Segmented Cell Culture Device with Orthogonal Substrates
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Solution Overview
Problem
Current in vitro cell culture methods are limited by their inability to simulate physiological conditions, such as shear forces, and restrict the growth and vitality of cell layers due to static conditions and limited perfusion capabilities, which hinders the cultivation of complex cell arrangements and interactions necessary for lifelike organ imaging.
Innovation Solution
A device with multiple cavities separated by porous membranes allows for the orthogonal alignment of cell substrates, enabling the sequential formation of cell layers and independent perfusion of fluid streams to create laminar or turbulent flow conditions, facilitating the cultivation of complex cell arrangements and direct microscopic observation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Device complexity
If static culture conditions are used, then device complexity is reduced, but cell growth and viability are restricted due to accumulation of catabolic substances
Solution Approach 1:
The device is segmented into multiple independent cavities (first cavity, second cavity, third cavity) that can be individually perfused. Each cavity can contain cell layers and be supplied with fresh nutrients independently, preventing catabolic substance accumulation while maintaining manageable device complexity through modular design
Solution Approach 2:
The invention implements fluid perfusion systems with inlet and outlet channels in each cavity to enable dynamic nutrient supply and removal of waste products. This hydraulic system allows continuous flow through the cell cultures, maintaining cell viability and growth without requiring overly complex mechanical structures
2Device complexity
If perfusion is applied from one side only, then device complexity is minimized, but cell growth and viability are limited due to insufficient nutrient supply
Solution Approach 1:
Each cavity is equipped with separate inlet and outlet channels positioned to enable perfusion from multiple directions. The first cavity has inlet channel (141) and outlet channel (142), the second cavity has inlet channel (143) and outlet channel (144), allowing independent multi-directional flow paths that enhance nutrient distribution without increasing overall device complexity
Solution Approach 2:
The device transitions from single-sided to multi-sided perfusion by adding vertical and lateral flow dimensions. Fluid can enter from top, bottom, and side channels, creating three-dimensional nutrient distribution throughout the cell layers, significantly improving cell viability while maintaining relatively simple device architecture
3Ease of operation
If maximum two-dimensional cell surface is cultivated, then ease of operation is improved, but adaptability is reduced for complex cell arrangements
Solution Approach 1:
The device divides the culture space into multiple cavities (first, second, third cavities) that can each independently accommodate different cell types and arrangements. This segmentation allows complex multi-layered organoid structures to be cultivated while maintaining ease of operation through modular, standardized cavity designs that simplify handling and observation
Solution Approach 2:
The invention enables transition from two-dimensional to three-dimensional cell cultivation by stacking multiple cavities vertically and horizontally. Cell layers can be arranged in complex spatial configurations across multiple levels, providing versatility for studying cell interactions while maintaining operational simplicity through standardized cavity interfaces and observation access
4Manufacturing precision
If channel systems are placed below culture surface, then manufacturing precision is improved, but measurement precision deteriorates due to obstruction of optical axis
Solution Approach 1:
The device separates observation and perfusion functions into different cavities. Cavities designated for observation (first and third cavities) have optimized optical paths without obstructing channels, while the second cavity handles perfusion functions. This segmentation allows high-precision microscopy without compromising manufacturing precision of the perfusion system
Solution Approach 2:
Porous membranes serve as intermediaries that separate optical observation paths from fluid channels. The membranes allow light transmission for microscopic observation while directing fluid flow through separate pathways, enabling both high measurement precision and manufacturing precision to be achieved simultaneously in different parts of the device
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
This approach allows for the dynamic cultivation and examination of multiple cell layers, simulating physiological conditions, enabling the study of cellular interactions and organoid structures, and reducing the risk of cell damage during assembly, while allowing for controlled nutrient supply and mechanical stress application.
Implementation Method 1
a cell suspension containing cells (9) is poured into the first cavity (2.1), the cells (9) are allowed to sediment and adhere to the cell substrate (6.2) to form a first cell layer (10.1)
Implementation Method 2
The first cavity (2.1) is oriented in such a way that a free surface of a cell substrate to be colonized is oriented orthogonally to gravity
Implementation Method 3
enabling the sequential formation of cell layers and independent perfusion of fluid streams to create laminar or turbulent flow conditions
Implementation Method 4
A device with multiple cavities separated by porous membranes allows for the orthogonal alignment of cell substrates
Implementation Method 5
the cells (9) are allowed to sediment and adhere to the cell substrate (6.2) to form a first cell layer (10.1)
Data Source
Figure 1~2
Figure 3~4
Figure 5
AI summary
The invention relates to a method for the in vitro production of arrangements of cell layers, wherein a first cavity (2.1) is provided, which is closed off from the surroundings of the first cavity except for a first inlet opening (4.1) and a first outlet opening (5.1) and which has a first wall (2.1.1) as a first cell substrate (6.1) and a second wall (2.1.2), which lies opposite and is separated from the first wall (2.1.1) by a first gap, as a second cell substrate (6.2), a free surface of a cell substrate (6.1, 6.2) to be populated with cells is oriented orthogonally to the gravitational force of the Earth, and cells are adhered to the cell substrate (6.1, 6.2) to be populated. The invention further relates to a method for maintaining the biological functionalities of the cell layers, to semi-finished products of a device for the in vitro production and cultivation of cell layers, and to a method for producing the device.