EP0580802A1 - Appareil destine a diffuser du gaz dans un liquide - Google Patents

Appareil destine a diffuser du gaz dans un liquide

Info

Publication number
EP0580802A1
EP0580802A1 EP92917314A EP92917314A EP0580802A1 EP 0580802 A1 EP0580802 A1 EP 0580802A1 EP 92917314 A EP92917314 A EP 92917314A EP 92917314 A EP92917314 A EP 92917314A EP 0580802 A1 EP0580802 A1 EP 0580802A1
Authority
EP
European Patent Office
Prior art keywords
liquid
container
walls
gas
diffusing gas
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.)
Withdrawn
Application number
EP92917314A
Other languages
German (de)
English (en)
Inventor
David Butz
Eric Berry
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.)
Costar Corp
Original Assignee
Costar 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 Costar Corp filed Critical Costar Corp
Publication of EP0580802A1 publication Critical patent/EP0580802A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F23/00—Mixing according to the phases to be mixed, e.g. dispersing or emulsifying
    • B01F23/20—Mixing gases with liquids
    • B01F23/23—Mixing gases with liquids by introducing gases into liquid media, e.g. for producing aerated liquids
    • B01F23/232—Mixing gases with liquids by introducing gases into liquid media, e.g. for producing aerated liquids using flow-mixing means for introducing the gases, e.g. baffles
    • B01F23/2321—Mixing gases with liquids by introducing gases into liquid media, e.g. for producing aerated liquids using flow-mixing means for introducing the gases, e.g. baffles by moving liquid and gas in counter current
    • B01F23/23211—Mixing gases with liquids by introducing gases into liquid media, e.g. for producing aerated liquids using flow-mixing means for introducing the gases, e.g. baffles by moving liquid and gas in counter current the liquid flowing in a thin film to absorb the gas

