Abstract
As implantable medical electronics (IMEs) developed for healthcare
monitoring and biomedical therapy are extensively explored and deployed
clinically, the demand for non-invasive implantable biomedical
electronics is rapidly surging. Current rigid and bulky implantable
microelectronic power sources are prone to immune rejection and
incision, or cannot provide enough energy for long-term use, which
greatly limits the development of miniaturised implantable medical
devices. Herein, a comprehensive review of the historical development of
IMEs and the applicable miniaturised power sources along with their
advantages and limitations is given. Despite recent advances in
microfabrication techniques, biocompatible materials have facilitated
the development of IMEs system toward non-invasive, ultra-flexible,
bioresorbable, wireless and multifunctional, progress in the development
of minimally invasive power sources in implantable systems has remained
limited. Here we summarise three promising minimally invasive power
sources, including energy storage devices (biodegradable primary
batteries, rechargeable batteries and supercapacitors), human body
energy harvesters (nanogenerators and biofuel cells) and wireless power
transfer (far-field radiofrequency radiation, near-field wireless power
transfer, ultrasonic and photovoltaic power transfer). The energy
storage and energy harvesting mechanism, configurational design,
material selection, output power and applications in vivo are also
discussed. It is expected to give a comprehensive understanding of the
minimally invasive power sources driven IMEs system for painless health
monitoring and biomedical therapy with long-term stable functions.
1. Introduction
Since Hans Berger introduced electroencephalography (EEG) to record the
electrical activity of the brain in 1929, electronics for physiological
measurement and biological stimulation have been of interest for more
than 90 years.[1-3] Over the past decades,
numerous wearable and implantable electronics were designed for
monitoring and measuring biological signals. According to Halperin et
al., over 25 million United State citizens rely on implantable medical
devices for life-critical functions in 2008,[4]the number of implantable cardioverter defibrillator implants 10-times
increased between 1990 and 2002,[5-6] the demand
for implantable medical electronics (IMEs) in 2015 in the United State
is about $52B.[7] At present, the implantable
medical device market is not just orientated to the growing geriatric
population and associated prevalence of chronic degenerative diseases,
younger populations pursuing a healthier and high-tech lifestyle also
drive the lucrative wearable and implantable electronics market. The
state-of-art technologies enabled biological signal recording including
electrophysiological, physiological (pulse, temperature), mechanical
(strain, pressure) and biochemical (glucose, pH)
information.[8-10] Each of these biological
signals is of vital importance for clinical research about physical
functioning and various diseases.
However, it is still challenging to get access to bio-signals with high
fidelity and stability from the target area of living organisms while
conventional IMEs still stay rigid and bulky. The recent advanced
technologies in microelectromechanical systems (MEMS), ultrathin
electronic devices, sensors and biocompatible/bioresorbable
encapsulating layers have broadened the application range of implantable
electronics from traditional rigid and bulky devices to soft
bioelectronics systems that interface with the complex geometries and
curved surfaces of the human body.[8, 11] Compared
with the first cardiac pacemaker
invented and implanted in the human body in
1958,[12] bio-integrated electronics with good
flexibility and stretchability shows huge progress and more benefits for
precise signal recording and pain alleviation from patients. Nowadays,
numerous miniaturised implants and wearable electronics have been
developed. For instance, electrocorticography (ECoG) and
electrocardiogram (ECG) sensors for neurological disorders study (e.g.,
Epilepsy, dementia, Parkinson’s disease and restless leg syndrome),
angioplasty tools, prosthetic eye/skin, optoelectronic nerve stimulator,
wearable pressure, strain, temperature sensors combined with drug
delivery and data storage devices, signal recording and real-time
treatment integrated with wireless data transmission, and wearable
energy storage system for portable and remote
healthcare.[8, 13-14] Though great progress has
been made over the past decades to minimise the dimension of implants, a
higher requirement towards more precise biomedical functions has also
been set. The dimensions of the medical electronic system probing these
signals are still orders of magnitude larger than those cells or
tissues, thus developing minimally invasive or injectable micro and
nanoscale medical electronic systems closely matching target tissues is
necessary for the evolution of new-generation
bioelectronics.
To provide energy for the
new-generation minimally invasive bioelectronics system, the size and
weight of the power source as a significant part of this system should
also be taken into consideration. Batteries as the most used
electrochemical energy storage devices developed for IMEs have enabled
the successful operation for the treatment of human disease. Though
energy requirements for the power sources vary with the IMEs functions,
high volumetric energy density and minimised dimension are highlighted
aiming to minimise discomfort for the patient.[15]However, conventional energy storage
devices (such as Li-ion batteries) are usually large and bulky with
inflexible packaging, leading to associated issues such as secondary
invasive surgery for replacement due to limited capacity and potentially
toxic substances leakage risk.[16] Therefore, new
challenges have been present for power source devices to match with the
soft, 3D and dynamically curved biological organisms while providing
enough energy to the biomedical system.[17] To
overcome the key limitations to the development of a minimally invasive
IMEs system, the prospective implantable power sources should be
developed towards the following features: minimally invasive,
lightweight, durable, high-capacity, flexible, biocompatible or
bioresorbable.
