Method and apparatus for the filtration of biological solutions
A system, method and device are disclosed for bio-processing a feed stream and providing a constant output by operating a continuous single-pass tangential-flow process. The single-pass process provides high conversion concentration while operating at relatively low feed flow rates, and the process can also be used to provide constant output diafiltration.
1. A single-pass tangential-flow filtration system comprising:
a plurality of substantially identical stages, each stage having a plurality of channels;
each of the channels has a length, a membrane area, a void volume, a specific membrane area σ C expressed as a ratio of the membrane area to the void volume, and a dimensionless length λ expressed as a product of the channel length and the specific membrane area; and
a dimensionless length of the system is greater than about 2,000;
a dimensionless length of at least one of the plurality of substantially identical stages is less than about 6,000 to provide relatively short flow paths for individual stages; and
wherein each of the substantially identical stages comprises a cassette.
2. The filtration system of claim 1 , wherein each of the substantially identical stages includes a series-parallel arrangement of channels.
3. The filtration system of claim 1 , wherein a specific membrane area of a channel in one of a plurality of substantially identical stages, is greater than about 40 cm −1 .
4. The filtration system of claim 1 , wherein the dimensionless length of the system is greater than about 4,000 and the dimensionless length of the at least one of the plurality of stages is less than about 3,500.
5. The system of claim 1 , wherein at least one cassette in a first stage comprises a feed manifold, a retentate manifold, at least one permeate channel, and at least one flow channel fluidly coupled to the feed manifold;
wherein at least one cassette in a second stage comprises a feed manifold and a retentate manifold;
further comprising a staging plate disposed between the at least one cassette in a first stage and the at least one cassette in a second stage; and
wherein the staging plate fluidly couples the retentate manifold of the at least one cassette in a first stage to the feed manifold of the at least one cassette in a second stage and blocks flow from the feed manifold of the at least one cassette in a first stage, thereby serializing retentate flow through the system.
6. The system of claim 5 , wherein the staging plate comprises a feed blocking plate separating the at least one cassette in a first stage and the at least one cassette in a second stage and which couples a retentate manifold of the at least one cassette in a first stage to a corresponding feed manifold of the at least one cassette in a second stage and blocks a flow from the feed manifold of the at least one cassette in a first stage.
7. The system of claim 6 wherein the feed blocking plate further comprises at least one pass through port aligned with the corresponding retentate manifold of the at least one cassette in a first stage and the corresponding feed manifold of the at least one cassette in a second stage.
8. The filtration system of claim 1 , wherein the dimensionless length of each stage is substantially equal to the dimensionless length of the longest serial flow path of each stage.
9. A single-pass tangential-flow filtration system comprising:
a plurality of substantially identical stages, each stage having a plurality of channels;
each of the channels has a length, a membrane area, a void volume, a specific membrane area σ C expressed as a ratio of the membrane area to the void volume, and a dimensionless length λ expressed as a product of the channel length and the specific membrane area; and
a dimensionless length of the system is greater than about 2,000;
a dimensionless length of at least one of the plurality of substantially identical stages is less than about 6,000 to provide relatively short flow paths for individual stages;
wherein the dimensionless length of each of the plurality of substantially identical stages is substantially identical; and
wherein a specific membrane area of a channel in one of a plurality of substantially identical stages, is greater than about 40 cm −1 .
10. The filtration system of claim 9 , wherein each of the substantially identical stages includes a series-parallel arrangement of channels.
11. The filtration system of claim 9 , wherein each of the substantially identical stages comprises a cassette.
12. The filtration system of claim 9 , wherein the dimensionless length of the system is greater than about 4,000 and the dimensionless length of the at least one of the plurality of stages is less than about 3,500.