Definitions

  • This invention relates to apparatus which enhances the diffusion of a gas into a liquid and more particularly to apparatus, such as oxygenators and aerators, for diffusing oxygen into a liquid.
  • an oxygenation method commonly used in cell culturing systems to introduce oxygen into liquid cell growth medium is to place the liquid medium in a long cylindrical container such as a bottle.
  • the container is only partially filled with the liquid so that a gas/liquid interface is formed. Air is introduced into the container so that oxygen diffuses into the growth medium at the interface.
  • the container is slowly rotated around its long axis by a mechanical device in order to agitate the gas/liquid interface.
  • One obvious problem with such an arrangement is that it is not a continuous process and the medium must be continually removed and replaced in the containers.
  • the nutrient supply must be periodically replenished through the labor-intensive process of dismounting, opening and reclosing the bottle, thereby further exposing the contents to contamination.
  • the second method of enhancing gas diffusion in a continuous system is to increase the surface area to volume ratio of the liquid by spreading the liquid in a thin film in an atmosphere containing the gas.
  • a common method of achieving a thin liquid film is to use stacked trays. Each of the trays holds a thin layer of liquid and as the liquid flows through the tray, it spills over to the next lower tray in the stack. The process continues until the liquid reaches the bottom of. the tray stack.
  • the effective surface area of the tray stack can therefore be a large multiple of the surface area of each tray.
  • Still other gas diffusion arrangements utilize rotating parts such as disks or cones -mounted in an atmosphere containing the gas. Liquid introduced onto such a moving part forms a thin film due to the rotation.
  • This latter apparatus can operate continuously, but requires mechanical seals to seal the moving parts and is thus prone to seal failures, contamination, and high maintenance costs.
  • the liquid is applied to a spreader plate which extends towards, and forms a narrow gap with, the container walls.
  • the liquid spreads out in a thin film across the spreader plate, fills the plate/wall gap and flows down along the container walls and exits the container at the container bottom.
  • the film on the container walls is sufficiently thin that gaseous diffusion is greatly enhanced.
  • the device is suitable for use in the continuous application since the liquid can be continuously introduced at one end of the container and withdrawn at the other. Sufficient space is available in the container to mount probes to monitor gas concentration and other parameters.
  • Figure 1 is a block schematic diagram of an illustrative continuous cell culture system in which the gas diffusion apparatus of the present invention- can be used.
  • Figure 2 is an exploded perspective view of one embodiment of the inventive gas diffusion apparatus.
  • Figure 3 is a partial cross-sectional diagram of the embodiment shown in exploded form in Figure 2.
  • Figure 4 is a partial cross-sectional diagram of the embodiment shown in Figures 2 and 3 illustrating the liquid flow path.
  • Figure 5 is a partial cross-sectional diagram of an alternative embodiment of the invention.
  • Figure 6 is a cross-sectional diagram of a first alternative embodiment of the spreader plate/wall area of the inventive gas diffusion apparatus.
  • Figure 7 is a cross-sectional diagram of a second alternative embodiment of the spreader plate/wall area of the inventive gas diffusion apparatus.
  • Figure 8 is a cross-sectional diagram of a third alternative embodiment of the spreader plate/wall area of the inventive gas diffusion apparatus.
  • Figure 9 is a cross-sectional diagram of a fourth alternative embodiment of the spreader plate/wall area of the inventive gas diffusion apparatus.
  • Figure 10 is a cross-sectional diagram of a fifth alternative embodiment of the spreader plate/wall area of the inventive gas diffusion apparatus.
  • Figure 11 is a cross-sectional diagram of a sixth alternative embodiment of the spreader plate/wall area of the inventive gas diffusion apparatus.
  • the present invention can be used in many applications in which it is desired to diffuse gas into a liquid, one such application for which the invention is particularly suited is a continuous cell culture system in which oxygen must be diffused into a continuously-flowing liquid cell culture medium in order to induce enhanced cell growth.
  • the inventive gas diffusion apparatus can be provided as part of a continuous cell culture system 80 as shown in Figure 1.
  • System 80 is a closed-loop system which incorporates a cell culture vessel 120, a gas diffusion apparatus and reservoir 110 which may illustratively be the inventive apparatus and a plurality of fluid conduits which convey a conventional cell culture medium between the various elements of the system.
  • a cell culture vessel 120 may, for example, be a readily-available, standard biological medium for cell culture.
  • Cell culturing actually takes place in culture vessel 120 which is supplied with replacement liquid medium from apparatus 110 via conduit 88.
  • oxygen is added by means of gas diffusion.
  • outlet port 84 of apparatus 110 is connected to the inlet port 86 of the culture vessel 120 via fluid supply conduit 88.
  • Outlet port 90 of cell culture vessel 120 is, in turn, in fluid communication with an inlet port 92 of apparatus 110 via fluid return conduit 94.
  • a pump 96 is positioned along fluid supply conduit 88 to continuously pump fluid medium from apparatus 110 through culture vessel 120 and back to apparatus 110.
  • a nutrient supply line 98 is connected to the fluid supply conduit 88 between pump 96 and culture vessel 120 so that additional medium and nutrients may be added to fluid supply conduit 88.
  • a separate pump 100 is provided for pumping the nutrients into the fluid supply conduit 88 via supply line 98.
  • Apparatus 110 is also provided with a product withdrawal conduit 102 connected to a withdrawal pump 104 for removing fluid medium and cultured cells downstream from the culture vessel, preferably continuously.
  • Gas diffusion apparatus 110 is provided for continuous resupply of oxygen and for carbon dioxide removal or addition to the culture medium.
  • gas diffusion apparatus 110 may include probes, such as gas and temperature probes (not shown), which are connected, via electrical leads 114, to a controller 112 which can control the concentration of oxygen, carbon dioxide and other gases introduced into the diffusion apparatus as will hereinafter be described to automatically maintain the oxygen or carbon dioxide levels in the medium at a predetermined value.
  • An additional probe 106 may be provided on return conduit 94 in order to sense various conditions of the medium and cell mixture. This probe, in turn, may be connected to a control device 108 (or alternatively, control device 112) which device controls the various pumps for pH balancing the gas concentrations in the medium/cell mixture.
  • the system is designed so that fresh medium is constantly being introduced into the circulating system and the cultured cell product is continuously being withdrawn from the system at a rate of circulation determined by the control device 108.
  • An illustrative system such as that illustrated in Figure 1 is shown in detail in U.S. Patent Application Serial No. 07/361,141 entitled “Continuous High Density Cell Culture System” filed by Eric Berry on June 1, 1989, and licensed to the assignee of the present invention. Since the details of this system are not important for an understanding of the operation of the gas diffusion apparatus of the present invention, they will not be discussed further herein.
