nanogenerators to power implantable medical systemsnesel.skku.edu/paper files/256.pdf ·...

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Please cite this article in press as: Yoon and Kim, Nanogenerators to Power Implantable Medical Systems, Joule (2020), https://doi.org/10.1016/j.joule.2020.05.003

Perspective

Nanogenerators to Power ImplantableMedical Systems

Hong-Joon Yoon1 and Sang-Woo Kim1,2,*

Context & Scale

Supplying sustainable, reliable,

and effective power to

implantable medical devices

(IMDs) is essential. Reliance on

primary batteries requires regular

surgeries for maintenance and has

motivated research into

alternative strategies. Among the

potential solutions,

nanogenerators (NGs), which

provide reliable and sustainable

energy conversion (mechanical-

electrical), have gained significant

attention with their variety of

available materials, compatibility

with modern IMDs, flexibility in

structural design, and their

durability.

Replacing implantable medical devices (IMDs) is essential for theircontinuous operation, for which surgery is inevitable. Nanogenera-tors (NGs) have gained attention as potential power solutions owingto their compactness and safety compared with electromagneticfield-based energy transfer technologies. Their working principle,which involves the generation of electrical potential from bodymovement, is suitable for sustaining IMDs’ instant monitoring andsensor capabilities inside the body. In this regard, NGs hold promisefor realizing self-powered IMDs that consume low power. For de-vices demanding a certain level of power required to operate sus-tainably, the realization of a powering system driven only by internalbiomechanical energy has faced obstacles. Ultrasound referring toexternal mechanical energy has been found to have potential tononinvasively power IMDs that require relatively greater energy.This perspective discusses current NGs that are capable of copingwith the IMDs’ power demand and thereof driven IMDs application.This paper also focuses on recent advances in ultrasound-drivenNGsand their future opportunities and strategies to be a competitivepowering device for IMDs.

In this perspective, we review

promising NGs-based IMDs

research focusing on biometric

sensors, monitoring units, and

stimulation device. While their

energy harvesting performance

relies on a given level of

biomechanical energy, NGs

intended to charge lithium (Li)-ion

batteries in IMDs present inherent

shortcomings due to a low level of

input biomechanical energy. In

this regard, this perspective

highlights ultrasound, referring to

externally applied input

mechanical energy, driven NGs

for tackling challenges in

powering IMDs, and its future

direction for advancement.

INTRODUCTION

Implantable medical devices (IMDs) are designed to perform or augment the func-

tions of existing organs by using monitoring,1 measuring, processing units,2 and

the actuation control.3 Conventional IMDs are powered with primary batteries that

require frequent surgeries for maintenance and replacement. Therefore, IMDs

require a new reliable and safe powering system to avoid the need for frequent sur-

geries.4 Wireless electromagnetic power transmission has been proposed as an

alternative powering system. However, there is an issue of excessive tissue heating

from these appliances, affecting the immune system and deoxyribonucleic acid

(DNA) synthesis. Nanogenerators (NGs), on the other hand, have been proposed

to harvest the mechanical energy produced by the human body. NGs based on

piezoelectricity require a cyclic stress in order to generate electricity.5 Triboelectric

nanogenerators (TENGs) are capable of generating electricity if there is a physical

contact or rubbing.6–8 Unlike piezoelectric NGs (PENGs) relying on limited group

of noncentrosymmetric materials (e.g., ZnO,9 GaN,10 Pb(Zr,Ti)O3,11 BaTiO3,

12 and

PVDF13), TENGs have gained attention in IMDs with the ease of fabrication and

the IMDs-related benefits derived from the diversity of materials.14

Among the IMD features, diagnostic sensing and monitoring units enable acceler-

ated medical care, identifying potential problems preemptively. Like an electrocar-

diogram (ECG) that measures the rate and rhythm of the heartbeat, a diagnostic tool

that assesses the muscular function routine is of equal importance.15 Considering

the working principle of NGs, they can serve as a biometric sensor by instantly

Joule 4, 1–10, July 15, 2020 ª 2020 Elsevier Inc. 1

Figure 1. Power Consumption of Current IMDs and an Estimate of Potential Biomechanical Energy Mapping through the Human Body

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converting mechanical energy (e.g., organ motion) into electrical signals (prognostic

information).16 This feature of NGs is now attracting researchers from diverse fields

of not only scientific community but also of medicine. Recent IMD-related NG

research includes monitoring units and sensor application, with emphasis on sensi-

tivity in recognizing the biomechanical behavioral characteristics. IMDs categorized

as active devices (e.g., cardiac pacemaker) require a level of power to cope with mul-

tiple functions that include sensing, processing, and actuation. NGs have been stud-

ied as powering devices that generate electricity from any movement in a wide fre-

quency range.

