4.3. Pyroelectric Nanogenerators

Pyroelectric nanogenerators [71] (PyNGs) are nanogenerators that harvest energy
based on the Seebeck thermal effect using the temperature difference between the two ends
of the material. The pyroelectric effect refers to the charge release phenomenon exhibited by
the change in polarization intensity with temperature. When the temperature of the material
is constant, the polarization intensity of the material does not change, and no current
is generated. When the material is heated, the temperature increases, the polarization
strength of the material decreases, and a thermal potential is generated. This generated
thermal potential drives the carriers from the electrodes to the external circuit. When the
temperature decreases, the polarization strength of the material increases, and a current in
the opposite direction is generated when the external circuit is connected [72]. Pyroelectric
nanogenerators have the advantages of high durability, environmental applicability, and
flexibility, and their output size is influenced by the pyroelectric coefficient of the material
and temperature changes. They are commonly used in fire alarms, heat sensing, thermal
imaging, pollution monitoring, and more [73,74].
Pyroelectric nanogenerators (PyNGs) are mainly used to collect the energy gener-
ated by temperature differences, which can be generated by human breathing. Luo et al.
proposed a wearable self-powered respiratory sensor using PyNGs for the energy supply
(Figure 4e) [75]. PyNGs collect the energy generated by human breathing, and due to the
temperature fluctuations caused by human breathing at an ambient temperature of 5 ◦ C,
PyNGs can generate output signals with an open-circuit voltage of 42 V and a short-circuit
current of 2.5 µA. With a maximum power of 8.31 µW and an external load of 50 MΩ, they
can be used to directly drive electronic devices such as LCDs and light-emitting diodes.
The electrical signals can be used for harvesting energy from the human body but also
reflect the respiratory state and ambient temperature. In addition, different nanogenera-
tors can be coupled together in order to harvest different energies in complex situations.
Wang et al. proposed a nanogenerator that integrates a mixture of frictional, pyroelectric,
and piezoelectric energy that can efficiently harvest energy from wind and water vapor
(Figure 4f) [76]. Each unit of the TENG, PENG, and PPENG (pyroelectric−piezoelectric
nanogenerator) can be used to harvest mechanical and thermal energy individually or
simultaneously. The hybrid nanogenerator has a higher power output than a single type of
nanogenerator. The significance of this is the simultaneous harvesting of different types of
energy, which is important in the case of simultaneous changes in airflow and temperature
(e.g., respiration).
Biosensors 2023, 13, 236
Biosensors 2023, 12, x FOR PEER REVIEW 11 of 21 11 o

Figure 4. Use of Figure 4. Use of aas

a nanogenerator nanogenerator as an device.
an energy supply energy supply device. (a)high-performance
(a) A stretchable A stretchable high-perform
PENG that can power an electronic watch [61]. Copyright 2018, Elsevier. (b) A highly biocompa
PENG that can power an electronic watch [61]. Copyright 2018, Elsevier. (b) A highly biocompatible
electronic skin powered using a PENG [62]. Copyright 2021, American Chemical Society. (
electronic skin powered using a PENG [62]. Copyright 2021, American Chemical Society. (c) A
nestable arch-shaped flexible TENG that can light up six LED bulbs [69]. Copyright 2020, Amer
nestable arch-shaped flexible
Chemical TENG
Society. (d)that can light multifunctional
A wearable up six LED bulbs [69]. with
TENG Copyright
a 10 cm2020,
× 10American
cm area that can d
Chemical Society. (d)LEDs
944 A wearable multifunctional
[70]. Copyright TENG (e)
2019, Elsevier. with 10 cm ×self-powered
A awearable 10 cm area that can that
sensor driveuses PyNG
944 LEDs [70]. Copyright 2019,[75].
energy supply Elsevier. (e) A2017,
Copyright wearable self-powered
Elsevier. (f) A hybridsensor that uses that
nanogenerator PyNG for
integrates frictio
piezoelectric,
energy supply [75]. Copyrightand thermoelectric
2017, Elsevier. (f) power
A hybridto harvest energy from
nanogenerator wind and water
that integrates vapor [76]. Co
frictional,
piezoelectric, andright 2018, American
thermoelectric powerChemical Society.
to harvest energy from wind and water vapor [76]. Copyright
2018, American Chemical Society.
4.4. Biofuel Cell
4.4. Biofuel Cell A biofuel cell (BFC) is a device in which an electrochemical reaction converts che
cal energy into electrical energy [77]. A BFC mainly consists of an anode, a cathode,
A biofuel cell (BFC) is a device in which an electrochemical reaction converts chemical
an electrolyte. The anode oxidizes the biofuel in the presence of a catalyst to generate e
energy into electrical energy [77]. A BFC mainly consists of an anode, a cathode, and an
trons and protons, the protons pass through the electrolyte to the cathode, and the e
electrolyte. The anode oxidizes the biofuel in the presence of a catalyst to generate electrons
trons flow through an external circuit to the cathode. There are many types of bio-c
and protons, the protons pass through the electrolyte to the cathode, and the electrons
The enzymatic biofuel cell (EBFC) is used for biosensing and energy harvesting beca
flow through an external circuit to the cathode. There are many types of bio-cells. The
of advantages such as good biocompatibility and small size. However, the loading cap
enzymatic biofuel cell (EBFC) is used for biosensing and energy harvesting because of
ity and electron transfer rate of enzymes in biofuel cells are the key factors affecting
advantages such as good biocompatibility and small size. However, the loading capacity
output performance of the cells, and researchers usually adopt structural design and
and electron transfer rate of enzymes in biofuel cells are the key factors affecting the output
terial synthesis to improve the cell performance, but it is still difficult to solve the p
performance of the cells, and researchers usually adopt structural design and material
lems of low output power and short service life.
synthesis to improve the cell performance, but it is still difficult to solve the problems of
With the development of biofuel cells and manufacturing technologies, biofuel c
low output power and short service life.
are being integrated into devices and fabrics and have many application scenarios. Bio
With the development of biofuel cells and manufacturing technologies, biofuel cells
cells combined with fabrics can be fabricated into clothing for more direct contact with
are being integrated into devices and fabrics and have many application scenarios. Biofuel
human body. Wang et al. proposed a flexible fabric-based biofuel cell capable of obtain
cells combined high
withpower
fabricsfrom
can be fabricated
body into clothing
fluids through for more
sustainable direct
energy contact with
conversion the 5a) [78].
(Figure
human body. Wang et al. proposed a flexible fabric-based biofuel cell capable
moisture management fabric (MMF) of sportswear can drive the free flow of molecuof obtaining
high power from To body fluids
increase thethrough sustainable
power output, MMFs energy
were conversion
designed and (Figure 5a) [78].
fabricated, andThe
six multi-s
moisture management fabric (MMF) of sportswear can drive the free flow
cells were integrated into an armband to supply energy to a sports watch. of molecules. To Wang e
increase the power output, MMFs
demonstrated were designed
a fabric-based printedandBFCfabricated, and six
that is flexible, multi-stack
stretchable, andcells
stretch-resis
were integratedand into
hasansuitable
armband to supply
fitting energy to
characteristics a sports
(Figure 5g) watch.
[79]. Its Wang et al. demon-
close-fitting characteristics m
strated a fabric-based printedfor
it well suited BFC that is flexible,
harvesting energy stretchable,
from the body and stretch-resistant
surface, and it can and has energy f
capture
suitable fitting sweat
characteristics (Figure 5g) [79]. Its close-fitting characteristics
on the human body surface with a noninvasive energy-harvesting function.make it well
suited for harvesting energyafrom
paper shows sock thewithbody surface, and
an integrated BFCit can
and capture energyand
other sensors, fromthesweat
real-time sig
on the human acquired
body surface with a noninvasive energy-harvesting function.
by the sensors in the sock can be accessed through smartphones and wireThe paper
shows a sock with an integrated BFC and other sensors, and the real-time signals acquired
devices.
by the sensors in the sock can be accessed through smartphones and wireless devices.
Biosensors 2023, 13, 236 12 of 21

