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

一种基于挥发性代谢物的快速、无创筛查和诊断多种疾病状态的新型装置

• 批准号: 10426603
• 负责人: Sophia Koo
• 金额: $ 102.41万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-10 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10426603
• 关键词: Address; Adoption; Animals; Biological; Biological Assay; Biosensing Techniques; Blinded; Characteristics; Clinical; Communicable Diseases; Detection; Development; Devices; Diagnosis; Diagnostic; Diagnostic Equipment; Diagnostic tests; Disease; Enrollment; Ensure; Environmental Risk Factor; Evaluation; Functional disorder; Gas Chromatography; Gases; Human; Individual; Inflammatory; Influenza; Malignant - descriptor; Mental disorders; Metabolic; Metabolism; Monitor; Morbidity - disease rate; Olfactory Pathways; Outcome; Patients; Population; Process; Reproducibility; Research Design; Sampling; Skin; Smell Perception; Source; Specificity; Spectrometry; Standardization; Study Subject; Technology; Testing; Therapeutic; Time; Training; Translating; Work; base; case control; comorbidity; design; detection limit; diagnostic strategy; diagnostic tool; disease diagnosis; human disease; improved; machine learning method; meetings; nervous system disorder; novel; point of care; portability; rapid detection; screening; skin organogenesis; volatile organic compound; wearable sensor technology

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.

项目摘要/摘要：人类排放一系列挥发性有机化合物 (VOC) 正常新陈代谢。许多疾病状态都会发生代谢变化，而高度敏感的动物 嗅觉系统可以经过训练，根据患者特有的气味来识别患有某些疾病的患者。 我们寻求将对这些通过皮肤散发的独特 VOC 的检测转化为更可靠、更可靠的检测方法。 标准化、机械化平台，易于适应疾病的筛查、诊断和监测 具有不同病理生理学的多种人类疾病状态。我们假设全身代谢 许多高负荷感染、炎症、代谢、恶性、精神和疾病的紊乱 神经系统疾病可以通过皮肤发射来识别。我们将采用一种新颖的便携式气相色谱法- 差动迁移谱 (GC-DMS) 装置可直接在现场快速检测挥发性样品 评估这些皮肤挥发性代谢特征的护理。该设备高度敏感，允许 对人类挥发性排放景观进行全面且具有生物学代表性的评估 比许多其他气体传感设备更能抵抗混杂因素和环境因素，具有长期的发展前景 在各种现实世界传感应用中成功使用的记录，并且已经进行商业化 的开发，这将极大地促进其针对这20种基于皮肤VOC的诊断的快速发展 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 针对这些疾病状态的方法，(1) 集成额外的过程分析技术 (PAT) 以确保 通过重复、大量的患者测试，确保样品和设备之间的仪器准确度和精密度 随着时间的推移进行测试并修改设备入口以进行皮肤挥发性分析，(2) 识别和验证 GC- DMS 特征和相应的一组皮肤挥发性代谢物可区分患有和 无需使用机器学习方法，集成自动检测这 20 种疾病状态中的每一种 GC-DMS 设备上的这些特征，以及 (3) 开发一种可穿戴传感器，用于至少一种具有 简单的易失性签名，决定了该可穿戴诊断设备的测试特性。缺乏 重现性是困扰挥发性代谢物分析领域的一个主要问题，通常是由于混杂和 研究设计缺陷。我们将尽一切努力最大程度地减少和消除任何混淆、偏见和错误的来源 当我们开发和评估这种基于气味的诊断方法时，会产生无关的变异性，以产生可推广的结果 每种疾病状态的特征。最终，成功完成这些目标将产生快速、非侵入性的结果 用于筛查、诊断和监测这些疾病的皮肤挥发性代谢物测定， 明确的二元（是/否）评估个体是否有这些疾病中的一种或多种的证据， 促进这些患者尽早接受适当的治疗并减轻临床症状 这些疾病的后果。