Over the past decade, NGs have intensively aimed at harvesting mechanical energy

sources.17,18 Some NGs have studied not only detecting19 but also harvesting20,21

sound wave (referred to mechanical energy sources) propagating through air; how-

ever, there have been very few reports on harvesting sound waves traveling through

the body to power IMDs. In 2019, there was a report that ultrasound transmitted

through the skin or tissue generates electricity via TENG successfully demonstrated

the practicability of charging rechargeable batteries.22 From this perspective, we

discuss the developments of IMDs-related NGs devices for biomechanical energy

conversion and their potential applications. Besides, this paper focuses on recent

advances in ultrasound-driven NGs that harvest ultrasound energy aimed at power-

ing IMDs, and we provide a discussion inspiring new perspectives on materials and

devices to advance NGs in the future.

1School of Advanced Materials Science andEngineering, Sungkyunkwan University (SKKU),Suwon 16419, Republic of Korea

2SKKU Advanced Institute of Nanotechnology(SAINT), Sungkyunkwan University (SKKU), Suwon16419, Republic of Korea

*Correspondence: [email protected]

https://doi.org/10.1016/j.joule.2020.05.003

POWER CONSUMPTION OF MODERN IMDs AND THEIR CHALLENGES

Figure 1A outlines power consumption requirements for modern IMDs. Among

them, pacemakers are designed to moderate pulse rates by continuously stimu-

lating the myocardium.23 These devices require a minimum amount of power

(<0.1 mW). Neurostimulator and infusion-pump power consumption depends on

the required stimulation thresholds and pulse characteristics measured by ampli-

tude (measured as a voltage) and its duration (measured in milliseconds). IMDs

have been developed for connecting all predefined sets of components, such as

sensors, processors, and data transmitters and receivers, requiring high levels of po-

wer consumption. To achieve longer IMD-battery service life, the amount of energy

required for data transmission should be reduced. Radio-frequency identification

(RFID) pressure sensors consume 10 mW via bluetooth low energy.24,25 Advanced

2 Joule 4, 1–10, July 15, 2020

mailto:[email protected]

https://doi.org/10.1016/j.joule.2020.05.003

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IMDs capable of measuring physiological and spatiotemporal parameters demand

high computation loads.26 Thus, their power consumption is often very high.

A Necessity of Power

Wireless energy transfer technologies can reduce power consumption, but most

IMDs still require primary batteries. Batteries are nowadays routinely recharged or

replaced using containers outside the body, connected through the body to the de-

vices. Nonetheless, modern IMDs, including pacemakers, require internal power

sources and mechanics that have to be replaced or repaired every 7–8 years.27 Sur-

gical protocol is believed to be safe, but any invasive surgery may cause a risk of

infection. Furthermore, the demand for pacing services is likely to continue to

grow into diverse age ranges.28 In this respect, the power transfer from the external

source in a wireless manner is truly preferred. Most power supply approaches have

been based on radio frequencies, although they cannot address the following

key challenges of IMDs: (1) extreme sensitivity to alignments and distances

between source and receiver and (2) regulatory power thresholds for general safety

concerns.

Research in Biomechanical Energy Harvesting

NGs have been explored to harvest biomechanical energy from various types of

muscular movements. Figure 1B displays the amounts of power that can be har-

vested from joints or other body parts during walking. The potential power derived

from the shoulder is 2.2 W, from the knee is 36.4 W, from a heel strike is 20 W, and

from ankle joints is 66.8 W.29 Besides, biomechanical pumping (0.93 W) involving

heartbeat30,31 and respiratory muscles movement (0.41 W) during breathing32–34

is also potentially harvestable. One interesting study reported the conversion of me-

chanical energy from walking into electrical energy using the inertial changes of the

center-of-mass motion (20 W). The maximum amount of energy that can be har-

vested is approximately 1 W/kg, based on device weight.29 This technique is more

appropriate to be realized outside the body. Furthermore, any solution should

only minimally interfere with the natural function of body parts. This, in fact, makes

NGs even more promising.