With the addition of biofuel cells, some devices can easily be self-powered. Yin’s
team [80] demonstrated a biofuel cell bracelet that can derive energy from lactic acid in
human sweat (Figure 5d). The bracelet uses a hydrophilic fabric to store sweat. By connect-
ing six biofuel cells in series to supply energy, the maximum power output increases from
74 µW for a single BFC to 681 µW for six BFCs, which can drive an electronic watch. This
exemplifies the potential of biofuel cells to power wearable electronics. A contact lactate
biofuel cell was proposed by Lu et al. (Figure 5e) [81]. Lactate-based biofuel cells (BFCs)
rely on the high lactate concentration in human sweat, and epidermal BFCs can easily
generate energy by using a lactate oxidase (LOX) bioanode and performing an oxygen
reduction reaction (ORR) at the cathode. This biofuel cell can perform energy harvesting
even during nighttime sleep without any active movement, and it can be integrated with
a piezoelectric generator for further energy harvesting. The energy-harvesting system
can be powered quickly to enable the self-powered sensing of sensors. Rogers et al. pre-
sented a miniaturized, flexible, battery-free microfluidic electronic system for skin surfaces
(Figure 5c) [82]. By combining biofuel cells, colorimetric analysis, NFC electronics, and
microfluidics, lactate, glucose, chloride, pH, and the sweat rate/sweat volume can be de-
tected simultaneously. The biofuel cell allows the target analyte to spontaneously generate
an electrical signal at the appropriate concentration. The NFC in the assembly allows the
portable device to read the electrical signal generated by the biofuel cell. Unlike using a
biofuel cell to store energy in the device battery, this is a new idea that can be self-powered.
A biofuel cell patch can be softly fitted to the human skin surface. Sun et al. pre-
sented the first example of a flexible wearable epidermal microfluidic human exogenous
ethanol/oxygen BFC (Figure 5b) [83]. This biofuel cell can be used in a real-time in situ
manner and, through skin abrasion, can sample from the sweat of the drinker and collect
continuous power. This epidermal ethanol biofuel cell extends energy acquisition from
endogenous to exogenous substances. Chen et al. proposed a stretchable, wearable enzy-
matic biofuel cell that can harvest energy from sweat (Figure 5f) [84]. The biofuel cell patch
has soft and stretchable properties and is attached to the surface of the human body where
it is prone to sweat. When the body sweats during exercise, the patch is activated; the lactic
acid in sweat is absorbed into the hydrogel electrolyte and permeates the electrodes, and
the anode and cathode generate a voltage and current and power the electronic device.
In in vitro experiments, the assembled BFCs have a high OCV of 0.74 V and a maximum
power density of 520 µW cm−2 . When applied to a volunteer’s arm, the BFC can generate a
maximum power of 450 µW. When connected to a booster, the BFC on the body is capable
of powering a light-emitting diode in both pulsed discharge and continuous discharge
modes during exercise. However, BFC devices still rely on exercise to produce sweat, which
limits their use for non-exercise purposes. The lactate (fuel) sweat concentration and the
resulting power may depend on the particular individual and their activity.
Biofuel cells can collect energy from the body surface in addition to converting glucose
into electricity in the body. Yin’s team [85] developed an enzyme-mediated needle-shaped
biofuel cell that can collect glucose from fruits and mice and convert it directly into elec-
tricity (Figure 5h). It can collect 8.5 w from the peritoneal cavity and 16.3 w from the heart
in mice. To increase the power from the collected energy and the lifetime of the BFC, the
anode needle was coated with an MPC polymer, and the cathode chamber was sealed with
waterproof tape. It has the potential to realize energy harvesting from body fluids in the
human body to supply energy to wearable devices.
 Biosensors 2023, 12, x FOR PEER REVIEW
Biosensors 2023, 13, 236 13 of 21 13 of

Figure 5. Application
Figurescenarios for biofuel
5. Application cells.for
scenarios (a)biofuel
A fabric-based
cells. (a) Aflexible cell that
fabric-based reliescell
flexible on that
sweat relies on sw
to generate
to generate electricity electricity [78].
[78]. Copyright 2020,Copyright
Elsevier. 2020,
(b) AnElsevier.
epidermal (b) An epidermal
biofuel biofuel
cell that cell that monit
monitors
sweat and derives sweat and from
energy derives energy
it [83]. from it [83].
Copyright Copyright
2021, 2021,
Elsevier. (c)Elsevier.
Image of (c) microfluidic
Image of microfluidic
patch patch w
embedded sensors and a lactate sensor [82]. Copyright 2019, Science. (d) A bracelet with six biof
with embedded sensors and a lactate sensor [82]. Copyright 2019, Science. (d) A bracelet with six
cells in series that derives energy from lactic acid in sweat [80]. Copyright 2021, Elsevier. (e) A c
biofuel cells in series that derives
tact biofuel energy
cell that from
collects lactic
energy acidlactic
from in sweat
acid in[80]. Copyright
sweat 2021, Elsevier.
[81]. Copyright 2021, Elsevier. (f
(e) A contact biofuel cell thatsoft
stretchable, collects energy
biofuel from
cell that canlactic acid in to
be attached sweat
human[81]. Copyright
skin to convert2021,
lacticElsevier.
acid from sweat i
(f) A stretchable, energy
soft biofuel cell that 2019,
[84]. Copyright can be attached
Wiley OnlinetoLibrary.
human(g) skin to convert
A biofuel lactic
cell that can acid from onto stret
be printed
sweat into energyable,
[84].soft fabric with
Copyright suitable
2019, Wiley fitting
Onlinecharacteristics
Library. (g) Atobiofuel
harvestcell
energy from
that can besweat
printed[79]. Copyri
onto stretchable, 2016, Royal with
soft fabric Society of Chemistry.
suitable (h) A needle-shaped
fitting characteristics biofuelenergy
to harvest cell thatfrom
converts
sweat glucose
[79]. in mice i
electricity [85]. Copyright 2020, Elsevier.
Copyright 2016, Royal Society of Chemistry. (h) A needle-shaped biofuel cell that converts glucose in
mice into electricity [85].2.Copyright
Table Summary of 2020, Elsevier. of different types of self-powered biosensors.
the parameters

Energy Table 2. Summary of the parameters of different types of self-powered biosensors.

Energy
Har- Materials Structures Output Size Re
Energy
Sources
vester Materials Structures Output Size Energy Sources Ref.
Harvester
Filler-elastomer- External defor-
PZT Filler-elastomer- 20 V 5 cm × 4 cm
External [61
PENG PZT based 20 V 5 cm × 4 cm mations
[61]
based deformations
PENG PZT-SEBS Composite elastomer 100 V 3 cm × 3 cm Stretching [62
PZT-SEBS Composite elastomer 100 V 3 cm × 3 cm Stretching [62]
Silicone rubber/Al Contact-separation 1.7 V 5 mm × 10 mm Finger flexion [69
TENG
Silicone rubber/Al Contact-separation 1.7 V 5 mm × 10 mm Finger flexion [69]
TENG PANI/PCL Contact-separation 1000 V 8 cm × 4 cm friction [70
PANI/PCL Contact-separation 1000 V 8 cm × 4 cm friction [70]
PyNG PVDF/Al Three layers 42V 3.5 cm× 3.5 cm Respiration [75
PyNG PVDF/Al Three layers 42V 3.5 cm× 3.5 cm Respiration [75]
Ambient ther-
TENG Ambient thermal mal and me-
TENG and PyNG and
Cu/FEP/PVDF Cu/FEP/PVDF Contact-separation
Contact-separation 20 V (18 m/s) 20cm
11.5 × 5 m/s)
V (18 cm and11.5 cm × 5 cm
mechanical [76] [76
energies (wind) chanical ener-
PyNG
Glucose/carbon 10 mm × 10 gies (wind)
Textile-based 1.08 V Sweat [78]
fabrics mm (one stack) 10 mm × 10
Glucose/carbon fabrics Textile-based 1.08 V Sweat [78
Biofuel
CNT stretchable ink Textile-based 0.46 V \ mm (one stack)
Sweat [79]

Biofuel
cell
LOD-based CNT
anodicstretchable ink Textile-based 0.46 V \ Sweat [79
fiber
LOD-based anodic fiber 20 V
Textile-based(6 in 20 V2(6
cell Textile-based cmin
2 series) 2 cm
Sweat 2
[80]Sweat [80
BOD-based cathodic series)
fiber
BFC-integrated
Carbon nanotube 0.55 V 1 cm2 Sweat [81]
touch-based
Biosensors 2023, 13, 236 14 of 21

Table 2. Cont.

