EP3801920A1 - Système centrifuge pour séparer des cellules en suspension - Google Patents

Système centrifuge pour séparer des cellules en suspension

Info

Publication number
EP3801920A1
EP3801920A1 EP19815510.3A EP19815510A EP3801920A1 EP 3801920 A1 EP3801920 A1 EP 3801920A1 EP 19815510 A EP19815510 A EP 19815510A EP 3801920 A1 EP3801920 A1 EP 3801920A1
Authority
EP
European Patent Office
Prior art keywords
centrate
concentrate
pump
opening
chamber
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
EP19815510.3A
Other languages
German (de)
English (en)
Other versions
EP3801920A4 (fr
Inventor
S Kessler
T Marro
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Pneumatic Scale Corp
Original Assignee
Pneumatic Scale Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Pneumatic Scale Corp filed Critical Pneumatic Scale Corp
Publication of EP3801920A1 publication Critical patent/EP3801920A1/fr
Publication of EP3801920A4 publication Critical patent/EP3801920A4/fr
Pending legal-status Critical Current

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B04—CENTRIFUGAL APPARATUS OR MACHINES FOR CARRYING-OUT PHYSICAL OR CHEMICAL PROCESSES
    • B04B—CENTRIFUGES
    • B04B5/00—Other centrifuges
    • B04B5/04—Radial chamber apparatus for separating predominantly liquid mixtures, e.g. butyrometers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B04—CENTRIFUGAL APPARATUS OR MACHINES FOR CARRYING-OUT PHYSICAL OR CHEMICAL PROCESSES
    • B04B—CENTRIFUGES
    • B04B5/00—Other centrifuges
    • B04B5/04—Radial chamber apparatus for separating predominantly liquid mixtures, e.g. butyrometers
    • B04B5/0442—Radial chamber apparatus for separating predominantly liquid mixtures, e.g. butyrometers with means for adding or withdrawing liquid substances during the centrifugation, e.g. continuous centrifugation
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B04—CENTRIFUGAL APPARATUS OR MACHINES FOR CARRYING-OUT PHYSICAL OR CHEMICAL PROCESSES
    • B04B—CENTRIFUGES
    • B04B11/00—Feeding, charging, or discharging bowls
    • B04B11/04—Periodical feeding or discharging; Control arrangements therefor
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D21/00—Separation of suspended solid particles from liquids by sedimentation
    • B01D21/26—Separation of sediment aided by centrifugal force or centripetal force
    • B01D21/262—Separation of sediment aided by centrifugal force or centripetal force by using a centrifuge
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D21/00—Separation of suspended solid particles from liquids by sedimentation
    • B01D21/30—Control equipment
    • B01D21/32—Density control of clear liquid or sediment, e.g. optical control ; Control of physical properties
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B04—CENTRIFUGAL APPARATUS OR MACHINES FOR CARRYING-OUT PHYSICAL OR CHEMICAL PROCESSES
    • B04B—CENTRIFUGES
    • B04B11/00—Feeding, charging, or discharging bowls
    • B04B11/02—Continuous feeding or discharging; Control arrangements therefor
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B04—CENTRIFUGAL APPARATUS OR MACHINES FOR CARRYING-OUT PHYSICAL OR CHEMICAL PROCESSES
    • B04B—CENTRIFUGES
    • B04B11/00—Feeding, charging, or discharging bowls
    • B04B11/08—Skimmers or scrapers for discharging ; Regulating thereof
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B04—CENTRIFUGAL APPARATUS OR MACHINES FOR CARRYING-OUT PHYSICAL OR CHEMICAL PROCESSES
    • B04B—CENTRIFUGES
    • B04B11/00—Feeding, charging, or discharging bowls
    • B04B11/08—Skimmers or scrapers for discharging ; Regulating thereof
    • B04B11/082—Skimmers for discharging liquid
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B04—CENTRIFUGAL APPARATUS OR MACHINES FOR CARRYING-OUT PHYSICAL OR CHEMICAL PROCESSES
    • B04B—CENTRIFUGES
    • B04B13/00—Control arrangements specially designed for centrifuges; Program control of centrifuges
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B04—CENTRIFUGAL APPARATUS OR MACHINES FOR CARRYING-OUT PHYSICAL OR CHEMICAL PROCESSES
    • B04B—CENTRIFUGES
    • B04B7/00—Elements of centrifuges
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B04—CENTRIFUGAL APPARATUS OR MACHINES FOR CARRYING-OUT PHYSICAL OR CHEMICAL PROCESSES
    • B04B—CENTRIFUGES
    • B04B7/00—Elements of centrifuges
    • B04B7/08—Rotary bowls
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • 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
    • C12M47/00—Means for after-treatment of the produced biomass or of the fermentation or metabolic products, e.g. storage of biomass
    • C12M47/02—Separating microorganisms from the culture medium; Concentration of biomass
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D2221/00—Applications of separation devices
    • B01D2221/10—Separation devices for use in medical, pharmaceutical or laboratory applications, e.g. separating amalgam from dental treatment residues
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B04—CENTRIFUGAL APPARATUS OR MACHINES FOR CARRYING-OUT PHYSICAL OR CHEMICAL PROCESSES
    • B04B—CENTRIFUGES
    • B04B5/00—Other centrifuges
    • B04B5/04—Radial chamber apparatus for separating predominantly liquid mixtures, e.g. butyrometers
    • B04B5/0442—Radial chamber apparatus for separating predominantly liquid mixtures, e.g. butyrometers with means for adding or withdrawing liquid substances during the centrifugation, e.g. continuous centrifugation
    • B04B2005/0464—Radial chamber apparatus for separating predominantly liquid mixtures, e.g. butyrometers with means for adding or withdrawing liquid substances during the centrifugation, e.g. continuous centrifugation with hollow or massive core in centrifuge bowl

