Same-Sample Antibiotic Susceptibility Test via Nucleic Acid Proportion

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Solution Overview

Problem

Current antibiotic susceptibility testing methods face challenges in achieving rapid and accurate detection of antibiotic susceptibility in microorganisms, particularly when determining resistance or sensitivity, as they often require additional marker detection and are prone to interference from biological events.

Innovation Solution

The same-sample antibiotic susceptibility test (AST) method involves detecting both extracellular and intracellular nucleic acids from a single sample, using the intra/extra NA proportion value to determine live and dead cells and antibiotic susceptibility without the need for additional marker detection, and accounts for confounding variables like cell number, background lysis, and lag time through mathematical modeling and statistical analysis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If additional marker detection is performed to determine antibiotic susceptibility, then measurement precision is improved, but device complexity and time consumption increase

Engineering Contradiction:
Improveantibiotic susceptibility detection accuracyVSAvoiddetection system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent extracts the nucleic acid marker detection from separate additional tests and integrates it into the same-sample AST process. By detecting both intracellular and extracellular nucleic acids from the same sample without requiring separate marker detection steps, the method reduces device complexity while maintaining measurement precision through the use of universal nucleic acid detection techniques

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The detection system performs multiple functions simultaneously: it detects both intracellular and extracellular nucleic acids, determines cell viability, and assesses antibiotic susceptibility all from a single sample using the same detection platform. This multi-functionality eliminates the need for separate marker detection systems while maintaining comprehensive diagnostic capability

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

2Measurement precision

If multiple separate samples are used for different detection steps, then measurement precision is improved, but loss of time and sample volume increase

Engineering Contradiction:
Improvedetection accuracyVSAvoidtesting duration
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent merges multiple detection objectives into a single sample analysis process. Both intracellular and extracellular nucleic acids are detected from the same sample without requiring separate sample preparations or additional detection steps, thereby reducing time loss while maintaining measurement precision through integrated analysis

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The method performs preliminary separation of intracellular and extracellular components from the sample before detection, allowing both types of nucleic acids to be measured in the same detection run. This preliminary action enables comprehensive analysis without requiring multiple separate testing steps, reducing overall testing time

Inventive Principle:
Principle #10Preliminary action

3Measurement precision

If biological events such as cell lysis and growth are accounted for through additional detection steps, then measurement precision is improved, but device complexity and time consumption increase

Engineering Contradiction:
Improvesusceptibility determination accuracyVSAvoidadditional detection time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent uses the ratio of intracellular to extracellular nucleic acid concentrations as a feedback mechanism to account for biological events. The intracellular/extracellular nucleic acid proportion serves as an indicator of cell membrane integrity and biological activity, allowing the system to compensate for cell lysis and growth effects without requiring additional detection steps or increasing device complexity

Inventive Principle:
Principle #23Feedback

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 enables rapid and accurate antibiotic susceptibility testing by minimizing the impact of confounding variables, allowing for precise determination of live and dead cell proportions and antibiotic susceptibility in a single sample, improving test accuracy and reducing the need for additional detection steps.

Implementation Method 1

separating the antibiotic-treated sample into an antibiotic-treated extracellular component and an antibiotic-treated cellular component

Methodology Applied
Scientific EffectSeparation based on cellular component location:

Implementation Method 2

detecting a nucleic acid concentration of the antibiotic-treated extracellular component to obtain an antibiotic-treated extracellular nucleic acid concentration value and detecting a nucleic acid concentration of the antibiotic-treated cellular component

Methodology Applied
Scientific EffectNucleic acid detection:

Data Source

PatentUS20220282304A1Same-sample antibiotic susceptibility test and related compositions, methods and systems
Publication Date: 2022.09.08 CALIFORNIA INST OF TECH
  • US20220282304A1 patent drawing
  • US20220282304A1 patent drawing
  • US20220282304A1 patent drawing

AI summary

Provided herein is an antibiotic susceptibility and related compositions, methods and systems based on nucleic acid detection based on detected intracellular and extracellular nucleic acid from a same sample, which allows determination of antibiotic susceptibility of microorganisms as well as the diagnosis and/or treatment of related infections in individuals.