Energy
Materials Structures Output Size Energy Sources Ref.
Harvester
CNT Island–bridge 1.1 mA \ Sweat [82]
Microfluidic module 1.01µWcm−2
PI/PET \ Sweat [83]
and BFC module (45.23 min)
Lactate oxidase
Island–bridge 0.74 V 0.18 cm2 Sweat [84]
and bilirubin oxidase
Enzyme/mediator/ Osmium-based poly- 0.5 V (murine
carbon nanotube mer/CNT/glucose abdominal
\ Glucose [85]
(CNT) composite oxidase/Os-based cavity and
fibers polymer/CNT. heart tissue)

5. Biosensor Application Demonstration

The daily physiological status of a person can reflect the health status of an individual.
Therefore, it is necessary to record these data, which can be used as a basis for analysis and
reference. Biosensors can easily measure the physiological data of the human body. Many
everyday wearable devices have been designed and developed and put on the market,
such as smart bracelets and watches, and usually, watches and bracelets have the function
of measuring the heart rate and steps. In addition to these products, biosensors can also be
used in different applications for monitoring human physiological information.
Sensors can be combined with pillows and footwear to be perfectly integrated into
daily living. Wang et al. proposed a smart pillow based on a flexible nanogenerator for
monitoring human sleep behavior (Figure 6a) [86]. This flexible and breathable nanogener-
ator (FB-TENG) is assembled by relying on porous polydimethylsilane (PDMS). The smart
pillow is an 8 × 8 self-powered pressure-sensing array laid on a common pillow to achieve
real-time monitoring of the static head position and head movement trajectory during
sleep, which allows people to fall asleep in a natural way compared to traditional devices
for monitoring sleep, such as eye masks and belts. In addition, the smart pillow can also act
as a self-powered alarm to serve an anti-fall warning function. The smart pillow can also
be expanded in the future to monitor diseases, such as brain diseases and cervical spine
diseases. Li Zhou’s group proposed an insole hybrid nanogenerator (IHN) based on the
design of a combination of a multilayer friction nanogenerator and an arch piezoelectric
nanogenerator (Figure 6b) [87]. It not only converts the mechanical energy of the foot into
electrical energy but also distinguishes three motion states: walking, striding, and jumping.
Human motion enables a maximum open-circuit voltage of 150 V and a short-circuit current
of 4.5 µA. After 8 min of walking, the IHN can charge a 100 µF capacitor to 2.5 V. The
energy captured by the IHN is stored in a large capacitor, and when the energy stored in
the capacitor reaches a preset high threshold, the capacitor then replaces the battery to
provide power. When the energy falls below a preset low threshold, it is powered by the
battery again. A self-powered dorsalis pedis artery monitoring system (SAMS) was then
also designed to monitor the dorsalis pedis artery pulse signal in real time. This integrated
design, which integrates energy collection, storage, and utilization, has important potential
in disease monitoring and exercise monitoring and guidance. The above two examples
incorporate sensor devices into pillows and insoles to monitor physical signals (posture) of
the human body.
In addition to this, everyday wearable products are also a trend of sensor combination,
such as electronic patches and bracelets. Sweat is an important source of biochemical indi-
cators. A flexible self-powered sweat sensor was proposed by Chang et al. (Figure 6c) [88].
It detects Na, K, and pH values in sweat and transmits them to the user interface via a
built-in Bluetooth module. Biomechanical energy from the human body is collected by
the PENG and supplies energy to the device. The device has some drawbacks and still
needs improvement: it is not miniaturized or integrated enough in practical applications,
which will affect movement to some extent; it needs a PENG to collect energy and then
Biosensors 2023, 13, 236 15 of 21

manage and store it before powering the sensors and circuits, and there is a lag in collecting
information. In contrast, blood pressure can be monitored in real time by sensors. Tan
et al. designed an AI-enhanced blood-pressure-monitoring bracelet/blood pressure predict
wristband (BPPW) based on nanogenerator sensing (Figure 6d) [89]. Based on the PENG,
the authors designed a mechanical sensor with excellent performance and chose a colum-
nar array microstructure to effectively improve the output performance of the sensor. Its
highlight is that after the sensor acquires the pulse wave signal from the wearer, it can be
used to predict the wearer’s blood pressure by comparing it with an established artificial
intelligence model. The authors used the BPPW on a subject at risk of hypertension for
three consecutive days and modeled the prediction of the acquired pulse signal, showing
that the predicted values matched the actual situation. A Band-Aid can be applied to the
surface of the body, yet it has no sensing function. Sun et al. developed an electronic smart
Band-Aid by simply coating a conventional Band-Aid with a network of silver nanowires
and a polytetrafluoroethylene/polydimethylsiloxane mixture (Figure 6e) [90]. This smart
Band-Aid has excellent frictional electrical properties (VOC = 380 V, ISC = 23 µA, power
density = 1.13 Wm−2 ) and strain-sensing properties. It can be used not only for wound pro-
tection but also for the self-powered sensing of motion and human–computer interaction.
This is a good way to serve the sensing function with a traditional Band-Aid.
For the monitoring of some human signals (e.g., respiration), wearable devices can
be used or implantable devices can be chosen. Yu et al. prepared a frictional electric
nanogenerator (TENG)-driven self-powered humidity sensor for human respiration moni-
toring (Figure 6f) [91]. Its highlight is the harvesting of human motion energy (respiration)
to power the sensor, which allows real-time respiration monitoring without an external
power source. While monitoring humidity, the TENG-RGTO humidity sensor recognizes
the state of breathing at different frequencies and intensities in real time. Inspired by
nature, bionic sensor systems are leading the development of a new generation of sensor
technologies with remarkable features, such as ultra-sensitivity, low power consumption,
and self-adaptation [92]. With the help of bionic sensor systems, human signals can be
quantified, and machines can be endowed with specific perceptions. Zou et al. proposed
a stretchable, multichannel respiratory sensor inspired by the shark gill cleft structure
(Figure 6g) [93]. The bionic shark gill (BSG) multichannel nanogenerator can be divided
into two layers according to its function: the upper layer is the main functional layer,
consisting of several parallel strips of power-gen, and also avoids interference from other
factors, which can more accurately identify physiological parameters such as the respi-
ratory rate and respiratory intensity. Respiratory status can reflect the characteristics of
certain diseases, which is important for remote-assisted medical diagnosis. By placing
the BSG-RS at the waist, the BSG-RS is gradually stretched as the respiratory depth in-
creases and more power-generating units are powered, and the respiratory depth can
be estimated synthetically from the respiratory waveform recorded by the multichannel
generator. Compared with the traditional single-channel sensor, the multiple channels of
BSG-RS can better reflect the changing trend of the respiratory rate recorded by different
channels over a period of time. There is also an example of using a wearable sensor to
monitor breathing. Ning et al. proposed a Helical Fiber Strain Sensor (HFSS). The HFSS
has a helical structure and is wearable (Figure 6h) [94]. Due to its unique helical structure,
the HFSS can sense the contraction and relaxation of the thorax and abdomen caused by
the heartbeat and respiration and generate electrical signals, even for small stretches of less
than 1%. By calculating and processing these electrical signals, the human respiratory rate,
exertional lung volume (FVC), exertional expiratory volume in one second (FEV1), and
peak expiratory flow rate (PEF) can be obtained. Ning et al. also developed a respiratory
monitoring system based on the HFSS, including smart spirometry and smart respiratory
alert. Smart lung metering can analyze whether the user has a respiratory disease based
on breathing; the smart respiratory alert can automatically call a preset cell phone for
help when the user stops breathing for more than 6 s. The above are typical examples of
three devices with respiration as an example. In terms of sensing, body deformation due
 Biosensors 2023, 12, x FOR PEER REVIEW 16 of

monitoring system based on the HFSS, including smart spirometry and smart respirato
alert. Smart lung metering can analyze whether the user has a respiratory disease bas
Biosensors 2023, 13, 236 16 of 21
on breathing; the smart respiratory alert can automatically call a preset cell phone for he
when the user stops breathing for more than 6 s. The above are typical examples of thr
devices with respiration as an example. In terms of sensing, body deformation due to re
to respiratory movement can be monitored
piratory movement directlydirectly
can be monitored from the exhaled
from airflow,
the exhaled as well
airflow, as as
well as exte
nally.isThe
externally. The same same
true is true for
for energy energy harvesting.
harvesting.

