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Chapter 7
Piezoelectric Materials for Medical Applications
Melodie Chen-Glasser, Panpan Li, Jeongjae Ryu and
Seungbum Hong
Additional information is available at the end of the chapter
This chapter describes the history and development strategy of piezoelectric materials for
medical applications. It covers the piezoelectric properties of materials found inside the
human body including blood vessels, skin, and bones as well as how the piezoelectricity
innate in those materials aids in disease treatment. It also covers piezoelectric materials
and their use in medical implants by explaining how piezoelectric materials can be used as
sensors and can emulate natural materials. Finally, the possibility of using piezoelectric
materials to design medical equipment and how current models can be improved by
further research is explored. This review is intended to provide greater understanding of
how important piezoelectricity is to the medical industry by describing the challenges and
opportunities regarding its future development.
Keywords: piezoelectric materials, biotechnology, biomedical applications and devices,
vital signs, sensors, cell regeneration
1. Introduction
Piezoelectricity is a quality of material asymmetry that leads to the conversion of electric
signals into physical deformation and conversely physical deformation into electric signal. An
applied pressure causes movement of the dipole moment within the material, and a flow of
charges if crystals are aligned [1]. This makes piezoelectricity useful for a variety of industry
purposes, particularly those related to vibrational generation and actuation. Commercialized
applications for piezoelectricity include timekeeping using quartz resonance, microphones,
radio antenna oscillators, speakers, hydrophones, and fuel injection [2, 3]. More experimental
technology includes energy harvesting and electronic sensing [2]. The most commonly used
ceramic piezoelectric material is lead zirconium titanate (PZT), because its physical properties
© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative
Commons Attribution License (, which permits unrestricted use,
distribution, and reproduction in any medium, provided the original work is properly cited.
can be tailored by composition, it has a high piezoelectric coefficient, and it is cheap to
manufacture [4]. The most common piezoelectric polymer, used for its large strain value, is
polyvinylidene fluoride (PVDF) and its copolymers, such as P(VDF-TrFE) [58]. A wide variety
of composites and nanostructure materials have also been developed and can be fabricated as
thin films, discs, or stacked sheets [2, 3, 913].
In the case of biomedical engineering, many conventional means of using piezoelectric devices
are not applicable because of the structure of biological systems. Issues such as size limitations,
biological compatibility, and flexibility have led to investigation into polymer, composite,
nanostructured, and lead-free piezoelectric materials. One way to develop biomedical devices
is to look at the piezoelectric structures inside the body and how they can be emulated to
develop piezoelectric medical technology. In the first section of this book, we discuss piezo-
electric materials present in the body. Then we describe how piezoelectric materials can be
used for diagnosing illnesses and providing medical treatment. Our purpose is to inform the
readers of challenges and different approaches applicable to developing a wide variety of
medical technology.
2. Biological piezoelectric materials
There are many reviews which cover subsections of biological piezoelectric materials; these
reviews explain topics such as piezoelectricity in bone [14] or biopolymers [15]. However, we
seek to present a broader overview of the topic and how it can be used to develop technology.
Much of the original work on discovering piezoelectricity in the body was done by Eiichi
Fukada [1518]. His work showed the presence of piezoelectricity in bone, aorta, muscles,
tendons, and intestines [1518]. Since that time, many further studies have contributed to the
overall knowledge of the bodys piezoelectric characteristics, their origins, and how they can
be applied in medical science.
The organic piezoelectric effects in the human body are attributed to the lack of symmetry in
most biological molecules, which may make piezoelectricity a fundamental biological prop-
erty [19]. In particular, proteins seem to drive the piezoelectric qualities of most organs. The
basic building blocks of proteins within the human body are amino acids. These make up
molecules such as collagen, keratin, and elastin which are highly prevalent in the organs
examined by Fukada and other researchers [1518]. Amino acids in pure form have their
own piezoelectric properties due to the presence of dipoles derived from the polar side
groups seen in Figure 1. It is the reorientation and change in dipole moments in biological
macromolecules under stress that gives them piezoelectric properties [20, 21]. At least 15
amino acids, mostly the Lform, exhibit piezoelectric properties; however, γ-glycine and
DL-alanine are the strongest amino acid piezoelectrics [22]. Most racemic, or DL mixtures of
amino acids do not show piezoelectric properties because their crystal forms are centrosym-
metric [23].
Piezoelectricity - Organic and Inorganic Materials and Applications126
Other biological piezoelectric materials include polymeric L-lactic acid, DNA, and the M13 bacte-
riophage [2527]. Like amino acids, the piezoelectricpropertiesoflacticacidcomefromthe
carbonoxygen double bond [25]. DNAs piezoelectric properties originate from internal rotation
of the dipoles created by phosphate groups; however, they were primarily observed at lower
water content, which makes the bonds holding the DNA helix together weaker [27]. This demon-
strates the importance of bonding, structure, and experimental conditions when determining
piezoelectric properties. The M13 bacteriophages piezoelectric effect is caused by extruding pro-
teins and it can be fabricated into thin films that exhibit strengths of 7.8 pm/V [26].
Like the bacteriophage, many organs contain macromolecules which give them piezoelectric
properties. Organs with piezoelectric properties can be viewed as amorphous organic material
containing structured fibers which give them their piezoelectric properties [19, 28]. Often these
fibrils will grow in a helix shape, preventing them from having centrosymmetric symmetry
[29]. The overall strength of the piezoelectric effect will depend on the ordering, quantity or
composition of these fibers. Bones and tendons have hexagonal symmetry and contain the
following piezoelectric constant d
in the form of Eq. (1) [30]. In this tensor, the isubscript
represents direction of electric field displacement and the jsubscript represents the mechan-
ical deformation associated with it [31].
dij ¼
000d14 d15 0
000d15 d14 0
d31 d32 d33 000
Molecular structure within the organ changes the organs overall piezoelectric nature. For
example, examination of the epidermis, horny layer, and dermis of the skin revealed that each
layer had its own piezoelectric coefficient, the highest being the horny layer. The dermis had a
less ordered collagen layer; the horny layer had parallel keratin filaments, and the epidermis α
helical keratin tonofibrils [28]. The structure of the keratin horny layer simplified its ability to
produce piezoelectric tensors, giving them the form of Eq. (2). The values of piezoelectric
coefficients varied based on temperature; however, the highest were seen in the horny layer,
on the order of 0.10.2 pC/N. The lack of consistency in these measurements is due to the
variety in how the molecules were ordered in each sample [28].
