## 4 Conclusions and Future Perspectives  
This proof-of-concept study demonstrates the feasibility to detect and monitor physiological relevant concentrations of AD biomarker A\(\beta\), using the commercial fluorescent probe CRNAAD-2 in a microfluidic-sensing platform. This technological achievement represents a critical step toward the integration of biosensors in advanced preclinical tools, such as BoCs, which promise to revolutionize the improvement of AD treatments and early diagnosis. For that, initial fluorescence experiments conducted in macroscale conditions validated the sensitivity and specificity of CRNAAD-2 for both oligomeric and fibrillar conformations. Static optimization of experimental parameters, including solvent selection, excitation/emission profiles, and probe concentration, confirmed robust fluorescence signals, with a strong preference for fibrillar A\(\beta\) over oligomers. These findings are in good agreement with the literature [23], which shows that CRNAAD-2 exhibits a great affinity for A\(\beta\) (Kd = 38 nM), especially fibrils, with rapid association and slow dissociation, making it a powerful tool for fluorescent imaging of A\(\beta\). These results established a baseline for assessing the probe's behavior under controlled conditions, ensuring a reliable foundation for subsequent microfluidic-sensing validation. The integration of optical sensing in microfluidic platforms revealed several advantages over macroscale setups. The nature of the microfluidic-sensing platforms requires a significantly smaller sample volume and lower reagent consumption, and it enables automated real-time monitoring of A\(\beta\) at multiple time points. Comparative analysis demonstrated that fluorescence properties remained consistent across scales. Additionally, the ability to isolate and detect A\(\beta\) fibrils in physiologically relevant concentrations highlights the potential of microfluidic systems for translational biomedical applications. The findings underscore CRANAD-2's optical properties as a fluorophore with (i) good molecular stability, (ii) consistent Stoke's shift, and (iii) specificity for fibrillated A\(\beta\). This shows its suitability to be used as fluorescent probe in optical biosensors integrated in advanced microfluidic devices, such BoCs. This work showcases the suitability for the development of new devices that catalyze new methods for Alzheimer's disease progression monitoring and the evaluation of new therapeutic strategies, more effective than the current ones. To enhance the compactness and scalability of the detection system, future integration steps could replace the current optical detection setup with a fully integrated solution comprising a CMOS-fabricated photodiode, LED source, and optical filters. The in-house-designed optical biosensor, integrated with the microplatform, will be used to detect and continuously quantify A\(\beta\) in real time, further expanding the scope of this research. This approach would not only reduce the system's overall footprint but also enable greater automation and portability, essential for high-throughput screening. The feasibility of such integration was demonstrated by [PERSON] et al. (2024), where CMOS-compatible photodetectors combined with on-chip optical components achieved efficient detection [30]. Moreover, to optimize the collection of the fluorescence signals, one could study the integration of lenses, waveguides, and total internal reflection geometries into the microfluidic die, which could also have a high impact on the sensitivity and reproducibility and in the reduction in errors resulting from optical components' alignment. The geometry of the lenses (degree of aperture, curvature, single or composite lenses, etc. ), waveguides, and reflection geometries can be tailored to obtain high efficiency in the convergence of excitation and emission light.