Figure 6. PracticalFigure 6. Practical

applications applications
of biosensors forofhuman
biosensors for human
condition condition(a)
monitoring. monitoring. (a) A nanogenera
A nanogenerator
pillow for monitoring human sleep state [86]. Copyright 2022, American Chemical Society. (b)
pillow for monitoring human sleep state [86]. Copyright 2022, American Chemical Society. (b) A
nanogenerator-based smart insole for gait monitoring and fall warning [87]. Copyright 2022, Wi
nanogenerator-based smart insole for gait monitoring and fall warning [87]. Copyright 2022, Wiley
Online Library. (c) A flexible self-powered sweat sensor that detects Na, K, and pH in sweat [8
Online Library. (c)Copyright
A flexible self-powered
2022, Elsevier. (d)sweat sensor that detects
A nanogenerator-based Na, K, and pH in sweatbracelet
blood-pressure-monitoring [88]. for mo
Copyright 2022, Elsevier.
toring the(d)pulse
A nanogenerator-based blood-pressure-monitoring
wave signal of the wearer [89]. Copyright 2022, MDPI.bracelet
(e) Aforself-powered
mon- sm
Band-Aid
itoring the pulse wave forof
signal motion and human–computer
the wearer [89]. Copyrightinteraction
2022, MDPI. [90].(e)
Copyright 2023, Elsevier.
A self-powered smart (f) A brea
Band-Aid for motioning and
alarm device that harvests
human–computer human motion
interaction energy for
[90]. Copyright power
2023, sensors(f)[91].
Elsevier. Copyright 2022, El
A breathing
vier. (g) A multi-pathway respiratory sensor inspired by the gill slit structure of sharks for respi
alarm device that harvests human motion energy for power sensors [91]. Copyright 2022, Elsevier.
tory monitoring [93]. Copyright 2022, Elsevier. (h) A stretchable stress sensor based on the heli
(g) A multi-pathway respiratory
structure of TENG sensor inspired by
for respiratory the gill slit
monitoring for structure of sharks for
in vivo implantation [94].respiratory
Copyright 2022, Am
monitoring [93]. Copyright
ican Chemical2022, Elsevier. (h) A stretchable stress sensor based on the helical struc-
Society.
ture of TENG for respiratory monitoring for in vivo implantation [94]. Copyright 2022, American
Chemical Society. 6. Conclusions
Biosensor devices have rapidly developed in recent years and have advanced or e
6. Conclusions panded in terms of their energy supply, performance, and application scenarios [95,9
The biggest
Biosensor devices havelimitation in the development
rapidly developed in recentofyears
biosensor
and devices is the energy
have advanced supply pro
or ex-
panded in terms of their energy supply, performance, and application scenarios [95,96]. The proper
lem: without a continuous and stable energy supply, these devices cannot work
With their gradual development, energy supply technologies such as nanogenerators an
biggest limitation in the development of biosensor devices is the energy supply problem:
biofuel cells have shown great promise in the energy supply of biosensor devices, provi
without a continuous and stable energy supply, these devices cannot work properly. With
ing a possible future solution for the energy supply of biosensor devices [97]. With t
their gradual development, energy supply technologies such as nanogenerators and biofuel
upgrading of materials and the improvement of structures, biosensor devices are also d
cells have shown great promise in the energy supply of biosensor devices, providing a
veloping from their original huge sizes in favor of miniaturization and low weight.
possible future solution for the energy supply of biosensor devices [97]. With the upgrading
order to meet comfort requirements for long-term contact with the human body, biosens
of materials anddevices
the improvement of structures,
are flexible [98] so that theybiosensor devicestoare
fit more closely thealso
skindeveloping
or organs; to meet t
from their original huge sizes in favor of miniaturization and low weight.
stability requirements of the device for long-term use, biosensor devicesIn orderare
toself-heali
meet comfort requirements for long-term contact with the human body, biosensor devices
are flexible [98] so that they fit more closely to the skin or organs; to meet the stability
requirements of the device for long-term use, biosensor devices are self-healing and have
the ability to recover to their previous state in both form and function; to reduce the impact
on the human and natural environments, biosensor devices are highly biocompatible [99]
and biodegradable, which means they can be naturally degraded in the human body or in
the natural environment. With the development of various classes of biosensor devices,
biosensor devices for the acquisition of different signals have been developed, which means
Biosensors 2023, 13, 236 17 of 21

that more and more parameters can be recognized by biosensor devices; on the other hand,
the accuracy of signal recognition is becoming higher and higher [100], which guarantees
more accurate health monitoring and early warnings for the human body. Some biosensor
devices made according to human daily life show their future application direction, and it
is easy to see that biosensor devices already have the ability to integrate into daily life and
perform health monitoring.

7. Challenges and Prospects

The advantages and challenges of current biosensors coexist in three main areas:
long-term biocompatibility, energy supply, and integration.
For the long-term biocompatibility of biosensors, biosensor devices can be made from
flexible materials, making them substantially more comfortable to wear; in addition, the
use of some materials makes them self-healing, degradable, and highly biocompatible.
There are many receptors that sense internal or external changes on the surface of the
body and inside the tissues, and larger implants can be rejected by the body. In order to
improve biocompatibility, many researchers have been conducting research for many years
to reduce rejection by the body by using biocompatible materials and miniaturizing the
device. Future applications to the human body also need to pay more attention to the safety
of implantable electronic devices and the stability of devices operating in the body fluid
environment.
In terms of energy supply, self-powered devices are already possible with the support
of nanogenerators and biofuel cells. However, nanogenerators convert mechanical energy
at low frequencies into electrical energy, and the energy-harvesting efficiency of nanogen-
erators is still at a low level compared to wireless transmission and other methods due
to the low frequency of mechanical movements of the human body (e.g., heartbeat and
breathing). Moreover, the impedance of the nanogenerator is not consistent with that of the
energy storage capacitor, so the energy storage efficiency is not high during the charging
process. Improving the efficiency of energy harvesting and the storage of implantable
nanogenerators using structural design, material optimization, and engineering techniques
is one of the next directions to be studied. Although biofuel cells can also be used for the
device’s energy supply, the loading capacity and electron transfer rate of the enzyme are
key factors affecting the battery output. Researchers usually improve the structural design
and material synthesis to improve the performance of the battery, but it is still more difficult
to address the characteristics of low output power and short service life.
Integration is mainly divided into functional integration and integration with daily
necessities. In terms of functional integration, biosensors can integrate different types of
sensors together, and single devices can achieve multifunctional sensing. The biosensor can
also integrate with the data transmission and processing system and analyze the signals
collected to achieve the monitoring, analysis, and processing of human physiological
signals and thus provide health warnings. In terms of integration with daily necessities,
many of the mentioned works have integrated sensors into masks, belts, pillows, watches,
and other items. The combination of a biosensor with daily items can make the sensor
more suitable for everyday life and lead to inductive and natural sensors. In the era of the
interconnection of all things, biosensors can act as Internet of Things nodes and improve
the Internet of Things in healthcare.

