Membrane Evaporation for High-Concentration Protein Therapeutics
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Solution Overview
Problem
Current methods for protein concentration, such as thermal and osmotic distillation, and ultrafiltration, face limitations in achieving high concentrations due to temperature sensitivity, osmotic pressure constraints, and protein damage, restricting achievable concentrations to around 200 grams per liter.
Innovation Solution
The method involves circulating a protein solution through an ultrafiltration device with a porous membrane and applying a flow of gas to the permeate side, allowing for the evaporation of solvent and concentration of proteins beyond conventional limits, achieving concentrations greater than 260 grams per liter with minimal formation of high or low molecular weight species.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If conventional ultrafiltration is used to concentrate protein solutions, then solvent is removed through pressure-driven flow, but the gel-point limits achievable concentration to about 200 grams per liter
Solution Approach 1:
The invention changes the driving mechanism from pressure-driven flow to evaporation-driven solvent removal. By applying a flow of gas to the permeate side to create evaporation, the system operates beyond the gel-point concentration limit of conventional ultrafiltration, achieving protein concentrations greater than 260 grams per liter while maintaining acceptable solvent removal rates
Solution Approach 2:
The invention replaces the mechanical pressure-driven filtration system with an evaporation-based system. Instead of using pressure differential to drive solvent through the membrane, the system uses gas flow to evaporate solvent from the permeate side, eliminating the gel-point limitation that constrains conventional mechanical ultrafiltration
2Quantity of substance
If thermal distillation is used to concentrate protein solutions, then solvent is removed through vapor pressure difference, but high temperatures damage protein solutes
Solution Approach 1:
The invention changes the temperature parameters of the evaporation process to be much lower than thermal distillation. By using gas flow evaporation at near-ambient or controlled low temperatures rather than high-temperature vapor pressure-driven processes, the system achieves effective solvent removal while preserving protein integrity and avoiding thermal damage
3Quantity of substance
If osmotic distillation is used to concentrate protein solutions, then solvent is removed through osmotic pressure difference, but achievable protein concentrations are limited by the osmotic pressure of the salt solution
Solution Approach 1:
The invention replaces the osmotic pressure-driven system with an evaporation-driven system. By using gas flow to evaporate solvent from the permeate side rather than relying on osmotic pressure differences, the system eliminates the concentration limits imposed by salt solution osmotic pressure, achieving protein concentrations greater than 260 grams per liter
Solution Approach 2:
The invention changes the driving force parameter from osmotic pressure to evaporation rate. By controlling gas flow rate and evaporation conditions rather than osmotic pressure, the system achieves much higher protein concentration levels without being constrained by the osmotic pressure limits of salt solutions
4Quantity of substance
If hydrophobic porous membrane is used for osmotic distillation, then solvent is removed through osmotic pressure difference, but the air-liquid interface damages some proteins
Solution Approach 1:
The invention changes the membrane hydrophobicity parameter to hydrophilic. By using hydrophilic porous membranes instead of hydrophobic ones, the system eliminates air-liquid interface formation within the membrane pores, thereby preventing protein damage while still achieving effective solvent removal through evaporation
Solution Approach 2:
The invention replaces the osmotic distillation mechanism with evaporation-driven concentration. This substitution eliminates the need for air-liquid interfaces that form in hydrophobic membrane systems, thereby preventing protein damage while achieving the desired concentration levels
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 approach enables the production of highly concentrated protein solutions with reduced storage and freeze-drying requirements, increased osmotic pressure for stability, and prolonged therapeutic protein residence time, while maintaining protein integrity.
Implementation Method 1
circulating a first protein solution through an ultrafiltration device with a porous membrane... allowing solvent to flow through the membrane of the device while proteins are retained
Implementation Method 2
applying a flow of gas to the permeate side of the porous membrane... evaporation of solvent from the protein solution
Data Source
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AI summary
The present invention relates to methods of generating highly concentrated protein solutions, e.g., an antibody solution, a therapeutic protein solution, etc. The methods of the invention include membrane evaporation, such as evaporation of protein-free solvent from the protein solution, which concentrates the protein. The methods of the present invention result in protein solution concentrations not previously achievable by conventional ultrafiltration methods, e.g., protein solution concentrations of greater than about 260 grams of protein per liter of solution.