# Material Design in Implantable Biosensors toward Future Personalized Diagnostics and Treatments
## 3 Classification of Implantable Biosensors Based on Material Design
### Electrochemical Active-Based Implantable Biosensors  
The two main constructive parts of each biosensor include a bio-recognition element that recognizes a target and a transducer that translates the molecular interaction into an electrical signal. Proteins, peptides, enzymes, antibodies, and nucleic acids are widely employed as detection components in biosensors. In electrochemical devices, electrodes that are transduction elements explore the intrinsic electron transfer nature of recognition elements throughout biochemical reactions. Electrochemical implantable devices are generally assembled on three-electrode or two-electrode systems with the latter having both the reference and counter electrodes combined into one. In such a system, the potential of the working electrode is influenced by a potentiostat to direct electrode reactions with immobilized enzymes for a complete catalytic turnover. The electrochemical biosensors, which can be divided into voltammetric and amperometric biosensors, can evaluate faradaic currents (fixed or varied potentials). They are ion-selective, conductometric, and field-effect transistor-based sensors. Amongst all metals, stainless steel or noble materials such as gold and other different alloys (i.e., platinum-tungsten or iridium oxide) are typically used as fundamental materials for forming strong metal electrodes. Regardless of the type of materials used, electrochemical implantable biosensors, based on their application, can be categorized into implantable glucose biosensors [41], implantable blood-gas, pH, electrolyte, and ion-selective field-effect transistor sensors [42; 43; 44]. In electrochemical implantable devices, using high-quality electrodes to diminish motion artifacts and record accurate, stable, and undistorted signals, are unavoidable and necessary. Other than changing the local analyte concentration at the sensing site due to the corrosive nature of the body liquid (provoking thrombus, inflammatory reactions, and capsule formation), they trigger a sequence of effects such as electrode passivation and membrane biodegradation, which limit the choice of materials. To avoid these issues, the most logical and practical solution is material biocompatibility improvement through the application of suitable bulk materials or modification of their derivatives to facilitate the adsorption of proteins and cells [45]. Among the developed biocompatible materials, polymers are coming in first place. Polymeric materials such as poly(ethyleneglycol), polyvinylchloride, polyurethane, silicon rubber, Nafion, cellulose, chitosan, and phospholipids exhibit good performance in electrochemical implantable devices. It is important to mention that in converting materials to biocompatible compounds, some of the functionalities of the original materials will be lost. This mostly happens for polymeric materials used in potentiometric sensors. Conducting polymers, on the other hand, are another category of polymers that have been used as sensing elements in implantable biosensors due to their ability to transduce biological signals into electrical signals. Additionally, conducting polymers can be easily modified to improve selectivity and sensitivity, making them an attractive choice for biosensing applications. However, the use of polymers in implantable biosensors also poses some challenges, such as the potential for foreign-body response and the need for biodegradability or bioseprobability in some contexts [46; 47]. Other than biocompatibility, permeability and permselectivity are two other important factors for selecting constructive materials in implantable electrochemical sensors. The performance of implantable amperometric sensors is defined by the electroactive species flow toward the electrode. Therefore, the selected materials in these sensors must have a certain degree of permselectivity, so the flow caused by interferents can be hindered or lowered to some extent.