# US 2014/0190888 A1 · Methods, Systems and Devices for Separating Tumor Cells > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2014/0190888 A1 - Document ID: US20140190888A1 - Status: Published application - Kind: A1 - Application number: 14/163,344 - Filed: 2014-01-24 - Published: 2014-07-10 - Earliest claimed: 2010-03-31 - Assignees: Viatar LLC - Applicants: Viatar LLC - Inventors: Cornelis Johannes Maria van RIJN; Jacob BAGGERMAN; Ilan REICH - Web page: https://patentgrep.com/patent/US20140190888A1 ## CPC - A61M 1/3633: {Blood component filters, e.g. leukocyte filters} - A61M 1/34: Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration - A61M 1/3403: {Regulation parameters} - B01D 63/087: {Single membrane modules} - B01D 67/0034: {by micromachining techniques, e.g. using masking and etching steps, photolithography} - G01N 33/491: {by separating the blood components (G01N15/05 takes precedence)} - G01N 33/5759: {involving compounds localised on the membrane of tumour or cancer cells} - A61M 2205/3331: Pressure; Flow - A61M 2205/3334: Measuring or controlling the flow rate - A61M 2205/50: with microprocessors or computers - B01D 2325/021: Pore shapes - B01D 2325/04: Characteristic thickness - A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)} - 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) - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) ## Abstract Embodiments of the present disclosure are directed to the separation/capture of specific cells and/or contaminants, as well as the determination, monitoring, and treatment of cancer. Moreover, some embodiments are directed to methods, systems and devices for removing cancer, stem and/or tumor cells in vivo or in vitro from a bodily fluid to prevent or impede the proliferation of a cancer. Some embodiments provide a blood-compatible filter comprising, for example, a membrane provided with a number of openings (preferably precise) which yield minimal detrimental effect both quantitatively and qualitatively on cells present in the bodily fluid during the separation process. For example, in some embodiments, a majority percentage of circulating tumor cells are captured by a filter while a majority percentage of leukocytes, for example, are allowed to pass, where the passed leukocytes retain their vitality. ## Claims ### Claim at position 1 1-45. (canceled) ### Claim 46 A method of separating circulating tumor cells from blood cells in a bodily fluid using a filter membrane that has a first side, a second side opposite the first side, and a plurality of pores extending from the first side to the second side, the blood cells including leukocytes, the method comprising: contacting the bodily fluid with the first side of the filter membrane; and applying a pressure differential across the filter membrane such that at least a majority of leukocytes in the bodily fluid pass through the pores to produce a filtrate at the second side of the filter and such that at least 75% of the circulating tumor cells are retained at the first side of the filter membrane, wherein the leukocytes that pass through the filter membrane retain their vitality, each of the pores of the filter membrane has a minimum dimension, in a plane of the first side, of between 3 μm and 8 μm, the filter membrane has a thickness in a direction from the first side to the second side that is less than the minimum dimension of each pore. ### Claim 47 (depends on 46) The method of claim 46, further comprising returning the filtrate and blood cells therein to a patient. ### Claim 48 (depends on 46) The method of claim 46, wherein the blood cells at the first side and in the filtrate are non-lysed whole cells. ### Claim 49 (depends on 46) The method of claim 46, wherein the pressure differential is less than or equal to 12 Torr. ### Claim 50 (depends on 46) The method of claim 46, wherein the blood cells include red blood cells, and the applying a pressure differential is such that hemolysis of the red blood cells after passing through the filter membrane is less than 1%. ### Claim 51 (depends on 46) The method of claim 46, wherein each of the pores has a circular opening in the plane of the first side, and the minimum dimension comprises a diameter of the circular opening. ### Claim 52 (depends on 46) The method of claim 46, wherein each of the pores comprises a slit in the plane of the first side, with a ratio of length to minimum dimension of each slit being greater than one with a shape that is either rectangular or elliptical and a width between 3 and 8 microns. ### Claim 53 (depends on 46) The method of claim 46, wherein the minimum dimensions of the pores differ by no more than 0.5 μm from each other. ### Claim 54 (depends on 46) The method of claim 46, wherein the filter membrane thickness is between 5% and 25% of the minimum dimension of each pore. ### Claim 55 (depends on 46) The method of claim 46, wherein the filter membrane thickness is less than 2.5 μm. ### Claim 56 (depends on 46) The method of claim 46, wherein the applying a pressure differential is such that at least a predefined percentage of the leukocytes in the bodily fluid at the first side are passed through the filter membrane to the second side where the predefined percentage is greater than about 75%, greater than about 