Figure 1. The general structure of amino acids. Reprinted and altered from Ref. [24].
Piezoelectric Materials for Medical Applications
dij ¼
000d14 00
000 0 d14 0
000 0 0 0
Similarly, piezoresponse force measurements (PFM) studies of collagen proved that collagen is
the main source of piezoelectricity in the bone and reveal different ordering of collagen fibers
results in different piezoresponses, as seen in Figure 2 [32]. In collagen, there are alternating
sections of overlap and gap regions. The collagen fibers are arranged in a staggered way that
result in the gap region having one less microfiber. In addition, the molecules in the gap region
have less uniform symmetry, and therefore that region does not have as high of a piezo-
response [32]. These two studies indicate the piezoelectric response is not merely dependent
on the molecular structure, but the structure of the entire organ. Table 1 gives a description of
organs with tested piezoelectric properties and their attributed molecule.
Despite many measurements, it is sometimes difficult for the scientific community to come to a
consensus on the exact nature and relevance of in situ piezoelectric characteristics. For exam-
ple, in the case of bone, two groups found contradicting results on the dependency of piezo-
electricity in terms of hydration [14, 37]. Some studies on the aorta indicate that it has
piezoelectric properties, though results were varied. Two studies, taken over forty years apart
showed different orders of magnitude for the studied properties [17, 38]. A lab attempting to
verify either of these studies found that there was no piezoelectric response from the aorta [39].
Figure 2. The images show (a) the topology of the collagen and (b) the piezoresponse force microscopy (PFM) image
where the collagen can be distinguished from the surrounding tissues and how the gap and overlap regions differ in
piezoelectric response. Reprinted from Minary-Jolandan and Yu [32] with permission from ACS Publications.
Piezoelectricity - Organic and Inorganic Materials and Applications128
Historically, piezoelectric potentials were thought to explain Wolffs Law, the fact that bone is
strong in areas that are subject to greater amounts of stress [40]. However, later research proved
streaming potentials, fluid and ions driven by mechanical loading, may have a greater impact in
determining bone properties [41]. However, Ahn et al. suggest that piezoelectricity could gener-
ate charges that affect the screening potential and the two work in conjunction to promote bone
development, a concept which requires experimental testing to verify [40]. Furthermore, the
generation of electric fields has been shown to increase bone healing during fracture [42, 43].
Despite the variety of results concerning piezoelectric qualities of the body, they do help in
understanding the bodys mechanics and how we can develop solutions for human problems.
Even if the exact purpose for piezoelectric properties in the body is not known, they still can be
used for developing biomedical solutions on both microscopic and macroscopic levels. For
example, knowing that amino acids and macromolecules composed of them have piezoelectric
properties has inspired the use of biomaterials for human sensors [44]. Using peptides to build
piezoelectric sensors eliminates the need for developing other biocompatible materials. For
example, the knowledge of previously mentioned virus, M13, led to the alignment of its phages
into nanopillars for enhanced piezoelectric properties [45]. The outer hair cell is another structure
that piezoelectric properties can be attributed to. Disruption of the cells electrical potential alters
its length; conversely, compression of the cell alters its membrane potential [46]. The motions of
the outer hair cell alter how the organ of Corti vibrates, and changes how the inner hairs receive
stimulation [36]. Recently, the development of a piezoelectric cochlear implant to mimic the
conversion of sound vibration into an electrical signal has been undertaken and will be covered
in a later section of this review [47]. Biological structures can serve as examples for the develop-
ment of piezoelectric structures and biocompatible piezoelectric materials.
In addition, the knowledge of piezoelectric properties can help in disease detection or injury
analysis. With the knowledge that piezoelectric tissue properties are determined by proteins,
diseases that affect the amount or distribution of these proteins can be detected by piezo-
electric sensors. One group proposed that the electromechanical coupling factor, controlled
by collagen, could aid in detecting breast cancer [35]. A similar idea was presented for the
Organ Piezoelectric molecule
Muscle Actin and myosin [18]
Hair Keratin [16]
Bone Collagen [32]
Tendon Collagen [33]
Lung tissue Elastin [34]
Skin (dermis) Collagen [28]
Skin (horny layer and epidermis) Keratin [28]
Breast tissue Collagen [35]
Outer hair cell Prestin [36]
Table 1. Tissues with piezoelectric properties and driving source of piezoelectricity.
Piezoelectric Materials for Medical Applications
detection of atherosclerosis in the aorta, however as mentioned in a prior paragraph the
validity of the aortas piezoelectric nature is still under debate [48]. In this paper, they
claimed the PFM amplitude increased as a function of advancing atherosclerosis and could
help with early detection of the disease.
Finally, once the effect of piezoelectricity on the body have been studied, piezoelectric mate-
rials can be used to promote disease healing. Though the exact reason for piezoelectric quali-
ties have not been fully discovered, studies into bone related injuries have revealed that
induced electrical fields can accelerate bone repair and promote the growth of neurons [49,
50]. Because of this, increasing the piezoelectric properties of a synthetic bone material has
potential to increase the speed of osteoconduction and subsequently bone repair [51]. Lead free
ceramics can be used in conjunction with synthetic bone; however, these materials have
problems with ion diffusion which can be controlled by embedding in a ceramic or polymer
matrix [50]. In terms of regenerating damaged bone or cartilage, a piezoelectric scaffold may
provide the necessary stimulation for cell regrowth, and diminish the need for other growth
factors [43]. Typically, scaffolds are made out of polymers, such as PVDF, and can also promote
the growth of neurons and wound healing [50].
