Nucleic Acid Detection for Rapid Antibiotic Susceptibility Testing

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Solution Overview

Problem

Existing methods struggle to rapidly and accurately determine antibiotic susceptibility, particularly for slow-growing microorganisms like Neisseria gonorrhoeae, which lack a classic transcriptional SOS response to DNA damage.

Innovation Solution

A method involving nucleic acid detection in antibiotic-treated samples, with or without lysis treatment, to quantify nucleic acid concentration ratios, indicating antibiotic susceptibility or resistance, using systems that include probes and reagents for lysis and separation treatments.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If traditional antibiotic susceptibility testing methods are used, then accuracy of susceptibility determination is improved, but testing time is excessive for rapid diagnosis needs

Engineering Contradiction:
Improveaccuracy of susceptibility determinationVSAvoidtesting time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent applies preliminary action by performing nucleic acid extraction and quantification before completing the full antibiotic treatment cycle. The method measures nucleic acid concentration at intermediate time points (e.g., 4-18 hours) to predict final susceptibility outcomes, avoiding the need to wait for complete bacterial growth inhibition or death to determine susceptibility.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent replaces traditional mechanical/cultural methods (visual inspection of bacterial growth on plates or in broth) with molecular detection methods. Instead of mechanically observing colony formation or turbidity changes, the system uses nucleic acid quantification (PCR, qPCR, or sequencing) to detect and measure bacterial DNA/RNA, providing faster and more precise susceptibility determination.

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

2Reliability

If conventional culture-based AST methods are applied, then reliability of susceptibility classification is improved, but the method fails for slow-growing microorganisms like Neisseria gonorrhoeae

Engineering Contradiction:
Improvereliability of susceptibility classificationVSAvoidapplicability to slow-growing microorganisms
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies universality by developing a nucleic acid-based susceptibility testing platform that works across diverse microorganism types regardless of growth rate. The method uses conserved nucleic acid sequences and universal detection principles (PCR amplification, sequencing) that function equally well for fast-growing bacteria, slow-growing bacteria like N. gonorrhoeae, and even organisms that are difficult to culture traditionally.

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

Solution Approach 2:

The patent replaces culture-based mechanical observation with molecular detection. Instead of relying on visible bacterial growth (which fails for slow-growers), the system directly detects and quantifies nucleic acids from the microorganisms, bypassing the need for extended culture periods and enabling reliable susceptibility assessment for previously intractable species.

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

3Productivity

If rapid nucleic acid detection methods are used, then testing speed is improved, but complexity of sample processing increases

Engineering Contradiction:
Improvetesting speedVSAvoidcomplexity of sample processing
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent applies segmentation by dividing the sample processing into distinct modular steps: nucleic acid extraction, quantification/detection, and susceptibility determination. Each step can be performed with specialized reagents and protocols optimized for that specific function, allowing the system to handle complex samples through a series of manageable, standardized operations rather than a single complex procedure.

Inventive Principle:
Principle #1Segmentation

Data Source

PatentUS12448655B2Antibiotic susceptibility of microorganisms and related methods and systems
Publication Date: 2025.10.21 CALIFORNIA INST OF TECH
  • US12448655B2 patent drawing
  • US12448655B2 patent drawing
  • US12448655B2 patent drawing

AI summary

Provided herein is an antibiotic susceptibility test and related compositions, methods and systems based on detection of a nucleic acid from a target microorganism in a sample in the presence or absence of a lysis treatment of the sample.