BIOMEDICAL APPLICATIONS BASED ON NGs POWERED BYBIOMECHANICAL ENERGY

Research in NGs and Emerging Thereby IMDs

PENG technology was first introduced in 2006. Since then, there have been exten-

sive discussions on the piezoelectric properties of various materials and possible ap-

plications that could take advantage of the mechanical-electrical conversion.35–38

PENGs rely on mechanical strain on materials (Figure 2B). TENGs, on the other

hand, are capable of generating electrical potentials through contact electrification,

induced by mechanical impacts (Figure 2C) and electrostatic induction. The first

TENG was reported in 2012,6 and since then, a great deal of research has been con-

ducted on a number of high-performing materials (i.e., those with high surface

charge density)39–41 and structures,42–44 theoretical predictions of systems,45 and

applications in various environments.46–48 In particular, its application includes the

internet-of-things sensors and self-powered electronics that convert mechanical en-

ergy from the environment into electrical energy. NGs are known to be suitable

powering devices when mechanical conditions are apt to be triggered in places

where there is no sustainable energy supply. The human body, likewise, cannot be

easily accessible, but energy is primarily provided by only the intake of nutrients.

Although various medical instrumentations are used to perform diagnosis and

Joule 4, 1–10, July 15, 2020 3

Figure 2. Biomedical Applications Based on Piezoelectricity and Triboelectricity Generated by Muscular Events inside the Body

Reproduced with permission.53 Copyright 2014, National Academy of United States of America. Reproduced with permission.50 Copyright 2014, Wiley-

VCH. Reproduced with permission.51 Copyright 2017, John Wiley & Sons. Reproduced with permission.54 Copyright 2017, Royal Society of Chemistry.

Reproduced with permission.55 Copyright 2017, Elsevier.

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analysis, conventional medical systems or protocols cannot keep track of patients’

heart rate,such as detecting an abnormal heart rhythm and restoring a normal heart-

beat. In this regard, researchers have started paying attention to body-implantable

systems to manage underlying risks in a more sustainable manner. In recent days,

NGs have been studied as serving biomedical devices.49 NGs studies have explored

applications to organs (e.g., heart, lungs, and stomach) where continuous muscular

events occur (Figure 2A). A level of electrical signal generated from NGs are used to

clinically sense the signs of organs to evaluate the status,50 monitor other organs

with powered medical devices,51 and to serve as a nerve stimulation device.52

NG-Based IMDs: Sensors, Monitoring Units, and Stimulation Devices

Since NGs are able to convert mechanical motion into electrical signals, NGs can be

developed as biomedical identifiers if the organs’ medical status can be determined

by mechanical exercises. According to a study by Dagdeviren et al. (Figure 2D),53

PZT-based PENG was used as a dynamic mechanical-electrical energy converter.

The level of the characterized output voltage was proportional to the measured

displacement, which could be used to predict organ behavior. Consistent sensing

characteristics were observed under different frequencies. Another study by Zheng

et al. showed that the movement of the lungs could be identified by placing a TENG

device on the diaphragm.50 As shown in Fig. 2E, TENG can precisely identify breath-

ing behaviors, which is the required feature to be a medical sensor.

In addition to measuring, sensing, and understanding biological movements,

research has shown that NGs can be used to treat the given measurable biometric

identifiers as processible information that can be viewed or recorded for additional

feedback responses. A study by Kim et al. (Figure 2F) showed that the electrical sig-

nals generated from PENG corresponded to ECG signals under cardiac oscillation

4 Joule 4, 1–10, July 15, 2020

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from the heart.51 Their NG was also used as a telemetry device. The harvested me-

chanical energy was used to charge a capacitor, and it successfully powered a wire-

less data transmission system. Ouyang et al. (Figure 2G) showed that TENG-based

cardiac pacemaker could monitor heart rates in vivo.56 Monitored heart-rhythm pac-

ing was analyzed and regulated to confirm the controllability of physiological activ-

ities. Their TENG was featured as a mechanically stable device (tested 100 M times),

making it suitable for monitoring devices that require long-term operation.

