Hollow Needle Perfusion Device for Cell Isolation

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Solution Overview

Problem

Current methods for isolating living target cells from biological tissue are cumbersome, time-consuming, and require skilled personnel, often involving elaborate perfusion processes that are not efficient in obtaining viable single cells.

Innovation Solution

A device with a plurality of hollow needles is used to deliver release agents directly into biological tissue, allowing for the disaggregation of cells into a single-cell suspension without the need for cannulating blood vessels, using a casing with a support for the tissue and a holder for the needles that penetrate the tissue upon closure, enabling efficient release of target cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If mechanical destruction of tissue infrastructure is used to isolate single cells, then cell isolation is achieved, but the yield of living unharmed cells is rather low

Engineering Contradiction:
Improveyield of living cellsVSAvoidcell damage
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The device segments the tissue processing function across multiple hollow needles arranged in an array, allowing simultaneous delivery of release agents to multiple locations. This segmentation enables gentle, distributed enzymatic digestion throughout the tissue rather than mechanical destruction, thereby isolating living cells while maintaining high yield and viability.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention introduces a biochemical intermediary (release agent/enzyme) delivered through hollow needles to mediate the separation of cells from tissue infrastructure. This enzymatic intermediary gently digests the extracellular matrix and cell junctions, replacing direct mechanical force and preserving cell integrity while achieving effective cell isolation.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If gentle perfusion process is used to isolate cells, then high viability of target cells is achieved, but the process is cumbersome and requires skilled personnel

Engineering Contradiction:
Improveviability of target cellsVSAvoidprocess complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The perfusion function is segmented and distributed across multiple hollow needles in an array configuration. This allows the release agent to be delivered simultaneously to multiple locations within the tissue, achieving thorough enzymatic digestion and cell isolation without requiring complex cannulation of blood vessels or specialized perfusion equipment.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention extracts the essential function of cell release (enzymatic digestion) from the complex vascular perfusion system. By delivering release agents directly into the tissue through hollow needles, the method removes the need for vascular access, complex perfusion pumps, and skilled cannulation techniques, while maintaining high cell viability.

Inventive Principle:
Principle #2Taking out (Extraction)

3Productivity

If elaborate perfusion processes are used to isolate cells, then cell isolation is achieved, but the process is time-consuming

Engineering Contradiction:
Improvecell isolation efficiencyVSAvoidisolation time
Core Design Contradiction:
ProductivityVSLoss of time

Solution Approach 1:

The use of multiple hollow needles in parallel allows simultaneous delivery of release agents to multiple tissue locations, dramatically accelerating the enzymatic digestion process compared to single-point perfusion. This segmented approach achieves complete cell isolation in significantly reduced time while maintaining simplicity of operation.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The hollow needles are pre-positioned in an array configuration before tissue processing, allowing immediate and uniform delivery of release agents upon activation. This preliminary arrangement eliminates the time-consuming steps of vascular cannulation and setup required in traditional perfusion methods, enabling rapid cell isolation.

Inventive Principle:
Principle #10Preliminary action

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 provides a high yield and viability of target cells, simplifying the process and reducing the need for skilled personnel, as demonstrated by successful isolation and culture of hepatocytes and other cell types.

Implementation Method 1

The hollow penetration structures (8) are in proximity to the holder (7) that holds the plurality of hollow penetration structures (8) by joining the first part (1) and the second part (9) to form the casing, the hollow penetration structures (8) penetrate at least in part into the biological tissue (6)

Methodology Applied
Scientific EffectPenetration:

Implementation Method 2

at least one agent to disaggregate the biological tissue into target cells is administered through the hollow penetration structures (8) into the biological tissue (6)

Methodology Applied
Scientific EffectDisaggregation: Enzyme

Data Source

PatentEP3171152B1Process and device for isolating cells from biological tissue
Publication Date: 2023.01.25 MILTENYI BIOTEC BV & CO KG
  • EP3171152B1 patent drawingFigure 1
  • EP3171152B1 patent drawingFigure 2
  • EP3171152B1 patent drawingFigure 3

AI summary

The invention is directed to a Perfusion device for biological tissues comprising - a casing having two parts, a first part (1) and a second part (9), - a holder (7) for a plurality of hollow penetration structures (8), wherein the hollow penetration structures (8) are provided with at least one orifice having fluid communication through the holder (7) - a support (5) for the biological tissue (6) characterized in that the support (5) for the biological tissue (6) is positioned in the casing at a distance to the holder (7) that by joining the first part (1) and the second part (9) to form the casing, the hollow penetration structures (8) are in proximity to the holder (7). Use of the perfusion device in a process for disaggregation of a biological tissue to yield target cells.