Process technology for biological product manufacturing and downstream purification
Inventors
Criscione, Jason M. • Ersen, Ali • Linton, John R. • Datwani, Sammy S.
Assignees
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Publication Number
US-11345723-B2
Publication Date
2022-05-31
Expiration Date
Abstract
Provided herein are, inter alia, biological manufacturing and downstream purification processes.
Core Innovation
The invention relates to a process for purifying a biological product by combining dynamic filtration, affinity-based purification, and continuous free-flow electrophoresis. A heterogeneous mixture containing the biological product is received via an input line and is clarified by dynamic filtration in a dynamic filtration module under negative pressure to produce a filtrate containing the biological product. The dynamic filtration apparatus includes a filter membrane extending between a feed reel and a collection reel, with substantially smooth contact surfaces and a vacuum collection system positioned between the feed reel and the collection reel.
After dynamic filtration, the filtrate is transferred to a first module that separates the solution into two or more fractions, wherein at least one fraction contains the biological product. The first module includes an affinity-based purification apparatus with at least one first inlet and at least one first outlet and permits fluid flow via a mechanical rotary system comprising a vessel carousel containing at least one discrete vessel comprising a suspension of beads.
The fraction containing the biological product is then transferred to a second module comprising at least one free-flow electrophoresis apparatus configured for continuous fluid flow between a second inlet and a second outlet. The biological product is recovered from the continuous free-flow electrophoresis module, which supports electrophoresis-based fractionation based on charge or isoelectric point.
Claims Coverage
The independent claim covers a multi-module purification process with three key inventive features.
Dynamic filtration under negative pressure with reel-to-reel membrane and vacuum collection
A dynamic filtration module with a filter membrane extending between a feed reel and a collection reel, substantially smooth contact surfaces, and a vacuum collection system positioned between the feed reel and the collection reel, used to produce a filtrate comprising the biological product under negative pressure.
Affinity-based purification using a mechanical rotary vessel carousel with beads
A first module that separates the solution into two or more fractions, wherein at least one fraction contains the biological product, using an affinity-based purification apparatus with a mechanical rotary system comprising a vessel carousel containing at least one discrete vessel comprising a suspension of beads.
Continuous free-flow electrophoresis for recovery of the biological product
A second module comprising at least one free-flow electrophoresis apparatus configured for continuous fluid flow between a second inlet and a second outlet, receiving the fraction containing the biological product for recovery.
The inventive concept is to combine negative-pressure dynamic filtration, affinity-based fractionation using a mechanical rotary vessel carousel containing beads, and continuous free-flow electrophoresis for recovery of the biological product.
Stated Advantages
Reduced membrane fouling.
Reduced footprint.
Continuous operation.
Improved processing economics, including a "no product loss" rationale for electrophoresis.
Bead recycling without packed columns.
Documented Applications
A continuous downstream purification train for purifying a biological product, including clarification by dynamic filtration, affinity-based fractionation, and recovery using a continuous free-flow electrophoresis module.
Downstream purification workflows for biological products integrating dynamic filtration, affinity-based modular magnetic purification with bead recycling, and optional continuous free-flow electrophoresis.
Clarification and downstream fractionation of biological products including electrophoretic dye/protein fractionation and recovery contexts referenced in the document.
Use of the described integrated modules in demonstrations and apparatus figures for membrane/material designs and experimental demonstrations of protein recovery and bead removal.
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