Automated MIC Determination via Microtiter Plate Growth Analysis

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Solution Overview

Problem

Current methods for determining the minimum inhibitory concentration (MIC) of antibiotics on bacteria are imprecise and dependent on human judgment, lacking robustness and precision due to limited sample numbers and subjective turbidity assessments.

Innovation Solution

A method involving the preparation of multiple samples with varying initial concentrations of a molecule, followed by incubation and measurement of microorganism growth, using a model-based approach to classify and determine the inhibitory capacity by analyzing growth dynamics, such as lag phase and exponential growth rates, to identify the transition zone of inhibitory effects.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Loss of time

If a small number of tubes are prepared for MIC measurement, then the preparation time and resources are reduced, but the precision and accuracy of MIC determination deteriorate

Engineering Contradiction:
Improvepreparation timeVSAvoidMIC determination precision
Core Design Contradiction:
Loss of timeVSMeasurement precision

Solution Approach 1:

The invention segments the measurement process by preparing a large number of microtiter plate wells (typically 96 wells per plate, multiple plates can be used) instead of a small number of tubes. Each well contains a different antibiotic concentration, creating a segmented concentration gradient that allows precise MIC determination through automated reading of multiple data points rather than relying on visual inspection of few tubes.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention uses optical copying/detection methods where a plate reader automatically measures optical density or fluorescence of each well, creating an automated digital record of bacterial growth at each antibiotic concentration. This replaces the manual visual copying/assessment by a technician, eliminating subjectivity and increasing precision through automated data collection from multiple samples.

Inventive Principle:
Principle #26Copying

2Device complexity

If visual inspection by technician is used to determine MIC, then the method is simple and requires minimal equipment, but the robustness and objectivity of detection deteriorate

Engineering Contradiction:
Improveequipment complexityVSAvoiddetection robustness
Core Design Contradiction:
Device complexityVSReliability

Solution Approach 1:

The invention replaces the mechanical/visual inspection system with an automated optical detection system (plate reader). The plate reader uses light absorption or fluorescence emission measurements to objectively quantify bacterial growth in each well, substituting the technician's visual judgment with an automated instrument that provides consistent, objective, and reproducible measurements across all samples.

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

Solution Approach 2:

The plate reader performs self-service by automatically measuring all wells without requiring technician intervention for each reading. The system autonomously collects data from all samples, processes the results, and determines MIC values, eliminating the need for manual visual inspection and reducing human error while maintaining operational simplicity.

Inventive Principle:
Principle #25Self-service

3Ease of operation

If manual visual assessment of turbidity is used, then the operational simplicity is maintained, but the accuracy and objectivity of MIC identification deteriorate

Engineering Contradiction:
Improveoperational simplicityVSAvoidMIC identification accuracy
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The invention replaces manual visual assessment with automated optical measurement using a plate reader. The instrument measures optical density or fluorescence at each well, providing precise quantitative data on bacterial growth. This substitution maintains ease of operation (the plate reader is simply loaded and operated with one button) while dramatically improving measurement precision through objective, automated detection rather than subjective visual judgment.

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

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 provides a more precise, automated, and reproducible determination of the true MIC concentration, reducing reliance on operator interpretation and improving accuracy by analyzing growth dynamics and identifying the transition zone between no and complete inhibition.

Implementation Method 1

measuring the growth of the microorganisms in the sample as a function of time

Methodology Applied
Scientific EffectMicrobial growth: Fermentation

Data Source

PatentUS11414692B2Method and device for characterizing the inhibitory capacity of a molecule on a microorganism
Publication Date: 2022.08.16 BIOMERIEUX SA
  • US11414692B2 patent drawing
  • US11414692B2 patent drawing
  • US11414692B2 patent drawing

AI summary

A method for determining a quantity Ginhib quantifying the inhibitory capacity of a molecule on a type of microorganism includes: preparing a plurality of samples, including microorganisms of the type, a nutrient medium for the microorganism and an initial amount of the molecule per microorganism increasing in a range [Qmin,Qmax] as a function of a classification of the samples; measuring the growth of the microorganisms in the samples as a function of time; and determining the quantity Ginhib as a function of the measurements of the growth. Determination of the quantity Ginhib includes: for each sample, calculating a value reflecting the growth of the microorganism of said type based on measurements of growth; classifying the values calculated for the samples as a function of the classification of the samples; and determining the quantity Ginhib as a function of the variation of the classified values.