Microporous Cellulose Acetate Membrane for Pegylated Protein Separation

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Solution Overview

Problem

Current methods fail to efficiently separate mixtures of mono-, di-, and poly-pegylated proteins into individual components, limiting rapid and cost-effective analysis in medical and biopharmaceutical applications.

Innovation Solution

A process utilizing a microporous cellulose acetate membrane to selectively adsorb and desorb polyalkylene-glycol-functionalized proteins, allowing for the separation and quantification of protein mixtures by exploiting the membrane's adsorption properties and controlled elution gradients.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If conventional chromatography methods (anion-exchange, size exclusion) are used to separate pegylated proteins, then separation can be achieved, but the process complexity increases and separation of mono-, di- and polypegylated components into individual fractions becomes inefficient

Engineering Contradiction:
Improveseparation precisionVSAvoidprocess complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent employs a microporous cellulose acetate membrane with specific pore characteristics to separate pegylated proteins. The porous structure enables size-based differentiation where mono-, di- and polypegylated proteins are retained to different extents based on their hydrodynamic radii, achieving efficient separation into individual fractions without complex chromatography systems

Inventive Principle:
Principle #31Porous materials

Solution Approach 2:

The patent utilizes controlled elution conditions including pH gradient and ionic strength variations to modulate the interaction between pegylated proteins and the cellulose acetate membrane. By adjusting these parameters, the membrane selectively releases different pegylation species at different stages, enabling precise separation while maintaining process simplicity

Inventive Principle:
Principle #35Parameter changes

2Manufacturing precision

If multiple chromatography steps are combined to separate individual pegylated components, then separation capability improves, but the analysis time and cost increase

Engineering Contradiction:
Improveseparation capabilityVSAvoidanalysis speed
Core Design Contradiction:
Manufacturing precisionVSProductivity

Solution Approach 1:

The patent applies segmentation by using the microporous membrane to directly fractionate the mixture of mono-, di- and polypegylated proteins into separate collectible fractions in a single pass. This eliminates the need for multiple sequential chromatography steps, significantly reducing analysis time while maintaining the ability to obtain individual components

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The cellulose acetate membrane serves multiple functions simultaneously: it acts as a size-based filtration barrier, an adsorption medium, and a fractionation device. This multi-functionality allows a single operation to achieve what would otherwise require multiple specialized chromatography steps, improving productivity without sacrificing separation capability

Inventive Principle:
Principle #6Universality (Multi-functionality)

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

Enables efficient and cost-effective separation of protein mixtures into individual components, facilitating rapid determination of their quantitative ratios, with the cellulose acetate membrane effectively distinguishing between nonpegylated and pegylated proteins through controlled elution.

Implementation Method 1

bringing the mixture of step a) into contact with a microporous cellulose acetate membrane with adsorption of the reaction product onto the cellulose acetate membrane

Methodology Applied
Scientific EffectAdsorption: Adsorption

Implementation Method 2

bringing the mixture of step a) into contact with a microporous cellulose acetate membrane

Methodology Applied
Scientific EffectFiltration: Filter (physical)

Implementation Method 3

desorbing the reaction product from the cellulose acetate membrane

Methodology Applied
Scientific EffectDesorption: Desorption

Data Source

PatentUS10100294B2Process for the separation of a mixture of a protein and its reaction product with a polyalkylene glycol
Publication Date: 2018.10.16 SARTORIUS STEDIM BIOTECH GMBH
  • US10100294B2 patent drawing
  • US10100294B2 patent drawing
  • US10100294B2 patent drawing

AI summary

The present invention relates to a process for the separation of a mixture of a protein and its reaction product with a polyalkylene glycol, comprising the steps: a) providing a mixture comprising the protein and the reaction product in a fluid, b) bringing the mixture of step a) into contact with a microporous cellulose acetate membrane with adsorption of the reaction product onto the cellulose acetate membrane, the protein not becoming adsorbed onto the cellulose acetate membrane, c) removal of the protein from the cellulose acetate membrane, and d) desorbing the reaction product from the cellulose acetate membrane, the reaction product being selected from the group comprising the protein which is mono- or polyfunctionalized by the polyalkylene glycol, or mixtures thereof.