3. Piezoelectric medical devices
Many biomedical piezoelectric applications exceed the aforementioned purposes of mimicking
or employing biological piezoelectric phenomena. In some cases, the choice of material
depends mostly on the strength of the piezoelectric effect and the cost of the material. PZT
(lead zirconium titanate) and quartz are common piezoelectric materials used in industry. PZT
is cheaper, has higher piezoelectric coupling coefficients, and can be manipulated by changing
the composition. Quartz, however, is more stable and has consistent properties over a broader
temperature range [4]. Developing implants or technology involving direct human contact has
more constraints. Ceramics, like quartz, barium titanate, and potassium sodium niobate, are
more biocompatible because they do not contain lead [50]. In addition, many biomedical
devices require higher flexibility than ceramics can provide, due to the dynamic nature of
human motion. Biocompatible polymers include most biological materials and PVDF copoly-
mers. So far, polymer applications of PVDF have included, but are not limited to, biomechan-
ical energy harvesting systems, sensors, and wound scaffolds [50, 52]. The piezoelectric
coefficient of the beta phase of PVDF is listed in Eq. (3) [53].
dij ¼
0000d15 0
000d24 00
d31 d32 d33 000
3.1. Piezoelectric sensors
Piezoelectric materials can be employed in monitoring many bodily signals because they convert
mechanical energy into an electrical signal. They are especially applicable to monitoring dynamic
pressure changes; many human vital signs consist of rhythmic activities like the heartbeat or
Piezoelectricity - Organic and Inorganic Materials and Applications130
breathing. Lower pressure systems from (1 Pa-10 kPa) include sound waves and tactile sensing.
In the higher end of that range are intraocular pressure and cranial pressure. Higher-pressure
systems (10 kPa100 kPa) correspond to blood pressure measurements and some bodily move-
ments. Piezoelectric sensors can be tailored by structure or material to match the pressure range
of the desired quality [54]. Implanted or wearable medical sensors have greater applicability, as
the Internet of Things becomes more fully developed. A medical professional or computer
algorithm can monitor a patient for early warning signs that may have been missed between
scheduled check-ups through their implanted device [55]. Tab l e 2 lists some literature studies of
piezoelectric sensors and their tested applications.
The variety of applications for piezoelectric sensors in the biomedical industry is promising,
however much of this technology is still in the research and development phase. Before reaching
the market, these devices need to have scalable manufacturing and guaranteed quality for every
device [52].
3.1.1. Developing synthetic skin
A specific application for piezoelectric pressure sensing is synthetic skin. As a bare minimum,
synthetic skin should provide the magnitude of contact force and approximate location of
Material Applications Device characteristics Refs.
Prawn cell Wrist pulse 100 Hz10 MHz range [56]
PVDF Human voice detection
Hand motion
Breathing rate
501000 Hz range [57]
(NKN) thin
Cardio mechanical electric sensor 10 Hz resonance [58]
PVDF Wrist pulse
Measuring peripheral arterial pressure
AlN Heart and respiration patterns for sleep
Tested over 0.110 Hz [60]
PVDF Heartbeat and respiration detection Tested 0.12 Hz [61]
Fish gelatin Joint movement
Human vocal cord movement
Radial artery pulses
20 pm/V
Stability over 108,000 cycles
PZT Eye fatigue via eyelid motion [63]
Poly-L-lactic acid Lung pressure
Eye pressure
Brain pressure
Stability over 108,000 cycles
Piezoelectric ceramic Vision correction Force sensitivity 0.1 10
PVDF Food detection by swallowing pattern Limit of detection: 1 Hz
Tested over 15Hz
Table 2. Examples of piezoelectric sensors and their applications.
Piezoelectric Materials for Medical Applications
contact with the sensitivity of normal skin [53]. For humans, mechanoreceptors have a range
from 3 to 400 Hz, and a spatial resolution of 12 mm [67]. Ideally, it would also provide
information about temperature changes or humidity [68]. Human skin itself acts as a vibra-
tional sensor; it is structured to amplify tactile stimulation [69]. Piezoelectric force transducers
offer a solution to quantifying and locating contact forces [53]. The use of polymers for
synthetic skin is popular because of their similarity in texture and flexibility to human skin
[70]. Polymers can be molded to emulate human characteristics, such as fingerprints to
enhance their sensitivity [69]. Processing techniques, such as electrospinning, can increase
response by aligning the molecular dipoles [25]. In a similar way, using hybrid materials or
structuring ceramics and polymers can yield higher piezoelectric properties [71, 72].
Though there are many materials, which can be used for this purpose, most are structured in
arrays. A unit in the array will send an electrical signal describing the characteristic of the
force. In prosthetics, the electric signal will arrive at a location which still can perceive tactile
senses [53]. One of the problems with arrays is interference between signals, otherwise known
as crosstalk. During crosstalk, neighboring units are affected by the unit undergoing force and
send their own signal. This can lead to an ill-defined contact region, which can be fixed using
the installation of transistors or through triangulation of the signal [53, 68].
3.1.2. Biological quartz microbalance
One other interesting application of piezoelectric sensors is the detection of disease or odor through
a change in chemical composition of a sensor. The quartz microbalance is used for a variety of
purposes, such as gas detection [73], composition analysis, and chirality classification [74]. It can
also sense changes in liquid density or viscosity [75]. This method relies on mass changes in a
coating film around the crystal. Quartz microbalances generally operate in a 510 MHz range; the
accumulation of mass can be quantified by the Sauerbreyequation(Eq.(4))[75,76].Anincreasein
mass indicates a decrease in the frequency of quartz vibration [76]. When this mass becomes too
great (>2%) this relationship becomes inaccurate, and a better approximation is needed [74]. In this
type of sensor, biological molecules are imbedded or attached to piezoelectric materials. This
technology can also be used for detection of bacteria and biomolecules.
The detection of bacteria or biomolecules usually involves the incorporation of a biomolecule
in an exterior film. One method of detecting glucose uses the enzyme hexokinase embedded in
a polymer matrix. The glucose binds to the enzymes at a rate proportional to its concentration
in solution [77]. In another glucose detection system, the frequency of the quartz was
increased. The sensor was coated with dextran and Concanavalin A. The dextran preferentially
binds to the glucose, therefore the presence of glucose causes the release of Concanavalin A.
Glucose has a lower molecular weight, and therefore the frequency increased with its detach-
ment. This method of glucose detection is advantageous because it does not involve the use of
enzymes; however has a lower detection range [78]. The quartz microbalance may also be
applicable to developing bioelectronic olfactory replacements. It has been used to detect
Piezoelectricity - Organic and Inorganic Materials and Applications132
hazardous odorants such as diacetyl, which can cause damage to the lung if inhaled, and could
be used to measure other odors [79]. Unfortunately, some of the quartz microbalance equip-
ment is bulky and requires complicated molecules as indicators. One of the olfactory biosen-
sors is 14 mm in diameter [80]. If the synthetic nose to be used for many compounds, the size
may be too large to be practical. In addition, sensors based on biomolecules, such as the
glucose have problems with biological stability [78]. These problems need to be fixed before
they can be viewed as commercially viable.
