CA2108665A1 - Apparatus for diffusing gas into a liquid - Google Patents
Apparatus for diffusing gas into a liquidInfo
- Publication number
- CA2108665A1 CA2108665A1 CA002108665A CA2108665A CA2108665A1 CA 2108665 A1 CA2108665 A1 CA 2108665A1 CA 002108665 A CA002108665 A CA 002108665A CA 2108665 A CA2108665 A CA 2108665A CA 2108665 A1 CA2108665 A1 CA 2108665A1
- Authority
- CA
- Canada
- Prior art keywords
- liquid
- container
- walls
- gas
- gap
- 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.)
- Abandoned
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
Landscapes
- Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Physical Or Chemical Processes And Apparatus (AREA)
Abstract
A liquid is applied to a horizontal spreader plate (2) which extends towards, and forms a narrow gap (50) with, the vertical walls of a gas diffusion apparatus. The liquid spreads out in a thin film across the spreader plate, fills the plate/wall gap and flows down along the container walls (10) and exits the container at the container bottom. The film on the container walls is sufficiently thin that when the container is filled with gas, gaseous diffusion into the liquid is greatly enhanced.
Description
~W O 9 2 / 1 8 2 2 8 2 ~ 8 ~ 5 ~ P c r, U S 9 2 / 0 3 1 9 9 APP~ FOR D J~ ;I~ G~; I~ A LIS~JXD
.
Fi~ld of_the Invention This i~vention relat~s to apparatus whi~h e~hanc~
the diffuæion of a g~ i~to a liquid ~nd more particularly ~o app~ratus, ~uch as oxygenators and aerator~, for diffusing oxygen into a liguid.
Bac~qround of the Inve tion There are presently many use~ for appara~u~ which enhances tha ~if~u6ioxl of gas into a ligu~d - ~or ~xa~ple, blood oxyge~ators, cell culture oxyge~a~ors and aerator6. ~nce ~iffu6io~ is ~ molecular pheno~
which oocur~ at the gas/l~quid inte~ac~, the ~ppara~u~
generally operate~ by i~crea~ing the i~terface area over which diffu~on take6 place or by ag~ta~ing ~he ga~liquid inter~a~e.
For exa~ple, an oxyge~ation method commonly u~ed in ~ell cultur~ng ~y~tems to introduce oxygen into liquid cell growth ~edium i~ to place the liguid m~dium in a long cylindrical container s~c:h as a ~ottle. The container is o~ly partially fille~ with the liquid BO
that a gas/liguid inter~ace i~ formed. Air is introdu~Qd int~ the container ~o that oxygen dif~u6es into the growth medium at the i~terfa~e. In order to enhance diffusion, the container is ~lowly rotated around its long axis by a mechanical device in order to agitate the gas~ uid inter~ace. One obvious problem with such an WO 92/l8222 1 0 8 6 6 ;~ Pcr/US92/03199 ~
arrangement is that it is not a continuou process and the m~dium must be ~ontinually removed and repla~sd in the con~ainer~. In addition, it is di~fic1llt to mo~itor the overall proc~ to determine when ~he proper l~el of gas di~fu~ion h~s occurred. Further, ~he ~utrie~t supply must be periodically repleni6hed through the labor-intensi~re proce~;s of diE;moun~ing, opening and reclosing ~he bo~tle, thereby furth~r ~xposir~g the eo~tQnt to ~ontami~ation.
In order to ~ercome the problems of ~on-~oIatinuouE;
operation and monitoring, other conven~ional apparatu6 is designed to increase the gas/liguid ~n~erface area.
One k2~0wn technigue involv0~ passing large ~umbers o~
very ~all gas bubbles through ~he l~quid. 8i~ce ~he bubble~ are small, their surfGce area to volu~e r~io is uite large as~d the large ~u~ober of bubble~ ~n~;ur~s that ~he cu~ulati~e ~urfai:e area of ~Q ga~ guid islg~rface i~ ~uite high a~d diffu~ion is ~er~by ~a~ced. qhis latter method is typically used in blood oxygerla~o~.
~uch a technique allows cor~tinuous opera~io~ in which the liquid can glow t;hrough ~he ~yst~m in a coatinuous ~tre~n. Howe~er, care ~ust be taken to remove gas bu~ble~ entrained in the blood prior to it~
reintroduction back into the p~ient in order to avQid problesns with emboli6m.
