TANGENTIAL FLOW FILTRATION DEVICE FOR PERFUSION APPLICATIONS
Filter elements ( 20, 100 ) for perfusion systems and methods are provided. A filter element sheet includes a microporous membrane ( 63, 112 ) having a mean pore size of at least about 0.65 μm and a feed spacer ( 25, 120 ) comprising woven fibers and having an open area of at least about 35%. The filter element sheet can be arranged within a filter element, for example, in a spiral-wound format or in a cassette format. A perfusion system includes at least one filter element and a pump configured to control flow of a liquid feed through the at least one filter element.
1 . A perfusion filter element sheet comprising:
a microporous membrane having a mean pore size of at least about 0.65 μm; and
a feed spacer comprising woven fibers and having an open area of at least about 35%.
2 . The filter element sheet of claim 1 , wherein the pore size is about 0.8 μm to about 10 μm.
3 . The filter element sheet of claim 1 , wherein the pore size is about 1.0 μm to about 5 μm.
4 . The filter element sheet of claim 1 , wherein the feed spacer has an open area of about 35-% to about 55%.
5 . The filter element sheet of claim 1 , wherein the feed spacer has a fiber density of about 6 fibers/cm to about 13 fibers/cm.
6 . The filter element sheet of claim 1 , wherein the feed spacer comprises fibers having an average fiber diameter of at least about 270 μm.
7 . The filter element sheet of claim 6 , wherein the feed spacer comprises fibers having an average fiber diameter of about 300 μm to about 500 μm.
8 . The filter element sheet of claim 1 , wherein the feed spacer comprises fibers woven in a two-over-one twill pattern or a one-over-one weave pattern.
9 . (canceled)
10 . A filter element comprising at least one filter element sheet of claim 1 .
11 . The filter element of claim 10 , wherein the filter element is a spiral-wound filter element.
12 . The filter element of claim 10 , wherein the filter element is a cassette filter element.
13 . A perfusion system comprising:
at least one filter element of claim 10 ; and
a pump configured to control flow of a liquid feed through the at least one filter element, the system configured to be operated in a tangential flow filtration (TFF) mode.
14 . The perfusion system of claim 13 , wherein the pump is a magnetic levitation pump.
15 . The perfusion system of claim 13 , wherein the pump is a peristaltic pump.
16 . The perfusion system of claim 13 , wherein the pump is a diaphragm pump.
17 . The perfusion system of claim 13 , wherein the system is configured to operate in a recirculation mode.
18 . The perfusion system of claim 13 , wherein the system is configured to operate in an alternating flow mode.
19 . A perfusion process, comprising:
passing a liquid feed through a feed channel of at least one filter element, the at least one filter element comprising a microfiltration membrane and a woven feed spacer located within the feed channel; and
separating the liquid feed into permeate and retentate by tangential flow filtration (TFF) in the filter element.
20 . The perfusion process of claim 19 , wherein the liquid feed comprises cells and a target protein, the process further comprising recovering the target protein in the permeate.
21 . (canceled)
22 . (canceled)
23 . The perfusion process of claim 19 , further comprising recirculating at least a portion of the retentate through the at least one filter element.
24 . The perfusion process of claim 19 , further comprising alternating a flow of liquid through the at least one filter element.
25 . (canceled)
26 . (canceled)
27 . The perfusion process of claim 19 , further comprising:
supplying a volume of fresh media to the retentate; and
returning the retentate to a bioreactor upstream of the at least one filter element.
28 . The perfusion process of claim 27 , wherein passing the liquid feed through the feed channel of the at least one filter element and returning the retentate to the bioreactor occurs on a continuous basis, the retentate being the liquid feed of a subsequent perfusion process.
29 .- 40 . (canceled)