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技术特别收集有关材料表面的信息，使其成为研究皮肤的理想选择。使用离体分析人体组织，FTIR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，其在体内皮肤研究中的应用受到实用性和敏感性问题的限制。安捷伦的手持式4300 FTIR光谱仪独特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针对风险最大的预防性治疗。在此基础上，我们目前正在进行一项临床研究，特应性湿疹风险皮肤测试（星星）研究，由利奥基金会资助，以验证FTIR作为AD风险生物标志物的潜在用途。该项目将为Agilent 4300光谱仪开发新的采样接口，以优化分析人体皮肤。与欧莱雅和安捷伦合作，我们将展示这种技术的新应用，以帮助开发新的个人皮肤护理和局部药物产品，提高功效和安全性。第1年和第2年确定新的采样接口的工作参数，并与现有接口进行比较。这将涉及确定哪些界面最适合于皮肤分析以及从皮肤表面内的什么深度收集信息。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志物。例如，通过制备模拟皮肤/皮肤组分样品来研究pH相关的变化。角质层pH现在被认为是皮肤稳态和功能的关键调节器，但目前还没有办法在体内测量角质层内的pH。与皮脂水平、角蛋白结构、脂质结构和组成、天然保湿因子水平、皮肤水合作用、黑色素水平和组织炎症/刺激相关的生物标志物也是感兴趣的。夸大的洗涤测试将提供一个有用的模型，因为许多这些属性受到侵蚀性清洁剂的不利影响。补充皮肤分析技术，包括经皮水分损失和电容测量将被用来帮助验证FTIR为基础的metricals.Use获得的知识，挖掘星星纵向出生队列研究FTIR数据的皮肤健康的新标志。一旦在2019年12月完成，星星数据库将包含175名婴儿在出生时，1个月大和12个月大时的FTIR测量结果，以及这段时间内皮肤健康和皮肤护理实践的全面信息。第2年和第3年设计并进行一项基本的人类队列研究，展示FTIR的潜力及其对化妆品和制药行业的价值。这可能涉及评估随着年龄增长而变化的皮肤结构组成，并帮助确定生命周期不同阶段对皮肤护理的不同需求。通过使用我们的皮肤屏障实验室，该研究可以结合光学相干断层扫描等补充技术，以了解FTIR测量的皮肤表面变化如何与胶原蛋白基质和血管系统的更深层次变化相对应。第3年和第4年根据开发的技术开展一系列影响活动。这将涉及与欧莱雅密切合作，以支持新产品的要求，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.