The second method of enhancing gas diffusion in a continuous sy6tem i6 to increa~e the ~urf ace area to volume ratio of the li~uid by 6preading ~he liquid in a thin film in an atmcsphere ~ontaining the gas. ~ common method of achieving a ~hin liguid ~ilm is to use stacked , ~ Wo ~2/182~8 ? ~ ~ ~ fi ~ ~; PCr/US92/03]99 trays. Each of the ~rays holds a ~hin lay~r of liguid and as the liguid flow~ through the tray, i.~ spills oler to the next lower tray in the stack. The process continues until the liquid rea~h~s the bot~:om of. ~he tray 2;tACl~. The eff~c~ive ~;ur~ace are~ o~ the tray stac~c can therefore be a large multiple of the ~;urface ~rea of each tray.
~ ;till other gas dif~usios~ arra~ge~t~ utilize rotating parts such ~E; d~E; or oo~e~ ~ou~te~
atmo~phere oo~tai~ing the ga~. Llguid intro~luced o~o such a moving par~ forms a t:hin film due to the rotation.
Thi6 l~tter app~ratus ca.~ operate 6~ontinuou~ly, but require6 mechanical saal~; to gea1 ~he mo~ring parts and i~ ~hu~ p~one to geal ~ilure~;, con~mination, azld high ~ai~tsTl~ace co~t~.
Accordingly, it is ~ object of the pres~t inve~ion to provide a ga~ d~ffug~o~ apparaSu~ ~hich ean operate co~tinuously.
~ t is another object of the pr~ent inven~io~ to provide ~ ga6 diffu~ion apparatus which contai~ no moving mechanical part~.
It i~ still nnother obj~ct of the present t~ve~tion to provide a gas d~ffusion apparatus which c~n be easily molded ~rom a polymeric pla6tic material.
It is yet snother ob;ect of the pre6~nt invention to provide a gas di~fu~ion apparatu~ whi~h is suitable for use in cell culture apparatus.
It is a ~urther object of the pr~sent inven~ion to provide a gas di~fusion apparatus in which the chance of entraining gas bubbles into a li~ui~ is reduced.
w092~822~ ` . PCT/VS92/031ss ~10~6~ 4 .
~ yet a further object of the pre~e~t inv0ntion to proYide a gas diffu~ion apparatu~ which ifi ea~y to maintai~ and service.
= ary of the InvQn~ion The foregoing obj~ct~ are achieve~ ~nd ~he ~or~going pxoblQms ar~ ~olved in one illu~trative e~bodiment Df the invention in which a liguid is constrained to ~orm Is th~n l~yer o~ d flow down, the ver~ical wall~ o~ a cont~iner ~illed with ~e ga~. The thin li~uid layer i~
subjec~ to e~hanced gas diffu~ion.
More p~r~icularly, the li~uid is applied to a ~pread0r plate which extQnds towards, and forms ~ narrow gap wi~h, the ~ontainar w~lls. Th~ l~qu~d spre~ds out in a thin fil~ across the ~preader pl~te, fills ~he plate/w~ll gap a~d flows down along the co~t~i~er wall~
~nd QXit8 the co~ai~er at the co~ai~er bottom. The film on the ~ontainer w~116 is sufficiently thin that gaseou6 d~ffu~ion is greatly anha~c~d.
The device iE suitable for use in the continuous application ~ince the liquid can ~e continuou61y introduced at one e~d o~ the container a~d wi~hdrawn at ~he other. 8uffi~ient space ~ a~ail~ble i~ the container to mount probe6 to monitor ga6 eoncentration and o~her parameters.
' ~,7 WO 92/18228 ~ fi 5 ~ PCT/~S92/03199 ... . . .
:
~rief Des~rip~ion of the Drawinq6 Figure 1 i6 a bloc~ sc~ematic diagram of ~n illu~trative continuous cell culture ~y~tem in which the gas di~fu~io~ apparatus of the pr~sent inYention.can be u~ed.
Figure 2 i6 an axploded per~pe~tive ~iew of one embod~ment of the inventiv~ gas diffu6ion apparatu6.
Figure 3 i~ a partial cros~-6e~tional diagram of ~he ~mbodiment ~hown in e~plodod form in F~gure 2.
Figure 4 i~ a partial cros~-~ec~ional diagram of the embodiment shown in Figuras 2 and 3 illu6trating the liguid flow path.
Figure S i~ a partial ~ross-sectional diagram of an alternat~ve Q~bodiment of the invent~on.
