FIGURE 2 Milestones in the
development history of implantable electronics, and an illustration of
the advanced minimally invasive electronics implanted in various parts
of the human body and perspective outlook for the features of
implantable electronics in the future. Reproduced with
permission.[43] Copyright 2006, PubMed Central.
Reproduced with permission.[46] Copyright 2008,
IEEE. Reproduced with permission.[47] Copyright
2011, IEEE. Reproduced with permission. Copyright 2019, Medtronic.
Reproduced with permission.[39] Copyright 2015,
Springer Nature. Reproduced with
permission.[24] Copyright 2020, Springer Nature.
Reproduced with permission.[52] Copyright 2021,
Science. Reproduced with permission.[53] Copyright
2022, Springer Nature. [55] . Reproduced with
permission.[56] Copyright 2019, ARVO. Reproduced
with permission.[57] Copyright 2021, Science.
Reproduced with permission.[58] Copyright 2007,
IEEE. Reproduced with permission.[59] Copyright
2018, Wiley-VCH GmbH.
3. Minimally Invasive Power Sources
Commonly a power source is contained
in a fully implanted biomedical device, the demand for minimally
invasive power sources will continue to increase as the minimally
invasive bioelectronic applications have been well developed and will
expand rapidly.[8] The commonly used power source
for IMEs is bulky electrochemical power sources such as batteries and
supercapacitors due to the mature technology and available
hardware.[60-61] Conventional lithium-ion
batteries can meet the requirement of energy supply due to their
reliability and high energy density (~400 Wh
kg-1).[15, 62] Nevertheless,
lithium-ion batteries in the bulky, rigid and large-size form will not
only result in the large total volume of the implant system but also
nonnegligible issues such as irritation and infections after surgery.
Additionally, issues such as battery replacement after charge depleting,
toxic material leakage of electrodes and electrolytes, and rigid shape
mismatched with 3D dynamically curved tissues may lead to the unprecise
interpretation of experimental data.[17, 35]Obviously, the dimension and lifespan of power sources represent the
major limiting factors for the development of the advanced biomedical
implantable electronic system at present. Therefore, a qualified
implantable power source for novel biomedical implants should possess
the following features: miniaturised, light-weight, adequate capacity,
and mechanically deformable properties that match well with soft
biological organs and tissues, composed of biocompatible
materials.[16] Since the power source plays a
crucial part in the development of IMEs, many efforts and enormous
enthusiasm of researchers have been dedicated to developing implantable
power sources to extend the lifespan of
IMEs.[63-64] With different functions and
diagnostic purposes, IMEs show different requirements towards the power
source. For short-term applications, biodegradable batteries with no
need for secondary surgery will be a desirable
choice.[65] For long-term applications, a power
source with enhanced capacity such as batteries or energy source
harvesting power wirelessly in-vivo and from the external of the human
body will be more suitable. There are many forms of energy sources
optional for IMEs such as thermal, kinetic, biochemical,
electromagnetic, acoustic, and radiative forms of
energy.[16] For example, energy derived from the
human body including glucose oxidation,[66]heartbeats, and organ motion,[67-68] can be
harvested by biofuel cells,[69] and
piezoelectric/triboelectric energy
harvesters.[70-71] Also, wireless power
transmission technologies including inductive
coupling/RF,[72]photovoltaic,[73] and ultrasound-induced power
transfer[74] can be used as direct power or to
assist in recharging the existing energy storage devices. Benefiting
from these energy solutions, self-powered IMEs can be realised. To
further discuss the practical application of different minimally
invasive power sources based on the above mechanisms to power the IMEs,
three categories were summarised: Energy storage devices (e.g.,
biodegradable primary batteries, rechargeable batteries, fibre
supercapacitors), human body energy harvester (e.g., PENG, TENG, biofuel
cell) and wireless power transfer (e.g., near-field magnetic resonant
coupling, far-field RF radiation, PV power transfer, ultrasonic power
transfer). Application contexts and advantages of each minimally
invasive power source will be discussed in detail.
3.1. Energy Storage Devices
3.1.1. Biodegradable primary batteries
Batteries, including the single-use primary battery and rechargeable
secondary battery, have been developed and can provide sufficient energy
for IMEs with a lifespan of years.[62] Various
IMEs including neurostimulators, cardiac pacemakers and cardiac
defibrillators have applied batteries as energy sources. Not like
batteries in other electronics, implantable batteries need to satisfy
strict and considerable requirements including high energy density,
stability, complete packaging, low self-discharge and a battery life of
years to not only support vital functions in human bodies but also
ensure the safe operation of devices. Also, small volumes and
lightweight are required in the limited space inside the human body.
Li-CFx (lithium-carbon monofluoride) and Li-SVO
(lithium-silver vanadium oxide) batteries have been applied in the
industry for cardiology applications for
decades.[62] As an example, the Reveal LinQ
insertable cardiac monitor fabricated by Medtronic in 2014 is a wireless
and powerful small insertable cardiac monitor ideal for patients
experiencing infrequent symptoms that require long-term monitoring or
ongoing management, the device consisted of two titanium nitride-based
recording electrodes, programmable electronic system and a
Li-CFx battery that powers the entire system up to 3
years.[48] Except for Li-CFx[75] and Li-SVO batteries[76], lithium-iodine (Li-I2)[77] and lithium manganese dioxide
(Li-MnO2) [78] have also been
developed and widely applied in IMEs.
