Countercurrent tangential chromatography methods, systems, and apparatus
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Publication Number
US-7988859-B2
Publication Date
2011-08-02
Expiration Date
Abstract
This invention relates to a breakthrough in the art of chromatography allowing 1) larger scale of operation; 2) faster processing time; 3) disposability; 4) reduction of media/resin expenses; and 5) a reduction of capital equipment investment. In this invention, the chromatography column is replaced by a module that consists of two or more interconnected tangential flow filters and static mixers. The chromatography resin flows through this module in a single pass, while similar operations to a regular chromatographic process are performed on the resin (binding, washing, elution, regeneration, and equilibration). The buffers for these operations are pumped into the module in a countercurrent direction to the flow of resin, and permeate solutions from later stages are recycled back into previous stages. This creates concentration gradients in the permeate solutions of the tangential flow filters in the countercurrent direction to resin flow, thus saving buffer volume and increasing process efficiency.
Core Innovation
The invention provides a module for countercurrent tangential chromatography in which a chromatography operation is implemented using a module of two or more interconnected tangential flow filters with mixers. An input solution flows through stage I filter and stage II filter in a single pass, while a recycled solution is introduced to flow countercurrent to the input solution into the module for mixing and subsequent stage II concentration.
The module includes a first mixer for mixing the input solution with a recycled solution from a second input port to produce a first mixed output, and a stage I filter that concentrates the first mixed output to produce a stage I retentate. Stage I permeate exits the module from a first output port, while stage I retentate is provided to a second mixer together with an optional buffer solution from a third input port to produce a second mixed output.
The second mixed output is concentrated in a stage II filter in series with the stage I filter to produce a stage II retentate, and stage II permeate exits the module from a third output port. The recycled solution from the third output port flows countercurrent into the module to the second input port, and permeate streams can be routed for waste versus product via dedicated output ports and associated plumbing.
Claims Coverage
The independent claim coverage centers on a two-stage, single-pass tangential filtration module using countercurrent recycling, with mixing in two stages and distinct output ports for stage I and stage II permeates, plus optional buffer input to the second mixer. Four inventive features are identified across the independent and dependent claims.
Two-stage module with single-pass filtration and countercurrent recycle
A module comprising a first input port for receiving an input solution, a first mixer for mixing the input solution with a recycled solution from a second input port to produce a first mixed output, a stage I filter for concentrating the first mixed output to produce stage I retentate with stage I permeate exiting via a first output port, a second mixer for mixing the stage I retentate and an optional buffer solution to produce a second mixed output, and a stage II filter in series to produce stage II retentate with stage II permeate exiting via a third output port, wherein the input solution flows through the stage I filter and the stage II filter in a single pass and the recycled solution from the third output port flows countercurrent into the second input port.
Static mixers for first and second mixing
The module wherein the first mixer and the second mixer are static mixers.
Tangential flow filters for stage I and stage II
The module wherein the stage I filter and the stage II filter are tangential flow filters.
Recycle connection from the third output port to the second input port
The module wherein the third output port is connected via a pump and a three-way valve to the second input port.
The claims define a two-stage module that performs single-pass tangential filtration while using a countercurrent recycled stream for mixing, concentration in stage I and stage II, and separate permeate exit ports, further constrained by static mixers, tangential flow filters, and specific recycle plumbing.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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