Patterned Cell Culture Substrate for Sac-Shaped Organoid Formation

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Solution Overview

Problem

Current methods for culturing stem cells or cancer cells to form intestinal tissue-like organoids or cancer tissue/cyst-like constructs are inefficient, requiring labor-intensive processes and often result in low yields and prolonged culture times, especially when trying to produce sac-shaped cell constructs with specific structural integrity.

Innovation Solution

A cell culture substrate with a surface featuring a non-cell-adhesive part surrounded by a cell-adhesive part, where the cell-adhesive part extends continuously or intermittently, promoting cell attachment and growth in a sac-shaped configuration, allowing for efficient induction of small intestinal epithelial cells and cancer cyst-like structures.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional cell culture methods are used to form intestinal tissue-like organoids, then cell constructs can be produced, but the process is labor-intensive and has low yield with prolonged culture times

Engineering Contradiction:
Improveyield of cell constructsVSAvoidculture time
Core Design Contradiction:
ProductivityVSLoss of time

Solution Approach 1:

The substrate surface is segmented into distinct cell-adhesive parts and non-cell-adhesive parts, creating specific patterns that guide cell arrangement. This segmentation allows cells to automatically organize into desired structures without manual intervention, thereby increasing yield and reducing culture time compared to conventional methods.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The substrate is pre-patterned with cell-adhesive and non-cell-adhesive regions before cell seeding. This preliminary structural preparation directs cell attachment and growth patterns from the outset, eliminating the need for labor-intensive manual manipulation during culture and significantly reducing the time required to form organized cell constructs.

Inventive Principle:
Principle #10Preliminary action

2Productivity

If conventional cell culture methods are used, then cell constructs can be formed, but the processes are labor-intensive requiring manual manipulation

Engineering Contradiction:
Improveproduction efficiencyVSAvoidoperational simplicity
Core Design Contradiction:
ProductivityVSEase of operation

Solution Approach 1:

The patterned substrate enables cells to self-organize into desired structures through their natural adhesion properties. Cells automatically attach to cell-adhesive parts and avoid non-cell-adhesive parts, forming organized constructs without manual manipulation. This self-organizing capability dramatically improves production efficiency and simplifies operation.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The invention changes the surface parameter of the substrate by creating spatial patterns of varying adhesion properties. This parameter modification directs cell behavior through physical cues rather than manual manipulation, making the process easier to operate while increasing productivity.

Inventive Principle:
Principle #35Parameter changes

3Manufacturing precision

If cells are cultured to form sac-shaped constructs with specific structural integrity, then organized tissue structures can be produced, but culture times are prolonged

Engineering Contradiction:
Improvestructural integrity of cell constructsVSAvoidculture period
Core Design Contradiction:
Manufacturing precisionVSLoss of time

Solution Approach 1:

The substrate exhibits local quality variations with distinct cell-adhesive and non-cell-adhesive regions. This local differentiation provides precise spatial cues that guide cells to form sac-shaped constructs with specific structural integrity. The localized adhesion patterns accelerate the organization process, achieving high structural quality without prolonged culture times.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The invention introduces a spatial dimension to cell culture by creating two-dimensional patterns of adhesion properties on the substrate surface. This dimensional approach guides cells to self-organize into three-dimensional sac-shaped constructs with proper structural integrity, significantly reducing the time required compared to conventional uniform culture surfaces.

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

4Manufacturing precision

If patterned substrates are used to induce differentiation, then cell organization can be improved, but the substrate complexity increases

Engineering Contradiction:
Improvecell arrangement precisionVSAvoidsubstrate structure complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The invention extracts the essential functional requirement for cell organization and implements it through a simple binary pattern of cell-adhesive and non-cell-adhesive parts. By taking out only the necessary adhesion guidance function and implementing it through straightforward surface patterning, the substrate achieves high cell arrangement precision without excessive structural complexity.

Inventive Principle:
Principle #2Taking out (Extraction)

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 substrate enables high-yield production of sac-shaped cell constructs with specific cellular markers, such as CDX2-positive cells, facilitating the formation of gut organoids and cancer cyst-like structures in a shorter culture period with improved collection efficiency.

Implementation Method 1

a cell-adhesive part extending continuously or intermittently along the periphery of the non-cell-adhesive part and surrounding the non-cell-adhesive part

Methodology Applied
Scientific EffectCell adhesion: Adhesive

Data Source

PatentUS20220106551A1Cell culture substrate
Publication Date: 2022.04.07 DAI NIPPON PRINTING CO LTD
  • US20220106551A1 patent drawing
  • US20220106551A1 patent drawing
  • US20220106551A1 patent drawing

AI summary

A cell culture substrate having surface S including cell culture part, wherein the cell culture part includes non-cell-adhesive part, and cell-adhesive part extending continuously or intermittently along periphery P of the non-cell-adhesive part and surrounding the non-cell-adhesive part. The present disclosure also relates to a kit for cell culture comprising this cell culture substrate.