80%, greater than about 85%, greater than about 90%, greater than about 95%, greater than about 99%, or greater than about 99.9%. ### Claim 57 (depends on 46) The method of claim 46, wherein the applying a pressure differential is such that a flow rate through the filter membrane is at least 1 ml/min per cm2 of surface area of the first side of the filter membrane. ### Claim 58 (depends on 46) The method of claim 46, wherein the applying a pressure differential is such that a flow rate through the filter membrane is between 1 and 10 ml/min per cm2 of surface area of the first side of the filter membrane ### Claim 59 (depends on 46) The method of claim 46, further comprising monitoring a first pressure at the first side and a second pressure at the second side, wherein the applying is responsive to the monitoring so as to maintain a constant pressure differential across the filter membrane. ### Claim 60 (depends on 46) The method of claim 46, wherein the filter membrane comprises a base material having a Young's Modulus greater than 10 GPa and a yield strength greater than 1 GPa. ### Claim 61 (depends on 46) The method of claim 46, wherein the coating is less than 500 nm thick. ### Claim 62 (depends on 46) The method of claim 46, wherein the bio-compatible coating comprises one or more zwitterionic polymeric materials, and the zwitterionic polymeric materials comprise phosphorylcholine, sulfobetaine, carboxybetaine, amine-N-oxide sub groups, or combinations thereof. ### Claim 63 (depends on 46) The method of claim 46, further comprising covalently linking the circulating tumor cells to antibodies attached to a surface. ### Claim 64 (depends on 63) The method of claim 63, wherein the antibodies are covalently linked to a surface of the filter membrane at said first side. ### Claim 65 (depends on 46) The method of claim 46, wherein the filter membrane has a coating of, or is formed of, a biocompatible or blood-compatible material. ### Claim 66 (depends on 46) The method of claim 46, wherein the filter membrane has a coating of a biocompatible or blood-compatible material. ### Claim 67 (depends on 46) The method of claim 46, wherein the filter membrane has a coating of, or is formed of, a biocompatible or blood-compatible material. ### Claim 68 A method comprising: contacting with a first side of a filter membrane a fluid containing blood cells and circulating tumor cells from a patient, the blood cells comprising non-lysed whole cells, the filter membrane having a second side opposite the first side and a plurality of pores extending from the first side to the second side, each of the pores having a minimum dimension, in a plane of the first side, of between 3 μm and 8 μm, the filter membrane having a thickness in a direction from the first side to the second side that is less than the minimum dimension of each pore, applying a pressure differential across the filter membrane such that blood cells pass through the pores to produce a filtrate at the second side of the filter and such that at least 75% of the circulating tumor cells are retained at the first side of the filter membrane; and returning the blood cells without the retained circulating tumor cells to the patient, the blood cells retaining their vitality after the applying a pressure differential. ### Claim 69 (depends on 68) The method of claim 68, wherein the blood cells from the patient include leukocytes and the applying a pressure differential is such that at least a majority of leukocytes at the first side pass through the pores and retain their vitality. ### Claim 70 (depends on 68) The method of claim 68, wherein the filter membrane has a coating of, or is formed of, a biocompatible or blood compatible material. ### Claim 71 (depends on 68) The method of claim 68, wherein the filter membrane has a coating of a biocompatible or blood compatible material. ### Claim 72 (depends on 68) The method of claim 68, wherein the blood cells include red blood cells, and the applying a pressure differential is such that hemolysis of the red blood cells after passing through the filter membrane is less than 1%. ### Claim 73 (depends on 68) The method of claim 68, wherein the filter membrane thickness is less than 2.5 μm. ### Claim 74 (depends on 68) The method of claim 68, wherein the applying a pressure differential is such that a flow rate through the filter membrane is at least 1 ml/min per cm2 of surface area of the first side of the filter membrane. ### Claim 75 (depends on 68) The method of claim 68, wherein the bio-compatible coating comprises one or more zwitterionic polymeric materials, and the zwitterionic polymeric materials comprise phosphorylcholine, sulfobetaine, carboxybetaine, amine-N-oxide sub groups, or combinations thereof. ### Claim 76 (depends on 68) The method of claim 68, further comprising covalently linking the circulating tumor cells to antibodies attached to a surface. ### Claim 77 (depends on 68) The method of claim 68, wherein the antibodies are covalently linked to a surface of the filter membrane at said first side. ### Claim 78 (depends on 68) The method of claim 68, wherein the applying a pressure differential is such that a flow rate through the filter membrane is between 1 and 10 ml/min per cm2 of surface area of the first side of the filter membrane.