  • FIGs 2 and 3 illustrate one embodiment of the gas diffusion apparatus 110 constructed in accordance with the inventive principles disclosed herein.
  • the apparatus consists of a body 10 which is illustrated as having a cylindrical cross-section, however, other cross-sectional shapes may be used in accordance with the principles of the invention without altering the operation of the device.
  • Body 10 is fabricated from a material which is inert with respect to the liquid and gas flowing through it.
  • a suitable material is glass, but other materials may also be used.
  • the inner wall 11 of body 10 is specially treated so that it is "wettable" by the liquid flowing through the unit. In the case where body 10 is fabricated of glass, inner wall 11 may illustratively be plasma treated, acid cleaned or chemically etched.
  • Body 10 is provided with a cover 12 which is clamped to body 10 by means of a clamping ring 14.
  • Ring 14 is constructed with a plurality of threaded studs 16 mounted thereon which project through holes in cover 12 into nuts 18 which can be threaded onto the studs to attach cover 12 to ring 14.
  • a lip 13 of body 10 is captured between cover 12 and ring 14 to hold the assembly together.
  • An annular elastomeric cushion 20 is provided between clamping ring 14 and body lip 13 to prevent damage to body 10 should the nuts 18 be overtightened.
  • lip 13 is sealed to cover 12 by means of an O-ring 22 (shown in Fig. 3).
  • a spreader plate 24 Attached to the underside of cover 12 is a spreader plate 24, the purpose of which is to evenly distribute liquid flowing into the apparatus via inlet 26, as will hereinafter be described. Liquid moving through the apparatus leaves by means of exit 30.
  • Ring 14 is supported on a circular base 34 by means of three upright supports 36.
  • the ends of supports 36 have threaded holes 38 into which bolts 40 and 42 can be screwed to fasten supports 36 to ring 14 and base 34.
  • the diffusion apparatus may also be fitted with various probes which project through the cover 12 in order to monitor various conditions of the gas and liquid inside body 10.
  • a pH probe. 4 and an oxygen probe 46 are illustrated, however other probes and metering devices may also be inserted through cover 12.
  • Such probes may be sealed to cover 12 by means of clamp nuts 55 or O-rings 54 (as shown in Figure 3) or by other means so that they project into the body 10.
  • Gap 50 is of such a size that surface tension of the liquid causes it to bridge the gap and form a thin film along the inner wall 11 of body 10.
  • the width of gap 50 is dependent on the viscosity and composition of the liquid with which the apparatus operates and may illustratively be in the range of .020-.040 inches.
  • gap 50 may be approximately 0.020 inches when the diffusion apparatus is used with standard biological cell culture medium of the type that may be used in the cell culturing system shown in Figure 1.
  • the inner wall 11 of body 10 must be treated to make it "wettable" with respect to the liquid so that the liquid will flow down the wall in a thin, even layer. This treatment may be done in a conventional fashion, for example, by plasma treating, chemically etching or acid etching the inner surface 11 of a glass body 10.
  • the surface area of the liquid is effectively the area of the inner wall 11. This area can be -expanded by simply making the device diameter larger.
  • a large surf ce area/volume ratio is established due to the thin film 72 and the large surface area/volume ratio enhances diffusion in a known manner.
  • the liquid in the film 72 runs down the wall 11 into a collecting pool 74 which forms in the bottom part of body 10. -The liquid in the collecting pool then leaves by means of a lower exit 30.
  • Fig. 5 shows an alternative embodiment of the present invention in which the spreader plate 24 is fabricated in the shape of a disk rather than the annular shape shown in Figures 2 and 3. In this embodiment, pH probe 44 and oxygen probe 46 extend through both cover 12 and spreader plate 24.
  • Probes 44 and 46 are provided with adapter tubes 100 and 112, respectively.
  • Adapter tube 100 seals to the top of cover 12 by means of threaded ring 102 and O-ring 104.
  • a spacer 106 and O-ring 108 seal adapter tube 100 against the bottom of cover 12.
  • Spreader plate 24 is held against spacer 106 by threaded ring 110.
  • adapter tube 112 seals to the top of cover 12 by means of threaded ring 114 and O-ring 116.
  • a spacer 118 and O-ring 120 seal adapter tube 112 against the bottom of cover 12.
  • Spreader plate 24 is held against spacer 118 by threaded ring 122. In any case, the probes 44 and 46 must be sealed against spreader plate 44 so that no liquid runs down the probes.
  • liquid inlet 26 is located in the center of the apparatus; this location has the advantage that liquid introduced into inlet 26 will spread more uniformly over plate 24.
  • gas inlet 60 may be moved to the side and must also pass through plate 24.
  • Gas outlet 62 (not shown in Figure 5) may also be placed in an off-center location.
  • Figures 6-11 show alternative embodiments of the spreader plate edge/wall area 52 shown in Figure 3.
  • the edge of the spreader plate 24 is provided with a small dam 80 which aids in maintaining a thin "pool" of liquid on the top of spreader plate 24 so that the liquid will spread more evenly over plate 24.
  • liquid will spill over the top of dam 80 into gap 50 and the apparatus would perform substantially as previously described.
  • Figure 7 shows an additional embodiment in which dam 80 has been extended in height to form a narrow gap 82 between the upper end of dam 80 and cover 12.
  • gap 50 is less critical since gap 82 (which may be smaller than gap 50) controls the release of liquid from spreader plate 24.
  • FIG. 8 An additional embodiment is shown in Figure 8 in which a knife edge 84 is provided at the outer periphery of plate 24 to provide the clearance in gap 50 between plate 24 and the wall 11 of body 10.
  • FIG. 9 Another embodiment is shown in Figure 9 in which a drip lip 86 is provided along the outer periphery of the lower edge of spreader plate 24. Lip 86 prevents liquid passing through gap 50 from running along the bottom surface of plate 24 and dripping from plate 24 directly into the pool of liquid at the bottom of the apparatus.
  • FIG. 10 A further embodiment is shown in Figure 10, in which the radius of the curved upper lip of body 10 is increased and the diameter of plate 24 is increased from the point where body 10 is sealed by O-ring 22 located in circular notch 15 so that the outer edge of spreader plate 24 fits into the space between the curved wall portion and the cover 12 as shown.
  • liquid spills off the edge of plate 24 against the curved portion 86 of body 10 and then runs along the curved portion and down the inside wall of body 10 as schematically illustrated by arrow 100.
  • FIG 11 Another embodiment is shown in Figure 11, which embodiment utilizes a slightly different body wall configuration.
  • notch 15 in cover 12 (shown in Figure 10) has been eliminated and a corresponding circular notch 19 has been molded into the top edge of body 10 to receive the sealing O-ring 22.
  • the upper inside wall of body 10 has a tapered section 102 which provides a slanted surface.
  • Spreader plate 24 has a tongue 108 which extends into the gap 106 between the body 10 and cover plate 12 formed by O-ring 22.
  • Spreader plate 24 has circular notches 102 and 104 cut into its underside. Notch 102 redirects liquid flowing along the underside of tongue 108 to provide both vertical and horizontal flow control.
  • Notch 104 acts as a drip gap to prevent liquid from running along the underside of spreader plate 24 and dropping off directly into the liquid pool in the device.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)

