Spherical Protein Agglomeration via Oscillatory Crystallization
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Solution Overview
Problem
Industrial crystallization of proteins results in long batch times and poor macroscopic flowability, leading to uncontrollable aggregation during freeze drying, necessitating a more controlled method for producing stable and flowable protein particles.
Innovation Solution
A novel spherical agglomeration method using a continuous oscillatory baffled crystallizer with a mixture of organic solvents, where a protein solution is injected through the crystallizer, allowing for rapid formation of spherical protein particles with controlled size and improved flowability by manipulating oscillatory mixing conditions and droplet size.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If industrial crystallization is used for protein purification, then protein purification is achieved, but production time is long (10 hours or more) and macroscopic flowability is poor
Solution Approach 1:
The patent utilizes liquid-liquid phase separation by adding a poor solvent (acetone or ethanol) to the protein solution, causing the protein to precipitate as spherical particles. This phase transition approach replaces traditional slow crystallization with rapid precipitation, reducing production time from 10+ hours to minutes while maintaining purification effectiveness.
Solution Approach 2:
The patent changes key process parameters including solvent composition (adding poor solvent), temperature control, and pH adjustment to optimize protein precipitation. By controlling the ratio of poor solvent to good solvent and adjusting temperature, the process achieves rapid particle formation with improved flowability and reduced production time.
2Reliability
If traditional crystallization is used, then protein purification is achieved, but macroscopic flowability is poor and aggregation is uncontrollable during freeze drying
Solution Approach 1:
The patent employs liquid-liquid phase separation to form spherical protein particles with controlled morphology. The rapid precipitation process creates uniform spherical particles that maintain stable flowability and resist uncontrollable aggregation during freeze drying, unlike traditional crystallization products.
Solution Approach 2:
The patent performs preliminary optimization of particle formation conditions before freeze drying. By controlling the precipitation process parameters (solvent ratio, temperature, pH) in advance, the protein particles are pre-formed with optimal properties that prevent aggregation during subsequent freeze drying operations.
3Reliability
If batch crystallization is used, then protein purification is achieved, but production efficiency is low due to long batch times
Solution Approach 1:
The patent transitions from batch crystallization to a continuous precipitation process. The protein solution continuously flows through the precipitation step where poor solvent is added, enabling continuous particle formation and improving production efficiency while maintaining purification quality.
Solution Approach 2:
The patent replaces slow batch crystallization with rapid liquid-liquid phase separation. This phase transition approach reduces the time required for protein particle formation from 10+ hours to minutes, dramatically improving production efficiency while maintaining effective purification.
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 method significantly reduces production time, enhances flowability, and maintains or even improves enzyme activity, achieving protein particles with enhanced micromeritic properties and stability, allowing for improved shelf life and transportability.
Implementation Method 1
providing a continuous oscillatory baffled crystallizer with an inlet and an outlet, and allowing the organic solvent mixture to run from the inlet of the continuous oscillatory baffled crystallizer and out form the outlet the organic solvent mixture; and injecting the aqueous solution of the protein through a middle point of the continuous oscillatory baffled crystallizer to allow the formation of protein crystals
Implementation Method 2
providing an organic solvent mixture comprising a first organic solvent as a poor solvent for the protein and a second organic solvent as a good solvent for the protein
Data Source
AI summary
The present disclosure relates to a novel spherical agglomeration method for proteins, and protein particles made by the spherical agglomeration method. By using continuous oscillatory baffled crystallizer, the method of the present disclosure is capable of maintain the biologically activities and providing protein particles with an average particle size between 1-500 μm.