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. An internally staged filter module comprising:
a housing;
a plurality of stages disposed within the housing, each stage having a plurality of channels comprising a filtration membrane and at least one manifold in fluid communication with the plurality of channels, each stage being in fluid communication with each adjacent stage preceding it and being in fluid communication with each adjacent stage that follows it; and
at least one diafiltration distributor disposed within the housing and in fluid communication with the at least one manifold of selected ones of the plurality of stages and having an inlet for supplying a diafiltrate; and
wherein each of the plurality of stages further comprises a feed spacer disposed adjacent a surface of corresponding filtration membrane.
2. The module of claim 1 , wherein the at least one diafiltration distributor comprises at least one counter current flow passage fluidly coupling the permeate from at least one channel in a first stage as the diafiltrate to at least one channel in a selected preceding stage.
3. The module of claim 1 wherein the at least one diafiltration distributor further comprises a plurality of diafiltration flow passages fluidly coupling the feed manifolds to the diafiltrate inlet.
4. The module of claim 3 wherein each of the plurality of diafiltration flow passages has a hydraulic resistance so as to introduce a predetermined volume of the diafiltrate into the at least one manifold.
5. The module of claim 4 further comprising a channel inlet fluidly coupled to an initial one of the plurality of channels and wherein the diafiltrate flow passage inlet pressure is about twice the channel inlet pressure.
6. The module of claim 3 further comprising a channel inlet fluidly coupled to an initial one of the plurality of channels and a channel outlet fluidly coupled to a last one of the plurality of channels, and wherein the at least one diafiltration distributor has a predetermined hydraulic resistance wherein the diafiltrate flow passage pressure is four times the average pressure difference between the channel inlet and outlet pressure.
7. The module of claim 1 further comprising a diafiltration spacer disposed in the at least one diafiltration flow passage providing a hydraulic resistance predetermined to control the flow rate of a diafiltrate along the at least one diafiltration flow passage.
8. The module of claim 1 wherein the housing is a cylindrical housing comprising:
an outer shell, an inner annular support ring and a plurality of supports coupled to the inner annular support ring;
wherein the diafiltration distributor comprises a diafiltration flow passage disposed within the cylindrical housing and coupled to the plurality of supports; and
the plurality of channels comprise a plurality of hollow fiber membranes disposed within housing between the outer shell and the inner annular support ring.
9. The method of claim 1 wherein the specific membrane area of the at least one channel is greater than about 40 cm −1 , and the dimensionless length of at least one of the plurality of stages is less than about 3,000.
10. The module of claim 1 , wherein each of the plurality of stages further comprises a cassette.
11. The module of claim 1 , wherein each of the plurality of stages further comprises a spiral-wound separation module.