3.1.3. Cochlear implants
The destruction of inner ear cells results in severe hearing loss and is most commonly treated
by cochlear implants. Though the current technology allows for recovery from deafness, it is
incompatible with water and has very high-power requirements [81]. Piezoelectric materials
can be used for creating an artificial basilar membrane (ABM). The membrane performs
mechanical frequency selectivity for the cochlea. Varying physical rigidity and thickness of
the basilar membrane allows it to perform its duty, and likewise piezoelectric materials can
filter out frequency based on their physical properties [82]. Ceramics, such as PZT or AlN
films, can be fabricated in beam or cantilever arrays with lengths corresponding with different
resonance frequencies [81, 83]. Alternatively, devices based on PVDF or P(VDF-TrFE) mem-
branes have been fabricated [47, 8385]. The typical range of human hearing is 20 Hz20 kHz.
The fabricated PVDF membrane was able to detect signals in the 100 Hz10 kHz range, which
encompasses the range of human vocalizations [84]. Many experimental cochlear ABMs need
increased sensitivity, stability, and size reduction to be practically used [83].
3.2. Beyond sensors
3.2.1. Piezoelectric surgery
In addition to creating implants, piezoelectricity can be used in a variety of medical treatments,
most of which depend on the vibrational properties of the piezoelectric device. Unlike
implanted devices, piezoelectric devices needed for surgery do not need to be biocompatible,
because they do not come in contact with human cells. Therefore, many external devices will
make use of lead zirconate titanate (PZT), as it is easier to produce [86]. The typical
piezosurgical devices will consist of stacked rings which are given an applied voltage. The
stacked actuator design increases the actuator efficiency because the electric field is determined
by the applied voltage and the thickness (Eq. (5)) [87]. The strain is proportional to the electric
field if the thickness of the actuator is decreased, a higher strain can be generated for the same
amount of voltage.
The resulting vibration will be transduced to the tip, which is installed in such a way that it
will amplify vibrations, because traditionally ceramics are more brittle and do not display
much displacement [88].
Piezoelectric Materials for Medical Applications
In surgery, piezoelectric devices, such as the ultrasonic lancet, are used for delicate operations
to preserve surrounding tissue. By controlling the micromovements of the oscillating device,
damage to soft tissues can be avoided, and the separation between interfaces is easily accom-
plished. Alternatives to piezosurgery, such as a chisel and hammer or rotating saw are seen as
more invasive, have potential to lacerate non-discriminatorily [89]. Hard tissues, such as
mineralized bones are damaged by frequencies of 2539 kHz, however neurovascular tissue
is cut at frequencies higher than 50 kHz. There are no macrovibrations which may cause
discomfort to the patient or disturbance of surrounding tissue [90]. The tip oscillates in a linear
direction, and can span the distance of 60200 μm [86].
Thefirstuseofpiezosurgerywasthedentalindustry, with applications like removal of implants,
bone harvesting, and inferior alveolar nerve detachment [91]. Many such surgeries require work-
ing in small spaces and do not require larger incisions on the bone material. The removal of
implants takes advantage of how the ultrasonic vibrations target the interfacial layer, and weaken
the implants attachment to bone. This reduces the adhesion forces and allows the implant to be
removed with fewer incisions. In a similar way, the collection of graft material is another excellent
use of an ultrasonic lancet. After making preliminary cuts with a saw, the ultrasonic vibrations
reduce the need for chisel strikes [91]. In surgery performed on the lower jawline, protecting the
inferior alveolar nerve is important to patient recovery [92]. As said previously, the use of
piezosurgery prevents the damage ofthese nerve tissues. Another benefit in all surgeries is particle
breakdown caused by ultrasonic activity, which makes visibility easier [92].
Piezosurgery has some other applications in neurosurgery and orthopedic surgery; however, it
is limited in equipment fragility and associated expenses [86, 90]. The tip of the device frac-
tures, creating the need for replacements [88]. It also takes longer to perform operations, and
can damage tissue through heating. Irrigation is required to keep the area cool, and larger scale
devices are used for macrosized surgeries [86].
3.2.2. Ultrasonic dental scaling
A piezoelectric dental scalar also has piezoelectric ceramic rings (Figure 3) on the inside to induce
axial vibrations, and operates at ultrasonic frequencies [93]. Ultrasonic dental scalers operate in
the range of 2550 kHz, and oscillate parallel to the tooth surface over a range of 10100 μm[94].
Its purpose is to remove accumulated biofilms from the tooth surface and for treatment of root
canals. The vibrations of the tip break down the calculus (tartar) and plaque which have formed
on the tooths enamel surface. Because of the tips quick speed, when the irrigation water passes
over the scalar, micro- and nanosized bubbles form around its curve and tip [95, 96]. When these
Figure 3. The stacked actuator design and other components of an ultrasonic dental scaler. Reprinted from Engelke et al.
[93] with permission from Hindawi.
Piezoelectricity - Organic and Inorganic Materials and Applications134
bubbles collapse, cavitation forces create shock waves cleaning the tooth. This adds to the
ultrasonic scalars effectiveness, and further investigation of the cavitations effects could lead to
new dental technology which further reduces scaler contact with teeth [97].
The oscillation pattern of the scaler depends on the type of tip chosen [93] and the effectiveness
of the scaler varies depending on how it is used. Influencing factors can be the lateral force, tip
angle, and power setting [98]. Increasing the power on the ultrasonic scalar too much will
scratch a tooths protective enamel surface, increasing the tooths surface roughness and
causing damage to the surrounding tissues. The variety of ultrasonic scalersoperating condi-
tions demonstrates the need for research on appropriate forces needed to remove dental tartar
without causing damage.
3.2.3. Microdosing
Microdosing is another application of piezoelectrics and has become popular because it con-
serves the amount of medication dispensed and can reduce discomfort by avoiding injections
[99, 100]. In some cases, an injected drug can be aerosolized in order to avoid injection. In this
case, piezoelectric vibrations can break the drug into fine particles which can be carried in an
air stream and inhaled by the patient [100]. In the case of solids, a stacked actuator design is
applicable by providing a single oscillation, rather than the consistent vibration of the previ-
ously mentioned ultrasonic devices. A glass tube is attached to the actuator and an electric
signal stimulates the actuator providing a force to the tube and displacing a certain amount of
the solid. Though the dispensing is very precise, it does have a minimum dosage and blockage
can occur in the glass tube [101].