In biomedical applications, too-high currents can cause adverse effects on living or-

ganisms, including metabolic imbalances and DNA incompatibilities caused by heat

generation. In this respect, an intriguing approach for NGs is the stimulation device,

with emphasis on its relatively low-current and high-voltage characteristics. Hwang

et al. (Figure 2H) demonstrated that PZT-based PENG devices, driven by minimal

movement (e.g., bending), could send electrical impulses via implanted electrodes

to specific target areas of the brain to treat behavior disorders, which refers to the

deep brain stimulation (DBS).54 Besides, TENG-based vagus nerve stimulation

(VNS) was also reported by Yao et al. (see Figure 2I), who found that stomach peri-

stalsis could control the level of food intake. Their VNS system was designed as a

TENG attached to the stomach, generating voltage pulses that effectively reduced

food intake by stimulating vagal afferent fibers. They achieved 35% weight-loss re-

sults within 18 days.52 This development demonstrated that TENGs with instant re-

sponsivity can be well adapted to peripheral neuromodulation. Another interesting

study by Lee et al. (Figure 2J) presented that TENG-based neurostimulation devices

could generate sufficient electric field levels to activate muscles. Preferential stimu-

lation of one or more nerve roots in a direct manner is required with modern neuro-

stimulation technologies. Lee et al. showed that different muscle-activation patterns

of gastrocnemius medialis and tibialis anterior muscles were successfully achieved.55

As introduced above, the benefits of NGs include instant response rates (i.e., me-

chanical-electrical energy conversion) and compatibility with existing biomedical

systems, especially electrical nerve stimulation units, which make NGs an excellent

treatment option for future medical applications.

NGs AS POWERING DEVICES FOR IMDs

Biomechanical Energy-Driven NGs

Apart frommedical applications, PENGand TENG technologies can harvest mechanical

energy to power various types of electronics. Figure 3 highlights a comparison of studies

involving the conversion of mechanical energy triggered by muscular events inside the

body into piezoelectricity and triboelectricity and other studies reporting generation of

piezoelectricity and triboelectricity by externally applied mechanical energy that travels

through the skin. A study by Dagdeviren et al. (Figure 3A) reported that PZT-based

PENGs generated approximately 1 mW/cm2 of output power when triggered by theme-

chanical deformations of heart pumping, providing a load displacement of �10 mm.53

Another study by Ouyang et al. (Figure 3B) showed that an implantable TENG achieved

�10 mW/cm2 output power.56 RFID tags and wireless sensors can be driven with 1–

10 mW/cm2.24 The amount of energy generated solely depends on working of the heart,

which may raise concerns regarding the effectiveness and safety of TENGs in powering

devices. Unlike various mechanical events occurring outside the body, very limited

amount of mechanical energy (e.g., muscular displacement of the heart’s outer wall dur-

ing heartbeat), extremely narrow space, and device dimension limitation inside the body

present challenges for NGs in becoming a promising power source for IMDs. Accord-

ingly, there is a need for noninvasive and sustainable NG-based powering system apart

from organ motion-driven NG systems.

Joule 4, 1–10, July 15, 2020 5

Figure 3. Powering IMDs with Piezoelectricity/Triboelectricity Generated from Different

Mechanical Energy Sources

Reproduced with permission.53 Copyright 2014, National Academy of United States of America.

Reproduced with permission.57 Copyright 2016, Macmillan Publishers Limited. Reproduced with

permission.22 Copyright 2019 AAAS.

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Ultrasound Energy-Driven NGs

Ultrasound has been approved by FDA for treatment methods in various applica-

tions. Sound waves can travel through biological tissue (e.g., transcutaneous skin)

to cause specific region to oscillate. The development of an ultrasound energy har-

vesting system based on piezoelectric materials has been discussed in previous

studies.58 Because ultrasound transducers utilize the inverse piezoelectric principle,

it may be possible to achieve high energy harvesting performance via advanced

piezoelectric materials and resonance design.59 Shi et al.57,60 demonstrated that mi-

croelectromechanical system-based piezoelectric ultrasound energy could be used

to power IMDs (Figure 3C). PENG-based PZT diaphragm array with a resonance fre-

quency of 240–250 kHz, generating up to 3.75 mW/cm2 at distance of 1 cm and 1

mW/cm2 of ultrasound intensity. To our knowledge, the supply of hundreds of mil-

liwatts of power transcutaneously to an implant, using piezoelectric ultrasonic en-

ergy harvesting, has been reported.61 However, there are still several technical chal-

lenges such as limited materials option and long-term mechanical durability for

PENG to be used as a power source for IMDs. Moreover, long-term stable operation

is also required. As alternative candidates, TENGs have been studied as a promising

implantable powering system because of their powering capabilities, regardless of

materials and their superior mechanical stability.62 Additionally, TENGs are consid-

ered suitable for use in confined spaces (e.g., human body), because they can

generate electricity as long as there is a minimal contact (<1 mm) betweenmaterials.

