# Advancements in Glucose Monitoring: From Traditional Methods to Wearable Sensors
## 3 Minimally Invasive Methods
### Fluorescence Methods  
Fluorescence-based techniques have gained significant attention due to their distinct advantages in bioanalysis and biomedicine, such as good selectivity, high sensitivity, visual detection, easy traceability, and non-invasive monitoring. The core principle of fluorescence-based glucose detection relies on the interaction between glucose and the fluorescent probes, where the presence of glucose induces changes in the fluorescence properties of the probe [47]. Fluorescence-sensing methods, which are highly sensitive, can be implemented with affordable light sources such as visible LEDs or ultraviolet (UV) lights [50, 51, 52]. Receptors, acting as intermediaries, are mostly used as labels in fluorescence-based glucose sensing. These receptors are engineered to bind with glucose molecules, leading to changes in fluorescence that are easier to detect. For instance, a novel colorimetric and ratiometric fluorescence sensor, which was recently developed, was designed using carbon quantum dots (CQDs) and o-diaminobenzene (ODB) [52]. In this method, glucose can be detected both quantitatively through ratiometric fluorescence and calorimetry and semi-quantitatively by observing the color changes under sunlight or ultraviolet light at 365 nm [52]. Various other types of receptors have also been reported for fluorescence-based glucose sensing, such as boronic acid derivatives [53], glucose-binding proteins (e.g., concanavalin A (ConA)) [54, 55], enzymes [56], quantum dots [32, 57], carbon nanotubes [8, 58], and so on. Especially, concanavalin A (Con A), with its four binding sites, exhibits strong glucose-binding properties, making it a popular choice for affinity-based glucose sensors. Recently, [PERSON] et al. designed a fluorescence resonance energy transfer (FRET) sensor involving quantum dots (QDs) and plasmonic gold nanoparticles (AuNPs) linked by Con A [59]. After the addition of glucose, Con A moves towards the glucose, owing to its higher affinity, and this makes the quantum dots to move apart from AuNPs, affecting the fluorescence intensity [59]. A recent study introduced a hydrogel glucose sensor with in vivo stability, utilizing boronic acid-based fluorescence intensity [60]. The sensor integrates two antioxidant enzymes, superoxide dismutase (SOD) and catalase, which protect the arylboronic acid from degradation by hydrogen peroxide in vitro. This protection helps maintain the boronic acid-based fluorescence intensity of the hydrogel glucose sensors in vivo for over a 28-day period. The glucose-sensing mechanism is illustrated in the schematic shown in Figure 5a(i) [60]. In the absence of glucose, the fluorescence of anthracene is quenched. However, when glucose molecules bind to the arylboronic acid, the fluorescence intensity increases, as depicted in Figure 5a(ii) [60]. In another study, [PERSON] et al. developed a gated mesoporous silica nanodevice where ruthenium bipyridine complexes were trapped within the silica mesopores through interactions between methylbenzamideido moieties on the pore openings and cyclodextrin-modified glucose oxidase (CD-GOx) [61]. This setup prevented the fluorescent probes from being released. Upon the addition of glucose, gluconic acid is produced, that triggers fluorescence recovery, as shown in Figure 5b. Several other biosensors have been reported, such as those using QDs as donors and dextran-bound malachite green as an acceptor [62], CDs as donors and graphene oxide (GO) as an acceptor [63], and Eu sulfoscetinimidyl dextran as the donor and Alexa Fluor 647 sulfosuccinimidyl as the acceptor [64]. [PERSON] et al. reported a modified fluorescent chemosensor with an advanced algorithm, designed to monitor real-time blood glucose [65]. The first and the modified version of the chemosensor is shown in Figure 5c [65]. The sensor can continuously monitor glucose up to 365 days with a single sensor and can be easily paired with an insulin pump.