# Advancements in Glucose Monitoring: From Traditional Methods to Wearable Sensors
## 5 Limitation of Current Methodologies  
The development of glucose sensors has significantly improved the monitoring and treatment of diabetes, aiding in glycemic control and preventing complications. However, enzyme-based glucose sensors [61, 114], while widely used, suffer from low thermal and chemical stability, as well as high costs, particularly with disposable strips. Non-enzymatic sensors and alternative biofluid monitoring methods have been introduced to address these limitations, though challenges remain in achieving high sensitivity and reliability [5]. Especially, wearable sensors for point-of-care glucose monitoring in biofluids have garnered significant interest due to their ease of use, portability, affordability, and non-invasive nature, minimizing user discomfort [115]. The detection of glucose in blood remains the gold standard for diabetes diagnosis and management. Extensive research has focused on  
Figure 12: A smart contact lens based a glucose-monitoring system. (**a**) The schematic diagram of the soft, smart contact lens, which includes a hybrid substrate, functional components (rectifier, LED, and glucose sensor), and a transparent, stretchable conductor for the antenna and interconnects. (**b**) The circuit diagram of the smart contact lens system. (**c**) The operation of the smart contact lens: wireless power is transmitted to the lens via the antenna, activating both the LED pixel and the glucose sensor. When the glucose level in the tear fluid exceeds a certain threshold, the LED pixel turns off. Reprinted with permission from [112]. wearable blood glucose sensors, but many of these devices remain invasive, introducing discomfort and the risk of infection [116]. Sweat and urine, due to their easy accessibility and non-invasive nature, have been the focus of many studies [89; 91; 117]. Wearable sensors based on gold fibers for sweat monitoring [89], biofuel cells for glucose detection in urine [91], and tear-based sensors using soft contact lenses [112] have shown significant promise. The smart contact lens, for example, integrates glucose sensors, wireless power transfer circuits, and display pixels, allowing for real-time glucose level visualization. This lens uses stress-tunable, transparent materials and stretchable electrodes made of ultralong metal nanofibers, wirelessly transmitting glucose data from tear fluid to a display system using LEDs, eliminating the need for bulky external equipment. However, challenges persist, including interference from nearby radiofrequency devices, difficulty distinguishing glucose from other biological components, and improving the sensitivity and accuracy of these sensors [91]. However, glucose detection in saliva [30] presents challenges, including discomfort during collection and the need for filtration or dilution, as well as low biomarker concentrations and variability in its composition. Despite these challenges, alternative methods for glucose detection are being explored, with optical glucose-sensing technologies offering a promising solution. Optical glucose-sensing technologies, particularly fluorescence [68] and Raman spectroscopy [9], hold promise due to their non-invasive nature and potential for continuous glucose monitoring (CGM). These methods do not consume glucose molecules, providing real-time, accurate readings and longer sensor lifespans compared to electrochemical sensors. Especially, methods like Raman spectroscopy have low glucose detection signals, though surface-enhanced Raman spectroscopy (SERS) can improve sensitivity at the cost of sensor lifespan and potential biotoxicity [9; 72]. Photoacoustic (PA) spectroscopy [107] and optical coherence tomography (OCT) [95; 98] show promise in vivo, but their sensitivity under physiological conditions is too low for precise measurements. Despite these benefits, optical methods like NIR spectroscopy face issues with signal strength and high costs, limiting their application in non-invasive CGM.