Design of a polymeric microneedles platform for non-invasive and real-time monitoring of physiological parameters

以家庭为基础的监测可以大大改善目前可用的诊断程序，并且是学术界和工业界积极研究的课题。***微针（MNs）是一种微米大小的针头阵列，能够无创地进入活体皮肤层，在药物输送方面提供了非常有希望的结果，目前正在研究诊断应用。事实上，皮肤层携带的个人健康状况信息比想象的要多得多。在诊断应用方面，MNs主要用作液体取样和生物电位测量的无痛设备。然而，这些过程受到真皮上部大多数生物标志物浓度的阻碍，这些生物标志物的浓度太低，无法重复提取。通过这个研究项目，我设想探索一种从皮肤中非侵入性提取生理信息的新策略。***这项工作的总体目标包括实现和表征一个多功能的聚合物MNs平台，用于非侵入性皮肤递送专门设计的荧光传感分子，能够实时监测和量化几种皮肤生物标志物。在本可行性研究方案中，我们将重点关注三个生理参数的监测：***1。炎症* * * 2。淋巴引流功能******将进行开创性的研究，为这些特定应用定制修饰荧光传感分子，并优化具有理想结构特性的纳米颗粒的微制造工艺。一旦应用在皮肤上，装载荧光传感探针的MNs将产生功能性纹身，允许使用简单的荧光检测器实时监测特定的生物标记物。这三种选择的应用是基于非常不同的传感机制，并将允许评估整个研究思路的实际多功能性和稳健性。然而，这种非侵入性的概念可以进一步扩展到其他几个应用，开辟新的令人兴奋的研究领域。总的来说，申请的资金将允许我调查这一愿景的实际潜力，并开始一个富有成效和独立的研究生涯。

Home-based monitoring could drastically improve currently available diagnostic procedures, and is the subject of active research from both the academic and industrial sectors. ***Microneedles (MNs), micron-sized needles arrays able to non-invasively access the living skin layers, have provided very promising results for drug delivery purposes, and are currently being investigated for diagnostic applications. Indeed, the skin layer carries by far more information on the health state of an individual than envisioned. For diagnostic applications, MNs have been mostly used as painless devices for fluid sampling, and biopotential measurements. However, these processes are hampered by the concentrations of most biomarkers in the upper dermis, which are too low to be reproducibly extracted. With this research program, I envisage to explore a new strategy for non-invasive extraction of physiological information from the skin. ***The overall goal of this work consists in implementing and characterizing a versatile platform of polymeric MNs for non-invasive dermal delivery of on-purpose-designed fluorogenic sensing molecules able to monitor and quantify in real-time several dermal biomarkers. In this feasibility research program, we will focus, in particular, on the monitoring of three physiological parameters:***1. Inflammation***2. Lymphatic drainage function***3. Skin enzymatic metabolism***Groundbreaking research will be performed to custom-modify fluorogenic sensing molecules for these specific applications, and to optimize the microfabrication process of MNs with ideal structural properties. Once applied on the skin, fluorogenic sensing probes-loaded MNs will generate functional tattoos allowing the real-time monitoring of specific biological markers using a simple fluorescence detector. The three selected applications are based on very different sensing mechanisms and will allow the evaluation of the actual versatility and robustness of the whole research idea. However, this non-invasive concept could be further extended to several other applications, opening new exciting research horizons. Overall, the requested funding will allow me to investigate the actual potentials of this vision and to start a fruitful and independent research career.