Miniaturization has played a pivotal role in driving innovation in microfluidic devices, particularly in their application across advanced technologies, such as Lab-on-chip platforms, Point-of-care systems, Organ-, Body-and Disease-on-a-chip technology. The personalized nature inherent in these systems, coupled with physiologically relevant read-outs, opens novel avenues for individualized disease diagnostics, Figure 1. Additionally, they offer personalized strategies for assessing treatment efficacy and safety. Furthermore, the advancement in micro-and nano-microfluidic fabrication allows parallel analysis of large samples sets and the evaluation of different parameters such as biological molecules, cells or drugs. This advancement also facilitates real-time monitoring, thereby enhancing the identification of drug responses.The integration of cutting-edge microfluidic technologies () (Dai et al., 2022; Shanti, Hallfors, Petroianu, Planelles, & Stefanini, 2021; Sunildutt, Parihar, Chethikkattuveli Salih, Lee, & Choi, 2023), compact detection systems (Chen et al., 2023), and advanced digital medicine platforms (Litvinova et al., 2023) has given rise to innovative tools capable of detecting disease biomarkers through the analysis of a single drop of a body fluid. This breakthrough enables rapid assessment within the timeframe of a doctor's visit, presenting a valuable feature that supports earlier identification of conditions and facilitates the implementation of personalized and more effective therapeutic options. (Litvinova et al., 2023). This digital pills are 75 increasingly viewed as an acceptable, practical, and beneficial technology within the medical system. 76The incorporation of these technologies into medicine practice is undeniably crucial for overcoming 77 challenges such as missed diagnoses, delayed treatment, and poor adherence to prescribed treatments, 78 preventing disease progression, disability, and, in some cases, death. Thus, improvements in health 79 care systems can be obtained, towards a medicine that is increasingly predictive, preventive, 80 personalized and participatory. 81
Lab-on-a-chip involve the use of devices, a critical aspect of their 83 development lies not only in adhering to engineering specifications and principles but also in 84 ensuring scalability, manufacturability, reproducibility, and accuracy. The evolution of 85 manufacturing technologies, optimizing conventional micro-and nano-lithographic methods, and 86 integrating additive manufacturing methods like 3D-printing, is expanding the fabrication and 87 applicability of microfluidic devices. 88Beyond lab-on-a-chip applications, the field of intelligent microfluidics is emerging, incorporating 89 machine learning for monitoring and controlling microfluidic systems. This presents new challenges 90 and opportunities to develop novel molecular signatures, the synthesis of new therapeutic drugs and 91 targets, and advancements in materials' discovery. 92Along with the integration of machine learning in the medicine, innovative drug-device technologies, 93 such as digital pills combining traditional medication with intelligent monitoring systems, lay the 94 foundation for the future medicine. This concept defines a new generation of the Digital Medicine 95System that holds the potential to transform unsustainable healthcare systems. 96 However, and as abovementioned, the implementation of personalized disease-on-chip systems faces 97 a significant challenge from medical and pharmaceutical communities, regulatory bodies, and 98 government agencies, primarily due to ethical concerns surrounding health data. Therefore involving 99 all biomedical stakeholders from clinicians and patients to pharmaceutical companies, becomes 100 crucial for the successful transition of personalized disease-on-chips to precision medicine. 101Collaborative efforts and ethical frameworks will be instrumental in addressing these challenges and 102 unlocking the full potential of microfluidic technologies in advancing healthcare. 103