Author Contributions: Writing—Original Draft, Z.X.; Writing—Review & Editing, L.W., J.Y. and
Z.X.; Resources, L.W. and J.Y.; Conceptualization, Project Administration, Funding Acquisition
and Supervision, G.X. and Y.W. All authors have read and agreed to the published version of
the manuscript.
Funding: This work was supported by National Key R&D Program of China (2022YFE0111700), Na-
tional Natural Science Foundation of China (82071970 and 82272123) and the Science and Technology
Project of Jianghan University (Grant No. 2022XKZX008).
Institutional Review Board Statement: Not applicable.
Biosensors 2023, 13, 236 18 of 21

Informed Consent Statement: Not applicable.

Data Availability Statement: Not applicable.
Conflicts of Interest: The authors declare no conflict of interest.

References
1. Zhao, L.M.; Li, H.; Meng, J.P.; Li, Z. The recent advances in self-powered medical information sensors. InfoMat 2020, 2, 212–234.
[CrossRef]
2. Liu, Z.; Li, H.; Shi, B.J.; Fan, Y.B.; Wang, Z.L.; Li, Z. Wearable and Implantable Triboelectric Nanogenerators. Adv. Funct. Mater.
2019, 29, 19. [CrossRef]
3. Koydemir, H.C.; Ozcan, A. Wearable and Implantable Sensors for Biomedical Applications. In Annual Review of Analytical
Chemistry; Bohn, P.W., Pemberton, J.E., Eds.; Annual Reviews: Palo Alto, CA, USA, 2018; Volume 11, pp. 127–146.
4. Dai, J.Y.; Li, L.L.; Shi, B.J.; Li, Z. Recent progress of self-powered respiration monitoring systems. Biosens. Bioelectron. 2021, 194, 17.
[CrossRef] [PubMed]
5. Zheng, Q.; Tang, Q.Z.; Wang, Z.L.; Li, Z. Self-powered cardiovascular electronic devices and systems. Nat. Rev. Cardiol. 2021, 18,
7–21. [CrossRef] [PubMed]
6. Wang, Z. Hydrogel-based composites: Unlimited platforms for biosensors and diagnostics. View 2021, 2, 20200165. [CrossRef]
7. Zhao, C.C.; Feng, H.Q.; Zhang, L.J.; Li, Z.; Zou, Y.; Tan, P.C.; Ouyang, H.; Jiang, D.J.; Yu, M.; Wang, C.; et al. Highly Efficient In
Vivo Cancer Therapy by an Implantable Magnet Triboelectric Nanogenerator. Adv. Funct. Mater. 2019, 29, 11. [CrossRef]
8. Hong, Y.; Cheng, X.L.; Liu, G.J.; Hong, D.S.; He, S.S.; Wang, B.J.; Sun, X.M.; Peng, H.S. One-step Production of Continuous
Supercapacitor Fibers for a Flexible Power Textile. Chin. J. Polym. Sci. 2019, 37, 737–743. [CrossRef]
9. Qu, X.C.; Liu, Y.; Liu, Z.; Li, Z. Assistive devices for the people with disabilities enabled by triboelectric nanogenerators. J. Phys.
Mater. 2021, 4, 17. [CrossRef]
10. Cha, S.; Kim, S.M.; Kim, H.; Ku, J.; Sohn, J.I.; Park, Y.J.; Song, B.G.; Jung, M.H.; Lee, E.K.; Choi, B.L.; et al. Porous PVDF As
Effective Sonic Wave Driven Nanogenerators. Nano Lett. 2011, 11, 5142–5147. [CrossRef]
11. Wang, Z.L.; Song, J.H. Piezoelectric nanogenerators based on zinc oxide nanowire arrays. Science 2006, 312, 242–246. [CrossRef]
12. Fan, F.R.; Tian, Z.Q.; Wang, Z.L. Flexible triboelectric generator! Nano Energy 2012, 1, 328–334. [CrossRef]
13. Haeberlin, A.; Zurbuchen, A.; Walpen, S.; Schaerer, J.; Niederhauser, T.; Huber, C.; Tanner, H.; Servatius, H.; Seiler, J.;
Haeberlin, H.; et al. The first batteryless, solar-powered cardiac pacemaker. Heart Rhythm. 2015, 12, 1317–1323. [CrossRef]
[PubMed]
14. Wang, Z.L. Towards Self-Powered Nanosystems: From Nanogenerators to Nanopiezotronics. Adv. Funct. Mater. 2008, 18,
3553–3567. [CrossRef]
15. Wang, Z.L. Self-powered nanotech-Nanosize machines need still tinier power plants. Sci. Am. 2008, 298, 82. [CrossRef] [PubMed]
16. Bandodkar, A.J.; Wang, J. Wearable Biofuel Cells: A Review. Electroanalysis 2016, 28, 1188–1200. [CrossRef]
17. Jinno, H.; Fukuda, K.; Xu, X.M.; Park, S.; Suzuki, Y.; Koizumi, M.; Yokota, T.; Osaka, I.; Takimiya, K.; Someya, T. Stretchable and
waterproof elastomer-coated organic photovoltaics for washable electronic textile applications. Nat. Energy 2017, 2, 6. [CrossRef]
18. Seol, M.L.; Jeon, S.B.; Han, J.W.; Choi, Y.K. Ferrofluid-based triboelectric-electromagnetic hybrid generator for sensitive and
sustainable vibration energy harvesting. Nano Energy 2017, 31, 233–238. [CrossRef]
19. Imani, S.; Bandodkar, A.J.; Mohan, A.M.V.; Kumar, R.; Yu, S.F.; Wang, J.; Mercier, P.P. A wearable chemical-electrophysiological
hybrid biosensing system for real-time health and fitness monitoring. Nat. Commun. 2016, 7, 7. [CrossRef]
20. Kumari, P.; Mathew, L.; Syal, P. Increasing trend of wearables and multimodal interface for human activity monitoring: A review.
Biosens. Bioelectron. 2017, 90, 298–307. [CrossRef]
21. Heikenfeld, J.; Jajack, A.; Rogers, J.; Gutruf, P.; Tian, L.; Pan, T.; Li, R.; Khine, M.; Kim, J.; Wang, J.; et al. Wearable sensors:
Modalities, challenges, and prospects. Lab Chip 2018, 18, 217–248. [CrossRef]
22. Park, J.; Kim, M.; Lee, Y.; Lee, H.S.; Ko, H. Fingertip skin-inspired microstructured ferroelectric skins discriminate static/dynamic
pressure and temperature stimuli. Sci. Adv. 2015, 1, 13. [CrossRef] [PubMed]
23. Yao, S.S.; Swetha, P.; Zhu, Y. Nanomaterial-Enabled Wearable Sensors for Healthcare. Adv. Healthc. Mater. 2018, 7, 27. [CrossRef]
[PubMed]
24. Ge, G.; Cai, Y.C.; Dong, Q.C.; Zhang, Y.Z.; Shao, J.J.; Huang, W.; Dong, X.C. A flexible pressure sensor based on rGO/polyaniline
wrapped sponge with tunable sensitivity for human motion detection. Nanoscale 2018, 10, 10033–10040. [CrossRef] [PubMed]
25. Boland, C.S.; Khan, U.; Backes, C.; O’Neill, A.; Mccauley, J.; Duane, S.; Shanker, R.; Liu, Y.; Jurewicz, I.; Dalton, A.B.; et al.
Sensitive, High-Strain, High-Rate Bodily Motion Sensors Based on Graphene-Rubber Composites. ACS Nano 2014, 8, 8819–8830.
[CrossRef] [PubMed]
26. Ameri, S.K.; Ho, R.; Jang, H.W.; Tao, L.; Wang, Y.H.; Wang, L.; Schnyer, D.M.; Akinwande, D.; Lu, N.S. Graphene Electronic Tattoo
Sensors. ACS Nano 2017, 11, 7634–7641. [CrossRef] [PubMed]
27. Liu, N.H.; Chiang, C.Y.; Chu, H.C. Recognizing the Degree of Human Attention Using EEG Signals from Mobile Sensors. Sensors
2013, 13, 10273–10286. [CrossRef]
28. Campana, A.; Cramer, T.; Simon, D.T.; Berggren, M.; Biscarini, F. Electrocardiographic Recording with Conformable Organic
Electrochemical Transistor Fabricated on Resorbable Bioscaffold. Adv. Mater. 2014, 26, 3874–3878. [CrossRef]
Biosensors 2023, 13, 236 19 of 21

