Cell Culture Container with Electrode Array for Neuron Adhesion

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Solution Overview

Problem

Human-induced pluripotent stem cell-derived neurons tend to separate from culture surfaces during high-density long-term culture and transportation, especially when subjected to vibration, making it difficult to detect and evaluate their action potential effectively.

Innovation Solution

Mixing pluripotent stem cells with astrocytes and seeding them in a cell culture container with an electrode array, followed by incubation, allows the cells to adhere to the surface and differentiate into neurons, thereby inhibiting separation and enhancing action potential detection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If pluripotent stem cells are cultured at high density for long time, then action potential detection capability is improved, but cells aggregate and separate from culture surface

Engineering Contradiction:
Improveaction potential detection capabilityVSAvoidcell adhesion to culture surface
Core Design Contradiction:
Measurement precisionVSStability of the object's composition

Solution Approach 1:

The patent introduces astrocytes as intermediary cells to mediate between the culture substrate and neurons. Astrocytes adhere firmly to the culture surface and provide structural support, preventing neuron aggregation and detachment while maintaining neuronal function for action potential detection

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent creates a composite cell culture system combining astrocytes and neurons in a specific ratio (1:4 to 4:1). This composite structure leverages the adhesive properties of astrocytes and the functional properties of neurons, achieving both stable attachment and detection capability

Inventive Principle:
Principle #40Composite materials

2Ease of operation

If ready-to-use plates are transported, then availability is improved, but vibration causes cells to separate from culture surface

Engineering Contradiction:
Improveavailability of ready-to-use platesVSAvoidcell adhesion during transport
Core Design Contradiction:
Ease of operationVSStability of the object's composition

Solution Approach 1:

The patent prepares cell cultures with enhanced adhesion properties beforehand, creating a cushioning effect that protects cells during subsequent transport vibrations. The astrocyte-neuron composite structure provides mechanical stability that withstands transport conditions

Inventive Principle:
Principle #11Beforehand cushioning (Prior cushioning)

3Measurement precision

If pluripotent stem cells are differentiated into neurons, then detection capability is improved, but cell aggregation occurs

Engineering Contradiction:
Improvedetection capabilityVSAvoidcell distribution uniformity
Core Design Contradiction:
Measurement precisionVSShape

Solution Approach 1:

Astrocytes serve as intermediary cells that maintain uniform distribution while neurons differentiate. The astrocyte network provides structural framework that prevents neuronal aggregation, enabling even cell distribution with maintained detection capability

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

This method effectively prevents neuron separation from the culture surface, allowing for reliable detection and evaluation of action potentials using microelectrode arrays and other analysis methods like immunostaining, even after prolonged culture periods.

Implementation Method 1

the pluripotent stem cells and the astrocytes adhere to the culture surface

Methodology Applied
Scientific EffectCell adhesion: Adhesive

Implementation Method 2

the pluripotent stem cells differentiate into neurons

Methodology Applied
Scientific EffectCellular differentiation:

Data Source

PatentEP3919610A1Method of producing cell-containing container
Publication Date: 2021.12.08 RICOH CO LTD
  • EP3919610A1 patent drawingFigure 1(a)~1(d)
  • EP3919610A1 patent drawingFigure 2(a)~2(b)
  • EP3919610A1 patent drawingFigure 3(a)~3(b)

AI summary

A method of producing a cell-containing container is provided, including a process in which pluripotent stem cells that have been induced to differentiate into neurons, and astrocytes are mixed and seeded in a cell culture container in which an electrode array is arranged on a culture surface, and a process in which the cell culture container is incubated, and as a result, the pluripotent stem cells and the astrocytes adhere to the culture surface, and the pluripotent stem cells differentiate into neurons.