Cell Culture Device With Segmented Grooves For Long-Term Monitoring

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Solution Overview

Problem

Conventional cell culture methods face challenges in maintaining uniform environmental conditions and preventing cellular aging, especially in long-term cultures, due to variations in the culturing environment and the inability to trace cell genealogy effectively.

Innovation Solution

A cell culture apparatus featuring a semipermeable membrane-covered substrate with narrow culture grooves and wider flow grooves, allowing continuous culture solution supply and controlled cell exchange, maintaining uniform conditions and preventing cellular aging.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of moving object

If cells are continuously cultured in a container over many generations, then the culture duration is extended, but the environmental conditions around cells vary and cellular physiological state changes due to aging

Engineering Contradiction:
Improveculture durationVSAvoidenvironmental condition uniformity
Core Design Contradiction:
Duration of action of moving objectVSStability of the object's composition

Solution Approach 1:

The device segments the culture system into narrow culture grooves (where cells are retained) and wide flow grooves (where waste is removed). This segmentation allows continuous culture over many generations while maintaining stable environmental conditions in the culture grooves, resolving the contradiction between extended culture duration and environmental uniformity.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The device extracts and removes waste products and aged cells from the culture system through the flow grooves while retaining fresh cells in the culture grooves. This continuous extraction maintains environmental stability and prevents cellular aging, enabling long-term culture without physiological state changes.

Inventive Principle:
Principle #2Taking out (Extraction)

2Productivity

If wide grooves are used to remove unnecessary cells, then cell exchange is improved, but the culturing environment becomes difficult to control uniformly

Engineering Contradiction:
Improvecell exchange efficiencyVSAvoidenvironmental condition control
Core Design Contradiction:
ProductivityVSStability of the object's composition

Solution Approach 1:

The device applies local quality by creating narrow grooves specifically for cell culture with controlled dimensions (e.g., 1-10 μm width) that provide stable environmental conditions, while wide grooves are dedicated to fluid flow and waste removal. This spatial differentiation of groove functions enables both efficient cell exchange and uniform environmental control.

Inventive Principle:
Principle #3Local quality

3Ease of operation

If conventional cell handling techniques are used to remove cells, then cell removal is achieved, but the work burden increases and continuous culture is limited to about ten generations

Engineering Contradiction:
Improvecell removal operationVSAvoidcontinuous culture generations
Core Design Contradiction:
Ease of operationVSDuration of action of moving object

Solution Approach 1:

The device enables self-service by allowing culture medium and waste products to flow automatically through the grooves driven by concentration gradients and pressure differences. This passive transport mechanism eliminates the need for manual cell handling operations, reducing work burden and enabling continuous culture over 200+ generations rather than limited to about ten generations.

Inventive Principle:
Principle #25Self-service

4Device complexity

If culture solution is exchanged through diffusion from wide groove, then simple structure is achieved, but environmental conditions vary considerably between regions closer to and far from the wide groove

Engineering Contradiction:
Improvestructure complexityVSAvoidenvironmental condition uniformity
Core Design Contradiction:
Device complexityVSStability of the object's composition

Solution Approach 1:

The device applies hydraulic principles by establishing continuous fluid flow through the narrow culture grooves via pressure gradients created by the flow grooves. This active convective transport mechanism ensures uniform distribution of culture solution and removal of waste products throughout the entire culture region, eliminating the environmental gradients that would occur with diffusion-only approaches while maintaining relatively simple device structure.

Inventive Principle:
Principle #29Pneumatics and hydraulics

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 long-term continuous cell culture and observation without variations in cellular physiological state, allowing for precise tracking of cell growth and genealogy over multiple generations.

Implementation Method 1

the both ends of the culture groove being connected to the flow grooves and the flow grooves being greater in width and depth than the culture groove; the semipermeable membrane is used so as to cover the culture groove and the flow grooves on the cell culture substrate

Methodology Applied
Scientific EffectSemipermeable membrane filtration: Semipermeable Membrane

Implementation Method 2

In this method, when the narrow groove is long, there is a problem that the environmental conditions considerably vary between the region closer to the wide groove and the region far from the wide groove

Methodology Applied
Scientific EffectDiffusion: Diffusion

Data Source

PatentEP2733199B1Cell culture device, device for long-term monitoring of cell culture, method for long-term cell culture, and method for long-term monitoring of cell culture
Publication Date: 2016.06.29 THE JAPAN SCI & TECH AGENCY
  • EP2733199B1 patent drawingFigure 1(A)~1(C)
  • EP2733199B1 patent drawingFigure 2
  • EP2733199B1 patent drawingFigure 3(A)~3(B)

AI summary

To provide a cell culture apparatus, an apparatus for long-term observation of cell culture, a method for long-term cell culture, and a method for long-term observation of cell culture, which are capable of continuously culturing and observing cells under a uniform environmental condition without variation in physiological state associated with aging of the cultured cells, and also tracing the history (genealogy) of a certain cell. A cell culture apparatus comprising a cell culture substrate, a semipermeable membrane, and a culture solution supply means, in which the cell culture substrate has, on a surface thereof, a narrow culture groove for holding and culturing cells and wide flow grooves for discarding the cells held and cultured in the culture groove, the both ends of the culture groove being connected to the flow grooves and the flow grooves being larger in width and depth than the culture groove; the semipermeable membrane is used so as to cover the culture groove and the flow grooves of the cell culture substrate; and the culture solution supply means is capable of continuously supplying culture solution to the cell culture substrate covered with the semipermeable membrane.