29. Xiong, P.W.; Wu, C.C.; Zhou, H.M.; Song, A.G.; Hu, L.Y.; Liu, X.P.P. Design of an accurate end-of-arm force display system based
on wearable arm gesture sensors and EMG sensors. Inf. Fusion 2018, 39, 178–185. [CrossRef]
30. Mullen, T.R.; Kothe, C.a.E.; Chi, Y.M.; Ojeda, A.; Kerth, T.; Makeig, S.; Jung, T.P.; Cauwenberghs, G. Real-Time Neuroimaging and
Cognitive Monitoring Using Wearable Dry EEG. IEEE Trans. Biomed. Eng. 2015, 62, 2553–2567. [CrossRef]
31. Ouyang, H.; Tian, J.J.; Sun, G.L.; Zou, Y.; Liu, Z.; Li, H.; Zhao, L.M.; Shi, B.J.; Fan, Y.B.; Fan, Y.F.; et al. Self-Powered Pulse Sensor
for Antidiastole of Cardiovascular Disease. Adv. Mater. 2017, 29, 10. [CrossRef]
32. Taborri, J.; Keogh, J.; Kos, A.; Santuz, A.; Umek, A.; Urbanczyk, C.; van der Kruk, E.; Rossi, S. Sport Biomechanics Applications
Using Inertial, Force, and EMG Sensors: A Literature Overview. Appl. Bionics Biomech. 2020, 2020, 18. [CrossRef] [PubMed]
33. Luo, N.Q.; Dai, W.X.; Li, C.L.; Zhou, Z.Q.; Lu, L.Y.; Poon, C.C.Y.; Chen, S.C.; Zhang, Y.T.; Zhao, N. Flexible Piezoresistive Sensor
Patch Enabling Ultralow Power Cuffless Blood Pressure Measurement. Adv. Funct. Mater. 2016, 26, 1178–1187. [CrossRef]
34. Mair, P.; Kornberger, E.; Furtwaengler, W.; Balogh, D.; Antretter, H. Prognostic Markers in Patients with Severe Accidental
Hypothermia and Cardiocirculatory Arrest. Resuscitation 1994, 27, 47–54. [CrossRef] [PubMed]
35. Zhang, S.; Bick, M.; Xiao, X.; Chen, G.; Nashalian, A.; Chen, J. Leveraging triboelectric nanogenerators for bioengineering. Matter
2021, 4, 845–887. [CrossRef]
36. Guo, H.Y.; Lan, C.Y.; Zhou, Z.F.; Sun, P.H.; Wei, D.P.; Li, C. Transparent, flexible, and stretchable WS2 based humidity sensors for
electronic skin. Nanoscale 2017, 9, 6246–6253. [CrossRef]
37. Lin, W.Y.; Chen, C.H.; Lee, M.Y. Design and Implementation of a Wearable Accelerometer-Based Motion/Tilt Sensing Internet of
Things Module and Its Application to Bed Fall Prevention. Biosensors 2021, 11, 428. [CrossRef]
38. Ferrari, M.; Harrison, B.; Rawashdeh, O.; Hammond, R.; Avery, Y.; Rawashdeh, M.; Sa’deh, W.; Maddens, M. Clinical Feasibility
Trial of a Motion Detection System for Fall Prevention in Hospitalized Older Adult Patients. Geriatr. Nurs. 2012, 33, 177–183.
[CrossRef]
39. Miyamoto, A.; Lee, S.; Cooray, N.F.; Lee, S.; Mori, M.; Matsuhisa, N.; Jin, H.; Yoda, L.; Yokota, T.; Itoh, A.; et al. Inflammation-free,
gas-permeable, lightweight, stretchable on-skin electronics with nanomeshes. Nat. Nanotechnol. 2017, 12, 907. [CrossRef]
40. Msc, E.J.M.M. Wearable sweat sensing for prolonged, semicontinuous, and nonobtrusive health monitoring. View 2020,
1, 20200077.
41. Wang, L.; Pan, M.M.; Xu, L.; Yu, X.; Zheng, S.Y. Recent Advances of Emerging Microfluidic Chips for Exosome Mediated Cancer
Diagnosis. Smart Mater. Med. 2021, 2, 158–171. [CrossRef]
42. Liu, X.; Liu, J.J.V. Biosensors and sensors for dopamine detection. View 2021, 2, 20200102. [CrossRef]
43. Bandodkar, A.J.; Wang, J. Non-invasive wearable electrochemical sensors: A review. Trends Biotechnol. 2014, 32, 363–371.
[CrossRef] [PubMed]
44. Gao, W.; Emaminejad, S.; Nyein, H.Y.Y.; Challa, S.; Chen, K.V.; Peck, A.; Fahad, H.M.; Ota, H.; Shiraki, H.; Kiriya, D.; et al. Fully
integrated wearable sensor arrays for multiplexed in situ perspiration analysis. Nature 2016, 529, 509. [CrossRef] [PubMed]
45. Wang, H.M.; Li, D.; Zhong, W.; Xu, L.; Jiang, T.; Wang, Z.L. Self-Powered Inhomogeneous Strain Sensor Enabled Joint Motion and
Three-Dimensional Muscle Sensing. ACS Appl. Mater. Interfaces 2019, 11, 34251–34257. [CrossRef]
46. Shi, Y.P.; Wei, X.L.; Wang, K.M.; He, D.D.; Yuan, Z.H.; Xu, J.H.; Wu, Z.Y.; Wang, Z.L. Integrated All-Fiber Electronic Skin toward
Self-Powered Sensing Sports Systems. ACS Appl. Mater. Interfaces 2021, 13, 50329–50337. [CrossRef]
47. Tan, P.C.; Han, X.; Zou, Y.; Qu, X.C.; Xue, J.T.; Li, T.; Wang, Y.Q.; Luo, R.Z.; Cui, X.; Xi, Y.; et al. Self-Powered Gesture Recognition
Wristband Enabled by Machine Learning for Full Keyboard and Multicommand Input. Adv. Mater. 2022, 34, 10. [CrossRef]
48. Cheng, X.L.; Xue, X.; Ma, Y.; Han, M.D.; Zhang, W.; Xu, Z.Y.; Zhang, H.; Zhang, H.X. Implantable and self-powered blood
pressure monitoring based on a piezoelectric thinfilm: Simulated, in vitro and in vivo studies. Nano Energy 2016, 22, 453–460.
[CrossRef]
49. Liu, Z.; Ma, Y.; Ouyang, H.; Shi, B.J.; Li, N.; Jiang, D.J.; Xie, F.; Qu, D.; Zou, Y.; Huang, Y.; et al. Transcatheter Self-Powered
Ultrasensitive Endocardial Pressure Sensor. Adv. Funct. Mater. 2019, 29, 10. [CrossRef]
50. Sheng, F.F.; Zhang, B.; Zhang, Y.H.; Li, Y.Y.; Cheng, R.W.; Wei, C.H.; Ning, C.; Dong, K.; Wang, Z.L. Ultrastretchable
Organogel/Silicone Fiber-Helical Sensors for Self-Powered Implantable Ligament Strain Monitoring. ACS Nano 2022, 16,
10958–10967. [CrossRef]
51. Yi, F.; Wang, J.; Wang, X.F.; Niu, S.M.; Li, S.M.; Liao, Q.L.; Xu, Y.L.; You, Z.; Zhang, Y.; Wang, Z.L. Stretchable and Waterproof
Self-Charging Power System for Harvesting Energy from Diverse Deformation and Powering Wearable Electronics. ACS Nano
2016, 10, 6519–6525. [CrossRef]
52. Liu, Y.J.; Cao, W.T.; Ma, M.G.; Wan, P.B. Ultrasensitive Wearable Soft Strain Sensors of Conductive, Self-healing, and Elastic
Hydrogels with Synergistic “Soft and Hard” Hybrid Networks. ACS Appl. Mater. Interfaces 2017, 9, 25559–25570. [CrossRef]
[PubMed]
53. Han, X.; Jiang, D.J.; Qu, X.C.; Bai, Y.; Cao, Y.; Luo, R.Z.; Li, Z. A Stretchable, Self-Healable Triboelectric Nanogenerator as
Electronic Skin for Energy Harvesting and Tactile Sensing. Materials 2021, 14, 1689. [CrossRef]
54. Chen, Y.H.; Pu, X.; Liu, M.M.; Kuang, S.; Zhang, P.; Hua, Q.; Cong, Z.; Guo, W.; Hu, W.; Wang, Z.L. Shape-Adaptive, Self-
Healable Triboelectric Nanogenerator with Enhanced Performances by Soft Solid-Solid Contact Electrification. ACS Nano 2019,
13, 8936–8945. [CrossRef] [PubMed]
55. Zheng, Q.; Zou, Y.; Zhang, Y.L.; Kuang, S.Y.; Zhan, P.P.; Hua, Q.L.; Cong, Z.F.; Guo, W.B.; Hu, W.G.; Wang, Z.L. Biodegradable
triboelectric nanogenerator as a life-time designed implantable power source. Sci. Adv. 2016, 2, 9. [CrossRef] [PubMed]
Biosensors 2023, 13, 236 20 of 21

