Tangential-flow filtration system

• US 6,054,051 A
• Filed: 12/17/1996
• Issued: 04/25/2000
• Est. Priority Date: 01/17/1996
• Status: Expired due to Term

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: van Reis, Robert D.
• Primary Examiner(s): FORTUNA, ANA M
• Application Number:
  US08/767,909
• Time in Patent Office: 1,225 Days
• Field of Search: 210/641, 210/651, 210/321.75, 210/321.74, 210/321.84, 210/446, 210/195.2, 210/636, 210/321.6
• US Class Current: 210/641
• CPC Class Codes: B01D 61/14 Ultrafiltration; Microfiltration
• CPC Class Codes: B01D 61/145 Ultrafiltration
• CPC Class Codes: B01D 61/146 comprising multiple ultrafiltration steps
• CPC Class Codes: B01D 61/147 Microfiltration

Abstract

The present invention includes a system and method for transferring a selected solute species from a fluid mixture to a fluid media. The system of the present invention includes a convergent channel for passing a fluid mixture containing a selected species tangentially across the first surface of a porous membrane. A fluid media is directed to flow tangentially over the second surface of the membrane. As the fluid mixture and the fluid media flow on opposite sides of the membrane, the selected species traverses the membrane leaving the fluid mixture and entering the fluid media. The volumetric loss to the fluid mixture associated with the loss of the selected species is compensated for by the convergency of the channel. As a result a constant velocity is maintained over the membrane, maximizing the selectivity of the filtration process.

Claims

1. A tangential-flow filter for selectively transferring a species from a fluid mixture to a fluid media, the filter comprising:

a filtration membrane having a first surface and a second surface;

a cassette formed with a first channel and a second channel, the first channel having an input port and an output port being disposed to establish a tangential flow of the fluid mixture over the first surface of the membrane, the first channel having a cross-sectional area with the cross-sectional area decreasing in the direction of the tangential flow, and the second channel having an input port and an output port being disposed to establish a tangential flow of the fluid media over the second surface of the membrane, wherein the decrease in cross-sectional area in the first channel is chosen so that the velocity of the tangential flow of the fluid mixture is substantially constant over the length of the first channel and a pressure differential is substantially constant over the length of the filtration membrane; and

means for creating the pressure differential between the fluid mixture in the first channel and the fluid media in the second channel to cause the species to traverse the membrane from the fluid mixture to the fluid media.

2. A tangential-flow filter as recited in claim 1 further comprising one or more secondary filtration membranes, the secondary filtration membranes disposed between the first surface of the filtration membrane and the first channel.

3. A tangential-flow filter as recited in claim 1 wherein the first channel and the second channel are positioned side-by-side.

4. A tangential-flow filter as recited in claim 1 wherein the first channel and the second channel are positioned coaxially.

5. A tangential-flow filter as recited in claim 1 wherein the means for creating a pressure differential maintains the pressure differential at a value which is less than the transition point pressure (TPP) of the tangential-flow filter.

6. A tangential-flow filter as recited in claim 1 wherein the decrease in the cross-sectional area in the direction of the tangential flow is chosen to compensate for volumetric changes to the fluid mixture caused by the traversal of the filtration membrane by the species.

7. A tangential-flow filter as recited in claim 1 wherein the filtration membrane is chosen to selectively pass species having a molecular weight of approximately 1 to 1000 kDa.

8. A tangential-flow filtration apparatus separating a fluid mixture into species of interest comprising:

a cassette formed with a layered sequence of side-by-side channels including a convergent first channel and a last channel, the convergent first channel and at least one intermediate channel configured as recirculating channels having an inlet and an outlet, the last channel configured as a non-recirculating channel having an outlet;

a series of filtration membranes, one filtration membrane positioned between each successive pair of channels in the layered sequence with each successive pair of channels in the layered sequence being separated by a filtration membrane having a successively smaller pore size,

wherein the convergent first channel converges between the inlet and the outlet so that the flow velocity of the fluid mixture is substantially constant within the convergent first channel and so that a predetermined pressure differential between the convergent first channel and at least the first intermediate channel is substantially constant over the length of the filtration membrane positioned between the convergent first channel and the intermediate channel;

means for creating the flow of the fluid mixture between the inlet and the outlet of each recirculating channel; and

means for creating and maintaining the predetermined pressure differential between each successive pair of channels in the layered sequence.

9. A tangential-flow filtration apparatus as recited in claim 8 wherein the cassette is formed to include one intermediate channel.

10. A tangential-flow filtration apparatus as recited in claim 8 wherein the cassette is formed to include two intermediate channels.

11. A tangential-flow filtration apparatus as recited in claim 8 wherein the outlet of each recirculating channel is connected in fluid communication to the inlet of the channel.

12. A tangential-flow filter as recited in claim 8 wherein the pressure means for creating a pressure differential maintains the differential between each successive pair of recirculating channels in the layered sequence at a value which is less than the transition point pressure (TPP) of the tangential-flow filter.

13. A tangential-flow filter as recited in claim 8 wherein the convergent first channel is dimensioned to compensate for volumetric changes to the fluid mixture caused by the traversal of the filtration membrane positioned between the convergent first channel and the intermediate channel by the species.

14. A process for selectively transferring a species from a fluid mixture, comprising the steps of:

passing the fluid mixture through a channel for tangential flow over a first surface of a primary filtration membrane, the channel shaped to have a cross-sectional area, the cross-sectional area decreasing in the direction of the tangential flow;

passing a fluid media for tangential flow over a second surface of the primary filtration membrane, the tangential flow of the fluid mixture adjacent to the tangential flow of the fluid media,

wherein the decrease in cross-sectional area in the channel is chosen so that the velocity of the tangential flow of the fluid mixture is substantially constant over the length of the channel and a predetermined pressure differential is substantially constant over the length of the filtration membrane; and

creating and maintaining the predetermined pressure differential between the fluid mixture in the channel and the fluid media to cause the species to traverse the primary filtration membrane from the fluid mixture to the fluid media.

15. A process as recited in claim 14 further comprising the step of filtering the fluid media by tangential flow filtration over a secondary filtration membrane, the secondary filtration membrane having a smaller pore size.

16. A tangential-flow filter for selectively transferring a species from a fluid mixture to a fluid media, the filter comprising:

filtration means having a first surface and a second surface;

a first channel which causes the mixture to flow tangentially at a first pressure over the first surface of the filtration means, the first channel having a length, the first channel being shaped to decrease from a first cross-sectional area to a second cross-sectional area over the length of the first channel;

wherein the decrease in cross-sectional area in the first channel is chosen so that the velocity of the tangential flow of the fluid mixture is substantially constant over the length of the first channel and a predetermined pressure differential is substantially constant over the length of the filtration membrane; and

means for causing the fluid media to flow tangentially at a second pressure over the second surface of the filtration means, the first pressure and the second pressure creating and maintaining the predetermined pressure differential over the filtration means between the mixture and the fluid media, the pressure differential causing the species to traverse the filtration means from the fluid mixture to the fluid media.

17. A tangential-flow filter as recited in claim 16 wherein the filtration means comprises a filtration membrane.

18. A tangential-flow filter as recited in claim 17 wherein the first cross-sectional area and the second cross-sectional area are chosen so that the decrease of cross-sectional area compensates for volumetric changes to the fluid mixture caused by the traversal of the membrane by the species.

19. A tangential-flow filter as recited in claim 16 wherein the filtration means comprises a plurality of filtration membranes.

20. A tangential-flow filter as recited in claim 16 wherein the filtration means is chosen to selectively pass species having a molecular weight of approximately 1 to 1000 kDa.