Definitions

  • Figure 13 is schematic view of a portion of a third example embodiment of a continuous concentrate discharge system, with a throttle mechanism for the centripetal pumps.
  • Figure 15 is an isometric view of the feed accelerator of Figure 14.
  • Figure 21 is a cross-sectional schematic view of an alternative continuous centrate and concentrate discharge centrifuge system.
  • Figure 24 is a schematic view of the control system for an exemplary continuous centrate and concentrate discharge centrifuge system.
  • Figure 27 is a cross-sectional view of an exemplary upper portion of a single use structure that includes vanes in the centrate pump chamber and the concentrate pump chamber for purposes of controlling the radial position of the air/liquid interface.
  • Figure 31 is a schematic view of an exemplary system for controlling a centrifuge system including centrate flow back pressure control.
  • the core 1510 and upper flange 1300 may comprise a single component, with a lower flange 1200 comprising a separate component, or the core 1510 and lower flange 1200 may comprise a single component with the upper flange 1300 comprising a separate component.
  • centrate pump chamber 1420 may vary.
  • Chamber 1420 will generally be an axially symmetric chamber near the upper end of the core structure 1500 which is in fluid connection with the separation chamber 1550 via holes or slits 1530 which extend from adjacent the exterior of the core 1515 into the centrate pump chamber 1420.
  • centrate pump chamber 1420 may be located in a recess within chamber 1550.
  • fins 1630 perpendicularly from the inner surface 1620 of the cap portion 1610.
  • six (6) fins 1630 are illustrated, but other embodiments may include fewer or more fins 1630.
  • fins 1630 form part of the inner face of cap 1620, but in other embodiments may comprise the upper surface 1620 of pump chamber 1420, which may take a form other than cap 1610.
  • fins 1630 are located above the paring disks 1410 of the centripetal pump 1400 in the chamber 1420. These fins 1630 transmit the angular rotation of the centrifuge 1000 to the centrate within in the pump chamber 1420.
  • FIG. 6 shows an exemplary embodiment of an improved core structure 1500 for use in high turbidity feeds.
  • Core structure 1500 includes a core 1510, upper flange 1300, and lower flange 1200.
  • Core 1510 has a cylindrical central cavity 1520 adapted to permit feed tube 2100 to be inserted into the central cavity 1520.
  • the distance from the central axis 1525 to the exterior of core 1515 (the core width, represented by dashed line 6000 in Figure 6) is larger than the corresponding distance in the embodiment illustrated in Figure 3.
  • the larger diameter core 1510 decreases the depth (represented by dashed line 6010) of the separation chamber 1550, making centrifuge 1000 operate as a shallow pool centrifuge.
  • pump chamber 4400 may have a different shape than that illustrated in Figures 10-12, but will generally be an axially symmetric chamber near the upper end of the core structure 1500 which is in fluid connection with the separation chamber 1550. As with pump chamber 1400, the pump chamber may be partially or entirely recessed within core structure 1500. If a centrate pump chamber 1400 is present near the upper end of the core structure 1500, the cell concentrate pump chamber 4400 will generally be located above it. A pump chamber 4400, for the removal of cell concentrate, will be in fluid connection with separation chamber 1550 via holes or slits 4540 which extend from adjacent the outer upper wall of separation chamber 1550, in order to collect the heavier cell concentrate which is urged there by centrifugal forces.
  • centrate pump 1400 is located at the base of the centrifuge 1000.
  • a centrate well 1555 is created between the pump chamber 1420 and the flexible liner 1100.
  • Holes 1530 extend from the core 1510, below the pump chamber 1420, into the centrate well 1555.
  • holes 1540 extend from the separation chamber 1550, adjacent the exterior surface 1515 of the core 1510, into the pump chamber 1420 to permit the centrate to be removed using centrate pump 1400.
  • Holes 4540 may also extend between the separation chamber 1550, adjacent its outer upper surface, into pump chamber 4420 to permit cell concentrate to flow into pump chamber 4420 to be removed using centripetal pump 4400.
  • feed mechanism 2000 also includes an additional pathway for the removal of cells, or cell concentrate.
  • a diluent such as sterile water or a buffer
  • a diluent pump 5150 may be pumped into the concentrate pump chamber 4420 through the diluent pathway 5000 using a diluent pump 5150 in order to cut the viscosity of the concentration.
  • a diluent pump 5150 may be controlled by an automated controller (not shown) responsive to a concentration sensor 4430 located in the concentrate discharge connection 2500.
  • the controller may be programmed to start, stop, or modify the pump rate for both diluent addition and concentrate removal responsive to the particle concentration in the concentrate, either independently, responsive to a concentration sensor 4430, in conjunction with a standard feed/discharge cycle, or as a combination.
  • the centrifuge includes a rotatable bowl 82.
  • the flow rate of the pump 120 may be a set value initially or alternatively may be varied depending on particular operating conditions that are determined through control circuit operation during the process.
  • the operation of the centrate discharge pump is represented by a step 150.
  • the exemplary single use structure shown in Figure 21 further includes a lower rigid or semi-rigid disc shape portion 232.
  • the rigid or semi-rigid material operates to maintain its shape during operation.
