A novel, hand-held, exhaled breath condensate sampler for the clinical research market; applications for asthma, pulmonary injury and inflammation.

一款面向临床研究市场的新型手持式呼出气体冷凝采样器；

• 批准号: 10323623
• 负责人: CRISTINA ELIZABETH DAVIS
• 金额: $ 25.55万
• 依托单位: SENSIT VENTURES, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10323623
• 关键词: Adoption; Adrenal Cortex Hormones; Aerosols; Agonist; Alveolar; Anesthesia procedures; Anti-Cholinergics; Asthma; Bacterial Infections; Biological; Biological Markers; Blood; Breath Tests; Chemicals; Child; Childhood Asthma; Clinical; Clinical Research; Clinical Trials; Clinical Trials Design; Collection; Communities; Complex; Detection; Devices; Diagnosis; Diagnostic; Disease; Drug Monitoring; Environmental Exposure; Epigenetic Process; Exhalation; Freezing; Future; Gases; Genotype; Hand; Health; Home; Human; Individual; Inflammation; Inflammatory; Inhalation; Injury; Intervention; Laboratories; Legal patent; Liquid substance; Lung; Market Research; Mass Spectrum Analysis; Measurement; Measures; Medical; Methods; Modern Medicine; Monitor; Noise; Painless; Patients; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Phenotype; Physiologic Monitoring; Physiological; Population Group; Procedures; Process; Production; Quality Control; Regimen; Research; Research Personnel; Rest; Sales; Saliva; Sampling; Scientist; Services; Small Business Technology Transfer Research; Standardization; Surface; Technology; Testing; Time; Virus Diseases; Water; Work; age group; asthmatic; asthmatic patient; base; clinical development; clinical trial participant; clinically relevant; commercialization; compliance behavior; cost; design; drug standard; drug testing; extracellular vesicles; human subject; improved; individual patient; innovation; insight; interest; manufacturing scale-up; metabolomics; method development; noninvasive diagnosis; notch protein; novel; operation; patient population; portability; quality assurance; respiratory; respiratory gas; response; scale up; sensor; tool; user-friendly; volatile organic compound

ABSTRACT Exhaled breath is one of the most non-invasive human effluents that can be captured and analyzed, and yet it has minimal presence as a common clinical endpoint measurement in any branch of modern medicine. There has been a persistent technology gap for both breath sampling and breath analysis, despite the many vulnerable patient populations and age groups that could be aided by its use. Exhaled gasses include the major respiratory gasses from the alveolar interface with the blood and hundreds of small volatile organic compounds (VOCs). Additionally, exhaled breath condensate (EBC) includes respiratory aerosols, extracellular vesicles and non-volatile compounds that originate from the liquid lining deep inside the lungs. Our group and others have shown EBC contains thousands of human metabolites and has tremendous diagnostic and therapy-monitoring potential. A portable breath sampler could also monitor drug regimen therapy compliance, which would substantially aid clinical trials where participants sometimes fail to appropriately take their treatments. This can contribute to an increase in statistical “noise” and overall cost and duration of a clinical trial. We have selected asthma for further demonstrations of clinical research utility because of the broad need to better understand the plurality of phenotypes of individual patients arising from the complex interplay of environmental triggers, genotypes, epigenetic/somatic expression and pharmaceutical response. This project will further the commercialization of a palm-sized hand-held EBC sampler that can be used by patients in their own homes to sample their breath for analysis. Our technology rests on a patented micro-condenser microfabricated “chip” (µCON) that efficiently samples the breath. The device has a disposable mouthpiece and can be cleaned and reused by the patient. Upon exhaling into the device for a short period of time, we obtain enough EBC for mass spectrometry analysis for clinically relevant information. We have previously demonstrated detection of over ~3,000+ untargeted metabolites, 30 inflammatory biomarkers as well as drugs and drug metabolites in EBC. Our first objective for this proposed work is to conduct proof-of-concept EBC testing to detect compliance in taking intervention drugs for asthma. We will select drugs categorized by different uses and mechanisms of action (e.g., β2-Agonist, inhaled corticosteroid, anticholinergic/antimuscarinic therapy, antileukotriene therapy). Healthy human EBC spiked with drug standards will be tested for method development and to demonstrate detectability in a native background. Secondly, we aim to improve the durability and extended use of our breath sampler by exploring alternative manufacturing methods. For this, we will develop innovative design strategies to consider machine choices to scale up for rapid manufacturing, interchangeable parts for a streamlined manufacturing pipeline, and innovations for device assembly and pre-commercial quality assurance / quality control (QA/QC) testing.

摘要 呼出的气体是可以被捕获和分析的最无创的人类流出物之一， 然而，在现代医学的任何分支中，其作为常见临床终点测量的存在很少。 呼吸采样和呼吸分析一直存在持续的技术差距，尽管有许多 易受伤害的患者群体和年龄组，可以通过使用它来帮助。呼出的气体主要包括 来自肺泡界面的呼吸气体与血液和数百种小的挥发性有机化合物 （VOC）。此外，呼出气冷凝物（EBC）包括呼吸气溶胶、细胞外囊泡和呼吸道微粒。 非挥发性化合物，源自肺部深处的液体内层。我们的团队和其他人 EBC含有数千种人体代谢物，具有巨大的诊断和治疗监测功能， 潜力便携式呼吸采样器还可以监测药物治疗方案的依从性， 实质性地帮助参与者有时不能适当地接受治疗的临床试验。这可以 导致临床试验的统计“噪音”和总成本以及持续时间的增加。我们选择 哮喘的临床研究效用的进一步证明，因为广泛需要更好地了解 由环境触发因素的复杂相互作用引起的个体患者的多种表型， 基因型、表观遗传/体细胞表达和药物反应。该项目将进一步 手掌大小的手持式EBC采样器的商业化，患者可以在自己家中使用该采样器， 采集他们的呼吸进行分析 我们的技术基于获得专利的微电容器微加工“芯片”（µCON）， 呼吸的样本。该器械具有一次性吸嘴，可由患者清洁和重复使用。 在短时间内呼气进入设备后，我们获得足够的EBC用于质谱分析 以获取临床相关信息。我们以前已经证明了检测超过3,000+非靶向 代谢物，30种炎症生物标志物以及EBC中的药物和药物代谢物。我们的第一个目标是 这项拟议的工作是进行概念验证EBC测试，以检测服用干预药物的依从性 治疗哮喘我们将选择按不同用途和作用机制分类的药物（例如，β2-激动剂， 吸入皮质类固醇、抗胆碱能/抗毒蕈碱疗法、抗白三烯疗法）。健康人EBC 将检测加标药物标准品的方法开发，并证明天然药物中的可检测性。 背景第二，我们的目的是改善我们的呼气采样器的耐用性和延长使用， 替代制造方法。为此，我们将制定创新的设计策略， 选择扩大规模以实现快速制造，可互换部件以实现流线型制造管道，以及 用于设备组装和商业前质量保证/质量控制（QA/QC）测试的创新。