# US 10,767,152 B2 · Tangential flow depth filtration systems and methods of filtration using same

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- Number: US 10,767,152 B2
- Document ID: US10767152B2
- Status: Granted
- Kind: B2
- Application number: 16/687,864
- Filed: 2019-11-19
- Published: 2020-03-12
- Granted: 2020-09-08
- Earliest claimed: 2018-03-08
- Assignees: Repligen Corporation
- Applicants: Repligen Corporation
- Inventors: Michael Bransby; Derek Carroll
- Web page: https://patentgrep.com/patent/US10767152B2

## CPC

- C12M 29/16: {Hollow fibers (hollow fiber modules in general B01D63/02)}
- B01D 61/18: Apparatus therefor
- B01D 67/00041: {by sintering}
- B01D 67/00042: {by deposition of fibres, nanofibres or nanofibrils}
- B01D 67/0088: {Physical treatment with compounds, e.g. swelling, coating or impregnation}
- B01D 69/02: characterised by their properties
- B01D 69/043: {characterised by the tube diameter}
- B01D 69/081: {characterised by the fibre diameter}
- B01D 71/261: {Polyethylene}
- B01D 71/262: {Polypropylene}
- B01D 71/48: Polyesters
- C02F 3/1273: {Submerged membrane bioreactors}
- C12M 29/10: {Perfusion}
- C12M 33/10: {by centrifugation (centrifuges in general B04B); Cyclones (cyclones in general B04C)}
- C12M 33/14: {with filters, sieves or membranes}
- C12M 47/10: {Separation or concentration of fermentation products (bioreactors combined with means for distillation or extraction of liquid fuel C12M43/02)}
- B01D 61/145: {Ultrafiltration}
- B01D 2311/04: Specific process operations in the feed stream; Feed pretreatment
- B01D 2311/2688: Biological processes
- B01D 2315/10: Cross-flow filtration
- B01D 2315/17: Depth filtration, asymmetric membranes arranged with wider pore size side towards feed
- B01D 2321/2066: Pulsated flow
- B01D 2323/39: Electrospinning
- B01D 2325/0283: Pore size
- B01D 2325/04: Characteristic thickness
- Y02W 10/10: Biological treatment of water, waste water, or sewage
- C12M: APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; {APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS}
- B01D: SEPARATION (separating solids from solids by wet methods B03B, B03D; by pneumatic jigs or tables B03B; by other dry methods B07; magnetic or electrostatic separation of solid materials from solid materials or fluids, separation by high-voltage electric fields B03C; centrifuges, vortex apparatus B04; presses per se for squeezing-out liquid from liquid-containing material B30B9/02; treatment of water C02F, e.g. softening by ion-exchange C02F1/42; {arrangements of air intake cleaners in gas turbine plants F02C7/05} ; arrangements or mounting of filters in air-conditioning, air-humidification or ventilation F24F13/28)
- C02F: TREATMENT OF WATER, WASTE WATER, SEWAGE, OR SLUDGE (separation in general B01D; special arrangements on waterborne vessels of installations for treating water, waste water or sewage, e.g. for producing fresh water, B63J; adding materials to water to prevent corrosion C23F; treating radioactively-contaminated liquids G21F9/04; regeneration of reactants for recirculation into processes, see the relevant places for the processes)
- Y02W: CLIMATE CHANGE MITIGATION TECHNOLOGIES RELATED TO WASTEWATER TREATMENT OR WASTE MANAGEMENT

## Abstract

The present disclosure relates to hollow fiber tangential flow filters, including hollow fiber tangential flow depth filters, for various applications, including bioprocessing and pharmaceutical applications, systems employing such filters, and methods of filtration using the same.

## Claims

### Claim 1

A bioprocessing system comprising:
a process vessel;
a tangential flow depth filtration (TFDF) unit comprising a thick-walled hollow fiber formed from at least one polymer and comprising a porous wall defining a lumen that is in fluid communication with the process vessel;
a permeate fluid outlet in fluid communication with an exterior surface of the porous wall; and
a pump in fluid communication with the lumen;
wherein a density of the hollow fiber is between 51% and 56% of the density of an equivalent solid volume of the polymer.