Abstract

Un liquide est appliqué sur une plaque d'étalement horizontale (2) qui s'étend en direction des parois verticales d'un appareil diffuseur de gaz et forme un espace étroit (50) avec lesdites parois. Le liquide s'étale en un film mince sur la plaque d'étalement, il remplit l'espace situé entre la plaque et la paroi, coule le long des parois (10) du conteneur et sort dudit conteneur à la base de ce dernier. Le film coulant sur les parois du conteneur est suffisamment mince pour que la diffusion de gaz dans le liquide soit fortement améliorée lorsque le conteneur est rempli de gaz.
EP92917314A 1991-04-18 1992-04-17 Appareil destine a diffuser du gaz dans un liquide Withdrawn EP0580802A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US687171 1984-12-28
US68717191A 1991-04-18 1991-04-18

Publications (1)

Publication Number Publication Date
EP0580802A1 true EP0580802A1 (fr) 1994-02-02

Family

ID=24759380

Family Applications (1)

Application Number Title Priority Date Filing Date
EP92917314A Withdrawn EP0580802A1 (fr) 1991-04-18 1992-04-17 Appareil destine a diffuser du gaz dans un liquide

Country Status (3)

Country Link
EP (1) EP0580802A1 (fr)
CA (1) CA2108665A1 (fr)
WO (1) WO1992018228A2 (fr)

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2563390A (en) * 1951-08-07 Carbonating apparatus
FR319059A (fr) * 1902-02-25 1902-11-03 Ruelf Disposition automatique pour la fabrication des eaux minérales, vins mousseux, etc.
GB197368A (en) * 1922-02-06 1923-05-07 Alfred Herring Shaw Improved method of and apparatus for impregnating liquids and solutions with soluble gases
US2195449A (en) * 1939-10-26 1940-04-02 Magnus N Delen Water cooling and carbonating device
GB609443A (en) * 1945-04-07 1948-09-30 Coca Cola Co Improved apparatus for carbonating and dispensing liquids
US2752137A (en) * 1953-03-27 1956-06-26 Sparkle Beverages Inc Carbonating apparatus
US3807712A (en) * 1973-01-05 1974-04-30 Gulf Oil Corp Water aeration equipment
FR2451771A1 (fr) * 1979-03-20 1980-10-17 Carboxyque Francaise Procede de saturation d'un liquide par un gaz et son application a l'epuration d'effluents basiques
US4788020A (en) * 1982-12-10 1988-11-29 General Atomics Method for effecting mass transfer

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9218228A2 *

Also Published As

Publication number Publication date
WO1992018228A3 (fr) 1992-12-10
WO1992018228A2 (fr) 1992-10-29
CA2108665A1 (fr) 1992-10-19

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