FIGURE 1. Overview of various alternative minimally invasive
power sources. “Biodegradable primary battery” Reproduced with
permission.[19] Copyright 2014, Wiley-VCH GmbH.
“Rechargeable battery” Reproduced with
permission.[26] Copyright 2021, Royal Society of
Chemistry. “Supercapacitors” Reproduced with
permission.[27] Copyright 2018, Elsevier.
“Triboelectric nanogenerator” Reproduced with
permission.[30] Copyright 2014, Wiley-VCH GmbH.
“Piezoelectric nanogenerator” Reproduced with
permission.[29] Copyright 2021, Elsevier.
“Biofuel cell” Reproduced with permission.[31]Copyright 2013, Royal Society of Chemistry. “Ultrasonic wireless
power” Reproduced with permission.[41] Copyright
2022, Elsevier. “Photovoltaic wireless power” Reproduced with
permission.[40] Copyright 2018, Proceedings of the
National Academy of Sciences. “Far-field RF radiation wireless power”
Reproduced with permission.[39] Copyright 2015,
Springer Nature. “Near-field wireless power” Reproduced with
permission.[37] Copyright 2017, Elsevier.
a better choice due to the minimised volume and better matching with
target organs. Take cochlear implant electrodes as an example, the
first-generation electrodes developed in the 1980s and 1990s
demonstrated severe insertion trauma,[45] and the
improved design of configuration can help avoid the severity of the
injury. A pre-moulded spiral cochlear electrode implanted with the
advanced off-stylet technique can reduce contact with the outer wall of
the scala tympani, soft top and silicone rubber surface is also helpful
to prevent internal tissue trauma.[46] Similarly,
a hermetic vision prosthesis with a wireless-operated subretinal
neurostimulator has been developed and implanted in a minipig eye in
2011.[47] To reduce the risk of infection caused
by wireless transmission coils under the delicate conjunctiva, the coils
were carefully wound on a spherical mandrel to match the curvature of
the eye and moulded in biocompatible flexible poly(dimethylsiloxane)
(PDMS) encapsulation. Another way to achieve minimally invasive
implantation was developed in 2014 by Medtronic, a medical device
company. A subcutaneous insertable cardiac monitor (the Reveal LinQ)
with a high aspect ratio structure was designed for continuous cardiac
monitor such as arrhythmia and atrial fibrillation, the parylene-based
encapsulation and minimal dimension (44.8 × 7.2 × 4.0
mm3) allows it to be inserted subcutaneously through
an incision size less than 1 cm without any post suturing
process.[42, 48] With the programmable electronic
system and lithium carbon monofluoride battery, the electronics system
can be inserted into an infant’s chest and work independently for up to
3 years with wireless data communication with medical
centres.[49] Even so, mechanically rigidness
inducing stress to the interface between devices and tissue is still a
nonnegligible issue, it’s still necessary to seek a flexible and
thin-film configuration for such kinds of IMEs. Soft and stretchable
materials with low modulus will be a desirable choice here. In 2015,
Park et al. constructed a
miniaturised, fully implantable soft optoelectronic system for wireless
optogenetics consisting of radio frequency harvester antenna for
wireless power and light-emitting diode (LED) arrays to activate
opsins.[39] Inside the area of only 3 × 3 mm, the
electrical interconnects and the circuits were sealed by flexible
polyimide with thickness of 3 um and low-modulus silicone elastomer with
thickness of 100 um. This design enabled the implanted system to
accommodate anatomical shapes and natural motions, and to achieve
minimally invasive fully implantation on multiple neural
interfaces.[50-51] Furthermore, soft and wireless
powered bioresorbable electronic were developed by Choi et al. for the
neuromuscular regeneration stimulator.[24]Bioresorbable dynamic covalent polyurethane (b-DCPU) was synthesised and
applied as substrate and biofluid barrier for deformable filamentary
serpentine interconnects, the elastomeric mechanics and low levels of
swelling in biofluids enable the implants to serve for over 30 days with
long-term stability during the stimulation operation. With wireless
power transmission technology and bioresorbable feature, the
bioresorbable electronics can be
implanted once for all and operate independently till full dissolution
into benign products without residues, which avoids surgical extraction
or secondary invasion for replacement. This kind of bioresorbable
wireless powered electronics are also desirable options for bone healing
treatment, spinal cord stimulation, brain therapy and cardiac pacing.
Recently, minimally invasive spinal cord stimulation via simple needle
puncture under local anesthetic instead of traditional bulky paddle-type
devices requiring invasion under general anesthetic have been
reported.[52] Since spinal cord implants are
softer and soft robotics has made great progress regarding the surgical
manipulators, Woodington et al. developed a minimally invasive spinal
cord stimulation which can be loaded into needle for percutaneous
implantation with low risk surgery.[52] A 14-gauge
Tuohy needles were used for the loading and insertion of the rollable
devices with dimension less than 2 mm including fluidic connections,
electrical connections and supporting tubing. Due to the narrow
footprint and flexibility, insertion trauma can be reduced, and
on-demand shape actuation can be achieved. Compared with the previous
rigid devices, it can offer far fewer surgical risks with simple
epidural needle insertion. Till now, huge progress has been made towards
the minimally invasive designation of implantable electronics as can be
seen from the milestones in the development history.