  • lower disc shape portion 232 has a conical shape and is in operative attached connection with the lower end of core 200 by vertically extending wall portions or other structures.
  • a plurality of angularly spaced fluid passages 234 extend between the upper surface of disc shape portion 232 and the radially outward lower portion of the core.
  • Fluid passages 232 extend radially outward and upwardly relative to the bottom of the second axial end 192, and enable the cells in the cell culture batch material that enters the interior area 186 through the opening 190 in feed tube 184, to pass radially outwardly and upwardly into the separation chamber 224.
  • At least one annular resilient seal 236 extends in sealing engagement operatively between the outer surface of the concentrate discharge tube 220 and the upper disc shape portion 194.
  • the at least one seal 236 maintains an air tight seal in a manner like that previously discussed, so that an air pocket may be maintained in the interior area 186 during cell processing so as to isolate the seal from the cell culture batch material being processed.
  • the air pocket maintained within the interior area of the single use structure is configured such that the centrate centripetal pump 208 and the concentrate centripetal pump 216 remain in fluid communication with the cell culture batch material.
  • a positive pressure may be maintained within the interior area so as to assure that an air pocket is present to adequately isolate the at least one seal 236 from the cell culture batch material being processed.
  • other approaches may be utilized for purposes of maintaining the isolation of the seal from the material being processed.
  • the vanes 246 extend upwardly from a bottom portion of disc shape portion 242 and at least some are in operative engagement with the core at radially outer portions thereof. In the exemplary arrangement the vanes 246 accelerate the cell culture batch to facilitate movement and separation within the interior area of the single use structure.
  • the centrate discharge tube 212 is in fluid connection with a centrate discharge line 262.
  • a centrate optical density sensor 264 is in operative connection with an interior area of the centrate discharge line 262.
  • the centrate optical density sensor is an optical sensor that is operative to determine the density of cells currently in the centrate passing from the single use structure. This is accomplished in the exemplary embodiment by measuring the reduction in intensity of light output by an emitter that is received by a receiver disposed from the emitter and which has at least a portion of the centrate flow passing there-be tween. The amount of light from the emitter that is received by the receiver decreases with the increasing density of cells in the centrate.
  • the concentrate discharge tube 220 is in operative connection with a concentrate discharge line 268.
  • a concentrate optical density sensor 270 is in operative connection with at least a portion of the interior area of the concentrate discharge line 268.
  • the exemplary concentrate optical density sensor may operate in a manner like the centrate optical density sensor previously discussed.
  • the concentrate optical density sensor may include different structures or properties, and that different types of cell density sensors may be used in other exemplary embodiments.
  • the concentrate discharge line 268 is in operative connection with a concentrate pump 272.
  • the concentrate pump 272 may include a peristaltic pump or other variable rate pump suitable for pumping the concentrate without causing damage thereto.
  • these structures and components are exemplary and alternative systems may include different or additional components.
  • the controller After the speed of the concentrate pump 272 is increased in step 288 the controller then operates responsive to the sensor 264 to determine in a step 290 if the optical density of the centrate is still above the set point a set time after the incremental increase in the speed (flow) of the concentrate pump. If it is, then the controller continues to monitor the optical density of the centrate until it is not higher than the set point.
  • the instructions include a set time period during which the centrate optical density must not be higher than the set point before the concentrate pump speed controller determines that the adjustment to the base speed is sufficient to maintain the optical density of the centrate at a level that is at or below the desired set point.
  • the lower concentrate centripetal pump chamber surface 334 extends radially outward from a lower concentrate centripetal pump chamber opening 338.
  • the lower concentrate centripetal pump chamber opening corresponds in size to and is continuous with the upper centrate centripetal pump chamber opening 324.
  • the feed tube 184 and the centrate discharge tube 212 extend through the lower concentrate centripetal pump chamber opening 338.
  • a pressure control valve 368 is in fluid communication with the source of pressurized air 362.
  • Control valve 368 is also in operative connection with the controller 274.
  • the control valve 368 is controlled to selectively apply precise pressure to the air tube 354 and the air pocket within the upper portion of the single use structure 352.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Biotechnology (AREA)
  • Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Zoology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Microbiology (AREA)
  • Sustainable Development (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Biomedical Technology (AREA)
  • Centrifugal Separators (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

