Sterility Testing via Angled Light Scattering on Membranes

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Solution Overview

Problem

Current methods for sterility testing in the pharmaceutical industry are culture-based and time-consuming, requiring 14 days, and existing rapid detection methods either risk contamination, use additional reagents, or are not suitable for closed device applications.

Innovation Solution

A method using a closed device to detect micro-colonies on a membrane or agarose medium by irradiating with light at a specific angle, imaging with a 3D camera, and analyzing reflected or scattered light to determine variations in height and intensity, allowing for rapid detection without contamination risks or additional reagents.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If culture-based methods are used for sterility testing, then reliability of detection is improved, but testing time increases to 14 days

Engineering Contradiction:
Improvedetection reliabilityVSAvoidtesting time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The method performs preliminary actions by placing the membrane in a sealed container with nutrient agar and incubating for only 18-48 hours to allow micro-colony formation, rather than waiting 14 days for full colony development. This preliminary growth phase enables subsequent rapid detection methods to work effectively on smaller, earlier-stage colonies.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The invention replaces traditional visual inspection methods with automated imaging and analysis systems. A camera captures images of the membrane, and software automatically detects and analyzes micro-colonies based on light scattering patterns, eliminating the need for manual examination and enabling rapid results.

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

2Productivity

If automated imaging systems are used to detect micro-colonies, then productivity is improved, but device complexity increases

Engineering Contradiction:
Improvedetection speedVSAvoidsystem complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The system uses a camera, which is a common and relatively simple device, to perform multiple functions: capturing images of the membrane, detecting micro-colonies through light scattering analysis, and providing data for automated interpretation. This multi-functional approach avoids the need for specialized complex instrumentation.

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

Solution Approach 2:

The system employs automated image analysis software that independently processes the captured images, automatically detects micro-colonies based on light scattering patterns, and generates results without requiring complex manual intervention or sophisticated additional hardware components.

Inventive Principle:
Principle #25Self-service

3Difficulty of detecting and measuring

If the membrane is scanned in an open environment, then detection capability is improved, but contamination risk increases

Engineering Contradiction:
Improvedetection capabilityVSAvoidcontamination risk
Core Design Contradiction:
Difficulty of detecting and measuringVSObject-affected harmful factors

Solution Approach 1:

The method extracts the detection function from the incubation environment by using a camera to capture images through the sealed container wall. This allows imaging to be performed without opening the container, thereby maintaining the sealed environment and preventing contamination while still enabling micro-colony detection.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The sealed container wall acts as an intermediary that allows optical transmission for imaging while maintaining physical separation and sealing. The container material permits light to pass through for camera imaging but prevents contamination from entering the sealed environment during the detection process.

Inventive Principle:
Principle #24Intermediary (Mediator)

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 reliable detection of micro-colonies within 5 days or less, preventing false positives and negatives, and maintaining a closed system to prevent contamination, thus meeting modern sterility testing requirements.

Implementation Method 1

detecting the light reflected or back scattered from the membrane or the surface of the agarose medium and/or the micro-colonies on the membrane and/or the micro-colonies on the agarose medium

Methodology Applied
Scientific EffectLight scattering: Scattering

Data Source

PatentEP3134848B1Method for detecting micro-colonies growing on a membrane or an agarose medium of a sample and a sterility testing apparatus
Publication Date: 2019.09.04 MERCK PATENT GMBH
  • EP3134848B1 patent drawingFigure 1
  • EP3134848B1 patent drawingFigure 2
  • EP3134848B1 patent drawingFigure 3

AI summary

The present invention is directed to a method and an apparatus for detecting micro-colonies growing on a membrane (1) or an agarose medium of a sample (5) in a closed device (3). According to the invention the sample (5) is irradiated with a light incident at an angle (β) with respect to the normal to the membrane (1) or the surface of the agarose medium from outside the device (3). An incident area (7) of the light on the membrane (1) or the surface of the agarose medium is imaged by means of a light receiving element (9) using an imaging angle (α) different from angle (β) with respect to the normal to the membrane (1) or the surface of the agarose medium from outside the device (3). The light reflected, scattered and/ or diffused from the membrane or the surface of the agarose medium and/or the micro-colonies on the membrane and/or the micro-colonies on the agarose medium is detected.