Automated Microscopy for Real-Time Bacterial Growth Monitoring

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Solution Overview

Problem

Conventional methods for monitoring cell culture growth, particularly bacterial growth, are time-consuming and cannot provide real-time assessments, making them unsuitable for time-critical applications such as antibiotic resistance testing.

Innovation Solution

An automated method using image processing software and a microscope with a movable image recording plane to select high-contrast images of miniaturized cell cultures, allowing for real-time tracking of bacterial growth by determining the size of the cell culture area over time.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional macroscopic methods are used to determine antibiotic resistance, then reliable results can be obtained, but the testing time is extended to 6-24 hours

Engineering Contradiction:
Improvereliability of antibiotic resistance determinationVSAvoidtesting time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent divides the observation task into individual cell-level imaging instead of macroscopic colony observation. By segmenting the measurement into discrete cellular units captured through microscopy, the system enables earlier detection of growth inhibition effects before colonies become visible to the naked eye, reducing testing time while maintaining reliability through automated image analysis.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent replaces manual macroscopic visual assessment with an automated optical imaging system coupled with image processing software. This substitution of mechanical/visual inspection with automated optical detection and computational analysis enables real-time monitoring of cell culture growth, dramatically reducing the 6-24 hour waiting period while preserving measurement accuracy.

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

2Measurement precision

If transmission optics are used to measure light intensity through bacterial suspension, then cell culture growth can be quantified, but the method only delivers reliable results after several hours

Engineering Contradiction:
Improvequantification of cell culture growthVSAvoidtime to reliable results
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent transitions from bulk suspension measurement in one dimension to spatially-resolved imaging in two dimensions. By capturing images of immobilized cells on a solid substrate and analyzing their spatial distribution and morphology through image processing, the system achieves precise growth quantification at earlier time points, bypassing the several-hour delay inherent in transmission optics methods.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

Solution Approach 2:

The patent applies preliminary action by immobilizing bacterial cells on a solid substrate before antibiotic exposure. This pre-positioning of cells enables immediate imaging and continuous monitoring from the start of the experiment, eliminating the delay associated with preparing suspensions for transmission optics measurement and allowing reliable results to be obtained much sooner.

Inventive Principle:
Principle #10Preliminary action

3Quantity of substance

If a large number of cells are observed or turbidity of bacterial suspension is measured, then antibiotic effect can be determined, but individual cell-level effects cannot be detected

Engineering Contradiction:
Improvenumber of cells observedVSAvoidindividual cell effect detection
Core Design Contradiction:
Quantity of substanceVSMeasurement precision

Solution Approach 1:

The patent applies segmentation by immobilizing individual bacterial cells on a solid substrate, separating them into discrete, addressable units. This segmentation allows the imaging system to resolve and analyze individual cell morphology, size, and viability rather than measuring bulk properties, enabling detection of antibiotic effects at the single-cell level while still observing populations of many cells across the field of view.

Inventive Principle:
Principle #1Segmentation

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

Enables rapid determination of bacterial growth and antibiotic effectiveness, significantly reducing the time required for resistance testing from 5 to 24 hours to 2 to 3 hours, while minimizing reagents and sample material usage.

Implementation Method 1

a microscope with a camera and an image recording plane that can be moved along the optical axis... an image of the nutrient medium is recorded using the camera of the microscope by moving the image recording plane along the optical axis through the receiving dish through the nutrient medium

Methodology Applied
Scientific EffectOptical imaging: Light

Data Source

PatentEP3149150B1Automatic method for monitoring cell culture growth
Publication Date: 2017.11.22 FRAUNHOFER GESELLSCHAFT ZUR FORDERUNG DER ANGEWANDTEN FORSCHUNG EV
  • EP3149150B1 patent drawingFigure 1~2
  • EP3149150B1 patent drawingFigure 3
  • EP3149150B1 patent drawingFigure 4A~4C'

AI summary

The invention relates to an automated method for monitoring cell culture growth, in particular bacterial growth, wherein a receiving dish (24) is provided with a nutrient medium (38), on and/or in which a cell culture is applied, in particular a sample of human or animal tissue, such as blood, to which bacteria has been added, and which also contains one or a number of reagents, in particular antibiotics. A microscope (10) having a camera (18) and an image-capturing plane that can move along the optical axis (20) is provided, and the receiving dish (24) is brought into the microscope (10) in the nutrient medium (38), in order to monitor a potential growth of the cell culture. An image of the nutrient medium (38) is captured using the camera (18) of the microscope (10), at pre-determinable time intervals in the in particular single-digit minute region.