La présente invention concerne un appareil pour séparer un matériau de suspension cellulaire en centrat et concentré, qui comprend une structure à usage unique (178, 240, 250) positionnée amovible dans une cavité dans un bol centrifuge rotatif à paroi solide (172). Le bol et les parties de la structure à usage unique tournent autour d'un axe (174). Un tube d'alimentation d'entrée fixe (184), un tube d'évacuation de centrat (212) et un tube d'évacuation de concentré (230) s'étendent le long de l'axe de la structure rotative à usage unique. Une pompe centripète (208) pour le centrat est en communication fluidique avec le tube d'évacuation de centrat. Une pompe centripète (216) pour le concentré est en communication fluidique avec le tube d'évacuation de concentré. Un dispositif de commande (274) fonctionne en réponse à des capteurs (264, 270) dans des lignes d'évacuation de concentré et de centrat respectives (262, 268), pour commander les débits d'une pompe de concentré (272) et d'une pompe de centrat (266) pour produire des flux de sortie de concentré de cellules et un centrat généralement exempt de cellules.
EP19815510.3A 2018-06-08 2019-06-06 Système centrifuge pour séparer des cellules en suspension Pending EP3801920A4 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201862682376P 2018-06-08 2018-06-08
PCT/US2019/035855 WO2019236895A1 (fr) 2018-06-08 2019-06-06 Système centrifuge pour séparer des cellules en suspension

