3D Antibody-Functionalized Membrane for Specific Stem Cell Isolation

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Solution Overview

Problem

Current cell separation technologies, such as those using magnetic particles, manual marker-based methods, and mechanical filtration, are inefficient and non-specific for isolating target stem cells from biological samples, often resulting in low yields and contamination with non-target cells.

Innovation Solution

A 3D membrane with biocompatible polymer layers and covalently bound target molecules, such as antibodies, specifically captures target stem cells based on antigen recognition, allowing for selective separation from a single-cell suspension in a physiological buffer.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If magnetic particle-based cell separation is used, then cell isolation can be achieved, but the method is not specific enough and requires additional equipment complexity

Engineering Contradiction:
Improvecell isolation specificityVSAvoidmagnetic field equipment
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The invention extracts and utilizes the natural antigen-antibody binding mechanism to achieve cell separation, eliminating the need for complex magnetic field generation equipment. The membrane carries antibodies that specifically bind to target cell antigens, allowing separation based solely on biological recognition without requiring external magnetic fields or complex instrumentation.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The membrane acts as an intermediary carrier that presents antibodies to target cells. This intermediary structure enables specific cell capture through antigen-antibody interactions while simplifying the overall system by replacing complex magnetic separation equipment with a passive membrane-based approach.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If manual marker-based separation methods are used, then cell separation can be performed, but the process is time-consuming and yields are low

Engineering Contradiction:
Improvecell separation yieldVSAvoidmanual processing time
Core Design Contradiction:
ProductivityVSLoss of time

Solution Approach 1:

The membrane is pre-loaded with antibodies against target cell antigens before use. This preliminary preparation allows cells to be separated immediately upon contact with the membrane, eliminating time-consuming manual processing steps. The pre-functionalized membrane enables rapid, high-yield separation as cells naturally bind to the pre-positioned antibodies during flow through the membrane.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The invention replaces manual mechanical separation operations with an automated flow-through system. Cells are passed through the antibody-loaded membrane in a controlled flow, allowing rapid separation based on antigen-antibody binding without manual intervention, thereby increasing productivity and reducing processing time.

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

3Reliability

If mechanical filtration is used, then cell concentration can be achieved, but non-target cells are not effectively separated

Engineering Contradiction:
Improvecell separation specificityVSAvoidtarget cell yield
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The membrane features locally concentrated antibodies at specific binding sites on the membrane structure. This localized functionalization ensures that only cells expressing the target antigen are captured, while non-target cells pass through unaffected. The specific antigen-antibody recognition at these localized sites provides high separation specificity without compromising target cell yield.

Inventive Principle:
Principle #3Local quality

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 membrane enables highly specific and effective separation of target stem cells, achieving high yields with known cell population size and viability, suitable for therapeutic and research applications without affecting cell characteristics.

Implementation Method 1

featuring covalently bound target molecules, preferably target antibodies - either on its surface and/or in the pores - recognizing characteristic antigens bound to the surface of target stem cells and thus binding the target stem cells to the membrane

Methodology Applied
Scientific EffectAntigen-antibody binding:

Data Source

PatentEP3687656B1Membrane for separation of stem cells from biological samples, production process of said membrane, and process and device for separation, comprising said membrane
Publication Date: 2022.03.30 BIO RECELL LTD
  • EP3687656B1 patent drawingFigure 1

AI summary

The subject of the invention is a membrane for separation of target stem cells from biological samples, more precisely from a single-cell suspension that was prepared from a biological sample. As a result, sterile target stem cells are obtained in physiological buffer. The membrane of the invention consists of a 3D carrier structure made of at least one layer of biocompatible polymer with specific pore size, as a carrier material, and covalently bound target molecules on its surface and/or in the pores. These target molecules are preferably target antibodies, which recognize characteristic antigens that are bound on the surface of the target stem cells and thus bind the target stem cells to the membrane. Target molecules can be either directly bound to the surface and/or in the pores of the carrier structure or are bound to the surface and/or in the pores of the carrier structure through specific functionalized nanoparticles, which are bound to or embedded into the 3D carrier structure of the membrane. In addition, the present invention includes the membrane production process as well as the process and device for the separation of target stem cells from a biological sample, which includes the above membrane as a constituent part.