Gas-Liquid Interface Cell Detachment for Selective Cell Harvesting

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Solution Overview

Problem

Existing methods for detaching cells from culture vessels, such as using proteolytic enzymes or local heating, either non-selectively detach all cells or require specialized equipment and coated vessels, lacking flexibility and efficiency.

Innovation Solution

A method and device that utilize a flow path in a liquid medium to introduce gas, forming an air bubble at the end, which contacts and moves along the cell surface to selectively detach cells, using a simple apparatus.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If proteolytic enzymes are utilized to detach cells, then all cells in a vessel are detached, but selective detachment cannot be achieved

Engineering Contradiction:
Improvecell detachment efficiencyVSAvoidselective detachment capability
Core Design Contradiction:
ProductivityVSAdaptability or versatility

Solution Approach 1:

The patent applies local quality by creating a gas/liquid interface at a specific location within the culture vessel. The gas is introduced through a flow path to form a localized interface that contacts only specific regions where cells are present, enabling spatially selective detachment rather than uniform detachment of all cells. This localized action allows targeted removal of cells from specific areas while leaving other regions unaffected.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The invention segments the cell detachment process by dividing the culture vessel into regions affected by the gas/liquid interface and regions that remain unaffected. The flow path system creates discrete zones of cell detachment, allowing independent control over which cell populations are removed. This segmentation enables selective harvesting of cells from specific locations or time points.

Inventive Principle:
Principle #1Segmentation

2Adaptability or versatility

If local heating method is used to detach cells, then selective detachment can be achieved, but a large-sized apparatus and coated vessels are required

Engineering Contradiction:
Improveselective detachment capabilityVSAvoidapparatus size and vessel coating requirements
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent employs pneumatic principles by introducing gas through a flow path to create a gas/liquid interface for cell detachment. This replaces the thermal field of local heating with a mechanical field based on gas flow and interface dynamics. The approach uses simple gas introduction equipment rather than complex heating apparatus, and requires no special vessel coatings, thereby reducing device complexity while maintaining selective detachment capability.

Inventive Principle:
Principle #29Pneumatics and hydraulics

Solution Approach 2:

The invention substitutes the thermal mechanism of local heating with a mechanical/gas-based mechanism. Instead of using heat to detach cells, the system uses gas flow to create a gas/liquid interface that mechanically interacts with cells at the interface. This substitution eliminates the need for heating elements and temperature control systems, simplifying the overall apparatus.

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

3Productivity

If proteolytic enzymes are used for cell detachment, then cell detachment is achieved, but enzyme contamination and loss of cell function may occur

Engineering Contradiction:
Improvecell detachment efficiencyVSAvoidenzyme contamination and cell function loss
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent replaces the chemical mechanism of proteolytic enzyme digestion with a physical/gas-based mechanism. The gas/liquid interface detaches cells through mechanical interaction at the interface rather than through enzymatic cleavage of adhesion molecules. This substitution eliminates exposure to proteolytic enzymes, preventing enzyme contamination and preserving cell function while still achieving effective detachment.

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

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

Efficient and selective detachment of cells from culture surfaces without enzymes, allowing for targeted cell removal and collection, suitable for applications like regenerative medicine and scratch assays.

Implementation Method 1

bringing a gas/liquid interface into contact with the adherent cells and moving the interface along the surface

Methodology Applied
Scientific EffectGas/liquid interface interaction: Surface Tension

Implementation Method 2

adhering the cells to the air bubble

Methodology Applied
Scientific EffectCell adhesion to air bubble: Adsorption

Data Source

PatentUS12504353B2Cell manipulation device and cell manipulation method
Publication Date: 2025.12.23 NIKON CORP
  • US12504353B2 patent drawing
  • US12504353B2 patent drawing
  • US12504353B2 patent drawing

AI summary

A cell manipulation method is provided including: culturing cells in a liquid; disposing a flow path through which a gas is able to be introduced in the liquid; forming an air bubble at an end portion of the flow path; and attaching the cells to the air bubble.