### Claim 2 (depends on 1)

The bioprocessing system of claim 1, wherein an average pore size of the thick-walled hollow fiber is about 0.2 μm to about 10 μm.

### Claim 3 (depends on 1)

The bioprocessing system of claim 1, wherein the density is about 53%.

### Claim 4 (depends on 1)

The bioprocessing system of claim 1, wherein the porous wall has a thickness ranging from 2 mm to 7 mm.

### Claim 5 (depends on 1)

The bioprocessing system of claim 1, wherein the pump is configured to provide a pulsed flow of fluid through the lumen.

### Claim 6 (depends on 1)

The bioprocessing system of claim 1, further comprising a polymer coating along an inside of the porous wall of the hollow fiber.

### Claim 7 (depends on 6)

The bioprocessing system of claim 6, wherein the coating is selected from the group consisting of polyolefin, polyethylene, polypropylene, and polyvinylidene fluoride (PVDF).

### Claim 8 (depends on 6)

The bioprocessing system of claim 6, wherein the coating on the porous wall reduces a pore size of the hollow fiber.

### Claim 9 (depends on 1)

The bioprocessing system of claim 1, wherein the hollow fiber comprises bi-component filaments having a core and a coating.

### Claim 10 (depends on 9)

The bioprocessing system of claim 9, wherein the core comprises polyolefin and the coating comprises polyester.

### Claim 11 (depends on 9)

The bioproces sing system of claim 9, wherein the core comprises polyethylene terephthalate and the coating comprises polypropylene.

### Claim 12 (depends on 11)

The bioprocessing system of claim 11, wherein the bi-component filaments are further coated with polyvinylidene fluoride (PVDF).

### Claim 13

A tangential flow depth filtration (TFDF) unit comprising:
a hollow fiber formed from at least one polymer and comprising a porous wall having a density between 51% and 56% of the density of an equivalent solid volume of the polymer, the porous wall defining a lumen;
an inlet in fluid communication with the lumen; and
a permeate fluid outlet in fluid communication with a permeate chamber comprising an exterior surface of the hollow fiber.

### Claim 14 (depends on 13)

The TFDF unit of claim 13, further comprising a polymer coating along an inside of the porous wall of the hollow fiber.

### Claim 15 (depends on 14)

The TFDF unit of claim 14, wherein the coating is selected from the group consisting of polyolefin, polyethylene, and polypropylene polyvinylidene fluoride (PVDF).

### Claim 16 (depends on 13)

The TFDF unit of claim 13, wherein the hollow fiber comprises bi-component filaments having a core and a coating.

### Claim 17

A method of filtering a fluid comprising cells, the method comprising:
flowing a fluid comprising the cells from a process vessel into a tangential flow depth filter (TFDF) unit comprising a thick-walled hollow fiber formed from at least one polymer and comprising a porous wall having a pore size and a density between 51% and 56% of the density of an equivalent solid volume of the polymer, the porous wall defining the lumen that is in fluid communication with the process vessel, the TFDF unit having a permeate fluid outlet in fluid communication with the porous wall,
wherein the fluid is separated into a retentate comprising the cells and a permeate, and wherein the retentate is returned to the process vessel.

### Claim 18 (depends on 17)

The method of claim 17, wherein the fluid is a culture medium and the cells of the culture medium have been cultured for a period of at least two days.

### Claim 19 (depends on 18)

The method of claim 18, further comprising the step of adding a fluid volume to the process vessel equivalent to a volume of permeate, thereby maintaining an overall volume of the fluid.

### Claim 20 (depends on 17)

The method of claim 17, wherein the permeate comprises a bioproduct produced by the cells.

### Claim 21 (depends on 17)

The method of claim 17, the TFDF unit further comprising a polymer coating disposed along an inside of the porous wall of the hollow fiber.

### Claim 22 (depends on 21)

The method of claim 21, wherein the coating is selected from the group consisting of polyolefin, polyethylene, and polypropylene polyvinylidene fluoride (PVDF).

### Claim 23 (depends on 17)

The method of claim 17, wherein the hollow fiber comprises bi-component filaments having a core and a coating.

### Claim 24 (depends on 17)

The method of claim 17, wherein the flow of fluid into the TFDF unit is a pulsed flow.