Stacked actuators in fluid pumps can administer small single doses or a continuous flow [102].
Fluid administration, like those for eye drops, often require small single doses [99]. A more
complex form of controlled microdosing can be accomplished through a diaphragm pump
[103]. This is more suited for some dosing systems such as insulin dispensing. One pump
design places four chambers in series, with electrodes connecting the gate so they operate in
tandem. Here the voltage controls the degree of membrane fluctuation and the phase of the
material controls its direction [104]. An alternative design has parallel cylinders which are
filled and emptied according to a certain sequence. The number of steps in the sequence
determines the flow rate [105]. Though PZT is a popular material for biomedical pumps,
polymer actuators such as PVDF-TrFE have been used as well [106].
3.2.4. Energy harvesting
In order to have implantable sensors within the body, they need to have a convenient source of
energy. If the sensor is battery powered, future surgery will be required to extract and replace
the battery. This is a current problem with pacemakers and limits the number of sensors placed
after surgery. Energy harvesting through the bodys movement via piezoelectricity is one way
to avoid the need for battery incorporation or replacement. Energy harvesting from organs or
the human body requires specific considerations, the most important being biocompatibility.
Like implants, energy harvesting devices ideally should not contain hazardous chemicals, like
lead, or must be sealable [107]. In the field of energy harvesting, one of the key modes of
energy harvesting, a vibrating cantilever, is not as applicable to in situ biological energy
Piezoelectric Materials for Medical Applications
harvesting because a vibrating cantilever has a very high resonance frequency for peak power
generation [108]. Though a cantilevers resonance frequency can be changed by altering its
physical characteristics, such as adding a proof mass or increasing size [109], an implant needs
to be small as to avoid interference with organ function [108]. Typically, piezoelectric biomed-
ical harvesters will be thin films that target tiny irregular vibrations caused by normal organ
deformation [110]. A piezoelectric energy harvester provides an AC power source, and the
most energy is gained near the resonance frequency of the film [111]. This adds another
engineering constraint as biological motions usually have low natural frequencies. The human
heart beats at around 39 Hz and the frequency of someone walking is around 1 Hz [108, 112].
The energy harvesting element also has to be small, as large devices may impede the normal
function of human organs or cause discomfort.
Most implanted devices should have some degree of flexibility for use in the human body.
Both polymer and ceramic flexible devices can be adhered to consistently moving body parts
to provide a source of energy. This could include wrapping a piezoelectric film around a
pulsing artery or anchoring it to an expanding diaphragm, lung, or heart [108]. The heart, or
locations near it, are advantageous places to put an energy harvesting device because they
could power a pacemaker. Ceramic nanoribbons are usually attached to some flexible film
such as polyimide, polyethylene terephthalate, or polyethylene naphthalate. The ceramic com-
ponents, made of PMN-PT, PZT, or BaTiO
, are fabricated in small units and then transferred
to the flexible film [110]. PVDF and PVDF-TrFE thin films can also be used to fabricate energy
harvesters. These films have the advantage of being biocompatible and do not have to be
transferred onto a flexible matrix [113].
In replacement joints, stacked ceramic sheets are preferred for energy harvesting. Knee surgery
is a difficult process and complications can arise after surgery [112]. The replacement joint
can become imbalanced, and be subject to wear, loosening, or even fracture. The presence of
sensors in the replacement joint vicinity would allow doctors to study how to improve knee
replacements and detect problems with greater speed. The stacked actuator is the best design
for energy harvesting in implanted joints. These actuators do not need to be as flexible, because
the downward force from the knee is compressive, rather than stretching [114]. Prospective
locations for the actuators could be in the tibial component of the joint or in the polyethylene
cartilage imitation [112, 114].
The main limitations of piezoelectric energy harvesting are low efficiency and power output.
This is large concern with biomedical devices, because they often do not operate at the devices
resonance frequency [115]. Another avenue of research focuses on enhancing the efficiency of
energy harvesting by mechanically scraping screening charges found on the surface of piezo-
electric materials [116119].
4. Conclusion
The purpose of this book chapter has been to give an overview of piezoelectric in the biomed-
ical industry. We have described the piezoelectric properties of biological materials and how
Piezoelectricity - Organic and Inorganic Materials and Applications136
they can be used to develop disease treatment. We also covered piezoelectric materials used in
sensors, and other devices to explore the current industries which can be improved by further
research. By describing these challenges, we hope to bring greater understanding of how
important piezoelectricity is to the medical industry and the opportunities it has for future
This research was supported by the KUSTAR-KAIST Institute, KAIST, Korea and Creative
Materials Discovery Program from National Research Foundation of Korea funded by the
Ministry of Science and ICT (NRF-2017M3D1A1086861). The authors gratefully acknowledge
Dr. Sangmin Shin for his advice and stimulating discussion.
Dr. Panpan Li was also supported by the Korea Research Fellowship Program funded by the
National Research Foundation of Korea (no. 2017H1D3A1A01054478).
Author details
Melodie Chen-Glasser, Panpan Li, Jeongjae Ryu and Seungbum Hong*
*Address all correspondence to:
Department of Materials Science and Engineering, KAIST, Daejeon, Korea
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Piezoelectric Materials for Medical Applications
... Therefore, that area has no piezoresponse. In general, two factors of molecular structure and the entire organ play a vital role in the piezoresponse ( Figure 5) [58]. ...
... Tissues with piezoelectric properties and driving source of piezoelectricity[58]. ...
Full-text available
Bone as a minerals' reservoir and rigid tissue of the body generating red and white blood cells supports various organs. Although the self-regeneration property of bone, it cannot regenerate spontaneously in severe damages and still remains as a challenging issue. Tissue engineering offers several techniques for regenerating damaged bones, where various biomaterials are examined to fabricate scaffolds for bone repair. Piezoelectric characteristic plays a crucial role in repairing and regenerating damaged bone by mimicking the bone niche behavior. Piezoelectric biomaterials show significant potential for bone tissue engineering. Herein we try to have a comparative review on piezoelectric and non-piezoelectric biomaterials used in bone tissue engineering, classified them, and discussed their effects on implanted cells and manufacturing techniques. Especially, Polyvinylidene fluoride (PVDF) and its composites are the most practically used piezoelectric biomaterials for bone regeneration. PVDF and its composites have been summarized and discussed to repair damaged bone tissues.
