A Novel Device for Rapid and Noninvasive Volatile Metabolite-based Screening and Diagnosis of Multiple Disease States

项目摘要/摘要：人类排放一系列挥发性有机化合物(VOCs)作为 新陈代谢正常。在许多疾病状态下都会有代谢变化，而高度敏感的动物 可以训练嗅觉系统，根据患者特有的气味识别患有某些疾病的患者。 我们试图将对这些通过皮肤散发的独特VOCs的检测转化为更强大的、 标准化和机械化平台，易于适应筛查、诊断和监测 人类疾病的各种状态，具有不同的病理生理学。我们假设全身新陈代谢 许多高负担的传染病、炎症性疾病、代谢疾病、恶性疾病、精神疾病和 神经系统疾病可以通过皮肤排泄物来识别。我们将采用一种新型的便携式气相色谱仪- 差示迁移率光谱分析(GC-DMS)设备，可直接快速检测挥发性样品 用于评估这些皮肤挥发性代谢物的特征。该设备高度敏感，允许 对人类挥发性排放的地貌进行全面和具有生物学代表性的评估，是 与许多其他气体传感设备相比，它对混杂和环境因素的适应能力更强，需要很长的时间 在各种真实世界传感应用中的成功使用记录，并已进入商业化阶段 开发，这将极大地促进其快速开发基于皮肤VOC的诊断这20 疾病状态。我们建议进一步开发和严格评估这种基于气味的诊断方法 针对这些疾病状态的方法，(1)集成其他过程分析技术(PATS)以确保 通过重复、大容量患者的样本和设备之间的仪器准确度和精密度 随着时间的推移测试和修改设备入口以进行皮肤挥发性分析，(2)识别和验证GC- DMS特征和相应的皮肤挥发性代谢物集合，区分患有和 没有使用机器学习方法的这20种疾病状态中的每一种，集成了 GC-DMS设备上的这些签名，以及(3)开发一种可穿戴的传感器，用于至少一种疾病 简单的挥发性特征，决定了这款可穿戴诊断设备的测试特性。缺乏 重复性是困扰挥发性代谢物分析领域的一个主要问题，通常是由于混淆和 研究设计缺陷。我们将尽一切努力最大限度地减少和消除任何混淆、偏见和 当我们开发和评估这种基于气味的诊断方法时，无关的可变性，以产生可推广的 每个疾病状态的签名。最终，这些目标的成功实现将产生快速、非侵入性的 皮肤挥发性代谢物分析用于筛查、诊断和监测每一种疾病，具有 对个人是否有一种或多种此类疾病的证据进行明确的二元(是/否)评估， 促进这些患者的早期应用适当的治疗方法，减轻临床 这些疾病的每一种的后果。

Project Summary/Abstract: Humans emit an array of volatile organic compounds (VOCs) as part of normal metabolism. There are metabolic shifts in many disease states, and animals with highly sensitive olfactory systems can be trained to identify patients with certain diseases based on their characteristic scent. We seek to translate detection of these unique VOCs emanating through the skin to a more robust, standardized, and mechanized platform, readily adaptable for the screening, diagnosis, and monitoring of a variety of human disease states with distinct pathophysiologies. We hypothesize that systemic metabolic derangements in many high burden infectious, inflammatory, metabolic, malignant, psychiatric, and neurologic diseases can be identified via skin emissions. We will adapt a novel, portable gas chromatography- differential mobility spectrometry (GC-DMS) device that rapidly examines volatile samples directly at the point of care for the assessment of these skin volatile metabolite signatures. This device is highly sensitive, allowing a comprehensive and biologically representative assessment of the landscape of human volatile emissions, is more robust to confounding and environmental factors than many other gas sensing devices, has a long track record of successful use in various real-world sensing applications, and is already undergoing commercial development, which will greatly facilitate its rapid development for the skin VOC-based diagnosis of these 20 disease states. We propose further development and rigorous evaluation of this scent-based diagnostic approach to these disease states, (1) integrating additional process analytical technologies (PATs) to ensure instrumental accuracy and precision between samples and devices through repeated, high-volume patient testing over time and modifying the device inlet for skin volatile analysis, (2) identifying and validating GC- DMS signatures and the corresponding set of skin volatile metabolites that distinguish individuals with and without each of these 20 disease states using machine learning methods, integrating automated detection of these signatures on the GC-DMS device, and (3) developing a wearable sensor for at least one disease with a simple volatile signature, determining the test characteristics of this wearable diagnostic device. A lack of reproducibility is a major issue plaguing the field of volatile metabolite analysis, often due to confounding and study design flaws. We will make every effort to minimize and eliminate any sources of confounding, bias, and extraneous variability as we develop and evaluate this scent-based diagnostic approach, to yield generalizable signatures for each disease state. Ultimately, successful completion of these aims will yield rapid, noninvasive skin volatile metabolite assays for the screening, diagnosis, and monitoring of each of these diseases, with a clear, binary (yes/no) assessment of whether the individual has evidence of one or more of these diseases, facilitating early administration of appropriate therapeutics in these patients and mitigating the clinical consequences of each of these diseases.