Skin Bioengineering: Noninvasive Transdermal Monitoring

描述(由申请人提供)：长期目标是开发和优化一种新的、非侵入性的、离子导入方法，用于通过皮肤进行临床监测。低水平的电流密度推动带电的和高极性的(但中性的)化合物以比被动扩散快得多的速度穿过皮肤。由于皮肤提供了一个独特的可接触的身体表面，通过它可以提取信息，我们假设可以开发出真正的非侵入性和高度敏感的设备，这种设备利用至少两种物质的独特配对流动，可以用于离子导入监测应用。该研究战略将优化离子导入和传感技术，以满足成功的三个关键标准：(A)对通过皮肤的电传输的基本了解；(B)可重复地增强经皮渗透，以确定通过皮肤的临床监测机会；以及(C)表征和验证简单、用户友好的样本采集设备以及灵敏和特定的分析工具。该项目的具体目标是：-[1]完善对皮肤电传输的理解；探索在外加电场存在的情况下溶质和离子流动的相互作用(和独立性)。[2]为了证明同时对目标分析物和体内浓度基本恒定的内源性物质进行“反向离子导入”提取，可以提供真正的非侵入性临床监测。[3]设计简单、美观、小体积(100亩L或以下)的原型装置，可有效地收集反向离子电泳法提取的样品。[4]将这些系统与高灵敏度和特定的色谱和电化学分析工具相结合，包括离线和最终在线的现场分析工具。原则证明针对三种重要的分析物：葡萄糖、苯丙氨酸和锂。此外，设想的生物工程和分析化学进展将允许对反向离子导入法提取(和可提取)的物质进行广泛的“大量筛选”，从而为这一方法提供了更多的机会。综上所述，该项目旨在评估人体体内的离子导入生物工程技术；具体地说，可预见在临床化学和治疗药物监测方面的应用。

DESCRIPTION (provided by applicant): The long-term objective is to develop and optimize a novel, noninvasive, iontophoretic approach for clinical monitoring via the skin. The low-level current density drives both charged and highly polar (yet neutral) compounds across the skin at rates much greater than passive diffusion. As the skin offers a uniquely accessible body surface across which information can be extracted, we hypothesize that truly noninvasive and highly sensitive devices, which exploit uniquely paired flows of at least two substances, can be developed for iontophoretic monitoring applications. The research strategy will optimize iontophoretic and sensing technology to satisfy three key criteria for success: (a) fundamental understanding of electrotransport across the skin; (b) reproducible enhancement of transdermal permeability to identify clinical monitoring opportunities via the skin; and (c) characterization and validation of simple, user-friendly devices for sample collection coupled with sensitive and specific analytical tools. The specific aims of the project are:- [1] To refine understanding of electrotransport across the skin; to exploit the interactions (and independence) of solute and ion flows in the presence of an applied electric field. [2] To demonstrate that the simultaneous, 'reverse iontophoretic' extraction of a target analyte, together with an endogenous substance of essentially constant concentration within the body, can offer truly noninvasive, clinical monitoring. [3] To engineer simple, elegant, prototypical devices, of small volume (100 mu-L or less), into which reverse iontophoretically extracted samples may be efficiently collected. [4] To couple these systems to highly sensitive and specific chromatographic and electrochemical analytical tools both off-line and, eventually, on-line, in situ. Proof-of-principle targets three analytes of significant interest: glucose, phenylalanine and lithium. Furthermore, the bioengineering and analytical chemistry advances envisaged will allow broad, 'mass-screening' of the substances extracted (and extractable) by reverse iontophoresis revealing additional opportunities for the approach. In summary, this project aims to evaluate iontophoretic bioengineering technology in vivo in man; specifically, applications with respect to clinical chemistry and therapeutic drug monitoring are foreseen.