Serum Biomarker Panel for Rapid Drug-Resistant Tuberculosis Detection

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Solution Overview

Problem

Current methods for detecting drug-resistant tuberculosis are complex, costly, and require high technical expertise, limiting their availability in economically underdeveloped regions, necessitating the development of simpler and more effective biomarkers and detection methods.

Innovation Solution

A set of 17 serum metabolic biomarkers, including taurine, homocysteine, uric acid, and others, are identified, along with a detection kit and a machine learning-based model using LDI MS and Random Forest algorithm, enabling rapid and accurate diagnosis of drug-resistant tuberculosis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If traditional bacteriological methods and molecular tests are used for drug-resistant tuberculosis detection, then detection accuracy is improved, but device complexity and operational difficulty increase

Engineering Contradiction:
Improvedetection accuracyVSAvoiddetection system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent extracts and measures specific metabolic biomarkers (taurine, homocysteine, uric acid, ascorbic acid, and other metabolites) from the complex tuberculosis diagnostic process. By focusing on a specific subset of metabolites that serve as indicators of drug resistance, the method simplifies the detection system while maintaining high accuracy in distinguishing drug-resistant from drug-sensitive tuberculosis cases.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent replaces complex mechanical and laboratory-based detection systems (bacteriological culture methods, molecular tests requiring specialized equipment) with a metabolic profiling approach that can be performed using mass spectrometry or other analytical instruments to measure metabolite concentrations, thereby reducing operational complexity and infrastructure requirements.

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

2Measurement precision

If traditional bacteriological methods and molecular tests are used for drug-resistant tuberculosis detection, then detection accuracy is improved, but cost increases

Engineering Contradiction:
Improvedetection accuracyVSAvoiddetection cost
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The patent extracts and measures specific metabolic biomarkers (taurine, homocysteine, uric acid, ascorbic acid, and other metabolites) from the complex tuberculosis diagnostic process. By focusing on a specific subset of metabolites that serve as indicators of drug resistance, the method simplifies the detection system while maintaining high accuracy in distinguishing drug-resistant from drug-sensitive tuberculosis cases.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent employs a metabolic profiling approach that uses consumable reagents for metabolite measurement rather than expensive, reusable specialized equipment. This substitution with more affordable, disposable-like measurement components significantly reduces the overall cost of detection while preserving diagnostic accuracy.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

3Measurement precision

If traditional bacteriological methods and molecular tests are used for drug-resistant tuberculosis detection, then detection accuracy is improved, but ease of operation deteriorates

Engineering Contradiction:
Improvedetection accuracyVSAvoidoperational simplicity
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The patent extracts and measures specific metabolic biomarkers (taurine, homocysteine, uric acid, ascorbic acid, and other metabolites) from the complex tuberculosis diagnostic process. By focusing on a specific subset of metabolites that serve as indicators of drug resistance, the method simplifies the detection system while maintaining high accuracy in distinguishing drug-resistant from drug-sensitive tuberculosis cases.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent replaces complex mechanical and laboratory-based detection systems (bacteriological culture methods, molecular tests requiring specialized equipment) with a metabolic profiling approach that can be performed using mass spectrometry or other analytical instruments to measure metabolite concentrations, thereby reducing operational complexity and infrastructure requirements.

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

4Measurement precision

If traditional bacteriological methods and molecular tests are used for drug-resistant tuberculosis detection, then detection accuracy is improved, but detection time increases

Engineering Contradiction:
Improvedetection accuracyVSAvoiddetection time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent measures metabolic biomarkers that reflect the current physiological state of the tuberculosis infection and drug resistance profile. By detecting metabolites that are already present in the system and directly related to drug resistance mechanisms, the method eliminates the need for time-consuming bacterial culture processes, enabling rapid detection while maintaining high accuracy.

Inventive Principle:
Principle #10Preliminary action

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 biomarker panel and detection kit provide high sensitivity (90%) and specificity (96%) for drug-resistant tuberculosis detection, facilitating mass screening with a small blood sample size.

Implementation Method 1

Analysis of each serum sample using the LDI MS technique, and recording the original metabolic fingerprints on an AutoFlex TOF/TOF mass spectrometer

Methodology Applied
Scientific EffectLaser desorption ionization: Laser

Data Source

PatentUS12385916B2Serum metabolic biomarkers and kit for detecting drug-resistant tuberculosis
Publication Date: 2025.08.12 ZHEJIANG SUKEAN PHARMACEUTICAL CO LTD
  • US12385916B2 patent drawing

AI summary

A set of serum metabolic biomarkers and detection kit for detecting drug-resistant tuberculosis are provided. The set of the serum metabolic biomarkers includes 17 serum metabolic biomarkers. The 17 serum metabolic biomarkers are verified to be associated with tuberculosis based on the level changes of these biomarkers. The 17 metabolites includes taurine, homocysteine, uric acid, ascorbic acid, suberylglycine, uridine, dopamine 4-sulfate, inosinic acid, glyceraldehyde phosphate, [3-methoxy-4-(phosphoryl)phenyl]carbonyl sulfonic acid, nuclomedone, n4-cyclopropyl-6-(2,3-dichlorophenyl)-1,2,3,4-tetrahydropyrimidine-2,4-diimine, 1-[2-chlorine-2-(2,4-dichlorophenyl)ethenyl]-1,2,4-triazole, tetrachloro-phthalic anhydride, malotilate, fulvic acid, and L-neopterin. The serum metabolic biomarkers and detection kit for detecting drug-resistant tuberculosis can assist doctors in accurately diagnosing the disease, which is of great significance for the diagnosis and mass screening for drug-resistant tuberculosis.