... Application areas include, timekeeping using quartz resonance, microphones, radio antenna oscillators, speakers, hydrophones, and fuel injection. Other emerging technologies include energy harvesting and electronic sensing systems [3,4]. By virtue of increasing global energy demand, research has been focused on developing technologies that can convert ambient environmental conditions such as mechanical vibration to useful energy or signal either as energy harvester or sensing system. ...
Full-text available
Piezoelectric effect is the ability of certain materials such as piezo-ceramics and piezo-polymers to generate an electric charge in response to applied mechanical stress. The process can also go in the reverse direction. This finds applications in the development of actuators, resonators, precision motors. This paper presents the study of the electrical output characteristic of electromechanical transducer for sensing application using Lead Zirconate Titanate (PZT-5H) as piezoelectric material. The results of the study showed that as the input mechanical forces range from 0 N to 8 N for applied linear mechanical force and from 0 N to sin(6πt) N for applied harmonic mechanical force, the corresponding electrical output voltages generated range from 0 V to 5.5x10-5 V for linear input and 0 V to 45x10-5 V for harmonic input. The amplification and measurement of the electrical response of the system as a direct proportion of the applied mechanical force is a suitable technique for the development of electromechanical transducer system.
... Piezoelectric actuators for positioning of the stacks type are increasingly present in a very large number of industrial processes affecting manufacturing, microscopic [1]- [4], medicine [5], [6], robotics [7], [8], and defence [9]. In reality, these systems this characterize by their reduced size, and low energy cost, and the good dynamic performance of the actuators are appreciated [10]- [14] The brake on their use and their development is the fact that the nonlinear phenomena (hysteresis, creep, vibration, and thermal drift) [15]. ...
Full-text available
The work carried out in this article essentially relates to the application of a synergetic control to the piezoelectric positioning mechanism or piezoelectric actuator (PEA). A LuGre model has been followed, capturing the most physical phenomena, in order to be able to follow the most realistic and representative model possible. From this model, which is then identified by particle swarm optimization (PSO), we apply the synergetic control technique, which is a very efficient control method that allows demonstrating the good functioning of the stability of nonlinear system in closed loop. The simulation results have been compared to those obtained when using sliding mode to confer the best performance in terms of tracking error and minimization of oscillations.
... Their high integrative power [5,6], low heat [7,8], and low noise levels [9,10] can provide relatively large efforts, high reliability, and biocompatibility [11][12][13][14]. Because of these benefits, the piezoelectric actuator has been widely used in a variety of industries, including space exploration [15,16], active shutters, pulsed jets [17][18][19], vibration control [20][21][22][23][24], optical path control [25][26][27][28], micro-motorization of instruments [29,30], valves and pumps for implants [31][32][33][34][35][36], magnetic resonance imaging (MRI) [37,38], microsurgery [39][40][41][42], and other micro-displacement techniques [43][44][45][46][47][48]. Position control is severely hindered by the unique piezoelectric actuator structure, nonlinear hysteresis behaviors, and additional sources of positioning precision loss, such as creep drift and temperature effects [49][50][51][52][53]. Extensive study has been done for the modeling and control of the nonlinearity of hysteresis. ...
For a class of system with nonlinear hysteresis, this paper presents an adaptive hybrid controller based on the hybrid backstepping-sliding mode, and describes the controller analytically by the LuGre model. Both backstepping and the sliding mode techniques are based on the Lyapunov theory. Drawing on this common point, the authors developed a new controller combining the two control techniques with a recursive design. The design aims to achieve two effects: assuring the stability of the closed loop system, and improving the continuous performance of the tracking position trajectory. The performance of the proposed hybrid controller was verified by implementing the identified Piezo model. The results show that our controller can track the system output desirably with the reference trajectory.
... Most of the glu-can in the biomass can be degraded with the help of a harsh acid treatment [20]. Chitosan is produced during the deacetylation of chitin by the removal the acetamide group in chitin, followed by substitution with the amino group [29]. Fig. 2 shows the chemical structure for the deacetylation of chitin where chitosan will be produced at the end of the reaction. ...
Fungal chitosan is one of the piezoelectric biomaterials that can be used in energy harvesting. Fungal biomass offers a sustainable source for chitosan, as an alternative to crustacean-based chitosan. However, the fungal chitosan yield is relatively lower than other conventional sources of chitosan. Therefore, this study aims to review different experimental procedures for the chemical extraction of chitosan from biomass. The selection of the most effective extraction method using Preference Ranking Organization Method for the Enrichment of Evaluations and Geometrical Analysis for Interactive Decision Aid (PROMETHEE-GAIA), a systematic multiple criteria analysis based on ranking and section of alternatives (i.e. different extraction methods). PROMETHEE-GAIA was performed as the critical and comprehensive discussion in this paper. The PROMETHEE-GAIA analysis showed that the microwave-assisted organic acid-alkaline treatment extraction method showed the highest ranking for the most effective fungal chitosan method due to positive response from the chitosan yield, degree of deacetylation, toxicity and temperature.
... Application areas include, timekeeping using quartz resonance, microphones, radio antenna oscillators, speakers, hydrophones, and fuel injection. Other emerging technologies include energy harvesting and electronic sensing systems [3,4]. By virtue of increasing global energy demand, research has been focused on developing technologies that can convert ambient environmental conditions such as mechanical vibration to useful energy or signal either as energy harvester or sensing system. ...
Full-text available
Piezoelectric effect is the ability of certain materials such as piezo-ceramics and piezo-polymers to generate an electric charge in response to applied mechanical stress. The process can also go in the reverse direction. This finds applications in the development of actuators, resonators, precision motors. This paper presents the study of the electrical output characteristic of electromechanical transducer for sensing application using Lead Zirconate Titanate (PZT-5H) as piezoelectric material. The results of the study showed that as the input mechanical forces range from 0 N to 8 N for applied linear mechanical force and from 0 N to sin(6πt) N for applied harmonic mechanical force, the corresponding electrical output voltages generated range from 0 V to 5.5x10-5 V for linear input and 0 V to 45x10-5 V for harmonic input. The amplification and measurement of the electrical response of the system as a direct proportion of the applied mechanical force is a suitable technique for the development of electromechanical transducer system.
... In the implant removal process, the ultrasonic wave passes through the interfacial layer thus weakening the bond between tooth and implant. So, implant is removed easily as adhesive force is lessened [125]. Similarly, the collection of graft material is also a very demanding use of piezo surgery. ...
