# Advancements in Glucose Monitoring: From Traditional Methods to Wearable Sensors
## 2 Invasive Methods
### Electrochemical Glucose Sensors
Reproduced with permission from [25]. ter [26; 27]. A typical fingertip glucose meter contains a glucose-sensing electrode and a signal acquisition module. It operates electrochemically by utilizing glucose oxidase (GOD) immobilized on the electrode. During testing, a lancet is used to draw blood from the fingertip, which is then put on the electrode. The enzyme on the electrode reacts with glucose, which produces electrons to alter the electrical current. This electric current is recorded by the signal acquisition system (Figure 2a) [26]. This method is widely used in clinical settings due to its ability to provide real-time blood glucose readings. It helps in tailoring treatments, assessing medication efficacy, and reducing the risks of undetected hypo- or hyperglycemia. While enzyme-based glucose sensors are widely used, they still exhibit several limitations, including the dependence of enzyme activity on factors such as temperature, humidity, and interference from other substances [21]. Due to these challenges, many researchers have shifted their focus towards developing enzyme-free glucose detection methods. Recent advancements in glucose biosensors have focused on enhancing the working electrode by incorporating nanomaterials [28], such as metals [29], metal oxides [30], and carbon-based nanomaterials [31; 32]. Due to their large surface area, excellent catalytic properties, and strong adsorption capabilities, nanomaterials are ideal for facilitating glucose oxidation reactions. Based on the material's good electrical and thermal conductivity, a series of glucose non-enzyme sensors have been developed. For example, [PERSON] et al. developed a non-enzymatic electrochemical glucose sensor using a gold nanowire array electrode [28]. The FESEM image of gold nanowire array is shown in Figure 2b. The detection principle of glucose is based on the partial and direct oxidation of glucose on the gold nanowire array electrode. The sensor has a detection limit of 30 \(\upmu\)M with a sensitivity of 41.9 \(\upmu\)A mM\({}^{-1}\) cm\({}^{-2}\) (Figure 2c) [28]. In a similar approach, [PERSON] et al. developed a highly stretchable electrochemical electrode using Enokitake mushroom-shaped Au NW films that allows glucose detection with a sensitivity of 4.55 \(\upmu\)A\(\cdot\)mM\({}^{-1}\)\(\cdot\)cm\({}^{-2}\) with a linear range of 0-800 \(\upmu\)M under 30% strain [33]. Apart from noble metal-based materials, various researchers have also focused on inexpensive and efficient metal-organic framework (MOF)-based porous materials. MOF materials, with large porosity, can have potential applications in glucose detection, energy storage, and catalysis [34]. [PERSON] et al. prepared a working electrode with a Co-MOF loaded on nickel foam (Figure 2d), with a sensor sensitivity of 10,886 \(\upmu\)A cm\({}^{-2}\) mM\({}^{-1}\) and a glucose detection limit as low as 1.3 nM (Figure 2e-g) [6]. In a different approach, [PERSON] et al. fused Carbon Nitride with different metals such as niobium (Nb) and ruthenium (Ru) to develop enzyme-free electrochemical glucose sensors [35; 36]. This approach has reported to provide better anti-interference ability with justifiable reproducibility, reusability, and stability. In addition to the metal-based and MOF-based materials, conductive polymers have also emerged as a promising class of materials for glucose sensing due to their unique electrical properties and versatility. In the case of conductive polymer materials, the main chain has a conjugated principal electron system, and it can reach the conductive state through doping. These includes various commonly used polymers such as polypyrrole (PPy), polyaniline (PANI), poly-phenylene-vinylene (PPV), poly(3,4-ethylene dioxythiophene) (PEDOT), etc. [37]. [PERSON] et al. synthesized a glucose electrocatalyst by combining CuO with PANI. The surface morphology of hollow PANI nanofibers is shown in Figure 2h) [38].