Single pass cross flow diafiltration module and method

1. A method of single pass, cross-flow diafiltration, comprising:

a. providing three or more filtration segments fluidly connected in series, each having an upstream side and a downstream side; wherein each of the three or more filtration segments comprises hollow fiber filter membranes

b. providing a first pump, mounted to urge fluid flow to the first filtration segment of the three or more filtration segments;

c. providing one or more points of introduction of a diadiluent, each at a point between two or more upstream segments and one or more downstream segments of the three or more filtration segments, wherein the two or more upstream segments have produced a volume of permeate;

d. providing one or more further pumps, each mounted between the three or more filtration segments to provide a single pump that urges fluid flow of retentate and introduced diadiluent from the one or more points of introduction of the diadiluent;

e. measuring the volume of permeate from at least two of the two or more upstream segments; and

f. introducing a volume of diadiluent to a retentate from the two or more upstream segments,

wherein the volume of diadiluent that is introduced to the retentate is substantially equal to a sum of the measured volume of permeate from the at least two upstream segments.

2. The method of claim 1 ,

wherein each of the three or more filtration segments has a length;

wherein the hollow fiber filter membranes of each of the three or more filtration segments have a selected lumen diameter;

wherein at least one selected lumen diameter differs from at least one other selected lumen diameter, and provided that the three or more filtration segments are arranged such that for a given filtration segment, having one of the selected lumen diameters, no filtration segment on the upstream side of the given filtration segment has a selected lumen diameter that is larger.

3. The method of claim 2 , wherein the lengths of each of the filtration segments are chosen to be from about 4 inches to about 100 inches.

4. The method of claim 2 , wherein the lengths of the three two or more filtration segments are chosen from 12 inches, 24 inches, and 41 inches.

5. The method of claim 2 , wherein the filtration segments comprise a housing having a housing inner diameter, and wherein the housing inner diameter of each of the three or more filtration segments is about 0.5 cm to about 26 CM.

6. The method of claim 2 , wherein the filtration segments comprise a housing having a housing inner diameter, and wherein the housing inner diameter of each of the three or more filtration segments is about 0.95 cm to about 16 CM.

7. The method of claim 2 , wherein the selected lumen diameters of each of the three or more filtration segments are about 0.1 mm to about 5 mm.

8. The method of claim 1 , wherein the fluid to be filtered comprises a viscosity lowering agent chosen from proline, histidine, lysine, arginine, glutamic acid, betaine, glutamine, asparagine, imidazole, pharmaceutically acceptable salts thereof and a combination of two or more thereof.

9. The method of claim 1 , wherein the hollow fiber filter membranes have pore sizes from about 1 nanometers to about 500 micrometers.

10. The method of claim 1 , wherein the hollow fiber filter membranes have pore sizes from about 10 nanometers to about 500 micrometers.

11. The method of claim 1 , wherein one or more points of introduction of a diadiluent comprise a metering pump.

12. The method of claim 11 , wherein the one or more points of introduction of a diadiluent comprise at least one reservoir.

13. The method of claim 1 , further comprising:

delivering the retentate from the two or more upstream segments into a reservoir;

delivering the volume of diadiluent to the reservoir to form a solution with the retentate in the reservoir; and

pumping the solution to one or more additional downstream segments of the three or more filtration segments.