This chapter describes the historical background, basic phenomenon associated with the piezoelectric materials. Both direct and inverse piezoelectric effect has been explained with their mechanisms. Various piezoelectric operational constants and parameters have been discussed. Various materials such as ceramic, polymer, metal, and composites in the bulk form as well as in the thin film have been explained with their basic flow diagram. The basic difference between the electrostrictive material which is a material nearly similar to piezoelectric materials has been explained. Various piezoelectric material properties and potential applications in aero-industries, marine industries, automobiles, biomedical, energy harvest, household, and other applications have been described. Various advantages and limitations of piezoelectric materials have been given briefly.
... Thus, to start the regeneration processes, biochemical and electric signals from the injury site of axons have to be transported to their cell body to promote a change in gene regulation. The porous biocompatible materials possessing piezoelectric activity, such as polyvinylidene fluoride (PVDF) and its copolymer polyvinylidene fluoride-trifluoroethylene (P(VDF-TrFE)), could be advantageous to guide growing neurites and migrating SCs [16][17][18][19]. ...
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Polyvinylidene fluoride (PVDF) and its copolymer with trifluoroethylene (P(VDF-TrFE)) are considered as promising biomaterials for supporting nerve regeneration because of their proven biocompatibility and piezoelectric properties that could stimulate cell ingrowth due to their electrical activity upon mechanical deformation. For the first time, this study reports on the comparative analysis of PVDF and P(VDF-TrFE) electrospun scaffolds in terms of structural and piezoelectric properties as well as their in vitro performance. A dynamic impact test machine was developed, validated, and utilised, to evaluate the generation of an electrical voltage upon the application of an impact load (varying load magnitude and frequency) onto the electrospun PVDF (15–20 wt%) and P(VDF-TrFE) (10–20 wt%) scaffolds. The cytotoxicity and in vitro performance of the scaffolds was evaluated with neonatal rat (nrSCs) and adult human Schwann cells (ahSCs). The neurite outgrowth behaviour from sensory rat dorsal root ganglion neurons cultured on the scaffolds was analysed qualitatively. The results showed (i) a significant increase of the β-phase content in the PVDF after electrospinning as well as a zeta potential similar to P(VDF-TrFE), (ii) a non-constant behaviour of the longitudinal piezoelectric strain constant d33, depending on the load and the load frequency, and (iii) biocompatibility with cultured Schwann cells and guiding properties for sensory neurite outgrowth. In summary, the electrospun PVDF-based scaffolds, representing piezoelectric activity, can be considered as promising materials for the development of artificial nerve conduits for the peripheral nerve injury repair.
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Micro-dosing of fine cohesive powders is the key technology in additive manufacturing and especially in high-potency active pharmaceutical ingredients (HPAPI). However, high accuracy micro-dosing (<5 mg) of fine cohesive powder is less trivial and still remains a challenge because it is difficult to eliminate the aggregation phenomena caused by the strong interparticle cohesive forces (in small capillaries). This paper presents a novel micro-dose method of fine cohesive powders via a pulse inertia force system. A piezoelectric actuator is used to provide a high enough pulse inertia force for a tapered glass nozzle and drive powder particles in the nozzle to be discharged from the nozzle orifice with the help of particle self-gravity. The nozzles with outlet diameters in the range of 100–2000 µm were fabricated via a glass heating process. The α-lactose monohydrate powder is used as the micro-dosing powder. The influences of the tapered nozzle outlet diameter, amplitude of the applied pulse voltage, and angle of the nozzle axis on micro-dosing mass are researched. The minimum mean dose mass is 0.6 mg for a single pulse inertia force. The coefficient of variation of dose mass, which represents the micro-dosing stability, can be controlled below 5% when the dose mass is relatively small.
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The knee replacement is one of the most common orthopedic surgical interventions in the United States; however, recent studies have shown up to 20% of patients are dissatisfied with the outcome. One of the key issues to improving these operations is a better understanding of the ligamentous balance during and after surgery. The goal of this work is to investigate the feasibility of embedding piezoelectric transducers in the polyethylene bearing of a total knee replacement to act as self-powered sensors to aid in the alignment and balance of the knee replacement by providing intra- and postoperative feedback to the surgeon. A model consisting of a polyethylene disc with a single embedded piezoelectric ceramic transducer is investigated as a basis for future work. A modeling framework is developed including a biomechanical model of the knee joint, a finite element model of the knee bearing with encapsulated transducer, and an electromechanical model of the piezoelectric transducer. Model predictions show that a peak voltage of 2.3 V with a load resistance of 1.01 M $\Omega$ can be obtained from a single embedded piezoelectric stack, and an average power of 12 μW can be obtained from a knee bearing with four embedded piezoelectric transducers. Uniaxial compression testing is also performed on a fabricated sample for model validation. The results found in this work show promising potential of embedded piezoelectric transducers to be utilized for autonomous, self-powered in vivo knee implant force sensors.
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Eye fatigue is a symptom induced by long-term work of both eyes and brains. Without proper treatment, eye fatigue may incur serious problems. Current studies on detecting eye fatigue mainly focus on computer vision detect technology which can be very unreliable due to occasional bad visual conditions. As a solution, we proposed a wearable conformal in vivo eye fatigue monitoring sensor that contains an array of piezoelectric nanoribbons integrated on an ultrathin flexible substrate. By detecting strains on the skin of eyelid, the sensors may collect information about eye blinking, and, therefore, reveal human's fatigue state. We first report the design and fabrication of the piezoelectric sensor and experimental characterization of voltage responses of the piezoelectric sensors. Under bending stress, the output voltage curves yield key information about the motion of human eyelid. We also develop a theoretical model to reveal the underlying mechanism of detecting eyelid motion. Both mechanical load test and in vivo test are conducted to convince the working performance of the sensors. With satisfied durability and high sensitivity, this sensor may efficiently detect abnormal eyelid motions, such as overlong closure, high blinking frequency, low closing speed and weak gazing strength, and may hopefully provide feedback for assessing eye fatigue in time so that unexpected situations can be prevented.