56. Wang, T.; Li, S.Y.; Tao, X.L.; Chen, Y.; Huang, F.J.; Li, H.X.; Chen, X.Y.; Bian, Z.F. Fully biodegradable water-soluble triboelectric
nanogenerator for human physiological monitoring. Nano Energy 2022, 93, 10. [CrossRef]
57. Yang, Z.; Lin, B.; Zhou, L.J. Recent progress in human body energy harvesting for smart bioelectronic system. Fundam. Res. 2021,
1, 364–382.
58. Gao, Y.; Wang, Z.L. Electrostatic potential in a bent piezoelectric nanowire. The fundamental theory of nanogenerator and
nanopiezotronics. Nano Lett. 2007, 7, 2499–2505. [CrossRef]
59. Rao, Y.; Qu, J.; Marinis, T.; Wong, C.P. A precise numerical prediction of effective dielectric constant for polymer-ceramic
composite based on effective-medium theory. IEEE Trans. Compon. Packag. Technol. 2000, 23, 680–683.
60. Li, Y.; Su, X.; Liang, K.; Luo, C.; Li, P.; Hu, J.; Li, G.; Jiang, H.; Wang, K.Y. Multi-layered BTO/PVDF nanogenerator with highly
enhanced performance induced by interlaminar electric field. Microelectron. Eng. 2021, 244, 111557. [CrossRef]
61. Chou, X.J.; Zhu, J.; Qian, S.; Niu, X.S.; Qian, J.C.; Hou, X.J.; Mu, J.L.; Geng, W.P.; Cho, J.D.; He, J.; et al. All-in-one filler-
elastomer-based high-performance stretchable piezoelectric nanogenerator for kinetic energy harvesting and self-powered motion
monitoring. Nano Energy 2018, 53, 550–558. [CrossRef]
62. Huang, X.M.; Qin, Q.H.; Wang, X.Q.; Xiang, H.J.; Zheng, J.L.; Lu, Y.; Lv, C.J.; Wu, K.L.; Yan, L.X.; Wang, N.; et al. Piezoelectric
Nanogenerator for Highly Sensitive and Synchronous Multi-Stimuli Sensing. ACS Nano 2021, 15, 19783–19792. [CrossRef]
[PubMed]
63. Wang, Z.L. Triboelectric Nanogenerators as New Energy Technology for Self-Powered Systems and as Active Mechanical and
Chemical Sensors. ACS Nano 2013, 7, 9533–9557. [CrossRef] [PubMed]
64. Wang, Z.L.; Chen, J.; Lin, L. Progress in triboelectric nanogenerators as a new energy technology and self-powered sensors.
Energy Environ. Sci. 2015, 8, 2250–2282. [CrossRef]
65. Chen, Y.; Li, D.; Xu, Y.; Ling, Z.; Nawaz, H.; Chen, S.; Xu, F. Surface-microstructured cellulose films toward sensitive pressure
sensors and efficient triboelectric nanogenerator. Int. J. Biol. Macromol. 2022, 208, 324–332. [CrossRef] [PubMed]
66. Xie, X.; Chen, Y.; Jiang, J.; Jiang, J.; Li, J.; Yang, Y.; Liu, Y.; Yang, L.; Tu, X.; Sun, X.; et al. Self-Powered Gyroscope Angle Sensor
Based on Resistive Matching Effect of Triboelectric Nanogenerator. Adv. Mater. Technol. 2021, 6, 2100797. [CrossRef]
67. Lu, X.; Li, H.; Zhang, X.; Gao, B.; Cheng, T. Magnetic-assisted self-powered acceleration sensor for real-time monitoring vehicle
operation and collision based on triboelectric nanogenerator. Nano Energy 2022, 96, 107094. [CrossRef]
68. Wu, Y.; Li, Y.; Zou, Y.; Rao, W.; Gai, Y.; Xue, J.; Wu, L.; Qu, X.; Liu, Y.; Xu, G. A multi-mode triboelectric nanogenerator for energy
harvesting and biomedical monitoring. Nano Energy 2022, 92, 106715. [CrossRef]
69. Liao, J.W.; Zou, Y.; Jiang, D.J.; Liu, Z.Z.; Qu, X.C.; Li, Z.; Liu, R.P.; Fan, Y.B.; Shi, B.J.; Li, Z.; et al. Nestable arched triboelectric
nanogenerator for large deflection biomechanical sensing and energy harvesting. Nano Energy 2020, 69, 9. [CrossRef]
70. Qiu, H.J.; Song, W.Z.; Wang, X.X.; Zhang, J.; Fan, Z.Y.; Yu, M.; Ramakrishna, S.; Long, Y.Z. A calibration-free self-powered sensor
for vital sign monitoring and finger tap communication based on wearable triboelectric nanogenerator. Nano Energy 2019, 58,
536–542. [CrossRef]
71. Yang, Y.; Guo, W.X.; Pradel, K.C.; Zhu, G.; Zhou, Y.S.; Zhang, Y.; Hu, Y.F.; Lin, L.; Wang, Z.L. Pyroelectric Nanogenerators for
Harvesting Thermoelectric Energy. Nano Lett. 2012, 12, 2833–2838. [CrossRef]
72. Lee, J.H.; Ryu, H.; Kim, T.Y.; Kwak, S.S.; Yoon, H.J.; Kim, T.H.; Seung, W.; Kim, S.W. Thermally Induced Strain-Coupled Highly
Stretchable and Sensitive Pyroelectric Nanogenerators. Adv. Energy Mater. 2015, 5, 6. [CrossRef]
73. Yang, Y.; Zhou, Y.; Wu, J.M.; Wang, Z.L. Single micro/nanowire pyroelectric nanogenerators as self-powered temperature sensors.
ACS Nano 2012, 6, 8456–8461. [CrossRef] [PubMed]
74. Wang, X.; Dai, Y.; Liu, R.; He, X.; Li, S.; Wang, Z.L. Light-triggered pyroelectric nanogenerator based on a pn-junction for
self-powered near-infrared photosensing. ACS Nano 2017, 11, 8339–8345. [CrossRef] [PubMed]
75. Xue, H.; Yang, Q.; Wang, D.Y.; Wang, D.Y.; Luo, W.J.; Wang, W.Q.; Lin, M.S.; Liang, D.L.; Luo, Q.M. A wearable pyroelectric
nanogenerator and self-powered breathing sensor. Nano Energy 2017, 38, 147–154. [CrossRef]
76. Zheng, H.W.; Zi, Y.L.; He, X.; Guo, H.Y.; Lai, Y.C.; Wang, J.; Zhang, S.L.; Wu, C.S.; Cheng, G.; Wang, Z.L. Concurrent Harvesting
of Ambient Energy by Hybrid Nanogenerators for Wearable Self-Powered Systems and Active Remote Sensing. Acs Appl. Mater.
Interfaces 2018, 10, 14708–14715. [CrossRef]
77. Singh, R.; Kaur, N.; Singh, M. Bio-compatible bio-fuel cells for medical devices. In Proceedings of the 11th International
Conference on Materials, Processing and Characterization (ICMPC), Indore, India, 15–17 December 2020; pp. 242–249.
78. Wang, C.; Shim, E.; Chang, H.K.; Lee, N.; Kim, H.R.; Park, J. Sustainable and high-power wearable glucose biofuel cell using
long-term and high-speed flow in sportswear fabrics. Biosens. Bioelectron. 2020, 169, 11. [CrossRef]
79. Jeerapan, I.; Sempionatto, J.R.; Pavinatto, A.; You, J.M.; Wang, J. Stretchable biofuel cells as wearable textile-based self-powered
sensors. J. Mater. Chem. A 2016, 4, 18342–18353. [CrossRef]
80. Yin, S.J.; Liu, X.H.; Kaji, T.; Nishina, Y.; Miyake, T. Fiber-crafted biofuel cell bracelet for wearable electronics. Biosens. Bioelectron.
2021, 179, 6. [CrossRef]
81. Yin, L.; Moon, J.M.; Sempionatto, J.R.; Lin, M.Y.; Cao, M.Z.; Trifonov, A.; Zhang, F.Y.; Lou, Z.Y.; Jeong, J.M.; Lee, S.J.; et al. A
passive perspiration biofuel cell: High energy return on investment. Joule 2021, 5, 1888–1904. [CrossRef]
82. Bandodkar, A.J.; Gutruf, P.; Choi, J.; Lee, K.; Sekine, Y.; Reeder, J.T.; Jeang, W.J.; Aranyosi, A.J.; Lee, S.P.; Model, J.B.; et al.
Battery-free, skin-interfaced microfluidic/electronic systems for simultaneous electrochemical, colorimetric, and volumetric
analysis of sweat. Sci. Adv. 2019, 5, eaav3294. [CrossRef]
Biosensors 2023, 13, 236 21 of 21