Comparatively, biomedical electronics with a high aspect ratio structure
such as a needle-like shape or integrated on a tubular carrier can solve
the problems of a large incision, and enables accurate and minimally
invasive injection of biomedical electronics into inhomogeneous
tissues.[51] Nowadays, injectable biomedical
devices were widely studied and applied in the field of brain sciences,
percutaneous therapies, reading vital clinical signs, and healing
diseases et al..[42] With a high aspect ratio
form, injectable biomedical devices with various designs can be applied
to almost every part of the human body. As illustrated in Figure 2 top
left, various state-of-the-art minimally invasive electronics were
developed and implanted in different parts of human body. For instance,
tissue-like neurotransmitter sensor for neuronal recording in the brain
and gut with minimal damage to other regions termed
NeuroString were designed by Li et
al..[53] As tissue-mimicking stretchable
neurochemical biological interface sensors, it enables long-term in vivo
real-time sensing in the brain and simultaneously serotonin dynamics
detecting in the gut of a behaving mouse with high data recording
fidelity. With easily stretched, twisted and even knotted structures,
the ultra-flexible NeuroString can get access to the twisting colon of a
mouse with no subsequent insertion trauma representing its high
compatibility with soft and complex tissues. It is expected to be
applicable for non-invasive biomolecular monitoring and dynamic signal
study throughout the body in primates. The cochlear implant is another
successful electronic prosthesis affecting millions of people worldwide,
it changed the lives of people with profound hearing loss by long
cable-like electrodes implanted into the spiral-shape cochlear area for
hearing aid and restoration.[46, 54] According to
Pinyon et al., cochlear implant electrode array integrated with
neurotrophin gene therapy can produce directed regeneration of spiral
ganglion neurite through stimulation in the guinea
pig.[55] It provides minimal extraneous electrical
stimulation for auditory nerve regeneration, nerve fibre can be restored
to the pre-deafness values.
Subretinal neurostimulators as a
novel technology can also help individuals suffering from retinitis
pigmentosa and macular degeneration to restore useful vision. The
reported neurostimulation array based on a soft polyimide substrate was
constructed and inserted through the scleral incision into the
subretinal space with only a 3 mm wide
incision.[56] After successful implantation,
excellent retina apposition and intact inner layers of the overlying
retina can be retained. For the cardiovascular system to deliver oxygen
and nutrients to the body, implantable catheter-type oximeters can help
to provide accurate real-time monitoring of vascular oxygen saturations.
Compared with existing glass fibre-optic catheters leading to blood
vessel damage and infection, the recently reported miniaturised wireless
optoelectronic catheter system is more patient-friendly with good
flexible construction and the absence of physical tethers, and
especially, the diameter of the probe is only 1.5
mm.[57] With the addition of wireless data
transmission, real-time local tissue oxygenation and respiratory
activity can be monitored during continuous operation with accuracy and
precision at clinical standards. Injectable subcutaneous chips like
radiofrequency identification (RFID) tags in subcutaneous areas of the
human body for recording and tracking personal healthcare information
have also been reported.[58] Through a 2 mm
incision, a mini transmitter about the size of a grain of rice can be
implanted subcutaneously for the control of doors, lights, and
computers, and can also provide personal medical information when
patients are in emergency unconscious situations. Under the subcutaneous
area, soft and flexible configurations can further alleviate irritations
and chronic damage to surrounding tissues with enhanced mechanical
compatibility with soft skin. To realise the minimally invasive
subcutaneous implantation, a flexible-device injector was reported and
an ultra-flexible optical pulse sensor was successfully implanted into a
live pig animal model with the injector via a small incision of 4
mm.[59] Finally, spinal cord implants for neuronal
activity measurement and stimulation as the oldest and most established
neuromodulation therapeutic electronics have now developed towards
injectable minimally invasive implants via simple needle puncture
compared with traditional bulky devices.[52]Though in various forms and with different advantageous functions, these
injectable biomedical devices are designed to be injected into aimed
sites inside organisms with minimal invasions.
Enormous advancements and continuous breakthroughs have been achieved in
implantable and injectable biomedical electronics, which hugely advanced
the quality of surgical and monitoring tools. The future development
tendency of the advanced biomedical implantable electronic system will
shift towards minimally invasive, ultra-flexible, bioresorbable,
wireless and multifunctional to achieve more pain-free surgical
implantation and high-accuracy bio functional monitoring.