According to the different functional requirements of the IMEs, the
designed and matched power source for the system varied. For short-term
implantable electronics that are designed to be implanted and operate
only for a prescribed time, biodegradable and
bioabsorbable materials provide a
unique opportunity. For instance, applications like muscle stimulation,
bone growth stimulation, neurostimulation and wound healing require the
power source to operate only for a short time compared with heart
stimulation working over the whole patient’s life, biodegradable and
bioabsorbable electronics can act as a desirable option to avoid the
second surgery for device retrieving and tissue
lesion.[18] As physically transient electronics,
biodegradable power sources including biodegradable primary
batteries,[19-22] biodegradable
supercapacitors[23] and bioresorbable power
harvesters,[24] can be fully dissolved into
biologically benign byproducts in biofluids through hydrolysis and thus
well resolve the problem of repeated surgery without secondary invasion.
For long-term applications, durable energy storage devices with high
energy density and energy harvesting devices with long-term stability
are necessary. Compared with the primary battery,
the rechargeable battery can provide
a longer serves time and has been developed for neurostimulators
operating in the milliwatt power range.[15] But
for the minimally invasive implantable electronic system, secondary
rechargeable batteries must also satisfy the requirements of
bioabsorbable primary batteries, including reduced invasion and
biocompatibility except for high energy density. In this case,
miniaturised rechargeable batteries with high aspect ratio form can well
solve the problem occurred with traditional bulky lithium-ion batteries
and achieve charge/discharge cycling process in vivo such as sodium-ion
batteries and fibre supercapacitors showed decent power capability and
good biocompatibility.[25-27] Alternatively, the
energy sources from the human body are also promising power options,
which can provide a continuous stream of energy for medical devices such
as pacemaker without restrictions like battery replacement and
cumbersome daily charging.[28] Emerging
biocompatible, ultra-flexible and miniaturised energy harvesters include
piezoelectric nanogenerators (PENG) and triboelectric nanogenerators
(TENG) for mechanical energy harvesting and biofuel cell for chemical
energy harvesting.[29-34] The human body as a
natural energy conversion factory can provide an abundant and constant
flow of available biochemical and kinetic energy, it provides unlimited
possibilities to support the IMEs during the whole lifetime of human and
even to prolong the human lifespan.[28] In
addition, wireless and battery-free technologies have also been widely
studied for the application in miniaturised and ultralightweight devices
probing signals with high chronic stability and signal
fidelity.[35-36] For electronics such as
optogenetic stimulator interfacing with neural tissues and micro
injectable needles for multisite recording on the cellular scale,
wireless power transmission technologies can provide reliable and
constant power supply with versatile design and deployment options. At
present, four main kinds of wireless power transmission technologies
have been developed including near-field magnetic resonant
coupling,[37] far-field radio frequency
(RF),[38-39] photovoltaic (PV) power
transfer,[40] and ultrasonic power
transfer.[41] It can be applied as independent
energy supply but also as complementary recharging technology to extend
the lifespan of implanted energy storage devices.
In this review, we provided an overview of the state-of-the-art
minimally invasive implantable electronics with an outlook of the smart
and injury-reduced implantable electronics in the future, and aim to
summarise various alternative miniaturised power sources for the
implantable electronic system. Three broad categories of minimally
invasive power sources were classified regarding their different energy
supply mechanism: Energy storage devices, human body energy and wireless
power transfer as summarised in Figure 1. The advantages and limitations
of each kind of power strategy was reviewed in detail. Finally, the
challenges and prospective future of minimally invasive electronics and
corresponding applicable power sources were discussed.
2. Recent Progress in Implantable Electronics
Conventionally, implantable electronics with hardware modules such as
bio-functional parts, circuits and energy storage devices are packaged
and sealed within bulky metal cases, then implanted into the vacant area
of the human body by open surgery.[42] Clinical
implants such as drug delivery devices, pacemakers and ECG monitors are
also in such conventional form. Figure 2 provides an overview of the
milestones in the development history of implantable electronics since
the first implantable battery-powered
cardiac pacemaker was invented in
1958.[43] However, many complications including
infection, thrombosis, lead failure and pneumothorax are related to this
kind of construct of the cardiac pacemaker, the traditional implantation
will cause large incisions and cannot exempt patients from secondary
surgery to take implants out after the energy of the system is running
out. Postsurgical complications caused by these invasive surgeries and
bulky implants have also been reported.[44] In
this case, an implantable device with an ultrathin structure and good
conformability will be