High efficiency continuous countercurrent tangential chromatography
Inventors
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-10324070-B2
Publication Date
2019-06-18
Expiration Date
Abstract
A system, module and method for continuous or batch single-pass countercurrent tangential chromatography are disclosed for bind/elute and negative chromatography applications. The system includes binding, washing, elution (for bind/elute), regeneration, and equilibration single-pass modules. The resin slurry flows in a continuous single pass at steady-state through each module, while corresponding buffers flow countercurrent to the slurry facilitating efficient product and impurity extraction. The module and system include retentate pumps for better process robustness and control. A resin tank configured to be reversibly isolated from the single-pass modules facilitates a closed and disposable system. The method includes receiving unpurified product solution and resin slurry, isolating the resin tank, binding product (bind/elute) or impurities (negative) to the resin slurry, washing impurities from the resin slurry, eluting and capturing pure product from the resin slurry (bind/elute), regenerating the resin slurry following elution, and providing buffer solutions to all of the single-pass steps.
Core Innovation
The invention provides high-efficiency continuous single-pass countercurrent tangential chromatography for bind/elute and negative chromatography. The system uses multiple single-pass modules for binding, washing, elution, regeneration, and equilibration, where resin slurry flows steady-state in a continuous single pass and buffers flow countercurrently to permeate to improve product/impurity extraction.
Each multi-stage module includes a stage I filter and a stage II filter in series to concentrate mixed outputs into stage I retentate and stage II retentate. Recycled solution flows countercurrent to the input solution into the module, and at least one retentate pump is arranged and disposed to drive and stabilize hydrodynamics of the module.
The architecture is described as robust against pressure gradients by using retentate pumps, and the system is reported to reduce pressure profile and overall pressure while enabling bypass and reversible isolation of a resin tank for closed or disposable operation. Modeling and expected results are provided, including yield/product recovery and buffer-to-resin flow ratio behavior for two-stage versus three-stage configurations, with examples including protein A capture and IgG.
Claims Coverage
The partial content identifies one independent claim directed to a module architecture for continuous single-pass countercurrent tangential chromatography using two filters in series, recycle countercurrent flow, and retentate pumping with unpressurized permeates. The claim is operationally structured around stage I and stage II concentration, mixing, and permeate handling, and it includes specific limitations on flow paths and pump pressurization of permeate streams.
Two-stage single-pass tangential concentration with stage I retentate and stage II retentate
A module having a stage I filter for concentrating a first mixed output to produce a stage I retentate, and a stage II filter in series for concentrating a second mixed output to produce a stage II retentate, with stage I permeate and stage II permeate exiting via respective output ports.
Countercurrent recycle of recycled solution into the input using an input and a recycled solution port
The input solution flows through the stage I filter and the stage II filter in a single pass, and recycled solution from the recycled solution port flows countercurrent to the input solution into the module.
In-module mixing using first and second mixers fed by recycled solution and stage outputs
A first mixer mixes the input solution with a recycled solution from a second input port to produce a first mixed output, and a second mixer mixes stage I retentate with an optional buffer solution from a third input port to produce a second mixed output.
Unpressurized permeates free from permeate pump pressurization
The stage I permeate and the stage II permeate are free from pressurization by a permeate pump.
Retentate pump arranged to drive and stabilize module hydrodynamics
At least one retentate pump is included, and it is arranged and disposed to drive and stabilize hydrodynamics of the module.
Overall, the independent claim coverage centers on a continuous single-pass, two-stage tangential chromatography module with countercurrent recycle, in-line mixing, and an unpressurized permeate handling arrangement, supported by retentate pumping to drive and stabilize hydrodynamics.
Stated Advantages
Reduced resin use up to ~80%.
Improved product/impurity extraction via countercurrent buffer flow and permeation.
Reduced overall pressure gradients.
Scalability beyond conventional column limits.
Potential for disposable operation via closed/disposable operation features, including reversible isolation and bypass of a resin tank.
Reduced equipment and controls through system architecture.
High yield/product recovery, including a reported example of greater than 95% yield.
Documented Applications
Protein A capture for IgG, including IgG capture from bioreactor harvest.
Bind/elute chromatography operations using the disclosed continuous single-pass countercurrent tangential chromatography system.
Negative chromatography operations using the disclosed continuous single-pass countercurrent tangential chromatography system.
Interested in licensing this patent?