Page 48 - Read Online

Page 30 of 43 Wang et al. Soft Sci 2024;4:41 https://dx.doi.org/10.20517/ss.2024.53

deliver optical stimulation and conditioning directly to the targeted implantation site via the LED
[Figure 13F]. Notably, the efficacy of optical stimulation is constrained by the inherent wavelength emission
of the LED, necessitating precise modulation of parameters such as wavelength, intensity, and emission
frequency to align with the therapeutic requirements at various treatment stages [34,219] . In 2017, Tamaki et al.
developed a neural probe equipped with eight recording sites and three light-emitting sites . This design
[19]
successfully facilitated both optical stimulation and electrophysiological signal recording in rat brain
experiments [Figure 13G]. As DBS electrode technology advances and exploration into novel stimulation
methods continues, a broader array of techniques is emerging. In 2023, Lee et al. introduced a conductively
stable and mechanically durable bilayer eutectic gallium indium (EGaIn) composite-coated stretchable
[95]
fiber , enabling both optical and electrical stimulation of neuronal cells of the mouse brain [Figure 13H].
Similarly, recently, Kim et al. proposed a multifunctional flexible thermally stretched fiber neural probe
designed for bi-directional synapse probing within the brain [Figure 13I]. Collectively, these
[220]
advancements in DBS technologies present new avenues for interrogating dysfunctional brain circuits and
assessing the therapeutic potential of modulating their outputs.

To sum up, the current selection of implantable neuroelectrode types primarily depends on the specific
requirements of the application. For long-term implantation, the stability of the electrode material and
structure over time must be carefully assessed through extensive animal and clinical studies. Additionally,
there is a growing trend towards the development of multifunctional neuroelectrodes that combine
recording and stimulation capabilities. Future efforts should concentrate on reducing electrode size through
reliable and high-precision manufacturing processes. Smaller electrodes result in smaller incisions and less
post-operative pain for patients, promoting greater acceptance of surgical interventions.

Implantable cylindrical biosensors
Implantable biosensors are sensors that utilize materials sensitive to biological substances and physiological
[24]
signals for the detection of biological organisms by implanting sensors into the human body . These
biosensors play a crucial role in providing in vivo sensing capabilities, expanding the integration and
application of sensors in medical devices. There are two main categories of biosensors based on the
information they detect: implantable biosensors that focus on detecting biomarkers such as glucose
[11]
[222]
sensors [12,221] , calcium sensors , and neurotransmitter sensors ; and implantable biosensors that focus on
detecting both electrophysiological signals of the organism and biochemical signals, such as temperature
sensors, pH sensors, and intracranial pressure sensors [223-225] .

Biosensors focusing on the detection of biomarkers have biosensitive materials as recognition elements,
which mainly consist of appropriate physicochemical transducers and signal amplification devices. In 2018,
Pu et al. proposed a cylindrical enzyme electrode glucose biosensor fabricated by inkjet printing
[12]
[Figure 14A]. In vivo experiments in rats demonstrated that the sensor has the potential to be used for
subcutaneous tissue implantation for continuous glucose monitoring. In 2020, Wang et al. suggested that
functionalized MWCNTs twisted into helical fiber bundles could be utilized to detect changes in calcium
ion and glucose concentrations in the blood, as well as hydrogen peroxide (H O ) concentration and
2
2
distribution [Figure 14B and C]. A continuous blood glucose monitoring system comprising a plastic
[11]
optical fiber, a diboronic acid receptor-based chemical indicator, reinforcing wires, and thermocouples
[226]
enables direct measurement of plasma glucose concentration within the patient’s blood vessels .
Furthermore, the immobilization of glucose oxidase (GOx) on the surface of carbon fibers enabled the
micro-cylindrical electrode to simultaneously monitor glucose and dopamine in vivo [Figure 14D-F].
[227]
The sensor demonstrated high sensitivity and selectivity, positioning it as a promising tool for reliable
metabolic studies and neurotransmitter monitoring.