83. Sun, M.M.; Gu, Y.N.; Pei, X.Y.; Wang, J.J.; Liu, J.; Ma, C.B.; Bai, J.; Zhou, M. A flexible and wearable epidermal ethanol biofuel cell
for on-body and real-time bioenergy harvesting from human sweat. Nano Energy 2021, 86, 11. [CrossRef]
84. Chen, X.H.; Yin, L.; Lv, J.; Gross, A.J.; Le, M.; Gutierrez, N.G.; Li, Y.; Jeerapan, I.; Giroud, F.; Berezovska, A.; et al. Stretchable and
Flexible Buckypaper-Based Lactate Biofuel Cell for Wearable Electronics. Adv. Funct. Mater. 2019, 29, 8. [CrossRef]
85. Yin, S.J.; Liu, X.H.; Kobayashi, Y.; Nishina, Y.; Nakagawa, R.; Yanai, R.; Kimura, K.; Miyake, T. A needle-type biofuel cell using
enzyme/mediator/carbon nanotube composite fibers for wearable electronics. Biosens. Bioelectron. 2020, 165, 6. [CrossRef]
[PubMed]
86. Kou, H.Y.; Wang, H.M.; Cheng, R.W.; Liao, Y.J.; Shi, X.; Luo, J.J.; Li, D.; Wang, Z.L. Smart Pillow Based on Flexible and
Breathable Triboelectric Nanogenerator Arrays for Head Movement Monitoring during Sleep. Acs Appl. Mater. Interfaces 2022, 14,
23998–24007. [CrossRef]
87. Du, M.X.; Cao, Y.; Qu, X.C.; Xue, J.T.; Zhang, W.Y.; Pu, X.; Shi, B.J.; Li, Z. Hybrid Nanogenerator for Biomechanical Energy
Harvesting, Motion State Detection, and Pulse Sensing. Adv. Mater. Technol. 2022, 7, 8. [CrossRef]
88. Li, H.; Chang, T.R.; Gai, Y.S.; Liang, K.; Jiao, Y.L.; Li, D.F.; Jiang, X.R.; Wang, Y.; Huang, X.C.; Wu, H.; et al. Human joint enabled
flexible self-sustainable sweat sensors. Nano Energy 2022, 92, 12. [CrossRef]
89. Tan, P.C.; Xi, Y.; Chao, S.Y.; Jiang, D.J.; Liu, Z.; Fan, Y.B.; Li, Z. An Artificial Intelligence-Enhanced Blood Pressure Monitor
Wristband Based on Piezoelectric Nanogenerator. Biosensors 2022, 12, 234. [CrossRef]
90. Yu, S.G.; Zhang, H.Y.; Zhang, J.; Hu, Z.Y. High-sensitivity RGO-TiO2 humidity sensor driven by triboelectric nanogenerators for
non-contact monitoring of human respiration. J. Alloy. Compd. 2023, 935, 10. [CrossRef]
91. Sun, Q.Z.; Wang, L.; Ren, G.Z.; Zhang, L.R.; Sheng, H.X.; Zhu, Y.M.; Wang, H.C.; Lu, G.; Yu, H.D.; Huang, W. Smart band-aid:
Multifunctional and wearable electronic device for self-powered motion monitoring and human-machine interaction. Nano
Energy 2022, 92, 10. [CrossRef]
92. Xue, J.T.; Zou, Y.; Deng, Y.L.; Li, Z. Bioinspired sensor system for health care and human-machine interaction. EcoMat 2022, 4, 28.
[CrossRef]
93. Zou, Y.; Gai, Y.; Tan, P.; Jiang, D.; Qu, X.; Xue, J.; Ouyang, H.; Shi, B.; Li, L.; Luo, D. Stretchable graded multichannel self-powered
respiratory sensor inspired by shark gill. Fundam. Res. 2022, 2, 619–628. [CrossRef]
94. Ning, C.; Cheng, R.W.; Jiang, Y.; Sheng, F.F.; Yi, J.; Shen, S.; Zhang, Y.H.; Peng, X.; Dong, K.; Wang, Z.L. Helical Fiber Strain
Sensors Based on Triboelectric Nanogenerators for Self-Powered Human Respiratory Monitoring. Acs Nano 2022, 16, 2811–2821.
[CrossRef] [PubMed]
95. Amjadi, M.; Kyung, K.U.; Park, I.; Sitti, M. Stretchable, Skin-Mountable, and Wearable Strain Sensors and Their Potential
Applications: A Review. Adv. Funct. Mater. 2016, 26, 1678–1698. [CrossRef]
96. Kim, J.; Campbell, A.S.; De Avila, B.E.F.; Wang, J. Wearable biosensors for healthcare monitoring. Nat. Biotechnol. 2019, 37,
389–406. [CrossRef]
97. Li, Z.; Zheng, Q.; Wang, Z.L.; Li, Z. Nanogenerator-Based Self-Powered Sensors for Wearable and Implantable Electronics.
Research 2020, 2020, 25. [CrossRef]
98. Lim, H.R.; Kim, H.S.; Qazi, R.; Kwon, Y.T.; Jeong, J.W.; Yeo, W.H. Advanced Soft Materials, Sensor Integrations, and Applications
of Wearable Flexible Hybrid Electronics in Healthcare, Energy, and Environment. Adv. Mater. 2020, 32, 43. [CrossRef]
99. Zhang, S.; Liu, C.; Sun, X.; Huang, W.J. Current development of materials science and engineering towards epidermal sensors.
Prog. Mater. Sci. 2022, 128, 20. [CrossRef]
100. Liu, X.; Cai, Z.; Gao, N.; Ye, S.; He, Y. Controllable Preparation of (200) Facets Preferential Oriented Silver Nanowires for
Non-invasive Detection of Glucose in Human Sweat. Smart Mater. Med. 2021, 2, 150–157. [CrossRef]

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