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: 10663172
• 负责人: Sophia Koo
• 金额: $ 98.26万
• 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/10663172
• 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; Volatilization; Work; case control; comorbidity; design; detection limit; diagnostic strategy; diagnostic tool; diagnostic value; 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：人类发射一系列挥发性有机化合物（VOC）作为一部分 正常代谢。许多疾病状态中都有代谢转移，并且具有高度敏感的动物 可以根据其特征性气味来识别嗅觉系统以识别患有某些疾病的患者。 我们试图将这些通过皮肤散发出的独特VOC的检测转化为更健壮的， 标准化和机械化平台，易于适应筛查，诊断和监测 具有不同病理生理的人类疾病状态。我们假设该系统性代谢 许多高负担，炎症，代谢，恶性，精神病和精神病的危险 可以通过皮肤排放识别神经系统疾病。我们将适应一种新颖的便携式气相色谱 - 差异迁移率光谱（GC-DMS）设备，该设备直接在该点迅速检查挥发性样品 护理这些皮肤挥发性代谢物特征的评估。该设备高度敏感，允许 对人类挥发性排放景观的全面和生物学代表性评估是 与许多其他燃气感应设备相比，对混淆和环境因素更健壮，具有很长的轨道 在各种现实世界传感应用中成功使用的记录，并且已经在商业上进行 开发，这将极大地促进其基于皮肤VOC的诊断的快速发展。 疾病状态。我们建议对这种基于气味的诊断的进一步发展和严格评估 对这些疾病状态的方法，（1）整合其他过程分析技术（PAT）以确保 通过反复的高量患者的样品和设备之间的工具精度和精度 随着时间的推移测试并修改设备入口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产物，这些代谢物与个人区分开 没有这20种疾病状态中的每一个都使用机器学习方法，将自动检测整合 这些签名在GC-DMS设备上，以及（3）至少一种具有一种疾病的可穿戴传感器 简单的挥发性签名，确定此可穿戴诊断设备的测试特性。缺乏 可重复性是困扰着挥发性代谢物分析领域的主要问题，通常是由于混淆和 研究设计缺陷。我们将尽一切努力最大程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，无关紧要的可变性，以产生可推广的 每个疾病状态的签名。最终，这些目标的成功完成将产生快速，无创的 皮肤挥发性代谢物分析，用于对每种疾病的筛查，诊断和监测， 清晰，二进制（是/否）评估个人是否有一种或多种疾病的证据， 促进这些患者的早期服用适当的治疗剂并减轻临床 每种疾病的后果。