SPION-Mediated Isolation of IgM-Producing B Cells

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Solution Overview

Problem

Current methods for isolating and enriching natural IgM-producing phagocytic B cells are labor-intensive and inefficient, making it difficult to produce IgM antibodies on a large scale for therapeutic use in immunotherapy, particularly for diseases like cancer, where these antibodies are rare and difficult to identify.

Innovation Solution

The development of a method using superparamagnetic iron oxide nanoparticles (SPIONs) that are specifically phagocytosed by natural IgM-producing phagocytic B cells, allowing for their isolation and enrichment using a magnet, followed by hybridoma cell line creation and screening for IgM antibody production.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If traditional methods are used to isolate and enrich natural IgM-producing B cells, then the isolation process can be completed, but it is extremely labor-intensive and inefficient

Engineering Contradiction:
Improveisolation efficiencyVSAvoidlabor intensity
Core Design Contradiction:
ProductivityVSEase of operation

Solution Approach 1:

The patent uses superparamagnetic iron oxide nanoparticles (SPIONs) as an intermediary substance that is specifically phagocytosed by natural IgM-producing B cells. These nanoparticles act as a mediator between the target cells and the magnetic separation system, enabling efficient isolation without labor-intensive manual procedures. The nanoparticles bind to the cells and allow magnetic enrichment, directly resolving the contradiction between isolation efficiency and labor intensity.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces traditional mechanical and manual isolation methods with a magnetic field-based separation system. Instead of labor-intensive manual isolation techniques, the invention uses magnetic fields to attract and separate cells that have phagocytosed SPIONs, substituting mechanical operations with a field-based approach that dramatically improves productivity while reducing labor requirements.

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

2Productivity

If magnetic beads are used to isolate B cells, then isolation can be achieved, but the beads interfere with the cell antibody-producing function

Engineering Contradiction:
Improveisolation efficiencyVSAvoidantibody-producing function
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent changes the physical parameters of the magnetic particles by using superparamagnetic iron oxide nanoparticles instead of traditional large magnetic beads. The nanoparticle size (typically 10-100 nm) is dramatically reduced compared to conventional beads, allowing them to be phagocytosed by B cells without interfering with antibody production. This parameter change in particle size and magnetic properties resolves the contradiction between isolation efficiency and maintaining cellular function.

Inventive Principle:
Principle #35Parameter changes

3Quantity of substance

If natural IgM antibodies are to be produced on a large scale, then therapeutic use becomes possible, but the source B cells are rare and difficult to identify

Engineering Contradiction:
ImproveIgM antibody production scaleVSAvoidcell identification difficulty
Core Design Contradiction:
Quantity of substanceVSDifficulty of detecting and measuring

Solution Approach 1:

The patent extracts and isolates the rare natural IgM-producing B cells from complex cell populations using magnetic enrichment with SPIONs. By specifically targeting these rare cells through phagocytosis of nanoparticles and subsequent magnetic separation, the invention enables their extraction in sufficient quantities for large-scale antibody production, overcoming the difficulty of identifying and obtaining enough rare source cells.

Inventive Principle:
Principle #2Taking out (Extraction)

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 enables the efficient isolation and large-scale production of IgM antibodies, which can be used for the treatment and prevention of diseases like cancer, with reduced inflammatory side effects and improved specificity, as the antibodies are naturally occurring and poly-reactive, recognizing a range of cancer cells.

Implementation Method 1

specifically phagocytize nanoparticles comprising superparamagnetic beads

Methodology Applied
Scientific EffectPhagocytosis:

Implementation Method 2

nanoparticles comprising superparamagnetic beads

Methodology Applied
Scientific EffectSuperparamagnetism: Superparamagnetism

Data Source

PatentUS10842816B2Compositions and methods for isolating and enriching IgM-producing cells and uses thereof
Publication Date: 2020.11.24 BOSTON MEDICAL CENTER INC
  • US10842816B2 patent drawing
  • US10842816B2 patent drawing
  • US10842816B2 patent drawing

AI summary

The technology described herein relates, at least in part, to compositions comprising and methods for isolating and enriching natural IgM-producing phagocytic B (NIMPAB) cells and methods of producing IgM antibodies using such cells, as well as uses of the antibodies produced by the methods for the prevention and treatment of diseases wherein immunotherapy with such natural IgM antibodies and their derivatives can be useful.