Cell Suspension Stirring with Optical Uniformity Detection

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Solution Overview

Problem

Existing cell culture methods lack an efficient technique to optimize the stirring process, leading to unnecessary prolonged execution times and suboptimal conditions for cell culture processing.

Innovation Solution

A method and apparatus that includes a cell stirring step, acquisition of physical quantities using an optical sensor, and a determination step to assess uniform diffusion based on variation, allowing for precise control of stirring time to achieve a uniform cell distribution.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If cell suspension is stirred for a longer time to achieve uniform diffusion, then cell distribution uniformity is improved, but execution time of cell culture processing increases

Engineering Contradiction:
Improvecell distribution uniformityVSAvoidexecution time of cell culture processing
Core Design Contradiction:
Stability of the object's compositionVSLoss of time

Solution Approach 1:

The patent applies feedback control by continuously monitoring the physical quantity (light transmission or scattering) during stirring and using this information to determine when uniform diffusion is achieved. The control unit adjusts the stirring time based on the detected degree of variation in the physical quantity, stopping the stirring process precisely when uniformity is reached rather than using a fixed predetermined time. This feedback mechanism resolves the contradiction by dynamically optimizing stirring duration to achieve uniform cell distribution without unnecessary prolonged stirring.

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The patent implements dynamic adjustment of the stirring process by continuously monitoring the physical quantity and adapting the stirring duration based on real-time conditions. Instead of using a static, fixed stirring time, the system dynamically determines the optimal stirring duration by evaluating the degree of variation in light transmission or scattering. This dynamic approach allows the system to achieve uniform cell distribution in the minimum necessary time, resolving the contradiction between uniformity and processing time.

Inventive Principle:
Principle #15Dynamics

2Productivity

If cell stirring step execution time is reduced to optimize processing, then productivity is improved, but cell distribution uniformity may be compromised

Engineering Contradiction:
Improvecell culture processing efficiencyVSAvoidcell distribution uniformity
Core Design Contradiction:
ProductivityVSStability of the object's composition

Solution Approach 1:

The feedback control mechanism monitors the physical quantity during stirring and provides real-time information about the diffusion state. By using this feedback, the system can confidently stop stirring as soon as uniformity is achieved, ensuring that cell distribution uniformity is maintained even with reduced stirring time. This enables productivity improvement without compromising uniformity, as the feedback ensures the minimum necessary stirring is performed.

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The patent replaces the traditional mechanical approach of fixed-duration stirring with an optical measurement system. Instead of relying on predetermined mechanical timing, the system uses optical sensors to detect the physical quantity and determine when uniform diffusion is achieved. This substitution allows for precise, adaptive control of stirring duration, enabling shorter processing times while maintaining uniform cell distribution.

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

3Measurement precision

If optical sensor measurement is implemented to detect uniform diffusion state, then stirring time precision is improved, but device complexity increases

Engineering Contradiction:
Improvestirring time precisionVSAvoidmeasurement and control system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent introduces an optical sensor as an intermediary to indirectly measure the uniform diffusion state. Instead of directly observing cell distribution, the system uses light transmission or scattering as an intermediary physical quantity that correlates with uniformity. This intermediary approach enables precise measurement of the diffusion state without requiring complex direct imaging or analysis systems, thus achieving measurement precision while limiting the increase in device complexity.

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

The method and apparatus enable optimized cell culture processing by reducing unnecessary stirring time and improving overall efficiency, resulting in improved cell survival and growth.

Implementation Method 1

the physical quantity may be at least one of an amount of transmitted light transmitted through the cell suspension and an amount of scattered light scattered by the cell suspension

Methodology Applied
Scientific EffectLight transmission: Light

Implementation Method 2

the physical quantity may be at least one of an amount of transmitted light transmitted through the cell suspension and an amount of scattered light scattered by the cell suspension

Methodology Applied
Scientific EffectLight scattering: Scattering

Data Source

PatentEP4660292A1Stirring method and stirring device
Publication Date: 2025.12.10 TERUMO KK
  • EP4660292A1 patent drawingFigure 1
  • EP4660292A1 patent drawingFigure 2
  • EP4660292A1 patent drawingFigure 3

AI summary

A stirring method includes: a cell stirring step of stirring cell suspension by circulating the cell suspension in a circulation path (130) including a bioreactor (24); an acquisition step of acquiring a predetermined physical quantity related to the cell suspension at a measurement target site in the circulation path (130) over time; and a determination step of determining that a uniform diffusion state in which cells are uniformly diffused in the cell suspension is reached on the basis of a fact that a degree of variation of the physical quantity is smaller than a predetermined degree.