FIGURE 7 (A) The first implanted biofuel cell operating in a living
snail and generating electrical power by the consumption of
physiologically produced glucose as a fuel.
Reproduced with
permission.[115] Copyright 2012, American Chemical
Society. (B) Implanted single glucose biofuel cells in rats as power
source devices with no immunological rejection. Reproduced with
permission.[116] Copyright 2013, Springer Nature.
(C) The miniaturised intravenous implantable biofuel cell based on
modified flexible carbon fibre electrodes. Reproduced with
permission.[31] Copyright 2013, Royal Society of
Chemistry.
3.3. Wireless Power Transmission Technologies
Compared with internal energy harvesting devices, wireless power
transmission technology through electromagnetic radiation, acoustic
vibrations and optical cells et al. show higher output power up to 500
mW and better stability,[119-120] yet the
flexibility and dimension are the main challenges for application in
IMEs. Four main strategies of external wireless power transmission
technologies are included in this section: Far-field RF radiation,
near-field wireless power transfer (magnetic resonant coupling),
photovoltaic power transfer and ultrasonic power transfer.
3.3.1. Far-field RF radiation
Far-field radio frequency power transfer can be achieved by emitting
radio frequency radiation with a frequency ranging from 420 MHz to 2.4
GHz and a wavelength from 0.1 m to 1 m, from a transmitting antenna to a
receiving antenna, and converting the harvested radio frequency
radiation into direct current with a
rectifier.[121] With specialized primary designs
of transmission and receiving antennae, continuous and stable radio
frequency power can be delivered over a long distance of up to several
meters. With optimized designs of transmission and receiver coil, output
voltages larger than 300 mV can be achieved at a distance of 4 mm, and
higher voltages can be reached even at 10 V, which can provide enough
power for various bioelectronic implants and even soft
robots.[122] For example, Park S et al. introduced
a strategy combining thin mechanically soft neural interfaces with fully
implantable stretchable wireless radio power antenna and rectifying
circuits into a fully implantable miniaturised optoelectronic system for
optogenetic modulation of the spinal cord and of peripheral nerves, as
illustrated in Figure 8A.[39] The antennas with
the dimension of 3 mm harvest radio frequency power through capacitive
coupling between adjacent serpentine traces, thereby enabling compact
and lightweight devices (overall weight of ~16 mg) with
low-modulus system-level mechanics that can accommodate irregular
anatomical shapes and natural motions. With a minimally invasive and
flexible structure, it can be expected to be used in chronic studies.
Figure 8B shows a soft wireless bioresorbable neuromuscular stimulation
platform for nerve regeneration with a radio frequency wireless receiver
antenna as the power source.[24] After packaging
with bioresorbable elastomers (polyurethane), implanted electronic
stimulator could operate reliably without failure for more than one
month, over periods related to recovery from traumatic nerve damage.
According to the new Institute of Electrical and Electronic Engineers
(IEEE) standard on human exposure to
radio frequency radiation, the safe range of frequency is from 3 kHz to
100 GHz.[123] Based on the absorption rate of
tissue in most parts of the human body, the maximum exposure of radio
frequency radiation amount is about 2 W kg-1, and
incident power densities range from 1000 W m-2 at 100
kHz to 10 W m-2 at 100 GHz with the minimum value of 2
W W m-2 between 30 and 400 MHz, which is established
to protect the body from damage caused by tissue heating. Also, the
transmission efficiency will be influenced by the orientations of the
transmitting antenna and receiving antenna, and the surrounding
obstacles such as metal and human tissue containing moisture will lead
to heat generation and limited operating ranges from 0.1 m to 3
m.[124] To avoid these disadvantages, a
specialized design is urgent needed for the implantable antenna. For
IMEs using wireless far-field radio frequency power transfer as energy
supply method, long-term applications should be considered carefully due
to the safety issues that radio frequency radiation exposure would bring
to living organisms.
3.3.2. Near-field wireless power transfer
The near-field wireless power transfer method adopts magnetic resonant
coupling (non-radiative electromagnetic energy) and relies on inductive
coupling between a transmitting coil and a receiving
coil.[16] This strategy can transmit wireless
power with high efficiency over short distances of about several
centimetres. Due to the non-radiative nature of magnetic resonant
coupling with frequencies ranging from 100 kHz to 200 MHz, the
near-field wireless power transfer method is relatively insensitive to
changes in dielectric environments such as moisture in tissues and to
the presence of obstacles such as metals compared with far-field radio
frequency power transfer. Also, near-field wireless power transfer
working at a low working frequency applied in IMEs will generate less
heat and reduce tissue absorption and therefore can be applied in
complex biological surroundings, which minimizes safety concerns during
long-term operation. Meanwhile, data transmission or remote wireless
control can also be realized when using wireless near-field power
transfer since near-field communication (NFC) protocols can be used at
the same carrier frequency.[125] With near-field
wireless power transfer, a fully implantable subcutaneous electronic
system with an ultrathin probe and a micro light emitting diode for
optogenetic stimulation of regions in the deep brain can be wirelessly
powered with reliable operation and good chronic stability, as
illustrated in Figure 8C.[37] Furthermore, the
near-field wireless power transfer and NFC are also applied in the
biomedical smart contact lens device with modules including ultrathin
electrical circuits, microcontroller chip for real-time electrochemical
biosensing and functions including on-demand controlled drug delivery,
the near-field wireless power transfer and data communication (Figure
8D).[126] The smart contact lens system is
demonstrated to be feasible for application in non-invasive and
continuous diabetic diagnosis and diabetic retinopathy therapy. It is
reported that near-field wireless power via magnetic resonant coupling
is a reliable energy supply method with power up to 12 mW for small
rodent-sized devices and about 13 mW cm-2 can be
achieved.[127] With these features including low
working frequency, less produced heat, minimized safety concerns,
insensitivity to environments and data communication functions,
near-field wireless power transfer method has consequently facilitated
its applications in various wireless, battery-free and fully implantable
electronics for localized tissue oximetry, for bioresorbable monitoring
of intracranial pressure and temperature, for optogenetic stimulation in
the central and peripheral nervous systems and for pharmacological
modulation. In comparison, this energy supply strategy is superior to in
vivo energy-harvesting strategies in terms of the amount and stability
of output power.