Publications (2)

Publication Number Publication Date
EP3801920A1 true EP3801920A1 (fr) 2021-04-14
EP3801920A4 EP3801920A4 (fr) 2022-07-13

Family

ID=68770662

Family Applications (1)

Application Number Title Priority Date Filing Date
EP19815510.3A Pending EP3801920A4 (fr) 2018-06-08 2019-06-06 Système centrifuge pour séparer des cellules en suspension

Country Status (8)

Country Link
EP (1) EP3801920A4 (fr)
JP (1) JP7336467B2 (fr)
KR (2) KR102568313B1 (fr)
CN (2) CN115254458A (fr)
AU (2) AU2019280856B2 (fr)
CA (1) CA3102600C (fr)
MX (2) MX2020011898A (fr)
WO (1) WO2019236895A1 (fr)

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US11878312B2 (en) * 2011-11-21 2024-01-23 Pneumatic Scale Corporation Centrifuge system for separating cells in suspension
US12350686B2 (en) * 2011-11-21 2025-07-08 Pneumatic Scale Corporation Centrifuge system for separating cells in suspension
US11065629B2 (en) * 2011-11-21 2021-07-20 Pneumatic Scale Corporation Centrifuge system for separating cells in suspension
US11957998B2 (en) * 2019-06-06 2024-04-16 Pneumatic Scale Corporation Centrifuge system for separating cells in suspension
AU2021335131A1 (en) * 2020-08-22 2023-04-06 Sunil Mehta An automated centrifugation device and methods to continuously separate components from different mixtures
CN112798393A (zh) * 2021-02-01 2021-05-14 中博瑞康（北京）生物技术有限公司 一种大体积生物细胞液浓缩洗涤系统及其方法
CN114682397B (zh) * 2022-03-28 2024-03-15 浙江大学 锥形液液轴向离心分离器及分离监控装置
IL316457A (en) * 2022-04-07 2024-12-01 Mirror Biologics Inc Artificial lymph node bioreactor

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Also Published As

Publication number Publication date
KR102568313B1 (ko) 2023-08-18
MX2022003223A (es) 2022-04-12
KR20210018796A (ko) 2021-02-18
CN115254458A (zh) 2022-11-01
CA3102600A1 (fr) 2019-12-12
CN112236236A (zh) 2021-01-15
AU2022204733A1 (en) 2022-07-21
WO2019236895A1 (fr) 2019-12-12
KR102568314B1 (ko) 2023-08-18
AU2019280856B2 (en) 2022-06-30
KR20220039841A (ko) 2022-03-29
JP7336467B2 (ja) 2023-08-31
AU2022204733B2 (en) 2024-07-04
JP2021526957A (ja) 2021-10-11
BR112020025083A2 (pt) 2021-03-23
CA3102600C (fr) 2024-06-11
AU2019280856A1 (en) 2020-12-17
EP3801920A4 (fr) 2022-07-13
MX2020011898A (es) 2021-01-15

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