Closed Tubing Cell Dispersion via Shear Nozzle

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Solution Overview

Problem

Existing methods for dispersing cell clumps into single cells in a closed tubing system are labor-intensive, time-consuming, and prone to contamination, as they require manual operation in an open environment and do not effectively disperse small cell clumps into single cells.

Innovation Solution

A device utilizing liquid flow shear force with a conical nozzle structure, featuring a larger inlet and smaller outlet, arranged in series or parallel connections, to disperse cell clumps into single cells within a closed tubing system, minimizing contamination risks.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If manual pipetting is used to disperse cell clumps, then cell dispersion can be achieved, but the process is time-consuming and labor-intensive

Engineering Contradiction:
Improvecell dispersion efficiencyVSAvoidtime for cell dispersion
Core Design Contradiction:
ProductivityVSLoss of time

Solution Approach 1:

The patent replaces manual mechanical pipetting operations with an automated closed-loop fluidic system. A pump drives liquid flow through a specialized dispersion structure (narrowing channel) that automatically shears cell clumps into single cells, eliminating the need for repeated manual blow-aspirate cycles and significantly improving productivity while reducing time investment.

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

Solution Approach 2:

The dispersion structure is designed to automatically disperse cell clumps as liquid flows through the narrowing channel. The system self-regulates the dispersion process through controlled fluid flow, eliminating the need for operator intervention and repeated manual operations, thereby reducing both time and labor requirements.

Inventive Principle:
Principle #25Self-service

2Ease of operation

If manual pipetting is performed in an open environment, then cell clumps can be dispersed, but contamination risk increases

Engineering Contradiction:
Improvemanual cell dispersion operationVSAvoidcontamination risk
Core Design Contradiction:
Ease of operationVSObject-affected harmful factors

Solution Approach 1:

The patent employs a closed-loop tubing system that acts as a flexible sealed enclosure for the cell suspension pathway. This closed environment prevents external contamination while allowing the cell dispersion function to be performed, effectively isolating the cell sample from the open laboratory environment throughout the entire process.

Inventive Principle:
Principle #30Flexible shells and thin films

Solution Approach 2:

The closed-loop system creates a protected environment for cell processing. By maintaining cell suspension within a sealed tubing system connected to sterile reservoirs, the patent establishes an inert, contamination-free environment that eliminates exposure to airborne contaminants while preserving ease of operation through automated fluid handling.

Inventive Principle:
Principle #39Inert atmosphere (Inert environment)

3Reliability

If vortex-shaking is applied to disperse cell clumps in a closed system, then some dispersion occurs, but small cell clumps remain undispersed

Engineering Contradiction:
Improveclosure of tubing systemVSAvoidcell dispersion effectiveness
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent introduces a localized high-shear region within the closed system through the narrowing channel structure. This creates a specific zone of intense fluid flow and shear stress that effectively breaks down even small cell clumps into single cells, while the rest of the system maintains its closed, protected configuration. The local quality enhancement at the dispersion point achieves complete cell separation without compromising system closure.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent changes the flow parameters (velocity, shear stress) locally at the dispersion structure by designing a narrowing channel that accelerates fluid flow. This parameter change creates sufficient shear force to disperse stubborn small cell clumps that vortex-shaking cannot break apart, while maintaining the closed system configuration throughout the process.

Inventive Principle:
Principle #35Parameter changes

4Extent of automation

If peristaltic pump cyclic blowing is used, then cell separation can be automated, but the workflow becomes complicated and error-prone

Engineering Contradiction:
Improveautomatic cell blowingVSAvoidworkflow complexity
Core Design Contradiction:
Extent of automationVSDevice complexity

Solution Approach 1:

The patent extracts the complex cyclic blowing mechanism and replaces it with a simple continuous flow system. Instead of using peristaltic pumps to repeatedly blow and aspirate cell suspension through multiple bottles, the invention uses a pump-driven continuous flow through a single narrowing channel, eliminating the complicated multi-step workflow and associated error risks while maintaining automation.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

Rather than using cyclic positive pressure (blowing) followed by negative pressure (aspiration) to achieve dispersion, the patent inverts the approach by using continuous unidirectional flow through a geometrically designed narrowing channel. This single-direction flow with controlled shear stress achieves cell separation without the need for complex cyclic pressure changes, simplifying the overall workflow.

Inventive Principle:
Principle #13The other way round (Inversion)

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 device effectively disperses cell clumps into single cells with reduced contamination risk, simplifying operations in a closed system, and can be applied to various cell processing techniques, including electrotransfection and single-cell analysis.

Implementation Method 1

utilizing liquid flow shear force

Methodology Applied
Scientific EffectShear force: Shear Stress

Data Source

PatentEP4239053A1Device, method and system for dispersing cell clump
Publication Date: 2023.09.06 ETTA BIOTECH
  • EP4239053A1 patent drawingFigure 1~2
  • EP4239053A1 patent drawingFigure 3~4
  • EP4239053A1 patent drawingFigure 5~6

AI summary

Present invention relates to a device for dispersing cell clumps by utilizing liquid flow shear force, and a method and a system using the device, wherein the device comprises a dispersion structure module that includes at least one structure for providing liquid flow shear force. Each structure for providing liquid flow shear force comprises an inlet for the cell clumps to be dispersed to enter the structure, and at least one outlet for the dispersed cell clumps to flow out of the structure. The diameter of the outlet is smaller than that of the inlet. The device for dispersing cell clumps by utilizing liquid flow shear force provided by the present invention can be used in a closed tubing system, and cell clumps are dispersed into single cells by utilizing liquid flow shear force, which is more efficient than using a pipettor to disperse cell clumps in open environment, and greatly reduces the risk of contamination of cell samples.