# Material Design in Implantable Biosensors toward Future Personalized Diagnostics and Treatments
## 3 Classification of Implantable Biosensors Based on Material Design
### Polymer-Based Implantable Biosensors
generated an in vivo wireless and implantable electrochemical biosensor that can measure oxygen pressure in intramuscular tissues to distinguish between hyperoxic and hypoxic statuses (Figure 9A,B) [71]. Some abnormal mechanisms in the body can result in aberrant ion concentrations that change the local pH value. The pH changes can be used purposefully as indicators for metabolic conditions assessment. For instance, [PERSON] et al. created an implantable electrochemical pH biosensor based on polypyrrole's protonation/deprotonation process [72]. The insertion of this biosensor inside the leg muscles of 11 rabbits exhibited an excellent sensitivity with low variation between pH 4.0 and pH 9.0. Moreover, enzyme-based transducers, considered the forerunners of the generation of implantable devices, are generally utilized for metabolism assessment of glucose detection [73]. Most commercialized implantable glucose biosensors are amperometric sensors that can detect products of glucose-enzyme reactions. The enzyme in this system is immobilized on the electrode surface to provide a redox reaction with an analyte and generate a current. Polymeric materials facilitate enzyme immobilization on the electrode surface either by chemically binding within the cross-linked polymer network or physically embedding within the materials. Other than immobilization, polymers can improve the sensitivity, biocompatibility, and lifetime of the biosensors. Additionally, [PERSON] et al. described an ingestible micro-bioelectronic device (IMBED) consisting of a probiotic sensor and ultralow-powered microelectronics [74]. This implantable biosensor is used to  
Figure 8: Demonstration of biophysical sensing using implantable biosensors. **(A,B)** Implantable piezoelectric device’s structure and implantation in mouse abdomen. **(C)** Depressed and relaxed progression measurement of the pressure signal response [69]. **(D,E)** Structure of a piezoresistic device for the measurement of temperature and pressure and its implantation in the brain. **(F,G)** Data of the temperature and pressure collected by the device in comparison with a commercial sensor. Reproduced with permission from ref. [22] ©2016 Springer-nature Ltd.  
detect gastrointestinal bleeding with its heme-sensitive probioticic component (Figure 9C). After bleeding, the released hem molecules from lysed red blood cells can increase the hem extracellular concentration. The entrapment of heme by bacteria triggers luciferase operon luxCDABE expression, which generates light that can be detected by photodetectors incorporated in the device and translated as bleeding levels (Figure 9D). This study demonstrated the in vivo applicability of this device to detect blood signals (Figure 9D,E). In another study, [PERSON] et al. reported a polymer-based ratiometric electrochemical biosensor that can monitor the brain's copper ions (Cu\({}^{2+}\)). The generation of reactive oxygen species (ROS) disrupts biological systems and upsets the balance of Cu\({}^{2+}\) and Cu\({}^{+}\) in the nerve center, leading to neurodegenerative disorders [75]. [PERSON] et al. developed a platform for catecholamine neurotransmitters (CA-NTs) detection in rat brains. In the proposed platform, the polymeric composite polyethylene terephthalate (PET), platinum (Pt-GATE), and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) were used as the active materials for covering the electrode surface (Figure 9F) [76]. The measurement of CA-NTs (dopamine, noradrenaline, and adrenaline) by the electrode (Pt-GATE electrode) is due to the oxidation of catechol groups in CA-NTs that generate Faradic currents (Figure 9G,H). Figure 9: Typical applications of biochemical sensing via implantable biosensors. (**A**) Oxygen sensor implanted in a rabbit. (**B**) Data collected from the biosensor demonstrating the relation between the in\(-\)vivo oxygen status and cathodic current data. Reproduced with permission from ref. [71] (\(\copyright\)2020 Elsevier. (**C**) Capsule\(-\)type biosensor composition.