# US 2019/0169559 A1 · Cell retention device and method > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2019/0169559 A1 - Document ID: US20190169559A1 - Status: Published application - Kind: A1 - Application number: 16/092,482 - Filed: 2017-04-13 - Published: 2019-06-06 - Earliest claimed: 2016-04-15 - Assignees: Boehringer Ingelheim International GmbH - Applicants: Boehringer Ingelheim International GmbH - Inventors: Jonathan COFFMAN; Scott GODFREY; Samantha WANG - Web page: https://patentgrep.com/patent/US20190169559A1 ## CPC - C12M 29/10: {Perfusion} - C12M 29/16: {Hollow fibers (hollow fiber modules in general B01D63/02)} - C12M 47/02: {Separating microorganisms from the culture medium; Concentration of biomass (separating microorganisms from their culture media C12N1/02)} - C12M 47/10: {Separation or concentration of fermentation products (bioreactors combined with means for distillation or extraction of liquid fuel C12M43/02)} - 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} ## Abstract The subject technology relates to a cell retention device and method for use in a perfusion cell culture system where the cell retention device includes a hollow-fiber filter having an average pore size ranging from about 0.5 to about 20 μm and having the ability to operate under perfusion cell culture conditions for up to 35 days without being clogged or losing its product sieving ability by more than 20%. ## Claims ### Claim 1 A cell retention device comprising a hollow-fiber filter having an average pore size ranging from about 0.5 to about 20 μm. ### Claim 2 (depends on 1) The cell retention device of claim 1, wherein the cell retention device is external to a perfusion cell culture vessel. ### Claim 3 (depends on 1) The cell retention device of claim 1, wherein the hollow-fiber filter has an average pore size selected from about 5 to about 8 μm, 5 μm to 15 μm, 5.2 μm to 12 μm, 5.5 μm to 8 μm, 5.2 μm to 7.7 μm, 5 μm, 6 μm, 7 μm, 8 μm, 9 μm, 10 μm, 11 μm, 12 μm, 13 μm, 15 μm, or any size above 5 μm that could retain the viable cells while allowing dead cells, cellular debris or macromolecules to pass through the filter. ### Claim 4 (depends on 1) The cell retention device of claim 1, wherein the hollow-fiber filter has an average pore size that is equal or greater than 5 μm but less than the size of viable cells being cultured in a cell culture vessel. ### Claim 5 (depends on 1) The cell retention device of claim 1, wherein the hollow-fiber filter has an average pore size greater than the size of a viable cell by 5 μm or less. ### Claim 6 (depends on 1) The cell retention device of claim 1, wherein the cell retention device is configured to operate by tangential-flow filtration (TFF) or by alternating tangential flow filtration (ATF). ### Claim 7 (depends on 5) The cell retention device of claim 5, wherein the TTF or ATF are configured to operate under a low shear rate of about 1000 s−1 to about 4000 s−1. ### Claim 8 (depends on 1) The cell retention device of claim 1, wherein the hollow-fiber filter has filter capacity of about 1000 to about 10,000 L/M2. ### Claim 9 (depends on 1) The cell retention device of claim 1, wherein the cell retention device is configured to operate in conjunction with a perfusion culture vessel. ### Claim 10 (depends on 1) The cell retention device of claim 1, wherein the hollow-fiber filter is made out of ceramic, polymer or metallic materials. ### Claim 11 (depends on 1) The cell retention device of claim 1, wherein the hollow-fiber filter operates for up to 35 days without being clogged or losing more than 10% of its product sieving ability. ### Claim 12 (depends on 10) The cell retention device of claim 10, wherein the hollow-fiber filter operates in TTF or ATF modes under a low shear rate of 2000 s−1 or less or a perfusion flow rate of equal or greater than 4000 Um2. ### Claim 13 (depends on 10) The cell retention device of claim 10, wherein the hollow-fiber filter is in a housing that facilitates the collection of filtrates. ### Claim 14 A method for harvesting recombinant protein products from a perfusion culture vessel, said method comprising the steps of: a. subjecting cell culture fluid of a perfusion culture vessel to a cell retention device to be filtered, wherein the cell culture fluid comprises cells and recombinant protein products produced by said cells and wherein the cell retention device comprises a hollow-fiber filter having an average pore size ranging from about 0.5 to about 20 μm; b. collecting filtrate from the cell retention device, wherein the filtrate comprises the recombinant protein products; c. Recirculating the filtered cell culture fluid to the perfusion culture vessel. ### Claim 15 (depends on 14) The method of claim 14, wherein the cell retention device is external to the perfusion cell culture vessel. ### Claim 16 (depends on 14) The method of claim 14, wherein the hollow-fiber filter filters the cell culture fluid by tangential-flow filtration (TFF) or alternating tangential flow filtration (ATF). ### Claim 17 (depends on 14) The method of claim 14, wherein the hollow-fiber filter has an average pore size selected from about 5 to about 8 micron, 5 μm to 15 μm, 5.2 μm to 12 μm, 5.5 μm to 8 μm, 5.2 μm to 7.7 μm, 5 μm, 6 μm, 7 μm, 8 μm, 9 μm, 10 μm, 11 μm, 12 μm, 13 μm, 15 μm, or any size above 5 μm that could retain the viable cells while allowing dead cells, cellular debris or macromolecules to pass through the filter. ### Claim 18 (depends on 14) The method of claim 14, wherein the hollow-fiber filter has an average pore size that is equal or greater than 5 micron but less than the size of the cells. ### Claim 19 (depends on 14) The method of claim 14, wherein the hollow-fiber filter has an average pore size greater than the size of the cells by 5 μm or less. ### Claim 20 (depends on 14) The method of claim 14, where in the hollow-fiber filter has an average pore size that is about the size of the cells. ### Claim at position 21 21-46. (canceled)