Flexible Substrate for 3D Cell Arrangement via Cellular Attraction

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Conventional methods for forming three-dimensional cell arrangements fail to accurately simulate natural living conditions for cells, as they restrict design freedom, limit nutrient supply, and disrupt natural cell interactions due to rigid substrates and limited deformation capabilities.

Innovation Solution

A flexible substrate with force application points that allow cells to exert attractive forces, causing deformation and shaping of the substrate into complex three-dimensional structures, enabling the formation of multicellular arrangements that mimic in vivo conditions without mechanical tools.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If cells are cultivated on a planar substrate, then nutrient supply and observation are improved, but the natural three-dimensional living conditions of cells are not simulated

Engineering Contradiction:
Improvenutrient supplyVSAvoidsimulation of natural living conditions
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent transitions from two-dimensional planar substrate cultivation to three-dimensional cell arrangements by forming cell aggregates, spheroids, or tissue structures that grow in multiple dimensions, thereby simulating the natural three-dimensional living conditions of cells while maintaining adequate nutrient supply through the volumetric structure

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

2Adaptability or versatility

If biopolymer layers are used to simulate three-dimensional cell arrangements, then spatial distribution is improved, but design freedom and nutrient supply are limited

Engineering Contradiction:
Improvespatial distributionVSAvoiddesign freedom
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent removes the biopolymer layer constraint by allowing cells to form three-dimensional arrangements directly on the substrate surface without embedding them in biopolymer matrices, thereby eliminating the limitations on design freedom and nutrient supply while maintaining spatial distribution capabilities

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The substrate surface acts as a flexible platform that can support various three-dimensional cell configurations including aggregates, spheroids, and layered structures, providing design freedom while maintaining spatial distribution through the flexible substrate geometry

Inventive Principle:
Principle #30Flexible shells and thin films

3Shape

If mold elements are used to shape cell material, then geometric shaping is improved, but design freedom is restricted and nutrient supply is limited

Engineering Contradiction:
Improvegeometric shapingVSAvoiddesign freedom
Core Design Contradiction:
ShapeVSAdaptability or versatility

Solution Approach 1:

The patent replaces the mechanical mold element system with a substrate-based geometric structuring approach where the substrate itself provides the geometric constraints and shaping forces, eliminating the need for complex movable mold elements and thereby restoring design freedom while maintaining geometric shaping capabilities

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

Solution Approach 2:

The patent changes the geometric parameters of the substrate surface (such as curvature, ridges, or patterned features) to directly influence cell arrangement geometry, allowing flexible geometric shaping without mechanical molds and enabling diverse designs including niches and cavities

Inventive Principle:
Principle #35Parameter changes

4Adaptability or versatility

If cells are arranged on both sides of the substrate, then three-dimensional structure is improved, but substrate interference with natural cell interactions increases

Engineering Contradiction:
Improvethree-dimensional structureVSAvoidsubstrate interference
Core Design Contradiction:
Adaptability or versatilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies different substrate properties to different regions or aspects of the cell arrangement, allowing the substrate to provide structural support and geometric definition where needed while minimizing interference in regions where natural cell-cell interactions should dominate, thereby enabling three-dimensional structures with reduced substrate interference

Inventive Principle:
Principle #3Local quality

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 method allows for the creation of defined three-dimensional cell structures with improved nutrient supply and complex topography, simulating natural cell environments while minimizing substrate interference, enabling applications in medical therapy and tissue engineering.

Implementation Method 1

biological cells 2 exert an attractive force FZ on the substrate surface 11

Methodology Applied
Scientific EffectCell adhesion force: Adhesive

Implementation Method 2

The attractive force is formed by forces of attraction of the cells, in particular by compressive and/or tensile forces caused by the inner cytoskeleton

Methodology Applied
Scientific EffectCytoskeletal force: Mechanical Force

Implementation Method 3

The substrate 10 is deformed under the action of the attractive force FZ of the cells 2

Methodology Applied
Scientific EffectElastic deformation: Elasticity

Implementation Method 4

The interaction of adherent cells with substrate surfaces, which can lead to deformation of flexible substrates in particular

Methodology Applied
Scientific EffectMechanical stress: Stress Relaxation

Data Source

PatentEP2167641B1Method and device for forming a three-dimensional arrangement of biological cells
Publication Date: 2015.05.06 FRAUNHOFER GESELLSCHAFT ZUR FORDERUNG DER ANGEWANDTEN FORSCHUNG EV
  • EP2167641B1 patent drawingFigure 1~3
  • EP2167641B1 patent drawingFigure 4A~6
  • EP2167641B1 patent drawingFigure 7A~8B

AI summary

A method for forming a three-dimensional cell arrangement (1) of biological cells is disclosed, comprising the steps of preparation of the cell arrangement (1) on a flexible substrate (10) and deformation of the substrate (10), wherein the deformation of the substrate (10) is brought about by an attractive force exerted by the cells (2) on the substrate (10). A substrate (10), is also disclosed, made from a flexible material and comprising a substrate surface (11) for adhesion of a cell arrangement (1) of biological cells, wherein the substrate surface (11) has a number of force attachment points arranged to exert an attraction force which may be transmitted from the cells to the substrate (10) and the substrate (10) has a flexibility such that the substrate (10) is deformable with the action of the attraction force.