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

ABSTRACTExhaled 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.PROJECT NARRATIVE Routine analysis of exhaled breath condensate offers the possibility of non-invasive diagnostics and monitoring personalized responses to therapy. It can be performed directly by individuals in their homes to monitor physiological responses to environmental exposures over time and in large clinical trials for patient phenotyping, measuring both drug responses and compliance. This project will advance to the market a novel, commercially scalable, and widely accessible tool for standardized collection of exhaled breath condensate samples.