Packed Bed Column for Truncated Proteoform Capture in Exhaled Breath

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Solution Overview

Problem

Current diagnostic methods for respiratory tract infections, particularly in critical care settings, lack non-invasive and reliable molecular biomarkers, leading to delayed and inaccurate diagnoses, especially in patients using mechanical ventilators, due to the difficulty in obtaining samples from the site of infection and the limitations of existing breath collection technologies.

Innovation Solution

A method using a packed bed column to capture truncated proteoforms in exhaled breath aerosols, which are then analyzed using MALDI-TOFMS, allowing for the detection of specific biomarkers such as IL10RA, PPR17, COL2A1, COL3A1, and C6, enabling rapid and specific diagnosis of respiratory diseases like tuberculosis and respiratory tract infections.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional microbiological culture methods are used for LRTI diagnosis, then diagnostic accuracy can be achieved, but diagnostic time is significantly delayed

Engineering Contradiction:
Improvediagnostic accuracyVSAvoiddiagnostic time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent extracts and analyzes host response biomarkers (proteins, peptides, metabolites) directly from exhaled breath condensate, separating the diagnostic approach from traditional pathogen-based methods. This extraction of host response markers enables rapid diagnosis without waiting for slow microbial culture growth, resolving the contradiction between diagnostic accuracy and time consumption.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent replaces the mechanical/biological process of microbial culture with mass spectrometry analysis. Instead of relying on slow biological growth mechanisms, the system uses advanced analytical instrumentation to detect and quantify host response biomarkers, achieving both high accuracy and rapid results within hours rather than days.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Loss of time

If NAAT-based molecular diagnostic approaches are used, then rapid results are obtained, but the ability to differentiate between colonization and infection is limited

Engineering Contradiction:
Improvediagnostic speedVSAvoiddifferentiation accuracy
Core Design Contradiction:
Loss of timeVSMeasurement precision

Solution Approach 1:

The patent introduces host response biomarkers as intermediary indicators that reflect the physiological state of the patient. These biomarkers serve as mediators between the presence of pathogens and the clinical state of infection, enabling differentiation between colonization (no host response) and true infection (host response present), while maintaining rapid NAAT-based detection speeds.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the diagnostic parameters from solely pathogen-based detection to include host response parameters (protein expression, metabolite levels). By measuring multiple parameters simultaneously - both pathogen presence and host response intensity - the system achieves accurate differentiation between colonization and infection while maintaining rapid diagnostic speed.

Inventive Principle:
Principle #35Parameter changes

3Ease of operation

If exhaled breath collection is used for biomarker detection, then non-invasive sampling is achieved, but capture efficiency of biomolecules is challenging

Engineering Contradiction:
Improvesampling invasivenessVSAvoidbiomarker capture efficiency
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The patent employs porous materials and advanced condensation techniques to enhance the capture efficiency of biomolecules from exhaled breath. The porous structure increases surface area and improves trapping efficiency of proteins, peptides, and metabolites in breath condensate, maintaining non-invasive sampling while significantly improving biomarker capture reliability.

Inventive Principle:
Principle #31Porous materials

Solution Approach 2:

The patent optimizes physical and chemical parameters of breath collection, including temperature control during condensation, flow rate management, and pH adjustment of collection media. These parameter optimizations enhance the efficiency of biomolecule capture from exhaled breath while preserving the non-invasive nature of the sampling method.

Inventive Principle:
Principle #35Parameter changes

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

This approach provides a non-invasive, efficient, and cost-effective means to capture and analyze aerosolized biomarkers, improving the accuracy and speed of respiratory disease diagnosis, with a capture efficiency greater than 99% and the ability to differentiate between infected and healthy individuals, facilitating early treatment and reducing disease transmission.

Implementation Method 1

capturing truncated proteoforms in the exhaled air aerosol produced by a patient using a sample capture element including a packed bed column

Methodology Applied
Scientific EffectAdsorption: Adsorption

Implementation Method 2

analyzing the one or more collected liquid samples using MALDI-TOFMS

Methodology Applied
Scientific EffectMatrix-assisted laser desorption ionization time-of-flight mass spectrometry: Time of Flight

Data Source

PatentUS20240074673A1Capturing truncated proteoforms in exhaled breath for diagnosis of tuberculosis
Publication Date: 2024.03.07 ZETEO TECH INC
  • US20240074673A1 patent drawing
  • US20240074673A1 patent drawing
  • US20240074673A1 patent drawing

AI summary

Methods and devices to capture and analyze aerosolized particles in exhaled air including protein biomarkers and their truncated proteoforms characteristic of tuberculosis to enable rapid detection of diseases. Methods and systems to selectively capture aerosolized particles using a packed bed column. The captured particles are eluted using one or more solvents and analyzed using devices including MALDI-TOFMS.