Development of novel dermatologic applications of in vivo FTIR molecular spectroscopy

傅里叶变换红外光谱(FTIR)是一种用于确定材料结构组成的技术。反射FTIR技术特别能收集材料表面的信息，使其成为研究皮肤的理想方法。FTIR被用于体外分析人体组织，已被证明成功地诊断了从动脉粥样硬化到肿瘤的一系列疾病。到目前为止，它在活体皮肤研究中的应用一直受到实用性和敏感性问题的限制。安捷伦的手持式4300 FTIR光谱仪独一无二地提供了高灵敏度和便携性，开辟了新的机会。我们已经证明，FTIR可以在体内用于量化湿疹患者的皮肤屏障缺陷，并且这种测量可以帮助指导对风险最高的患者进行预防性治疗。在此基础上，我们目前正在进行一项临床研究，由利奥基金会资助的特应性湿疹风险皮肤测试(STAR)研究，以验证FTIR作为AD风险生物标记物的潜在用途。该项目将为安捷伦4300光谱仪开发新的采样接口，该光谱仪经过优化，可以在活体内分析人体皮肤。我们将与L的欧莱雅和安捷伦合作，展示这项技术的新应用，以帮助开发效率和安全性更高的新个人护肤品和局部药物产品。第1年和第2年识别新采样接口(S)的工作参数并与现有接口进行比较。这将涉及确定哪些界面最适合皮肤分析，以及从皮肤表面的哪个深度收集信息。通过进行一系列小型人类队列研究和体外实验，识别和验证皮肤化学/生理学的光谱生物标记物。例如，通过制备模拟皮肤/皮肤成分样本来研究与pH相关的变化。角质层的pH值现在被认为是皮肤动态平衡和功能的关键调节因素，但目前还没有办法在体内测量角质层的pH值。与皮脂水平、角蛋白结构、脂肪结构和成分、天然保湿因子水平、皮肤水合、黑色素水平以及组织炎症/刺激有关的生物标志物也是令人感兴趣的。夸张的洗涤测试将提供一个有用的模型，因为这些特性中的许多都会受到侵略性清洁剂的不利影响。补充皮肤分析技术，包括经皮肤水分损失和电容测量，将帮助验证基于FTIR的指标。利用获得的知识挖掘明星纵向出生队列研究FTIR数据，以寻找皮肤健康的新标记物。2019年12月完成后，STAR数据库将包含对175名出生时、1个月大和12个月大的婴儿进行的FTIR测量，以及在此期间有关皮肤健康和护肤实践的全面信息。第2年和第3年设计和进行一项基本的人类队列研究，证明FTIR的潜力及其对化妆品和制药行业的价值。这可能包括评估随着年龄的增长而变化的皮肤结构成分，并帮助确定生命周期不同阶段对皮肤护理的不同需求。通过进入我们的皮肤屏障实验室，这项研究可以结合补充技术，如光学相干断层扫描，以了解FTIR测量的皮肤表面变化如何与胶原基质和血管系统的更深层次变化相对应。第三年和第四年根据开发的技术开展一系列影响活动。这将涉及与L欧莱雅密切合作，支持新产品声明，并将重点放在‘清洁不妥协’的主题等。

Fourier transform infrared spectroscopy (FTIR) is a technique used to determine the structural composition of materials. Reflectance FTIR techniques in particular collect information about the surfaces of materials, making it ideal to study skin. Used ex vivo to analyse human tissue, FTIR has proved successful in the diagnosis of a range of diseases from atherosclerosis to neoplasms. Until now its application for in vivo skin research has been limited by issues of practicality and sensitivity. Agilent's hand-held 4300 FTIR spectrometer uniquely offers high-sensitivity and portability opening up new opportunities. We have already shown that FTIR can be used in vivo to quantify the skin barrier defect in patients with eczema, and that this measurement could help direct preventative therapies towards those most at risk. On the back of this we are currently undertaking a clinical study, The Skin Testing for Atopic eczema Risk (STAR) study, funded by the Leo Foundation to validate the potential use of FTIR as a risk biomarker for AD. This project will see the development of new sampling interfaces for the Agilent 4300 spectrometer optimized to analyse human skin in vivo. Working in partnership with L'Oreal and Agilent we will demonstrate new applications for this technique to aid the development of new personal skin care and topical pharmaceutical products with enhanced efficacy and safety.Years 1 and 2Identify the working parameters of the new sampling interface(s) and compare with existing interfaces. This will involve determining which interfaces are most appropriate for skin analysis and from what depth within the skin surface information is collected. Identify and verify spectral biomarkers of skin chemistry/physiology by conducting a series of small human cohort studies and in vitro experiments. For instance, by preparing mock skin/skin component samples to study pH-associated changes. Stratum corneum pH is now recognised as a key regulator of skin homeostasis and function, yet there is no way to currently measure the pH within the stratum corneum in vivo. Biomarkers relating to sebum levels, keratin structure, lipid structure and composition, Natural Moisturising Factor levels, skin hydration, melanin levels, and tissue inflammation/irritation are also of interest. Exaggerated washing tests will provide a useful model as many of these properties are adversely affected by aggressive cleansers. Complementary skin analysis techniques, including transepidermal water loss and capacitance measurements will be utilized to help validate FTIR-based metrics.Use knowledge gained to mine the STAR longitudinal birth cohort study FTIR data for new markers of skin health. Once complete in December 2019 the STAR database will contain FTIR measurements taken from 175 babies at birth, 1 month of age and 12 months of age, coupled with comprehensive information on skin health and skin care practices during this time.Years 2 and 3Design and undertake a fundamental human cohort study that demonstrates the potential of FTIR and its value to the cosmetics and pharmaceutical industries. This could involve assessing the changing structural composition of the skin with advancing age, and help identify the differing needs of skin care at different stages of the lifecycle. With access to our skin barrier laboratory the study can incorporate complementary techniques such as Optical Coherence Tomography, to understand how skin surface changes measured by FTIR correspond with deeper changes to the collagen matrix and vasculature for example.Years 3 and 4Undertake a series of impact activities based around the techniques developed. This will involve working closely with L'Oreal to support new product claims, and will focus on the theme of 'cleansing without compromise' amongst others.