Immunoassay Sample Prep for Microbial Detection

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Solution Overview

Problem

Current methods for diagnosing microbial infections, such as native joint infection and periprosthetic joint infection, face challenges with false negative results and poor clinical sensitivity due to damaged bacteria and antimicrobial substances, limiting the effectiveness of culture-based methods and direct detection techniques like immunoassays and PCR.

Innovation Solution

A biological sample preparation method involving a combination of enzymes, detergents, and heat treatment is used to increase the availability of microorganism antigens for detection, followed by immunoassay techniques to directly detect and identify bacteria and fungi in synovial fluid samples, even in culture-negative cases.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If culture-based methods are used to detect microorganisms, then the gold standard for diagnosis is achieved, but the time-to-results is long (several days to weeks) and false negative rates are high

Engineering Contradiction:
Improvediagnostic accuracyVSAvoidtime-to-results
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent extracts and detects specific microbial antigens directly from patient samples using immunoassay techniques, bypassing the need for prolonged culture growth. This extraction approach allows rapid identification of microorganisms without waiting for culture results, resolving the contradiction between diagnostic reliability and time-to-results.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent performs preliminary detection of microbial antigens before culture results are available. By using immunoassays to detect antigens in advance, the system provides early diagnostic information that guides treatment decisions while culture results are still pending, thus reducing the effective time-to-results without sacrificing diagnostic accuracy.

Inventive Principle:
Principle #10Preliminary action

2Loss of time

If direct detection methods like immunoassay and PCR are used, then time-to-results is reduced, but sensitivity and specificity are poor and false negative results increase

Engineering Contradiction:
Improvetime-to-resultsVSAvoidsensitivity and specificity
Core Design Contradiction:
Loss of timeVSReliability

Solution Approach 1:

The patent optimizes multiple parameters of the immunoassay system including antibody selection, sample preparation conditions, and detection thresholds. By carefully adjusting these parameters, the system achieves both rapid results and high sensitivity/specificity, resolving the contradiction between speed and reliability of direct detection methods.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses specifically selected antibodies as intermediaries to detect microbial antigens. These antibodies serve as mediators that enhance the sensitivity and specificity of the detection system, allowing accurate identification of microorganisms through rapid immunoassay methods without the time delay of culture techniques.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If sample preparation techniques are applied to separate, purify or concentrate bacterial antigen, then detection sensitivity is improved, but the complexity of the overall method increases

Engineering Contradiction:
Improvedetection sensitivityVSAvoidsample preparation complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent employs a universal sample preparation protocol that effectively separates, purifies, and concentrates bacterial antigens using a standardized approach. This multi-functional preparation method works across different sample types and microbial targets, improving detection sensitivity while maintaining consistent procedural complexity rather than requiring separate complex protocols for each scenario.

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

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 enhances the sensitivity and specificity of microbial detection, allowing for accurate diagnosis of infections, particularly when traditional culture methods fail, and provides information on the type of infecting microorganism to inform antibiotic treatment.

Implementation Method 1

A biological sample preparation method involving a combination of enzymes, detergents, and heat treatment is used to increase the availability of microorganism antigens for detection

Methodology Applied
Scientific EffectEnzyme digestion: Enzyme

Implementation Method 2

A biological sample preparation method involving a combination of enzymes, detergents, and heat treatment is used to increase the availability of microorganism antigens for detection

Methodology Applied
Scientific EffectHeat treatment: Heating

Implementation Method 3

A biological sample preparation method involving a combination of enzymes, detergents, and heat treatment is used to increase the availability of microorganism antigens for detection

Methodology Applied
Scientific EffectDetergent solubilization: Surfactant

Implementation Method 4

followed by immunoassay techniques to directly detect and identify bacteria and fungi in synovial fluid samples

Methodology Applied
Scientific EffectImmunoassay binding: Absorption (physical)

Data Source

PatentEP3535409B1Direct detection of microorganisms in patient samples by immunoassay
Publication Date: 2024.03.20 CD DIAGNOSTICS INC
  • EP3535409B1 patent drawingFigure 1
  • EP3535409B1 patent drawingFigure 2A
  • EP3535409B1 patent drawingFigure 2B

AI summary

Methods are provided for preparing patient samples for direct detection and identification of microorganisms in the patient samples using multiplex immunoassays. The method includes enzymatic treatment of the patient sample, boiling and centrifugation of the sample to provide a treated sample that may be used in an immunoassay. There are also provided immunoassay compositions and systems for the direct detection and identification of microorganism in patient tissue.