Volatile Biomarker Breath Analysis for Colorectal Cancer Detection

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Solution Overview

Problem

Current diagnostic methods for colorectal cancer are invasive, costly, and have poor predictive values, with existing breath tests being semi-quantitative and not suitable for high-throughput analysis, necessitating a reliable non-invasive marker for early detection and prognosis.

Innovation Solution

Identification of specific volatile organic compounds (VOCs) in exhaled breath using Gas Chromatography Mass Spectrometry (GC-MS) and Selected Ion Flow Tube Mass Spectrometry (SIFT-MS) to diagnose and monitor colorectal cancer, with 15 statistically significant VOCs demonstrating sensitivity and specificity for CRC detection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If faecal occult blood test is used for CRC detection, then sensitivity is improved (87-98%), but specificity deteriorates (13-79%) requiring multiple stool samples

Engineering Contradiction:
ImprovesensitivityVSAvoidspecificity
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The invention uses a multi-component VOC signature profile comprising multiple volatile organic compounds (dimethyl sulphide, phenol, esters, alcohols, alkanes, cyclic hydrocarbons) detected together in breath samples, rather than relying on a single marker. This multi-functional approach improves both sensitivity and specificity simultaneously by capturing the complex metabolic fingerprint of CRC.

Inventive Principle:
Principle #6Universality (Multi-functionality)

2Measurement precision

If GC-MS is used for VOC identification, then VOC identification capability is improved, but analytical time increases and throughput decreases

Engineering Contradiction:
ImproveVOC identification capabilityVSAvoidthroughput
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The invention performs preliminary action by collecting and concentrating VOCs from breath samples into absorbent tubes before analysis. This pre-concentration step enables faster subsequent analysis using either GC-MS or SIFT-MS, improving throughput while maintaining identification capability. The breath collection and sample preparation are optimized to allow rapid processing of multiple samples.

Inventive Principle:
Principle #10Preliminary action

3Productivity

If quantitative VOC analysis is performed using SIFT-MS, then real-time analysis capability is improved, but device complexity increases

Engineering Contradiction:
Improvereal-time analysis capabilityVSAvoidinstrumentation complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The invention replaces the complex mechanical GC-MS system with SIFT-MS technology for quantitative VOC analysis. SIFT-MS uses chemical ionization and mass spectrometry without requiring the complex chromatographic separation system of GC-MS, thereby reducing mechanical complexity while enabling real-time quantitative analysis of breath VOCs.

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

4Measurement precision

If colonoscopy is used as gold standard investigation, then diagnostic accuracy is improved, but resource implications and cost increase

Engineering Contradiction:
Improvediagnostic accuracyVSAvoidresource consumption
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The invention introduces breath VOC analysis as an intermediary test between initial screening and colonoscopy. The breath test using VOC signature profiling serves as a non-invasive intermediate investigation that triages patients, reducing the number who require resource-intensive colonoscopy while maintaining high diagnostic accuracy for CRC detection.

Inventive Principle:
Principle #24Intermediary (Mediator)

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

The method provides a robust, non-invasive, and cost-effective means for diagnosing and monitoring colorectal cancer with high sensitivity (77%) and specificity (87%), enabling early detection and effective treatment planning.

Implementation Method 1

Researchers using gas chromatography mass spectrometry (GC-MS) have suggested the existence of a breath VOC profile specific to CRC

Methodology Applied
Scientific EffectGas Chromatography: Chromatography

Implementation Method 2

Gas Chromatography Mass Spectrometry (GC-MS)

Methodology Applied
Scientific EffectMass Spectrometry:

Implementation Method 3

Selected ion flow tube mass spectrometry (SIFT-MS) has the advantage of being quantitative and permits real-time analysis

Methodology Applied
Scientific EffectMass Spectrometry:

Data Source

PatentUS20240302347A1Volatile biomarkers for colorectal cancer
Publication Date: 2024.09.12 IMPERIAL COLLEGE INNVOATIONS LTD
  • US20240302347A1 patent drawing
  • US20240302347A1 patent drawing
  • US20240302347A1 patent drawing

AI summary

The invention relates to biomarkers, and to novel biological markers for diagnosing colorectal cancer. In particular, the invention relates to the use of these biomarkers as diagnostic and prognostic markers in assays for detecting colorectal cancer, and corresponding methods of detection. The invention also relates to methods of determining the efficacy of treating colorectal cancer with a therapeutic agent, and apparatus for carrying out the assays and methods. The assays are qualitative and/or quantitative, and are adaptable to large-scale screening and clinical trials.