Optical Density Measurement in Shaken Reactors
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for determining optical density and its changes in shaken reactors during ongoing shaking operations are unreliable due to fluctuating signal strengths, mechanical instability, and limited measurement ranges, especially at low cell concentrations and varying operating conditions, leading to inaccurate results and contamination risks.
Innovation Solution
A method and system that utilize non-invasive measurement of optical density by positioning light sources and sensors to record periodic fluctuations in the reaction mixture's distribution, allowing for reliable determination of optical density and changes through mathematical modeling, even at low and high concentrations, and enabling real-time process monitoring with minimal calibration and reduced contamination risk.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If sampling-based measurement methods are used to determine optical density in shaken reactors, then measurement can be performed, but contamination risk increases and measurement effort increases
Solution Approach 1:
The patent replaces mechanical sampling operations with a non-invasive optical measurement system. Light sources and sensors are positioned to measure optical density through the reactor wall without physical contact with the reaction mixture, eliminating contamination risk while enabling automated high-throughput measurements across multiple reactors simultaneously
Solution Approach 2:
The patent uses the reactor wall as an intermediary medium to transmit light between the measurement system and the reaction mixture. By positioning light sources and sensors on opposite sides of the reactor wall, the system enables optical measurements without penetrating the sealed reactor environment, maintaining sterility while obtaining measurement data
2Reliability
If measurements are taken during ongoing shaking operation, then process continuity is maintained, but signal fluctuations increase and measurement reliability decreases
Solution Approach 1:
The patent exploits the periodic nature of shaking motion by synchronizing measurements with specific phases of the shaking cycle. By taking measurements at consistent points in the periodic shaking motion, the system captures reproducible optical density values while maintaining continuous process operation, transforming the harmful signal fluctuations into a predictable periodic pattern that can be systematically measured
Solution Approach 2:
The patent positions the light sources and sensors to capture measurements before significant signal fluctuations occur during each shaking cycle. By anticipating the optimal measurement window in the periodic motion, the system obtains reliable data at predetermined points in the shaking cycle, ensuring measurement consistency without interrupting the process
3Measurement precision
If conventional optical density measurement is performed in shaken reactors, then measurement can be obtained, but accuracy decreases at low cell concentrations and varying operating conditions
Solution Approach 1:
The patent systematically varies measurement parameters including light wavelength, source-sensor positioning angles, and measurement timing within the shaking cycle to optimize accuracy across different operating conditions. By adapting these parameters based on specific reactor configurations, cell concentrations, and shaking intensities, the system maintains high measurement precision whether measuring low cell densities in shake flasks or higher concentrations in T-flasks
Solution Approach 2:
The patent designs a measurement system that functions universally across multiple reactor types (shake flasks, T-flasks, microtiter plates) and operating conditions through adjustable light sources and sensors. The system can adapt its geometry and measurement parameters to accommodate varying filling volumes, shaking frequencies, and reactor dimensions, providing accurate optical density measurements across a broad range of biotechnological applications without requiring condition-specific calibration
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 robust, reliable, and accurate measurement of optical density and process parameters in shaken reactors across a wide range of conditions, reducing measurement errors and contamination risks, while allowing for precise process control and high-throughput screening.
Implementation Method 1
The well-known basis of these technologies is the scattering and/or transmission of light by matter in the light path. The scattered and transmitted intensities are in a mathematically modelable relationship with the concentration of the matter in the light path and interacting with the light
Implementation Method 2
The well-known basis of these technologies is the scattering and/or transmission of light by matter in the light path. The scattered and transmitted intensities are in a mathematically modelable relationship with the concentration of the matter in the light path and interacting with the light
Data Source
Figure 1
Figure 2
Figure 3
AI summary
The invention relates to a method, to a device, and to a system for the automated determination of optical densities or of the change in optical densities of reaction mixtures in shaken reactors during shaking operation. Methods and devices currently used therefor are often unreliable, are susceptible to environmental and process factors, or require interruptions to the shaking operation that impair the process control. The problem addressed by the invention is that of specifying a method and a device for the automated determination of optical densities or of the change in optical densities of reaction mixtures in shaken reactors during shaking operation that operate reliably under various environmental and process conditions. This problem is solved by means of a new measurement method, wherein the reaction mixture distribution, which periodically fluctuates because of the shaking action, is used to record measurement points (20/21) of transmission/scattered-light measurements, which measurement points fluctuate periodically as a result of shaking. All measurement points (20/21) of a measurement operation are combined into a measurement series (34), from which the optical density and/or the change in the optical density, and other process parameters, can be determined with high reliability by means of suitable mathematical methods. The invention is suitable in particular for biotechnological, pharmaceutical, chemical, and biochemical screening and optimization and process-monitoring applications.