At the same time, the primary batteries have limitations such as rigid
structure, capacity loss and battery failure, and therefore cause
non-healing incisions as well as the risk of complications after
insertion. With the emerging transient electronics technology, an
alternative strategy is to develop biocompatible or biodegradable
batteries.[79-82] Considering the safety issue
which might be caused by the leakage of the metal-based material, metals
like Mg and Zn are safer than Li inside the human body. In 2014, Yin et
al. first reported fully biodegradable batteries consisting of
dissolvable Mg-X (X = Fe, W, or Mo) foils as anodes and cathodes, and
polyanhydrides for encapsulation. For short- and medium-term
applications, biodegradable features are desirable so that a second
surgical removal is not required.[16] Recently,
Mg- and Zn-based batteries have made great progress. For instance, Mg
and its alloys with high theoretical capacity (2.2 Ah
g-1) are promising anode materials and represent
excellent biocompatibility (daily allowance ≈300 mg
d-1).[22] According to Huang et
al., they designed a completely biodegradable primary
magnesium-molybdenum trioxide (Mg-MoO3) battery with
high performance as illustrated in Figure 3A. In their design, a
single-cell battery with a stable output voltage (1.6 V) can achieve a
high energy density of 6.5 mWh cm-2. The battery can
work for about 13 days after encapsulation with biodegradable
polyanhydride and poly(lactide-co-glycolide) (PLGA), and complete
biodegradability of the battery can be observed in vivo experiments.
With stable output voltage and a relatively long lifespan, this battery
system could meet the requirements of short-term/medium-term and
implantable electronics requiring ultralow power, which represents a
promising method for self-powered IMEs. Similarly, Yin et al. reported a
water-activated primary batteries with magnesium foils as anodes and
metal foils based on Fe, W or Mo as the
cathodes.[19] The primary battery was encapsulated
by biodegradable polyanhydrides, it can provide a stable voltage output
of about 1.6 V for up to 6 hours when discharging at a current density
of 0.1 mA cm-2 as shown in Figure 3B. From the
degradation process, it can be observed that the polyanhydride cover
dissolved first followed by the degradation of Mg and Mo foils in
phosphate-buffered saline (PBS) solution at 37 °C, and the primary
battery was fully degraded after 19 days by increasing the temperature
to 85 °C. Based on their transient batteries, the minimum dimension
required to power the wireless implantable sensing is 5 mm with a
thickness of 3.46 mm for operation for 1 year, which is a fully
biocompatible and environmentally benign power source for IMEs. In
addition, zinc primary battery is another option while Zn metal has a
slower degradation rate, it can avoid local pH increases and alleviate
the evolution of gaseous hydrogen. According to Dong et al., a
bioresorbable zinc primary
battery was constructed with zinc microparticle network coated with
chitosan and Al2O3 double shells as the
anode.[20] When discharged at a current of 0.01 mA
in saline, the battery can generate stable voltage output of 0.55 V with
a cross-sectional area of only 0.17 × 2 mm2. With 15
mm Zn anode, the battery can discharge stably for 200 h and can be fully
dissolved in the saline solution, as can be observed in Figure 3C,
indicating a significant potential for in vivo powering transient IMEs.
In some cases, ionic liquids (ILs) with stable potential window and high
ionic conductivity can be utilised as additives for biopolymers and
biocompatible electrolytes.[83] As Jia et al.,
demonstrated, a biodegradable thin film magnesium primary battery was
designed with biocompatible IL (choline nitrate) and ion-conducting
free-standing membrane of biodegradable silk
fibroin.[21] The silk protection layer can help
protect and control degradation. With another layer of silk fibroin,
stable open-circuit voltages above 1.21 V for more than 100 min can be
observed and then finally be fully decomposed as can be seen in Figure
3D.
At present, bioresorbable electronics or transient electronics have been
widely studied and have now achieved significant progress in mechanism
and applications, it becomes an emerging technology in the field of
innovative healthcare electronics.[84] Benefiting
from the existing bioresorbable materials (e.g., Mg, Zn, Mo, polylactic
acid, polyglycolic acid, polylactic-co-glycolic acid, carbon nanotubes,
graphene),[85-89] biodegradable primary batteries
can provide power for the bioelectronic functions such as post-surgical
monitoring of organ, tissue, and wound healing for a period from seconds
to months, and finally fully decomposed into biological safe byproducts
through hydrolysis and enzymatic degradation, which significantly
reduced the risk of irritations and complications caused by surgery. It
is high expected to lead a revolutionary change in the field of power
sources for minimally invasive IMEs, while at the meantime, there are
some critical challenges including the high-cost fabrication techniques,
uncontrollable packaging methods, and the dissolution mechanisms of
bioresorbable electronics still exist and require further exploration.