Diagnosis of respiratory diseases using analysis of exhaled breath and aerosols
Inventors
Chen, Dapeng • Bryden, Wayne A. • McLoughlin, Michael
Assignees
Publication Number
US-12364411-B2
Publication Date
2025-07-22
Expiration Date
2040-08-26
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Abstract
Methods and devices for analyzing non-volatile organics in exhaled breath and other aerosols using various diagnostic tools that enable rapid, low-cost point of care assays for several diseases including respiratory tract diseases such as COVID-19. The disclosed methods and systems selectively capture non-volatile organics in exhaled breath and other aerosols in a packed bed column. The non-volatile organics are eluted and samples are analysis using diagnostic devices including MALDI-TOFMS. The disclosed systems and methods provide for a diagnostic test result in less than about 20 minutes and provides for autonomous operation with minimal human intervention.
Core Innovation
The invention relates to methods and devices for analyzing non-volatile organics in exhaled breath and other aerosols to enable rapid, low-cost, and autonomous point-of-care assays for respiratory tract diseases. The system selectively captures non-volatile organics in exhaled breath aerosols using a packed bed column, elutes the captured organics, and analyzes samples using diagnostic tools such as MALDI-TOFMS. The system aims to provide diagnostic test results in less than about 20 minutes with minimal human intervention.
The problem being solved concerns the limitations of current diagnostic methods for respiratory diseases such as tuberculosis and COVID-19. Existing diagnostics often rely on sputum samples, which can be difficult to collect, particularly from children and ill patients, pose occupational hazards to healthcare workers, and are laborious and time-consuming. PCR-based assays like GeneXpert Ultra are costly and require extended sampling and analysis times inappropriate for active case finding (ACF) and point-of-care testing. Current breath aerosol analysis methods lack efficient collection and concentration techniques for trace analytes, an ability to assess adequate sample volume, and integration with rapid diagnostic devices, hindering their practical diagnostic utility.
Claims Coverage
The patent includes several independent claims focused on a breath sample collection system and systems integrating sample extraction and diagnostic analysis, with inventive features concerning structural and functional aspects of the system components.
Breath sample collection system with integrated packed bed column and humidifier
A breath sample collection system including a breath collection element that forms a tight fit with an individual's face and a sample capture element with a packed bed column removably and directly connected to a port near the chin without interconnecting tubing, configured to selectively capture aerosolized particles including proteins. A pump draws exhaled breath into the capture element, and a humidifier is disposed upstream of the capture element to humidify the packed bed column.
Capture of aerosolized proteins associated with respiratory viruses and lower respiratory airways
The sample capture element is configured to capture aerosolized particles including proteins associated with viruses such as SARS-CoV, MERS-CoV, or SARS-CoV-2, and proteins originating from lower respiratory airways including serum albumin, keratins, glycoproteins, cystatin, dermcidin, or S100 proteins.
High particle capture efficiency and specific breath collection elements
The system achieves a particle capture efficiency greater than 99%. The breath collection element can include devices such as a CPR rescue mask, CPAP mask, or ventilator mask.
Functionalized packed bed columns with specific bead chemistries
The packed bed column includes resin beads with C18 functional groups on the surface, heparin covalently linked to sepharose beads, or solid particles having functional groups immobilized on their surface such as glycan, heparin, heparan sulfate, or carbohydrates including dextran.
Fluidic and flow control components
Use of a diaphragm pump to draw exhaled breath through the capture element, with particle flow rates between about 200 ml/min and 600 ml/min. A trap disposed between the sample capture element and the pump traps exhaled breath condensate (water vapor, volatile organic components, and non-volatile organics) and is cooled below ambient temperature.
Integrated detection system with sample extraction, digestion, and diagnostic analysis
A system combining the breath sample collection system with a sample extraction system that flushes the packed bed column with solvents (e.g., acetic acid, TFA, formic acid, isopropanol, HCl), a sample processing system capable of hot acid digestion to generate peptide samples from captured proteins, and diagnostic devices including PCR, ELISA, rt-PCR, mass spectrometry methods such as MALDI-MS and MALDI-TOFMS for analyzing peptide samples.
The independent claims cover a breath sample collection system with a functional, directly connected packed bed capture element and humidifier for efficient aerosol capture, specific chemistries for capturing viral and protein biomarkers, high particle capture efficiency, and integration with sample extraction and diagnostic modalities including mass spectrometry to provide rapid, autonomous respiratory disease diagnosis.
Stated Advantages
Provides rapid diagnostic test results in less than about 20 minutes.
Enables autonomous operation with minimal human intervention.
Offers a low-cost point-of-care assay suitable for active case finding, particularly in developing countries.
Achieves highly efficient capture of non-volatile organic molecules including biomarkers from exhaled breath aerosols.
Improves safety and sample collection compared to sputum and blood sampling.
Uses mass spectrometry, especially MALDI-TOFMS, for rapid, sensitive, and specific analysis.
Documented Applications
Diagnosis of respiratory tract diseases including COVID-19, tuberculosis, influenza, pneumonia, and other bacterial or viral infections.
Active case finding (ACF) for tuberculosis and other respiratory diseases outside of the healthcare system.
Point-of-care diagnostics for respiratory diseases with rapid test turnaround time.
Differentiation between viral and bacterial infections in the respiratory tract.
Detection and identification of specific viral particles such as SARS-CoV, MERS-CoV, and SARS-CoV-2 from exhaled breath.
Analysis of biomolecules in exhaled breath for lung cancer and potentially other systemic diseases through biomarkers transferred into peripheral lung fluid.
Capture and analysis of aerosol chemical particles such as biotoxins (e.g., ricin) to prevent chemical attack threats.
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