3.3.3. Ultrasonic power transfer
The ultrasonic power transfer
wireless energy harvesting method is an emerging energy transfer
technology by converting ultrasound waves to electricity through
piezoelectric semiconducting coupling.[128]Ultrasound is an acoustic sound wave with a frequency higher than 20 kHz
but much shorter wavelengths than radio frequency radiation, focused
power delivery to implantable medical devices can be achieved with high
spatial resolution.[129] Therefore, compared with
traditional wireless energy harvesting based on electromagnetic
coupling, ultrasonic power transfer possesses several advantages in the
applications of IMEs, such as small attenuation of ultrasonic power in
biological tissues and excellent spatial resolution. For example, a
biodegradable PENG driven by external ultrasound power without any
transcutaneous leads was fabricated for sustained delivery of in vivo
electrical stimulation to promote the repair of peripheral nerve
injuries.[41] Under an ultrasound power intensity
of 0.7 W cm-2 for short-term excitation, the current
for stimulation driven by ultrasonic power is about 40 μA and the
voltage of single stimulation is 10 mV with the pulse width of 1 ms
demonstrating the feasibility of non-invasive monitoring of the nerve
repairing dynamics (Figure 8E).
However, this feature also brings disadvantages, for example, the
ultrasonic waves propagate in a specific direction, and the slight
misorientations between the external transducer and the implanted
receiver will cause evidently reduced coupling
efficiency.[35] To avoid a substantial impedance
mismatch at the tissue-air interface, it is essential to make sure of
close contact of the transducer with the
skin. The relatively moderate
absorption of ultrasound by soft tissues potentially enables large
penetration depths,[130] but the presence of
highly absorbing bone may also induce significant heating
effects,[131] and low ultrasonic frequencies may
induce cavitation which may also bring safety
problems.[132] Also, ultrasonic power transfer
devices are usually rigid and large in size, which is not suitable for
curvilinear and soft tissue and organs. Recent advances in ultrasonic
power sources with sufficient penetration depth and excellent spatial
resolution represented a promising application in non-invasive power
sources for IMEs and challenges remain to be solved regarding the
flexibility and the coordination with drag force generated in harsh
environments in human body.
3.3.4. Photovoltaic power transfer
Photovoltaic power transfer captures
the energy from electromagnetic radiation in the form of visible and
near-infrared light and converts them into electric energy by
photodiodes.[133] For IMEs, photovoltaic power
transfer devices need to be enfolded in soft living tissues, such as
skin, fats and muscles, so within the near-infrared spectrum
(700-2500 nm), high-scattering
tissue can be penetrated more efficiently by the light. For optogenetic
experiments, optical fibres were required to be inserted into the brain
tissue with another end attached to a remotely located light source such
as a laser or light-emitting diode, but the fibre tethers limited the
movement of the animals and caused entanglement which led to the
prohibition of neuroscience studies regarding the social interactions
and home cage manipulations of small animals in complex
environments.[134] Compared to previously reported
systems, injectable optoelectronics under cellular-scale for wireless
optogenetics has been reported with six times smaller dimensions and
thirty-fold lighter weight.[51]In this case, wireless,
ultra-miniaturised LEDs that can be implanted directly into the brain
will well solve the constraints, the miniaturised photovoltaic cells can
provide wireless power for the optogenetic electronics and can
significantly expand the movement range of the experiment animals. The
enhanced photovoltaic systems with dual junction gallium arsenide (GaAs)
solar cells array have an open-circuit voltages of 2.31 V and
short-circuit currents of 11.17 mA with the efficiency of 25%, and can
provide 4 V to support the wireless power for control logic circuits and
optogenetic stimulation under illumination with sunlight and desk
lamp.[134] It can supply the power for blue and
yellow micro light emitting diodes at intensities of 3.5 and 2.3 mW
mm-2. Furthermore, optoelectronic devices based on
semiconductor optoelectronic technologies have been developed for power
harvesting in ultraminiaturised wireless implants for optogenetic
neuromodulation.[40] A thin-film optoelectronic
device combining an infrared double-junction photodetector and a visible
LED was designed and realized near-infrared (∼810 nm) to visible (630 nm
(red) or 590 nm (yellow)) up conversion (Figure 8F). It can capture
photons from external incoherent low-power infrared LED bulbs and
generates an upconverted red emission power density of about 1.1 mW
mm-2 on the device surface, which can effectively
manipulate the activated ChrimsonR-expressing
neurons.[135] As an implantable photovoltaic power
source for wireless optogenetic control of in vitro and in vivo
neuroactivities, it can be used for deep-tissue light stimulation and
provided the unprecedented potential for the application in optical bio
interface. Compared with systems with far-field RF power, the
photovoltaic power transfer can achieve high conversion efficiency with
solar cells (10 times less power required compared with far-field
power).[134] However, similar to all the external
power transfer methods, the output power of solar cells strongly depends
on incident angles,[136] additional optical
imaging or tracking systems are necessary for the optics focusing, which
will put a limitation on the experimental area and lead to constrained
behaviours of experimental animals and human body using this power
strategy for IMEs.