Diagnosis of respiratory diseases using analysis of exhaled breath and aerosols
Inventors
Chen, Dapeng • Bryden, Wayne A. • McLoughlin, Michael
Assignees
Publication Number
US-11839463-B2
Publication Date
2023-12-12
Expiration Date
2040-08-26
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
Disclosed are 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 provides methods and devices for analyzing non-volatile organics, including aerosolized bacteria and virus particles, in exhaled breath and aerosols. The system comprises a breath collection element that forms a tight-fit with the individual's face, a sample capture element containing a packed bed column for selective capture of non-volatile organic components, and a pump to draw exhaled breath into the sample capture element. The packed bed column includes solid particles with functionalized surfaces that target specific analytes such as microbes, virus, metabolites, lipid biomarkers, and proteomic biomarkers.
A key aspect of the system is its ability to efficiently collect and concentrate trace amounts of analytes from exhaled breath at high flow rates, resulting in sample collection with capture efficiency greater than 99%. The collected non-volatile organics are then extracted from the packed bed column using solvents and analyzed by diagnostic devices, preferably mass spectrometry methods such as MALDI-TOFMS. The system is designed for rapid, low-cost, and autonomous operation, delivering a diagnostic result in less than about 20 minutes with minimal human intervention.
The invention addresses the problem that existing diagnostic methods for respiratory diseases, such as tuberculosis and COVID-19, are limited by the difficulties of collecting sputum samples, invasive procedures for blood collection, slow analysis times, and high costs. By leveraging non-invasive exhaled breath analysis, the disclosed methods and devices offer a user-friendly and rapid alternative for the detection and diagnosis of various respiratory diseases at the point of care.
Claims Coverage
The independent claims define four primary inventive features covering breath sample collection systems, diagnostic systems for respiratory disease, sample capture elements, and specialized mask-based systems for exhaled breath analysis.
Breath sample collection system with packed bed column and tight-fit mask
A breath sample collection system comprising: - A breath collection element configured to receive an individual's face, forming a tight fit, and collecting aerosolized bacteria and virus particles from exhaled breath. - A sample capture element with a packed bed column that selectively captures the aerosolized bacteria and virus particles, removably connected to a port located near the individual's chin without interconnecting tubing. - A pump in fluid communication with the sample capture element, drawing exhaled breath into the packed bed column. - The system achieves a particle capture efficiency greater than 99%.
System for diagnosis of respiratory disease using exhaled breath
A diagnostic system comprising: - The breath sample collection system as described above. - A sample extraction system designed to extract captured virus and bacteria particles from the packed bed column. - A sample analysis system including: - A sample processing system for treating and concentrating the collected sample onto a sample plate. - A diagnostic device for analyzing the sample.
Sample capture element with functionalized packed bed column
A sample capture element designed for diagnosis of respiratory disease using exhaled breath, featuring: - A packed bed column that selectively captures aerosolized bacteria and virus particles as exhaled breath is drawn through it by a pump. - Solid particles in the column, sized between about 12 μm and about 20 μm, composed of materials such as resins, cellulose, silica, agarose, and hydrated Fe3O4 nanoparticles. - Functional groups immobilized on the surface of the solid particles, including at least one of: C18 (octadecyl), octyl, ethyl, cyclohexyl, phenyl, cyanopropyl, aminopropyl, 2,3-dihydroxypropoxypropyl, trimethyl-aminopropyl, carboxypropyl, benzenesulfonic acid, propylsulfonic acid, ion exchange phases, polymer phases, antibodies, glycans, lipids, DNA, and RNA. - The element achieves a particle capture efficiency greater than 99% at flow rates between about 200 ml/min and about 600 ml/min.
Breath sample collection system using a mask with integrated capture and filtration
A system including: - A mask configured for a tight fit on an individual's face to collect aerosolized bacteria and virus particles from exhaled breath, with a stem and a port positioned near the individual's chin. - A HEPA filter removably and fluidly connected to the mask stem. - A sample capture element with a packed bed column for selective capture of aerosolized bacteria and virus particles, removably connected to the port. - A pump that pulls exhaled breath through the packed bed column at a flow rate between about 200 ml/min and about 600 ml/min. - The sample capture element achieves greater than 99% particle capture efficiency.
The claims establish systems and components for efficient, high-specificity collection and analysis of non-volatile organics and pathogens from exhaled breath, integrating features such as specialized packed bed columns, tight-fitting breath collection interfaces, high capture efficiency, and compatibility with rapid diagnostic modalities.
Stated Advantages
Provides a rapid diagnostic test result in less than about 20 minutes.
Enables autonomous operation with minimal human intervention.
Achieves a particle capture efficiency greater than 99% during sample collection.
Allows rapid, low cost, and point-of-care assays for respiratory diseases.
Uses non-invasive exhaled breath collection, making it easier, safer, and more uniform to collect.
Eliminates the need for expensive consumable assays per analysis.
The system can be integrated with mass spectrometry for high sensitivity and specificity.
Documented Applications
Diagnosis of respiratory tract diseases such as COVID-19 using analysis of exhaled breath and aerosols.
Rapid detection and diagnosis of tuberculosis (TB) by analyzing non-volatile organics in exhaled breath.
Active case finding (ACF) of TB and other respiratory diseases outside primary healthcare settings.
Point-of-care diagnostics for influenza and other pathogenic viruses using exhaled breath analysis.
Detection and identification of aerosolized bacteria and virus particles, including SARS-CoV, MERS-CoV, and SARS-CoV-2.
Detection of non-volatile biomarkers for diseases beyond respiratory infections, such as lung cancer.
Capture and analysis of aerosol chemical particles such as ricin to prevent chemical attack threats.
Interested in licensing this patent?