Glycol Ether Phase Separation for Protein Concentration
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Solution Overview
Problem
Existing methods for concentrating proteins in aqueous solutions, such as ultrafiltration and chromatography, often result in protein deactivation, and liquid-liquid extraction processes are costly due to multiple steps, unfavorable partitioning, and poor selectivity.
Innovation Solution
A method using glycol ethers with inverse solubility in water to extract water from aqueous protein solutions, maintaining protein activity by intermixing the solution with glycol ethers above the lower critical solution temperature to form a concentrated protein phase and a liquid organic phase, which are then separated.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If conventional methods such as ultrafiltration and chromatography are used to concentrate proteins, then protein concentration is improved, but protein deactivation occurs
Solution Approach 1:
The invention changes the physical-chemical parameters of the system by introducing a dehydration agent that forms a third phase with water, altering the solvation environment to concentrate proteins without the mechanical stress or chemical denaturation caused by conventional methods. This parameter change enables concentration while preserving protein activity.
Solution Approach 2:
The dehydration agent acts as an intermediary substance that mediates between the aqueous protein solution and the concentrated protein phase. It selectively binds water to form a separate phase, enabling protein concentration without direct contact with harsh concentrating forces or denaturing agents.
2Productivity
If liquid-liquid extraction processes are used to concentrate proteins, then concentration efficiency is improved, but process cost increases due to multiple steps and poor selectivity
Solution Approach 1:
The invention applies local quality by designing a system where the dehydration agent creates distinct phase regions with specific properties: a water-rich phase, a dehydration agent-rich phase, and a protein-concentrated phase. This localized phase differentiation enables selective protein concentration in one step without multiple extraction stages.
Solution Approach 2:
The third phase system performs multiple functions simultaneously: it dehydrates the solution, concentrates proteins, and enables phase separation all in a single extraction step. This multi-functionality eliminates the need for multiple sequential operations, reducing process complexity and cost.
3Quantity of substance
If temperature-sensitive proteins are concentrated using conventional methods, then concentration is achieved, but protein deactivation increases
Solution Approach 1:
The invention replaces mechanical concentration methods (ultrafiltration, centrifugation) and thermal methods (evaporation, freeze-drying) with a chemical-phase based extraction system. This substitution eliminates the mechanical stress and thermal exposure that deactivate temperature-sensitive proteins while achieving the same concentration effect.
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 effectively concentrates proteins without significant deactivation, offering a cost-effective and efficient process suitable for enzymes and therapeutic proteins, including temperature-sensitive varieties, by using glycol ethers that are biodegradable and have low toxicity.
Implementation Method 1
Process for removing water from aqueous solutions of proteins by liquid-liquid extraction
Implementation Method 2
glycol ethers with inverse solubility in water to extract water from aqueous protein solutions, maintaining protein activity by intermixing the solution with glycol ethers above the lower critical solution temperature to form a concentrated protein phase and a liquid organic phase
Data Source
AI summary
A method for extracting water from an aqueous solution of a protein comprising the steps of:(a) intermixing the aqueous solution of the protein with a sufficient quantity of at least one glycol ether at a temperature at least 30 centigrade degrees above the lower critical solution temperature (LCST), preferably at least 20 centigrade degrees above the LCST, and most preferably at least 10 degrees above the LCST, to form a suspension comprising a concentrated aqueous protein phase and a liquid organic phase comprising said at least one glycol ether and at least 10 percent water extracted from the aqueous solution of the protein, wherein the glycol ether has an inverse solubility in water, with the proviso that the solubility of the glycol ether in water is significantly less than the solubility of water in the glycol ether, and the glycol ether does not significantly deactivate the protein, and(b) separating the concentrated aqueous protein phase formed in step (a) from at least a portion of the liquid organic phase.