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Aim: Conventional eyedropper-delivered volumes (25-50 µl) exceed the eye's usual tear-film volume (7 µl) and precorneal reservoir capacity, risking overflow and ocular/systemic complications. Piezoelectric high-precision microdosing may circumvent these limitations. Results & methodology: In this masked, nonrandomized, cross-over study, subjects (n = 12) underwent pupil dilation with topical phenylephrine (PE) administered by 32-µl eyedropper (2.5% or 10% formulation) and 8-µl electronic microdosing (10% formulation). Microdosing with PE-10% achieved comparable peak dilation as 10% eyedropper-delivery and superior dilation to 2.5% eyedropper-delivery (p = 0.009) at 75 min. Microdosing significantly reduced 20-min plasma PE levels versus PE10% eyedropper; neither treatment altered heart rate/blood pressure. Eye irritation occurred significantly less frequently with microdosing than PE10% eyedrops. Conclusion: Piezo-ejection PE microdosing achieves comparable biological effect as eyedropper dosing; reduced systemic absorption may decrease risk of systemic side effects.
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Recently reported piezoresponse force microscopy (PFM) measurements have proposed that porcine aortic walls are ferroelectric. This finding may have great implications for understanding biophysical properties of cardiovascular diseases such as arteriosclerosis. However, the complex anatomical structure of the aortic wall with different extracellular matrices appears unlikely to be ferroelectric. The reason is that a prerequisite for ferroelectricity, which is the spontaneous switching of the polarization, is a polar crystal structure of the material. Although the PFM measurements were performed locally, the phase-voltage hysteresis loops could be reproduced at different positions on the tissue, suggesting that the whole aorta is ferroelectric. To corroborate this hypothesis, we analyzed entire pieces of porcine aorta globally, both with electrical and electromechanical measurements. We show that there is no hysteresis in the electric displacement as well as in the longitudinal strain as a function of applied electric field and that the strain depends on the electric field squared. By using the experimentally determined quasi-static permittivity and Young's modulus of the fixated aorta, we show that the strain can quantitatively be explained by Maxwell stress and electrostriction, meaning that the aortic wall is neither piezoelectric nor ferroelectric, but behaves as a regular dielectric material.
Conference Paper
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This paper presents design and fabrication of a MEMS-based thin film piezoelectric transducer to be placed on an eardrum for fully-implantable cochlear implant (FICI) applications. Resonating at a specific frequency within the hearing band, the transducer senses eardrum vibration and generates the required voltage output for the stimulating circuitry. Moreover, high sensitivity of the sensor, 391.9 mV/Pa @900 Hz, decreases the required power for neural stimulation. The transducer provides highest voltage output in the literature (200 mVpp @100 dB SPL) to our knowledge. A multi-frequency piezoelectric sensor, covering the daily acoustic band, is designed based on the test results and validated through FEA. The implemented system provides mechanical filtering, and mimics the natural operation of the cochlea. Herewith, the proposed sensor overcomes the challenges in FICI operations and demonstrates proof-of-concept for next generation FICIs.
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As smartphone penetration saturates, we are witnessing a new trend in personal mobile devices — wearable mobile devices or simply wearables as it is often called. Wearables come in many different forms and flavours targeting different accessories and clothing that people wear. Although small in size, they are often expected to continuously sense, collect, and upload various physiological data to improve quality of life. These requirements put significant demand on improving communication security and reducing power consumption of the system, fuelling new research in these areas. In this article, we first provide a comprehensive survey and classification of commercially available wearables and research prototypes. We then examine the communication security issues facing the popular wearables followed by a survey of solutions studied in the literature. We also categorise and explain the techniques for improving the power efficiency of wearables. Next, we survey the research literature in wearable computing. We conclude with future directions in wearable market and research.
Significance Measuring physiological pressures such as lung pressure, brain pressure, eye pressure, etc. is important for monitoring health status, preventing the buildup of dangerous internal forces in impaired organs, and enabling novel approaches of using mechanical stimulation for tissue regeneration. Pressure sensors are often implanted and directly integrated with soft biological systems. Therefore, the devices should be flexible and at the same time biodegradable to avoid invasive removal surgery. Here, we present the study and processing of a biodegradable polymer which can convert mechanical force to electricity, and employ the polymer to develop a biocompatible implanted force sensor. The sensor, relying solely on common medical materials, can monitor important biological forces and eventually self-vanish, causing no harm to the body.
This paper presents the design, fabrication, and performance evaluation of a biocompatible piezoelectric membrane actuator (PMA) using polyvinylidene fluoridetrifluoroethylene (PVDF-TrFE). Electrode structure optimization was verified by a finite element method simulation software. Fabrication was done utilizing only standard microfabrication techniques. 1-μm-thick membrane and 1.5-μm-thick actuator layers were formed by spin coating using PVDF-TrFE. The surface roughness of the fabricated film was measured as 7.9 nm using a tabletop atomic force microscope (AFM) and remnant polarization at 200 V was measured as 5.38 μC/cm <sup xmlns:mml="" xmlns:xlink="">2</sup> . Deflection measurements were performed with an Al coated tipless AFM probe using a precision nano displacement system, which consists of a ferroelectric tester, a table top AFM, and a computer. A 432 nm displacement was obtained at 9 V under non-resonant conditions from a PMA with 2250 μm diameter. Since all moving structures were fabricated from a polymer material, high displacements could be obtained without fracture. The results demonstrated that the proposed PMA can be a good candidate for membrane type micropumps, especially to be used in biomedical applications, where low driving voltage and biocompatibility are required.
Flexible and wearable piezoelectric bio e-skin (PBio-e-skin) based on electrospun poly(L-lactic acid) PLLA nanofiber membrane is demonstrated for non-invasive human physiological signal monitoring and detecting dynamic tactile stimuli. The molecular orientations of the C=O dipoles by electrospinning technique results in a longitudinal piezoelectric charge co-efficient, d33 value of ~ (3±1) pm/V realized by piezoresponse force microscopy, allowing the PBio-e-skin for pressure sensing applications. The robust mechanical strength (Young’s modulus ~ 50 MPa) of nanofiber membrane ensures PBio-e-skin’s superior operational stability over 375,000 cycles. Owing to the superior mechanosensitivity of ~ 22 V/N, PBio-e-skin has the ability to measure subtle movement of muscle in the internal organs such as esophagus, trachea, motion of joints and arterial pressure by recognition of strains on human skin. This flexible and light weight PBio-e-skin precisely detects vital signs and providing important clinical insights without using any external power source. Eventually, the low cost, environmental friendly PBio-e-skin will have a huge impact in broad range of applications including self-powered wearable health care systems, human–machine interfacing devices, artificial intelligence and prosthetic skin.