As shown in Figure 3D, Hinchet et al. presented an ultrasound energy harvesting

technology based on TENG intended to power IMDs. Ultrasound TENG (US-

TENG) was triggered with an applied 20-kHz ultrasound at 3 W/cm2 reaching 9.71

V(root mean square [RMS]) and 427 mARMS. The measured output current was enhanced

two orders of magnitude compared with conventional TENGs, with a similar level

of s0 (surface charge density), triggered in low-frequency mechanical environments.

6 Joule 4, 1–10, July 15, 2020

Figure 4. Outlook for Research on Ultrasound-Driven NGs for Powering IMDs

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Because the output current is defined as i = dq/dt, the relatively high output current

of US-TENG (z31.2 mA/cm2) is relevant to taking a short period of time (50 ms) for

one full contact-separation. Interestingly, to experimentally simulate clinical condi-

tions closer to human in the laboratory, Hinchet et al. inserted US-TENG under

porcine tissue, showing that it fully charged a rechargeable Li-ion battery having a

capacity of 0.7 mAh. From this aspect, the power generated was high enough to

recharge small IMDs batteries (e.g., pacemaker and neurostimulators) that consume

only 1–100 mW.24

SUMMARY AND PERSPECTIVE

By providing sustainable operational mechanical-electrical conversion using

dependable muscular events inside the body, the use of NGs for IMDs sensor and

monitoring units, and (neuro) stimulation devices has drawn significant attention in

the fields of materials science and medicine in recent days. The energy harvesting

property of NGs is an indispensable aspect of IMDs application, and a noninvasive

solution would be a remarkable advancement. Since the level of electrical energy

generated by NGs relies heavily on the input mechanical energy (i.e., givenmuscular

event), taking matured theoretical models of NGs into account, first, measurable

mechanical energy in various environmental scenario should be understood in a

biomechanical aspect. Next, materials can be designed having an optimum level

of surface charge density—(1) to achieve effective contact/separation even in

confined space and evaluate their energy conversion property in device scale and

Joule 4, 1–10, July 15, 2020 7

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(2) tomechanically synchronize with the activity of the moving organs (e.g., heart and

lung) to carry identical information. Based on this, concerning the efficiency and rele-

vant applications, electrical engineers can be involved to develop applicable cir-

cuitry. Since biomechanical energy-driven NGs cannot generate electrical energy

beyond measurable biomechanical energy inside the body, those could guarantee

charging a limited range of IMDs batteries. In this respect, transcutaneous ultra-

sound through the skin has been proposed as an attempt to elevate NG energy

output. This advancement promises the capability to generate higher power levels

than conventional methods. To make desirable ultrasound-driven NGs that power

IMDs, certain issues should be addressed in future studies (Figure 4). High NG effi-

ciency is desirable under a certain level of ultrasound energy, which is required for

miniaturization. Regarding US-TENG, dielectric layer design and surface charge

density have been found to successfully improve output performance. There is a

need to study the input ultrasound energy at certain depths. Implantation depth

varies depending on the IMD application (e.g., mean implantation depth is

�10mm),22 andmechanical energy should be estimated under different working en-

vironments in terms of mechanical properties of layers and implantation depths.

Moreover, all media attenuate ultrasound due to absorption and scattering effects,

which could potentially reduce NG input energy. Ultrasound field disturbances

should be addressed with protective packaging materials in commercial IMDs.

Finally, the stability of NGs over long periods should be tested. Performance data

should be collected and analyzed under different working conditions, and the work-

ing and degradation mechanism of NGs should be statistically identified.

ACKNOWLEDGMENTS

This work was financially supported by the Basic Science Research Program

(2018R1A2A1A19021947) through the National Research Foundation (NRF) funded

by the Ministry of Science and ICT of Korea and the GRRC program of Gyeonggi

Province (GRRC Sungkyunkwan 2017-B05).

AUTHOR CONTRIBUTIONS

S.-W.K. conceptualized this perspective. H.-J.Y. investigated the literature. All au-

thors contributed equally to the writing of the manuscript. S.-W.K. revised the

manuscript.

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