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

基于家庭的监测可以极大地改进目前可用的诊断程序，是学术界和工业界积极研究的主题。*微针(MN)是一种微米大小的针阵列，能够非侵入性地进入活的皮肤层，已经为药物输送目的提供了非常有希望的结果，目前正在研究诊断应用。事实上，到目前为止，皮肤层携带的关于个人健康状态的信息比人们想象的要多得多。对于诊断应用，MNS主要被用作流体采样和生物电势测量的无痛设备。然而，这些过程受到上层真皮中大多数生物标志物浓度的阻碍，这些浓度太低，无法重复提取。通过这项研究计划，我设想探索一种新的策略，从皮肤中非侵入性地提取生理信息。*这项工作的总体目标在于实现和表征一种多功能的聚合物MN平台，用于非侵入性地将专门设计的荧光传感分子送入皮肤，能够实时监测和量化几种皮肤生物标志物。在这一可行性研究计划中，我们将特别关注三个生理参数的监测：*1.炎症*2.淋巴引流功能*3.皮肤酶代谢*将进行开创性的研究，以定制针对这些特定应用的荧光传感分子，并优化具有理想结构特性的MN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志物。这三个选定的应用程序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通用性和稳健性。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视野。总体而言，申请的资金将使我能够调查这一愿景的实际潜力，并开始富有成效的独立研究生涯。

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.