F~gure ~ i~ a c~o~ eotional diagram of ~ fir~t alter~ative ~mbodi~ent of the ~preader plate~wall area of ~he inventive ga~ diffusion apparatus.
Figure 7 i6 a cro~ ectional diagram of a ~ec~d alternative embodiment of the spreader plate/wall ar~a of the inventiv2 ga~ diffusion apparatu~.
Figure 8 i~ a cro~s-sectional diagram of a ~hird alterna~ive embodiment of the s2reader plat~/wall area of the inventive gas diffu~ion apparatu6.
Figure 9 is a cros~-~ec~ional diagra~ of a fourth al~ernative embodi~ent of the spreader plate/wall area of the inventive gas diffusion apparatu~.
Figure 10 i6 a cro6s-~ectional diagram of a fifth alternative embodiment of the spreader plate/wall area of the inventive gas dif~u~ion apparatus.
:-Wo 92/18228 ~; Pcr/us92/03199 ~ ~ 0 8 ~
Figure 11 i6 a cro~;g-;ectiorlal diagr~n of a ~i~th al~ernative ~mbodiment of ~he spreader plate~wall area of the inventi~e gas diffu~ion apparatu~.
Detailed DQ~CriPtiOn of ~he Preferr~ EDbodiment~
Although the present iI~v~ntion ca~ b~ us~d ln ma:rly applicatio~ in which it i~; de ir~d to di:~u~e ga5 into a liquid, orl6 such ap~lication for which the ~:a~ention is particularly su~ted i~ ~ conti~uou~ c~ll culture ~ystem in which ox~en must be diffu~ed :;~to ~
contirluou~ly-~lowing l~quid cell culture ~nedium i~ oxder to induca enhanced cel 1 gro~,rth . For ex~mple, th2 inventive gas diffusion ~pparatus can be provided a6 part of a co~t~nuous cell ~ulture sy~t~m ~0 as shown in ~igure 1.
8ys~n ~0 i~ a clos~d-lo~p sy~em whi~h inaorpor~te~
a cell oul~ure ~s~sel 120, ~ gas dif~usio~ app~ra~us and r~ervoir 110 which may illu~ratavely be t~e i~Yentive appa~atus and a plurali~y o~ fluid co~duits which co~vey a conve~tional cell cul~ure medium b~t~een the variou6 ~lemen~ o~ the ~ystem. 6uch ~edium may, for exam~le, be a rea~ly-available, ~tandard ~iological medium for cell ~ultura. Cel} culturing actuslly ta~s plac~ in culture ve6sel 120 which i~ supplied with replac~mQ~t liquid medium ~rom apparatu6 110 ~ia conduit 88. As the medium i~ pas6ing through apparatu~ 110, oxygen i6 added by mean6 of gas difu~ion.
~O ~2/18228 2 ~ 9 8 6 6 ~ P~r/US92103199 More particula~ly, outlet port 8~ of alppara~u~i llO
i~ connected ~o the inlet port 86 o~ the culture ve~el 120 ~ia f luid supply co~duit 88 . Outlet por~ 90 of cell cultur~ vas~el 120 i~, in turn, in fluid co1~iG~tion with an inlet port 92 cf 2~ppal:a~u~; llO via fluid return conduit 9~. A pump ~16 i6 po~itior~ed alo~g fluid supply conduit 88 to co~tinuously p~mp ~luid mediuM from apparatus llO through culturE~ ~re~s~l 120 a~d ba k to appar~tu6 llO .
I~ ~rder to add ~luid ~e~ium to ~he appara~us, a ~utrie~t ~upply line 98 i6 con~ectad to ~he fluid sup~?ly co~duit 88 be~woen pump 96 a~d t~ulture Ye~sel 120 so that addi~ional medium and nutrie~ts may be a~ded~ to ~lu~d supply cc~nduit 8~. A separat0 pump lO0 is provided for pu~p~ng ~he nut:rie~ts into the s~luid ~upply co~uit 88 via ~upply line 98.
Apparatu~ 110 i8 al~o provide~ with ~ ~roduct withdr~wal co~duit 102 conn~ted to a wi~hdr~wnl ~u~p 104 ~or r~ovi~g ~luid medium and ~ul~ured cells down~tre~m from the culture ve~el, preferably ~o~inuously.
~ a~ di~fusion app~ratu~ lla is provided for continuou6 ~e~upply af oxygen ~nd for carbon ~iox~de rff~oval or add~tion to ~he culture ~alum. ~ptionally, gas ~if~usion apparatu~ 110 may i~clude probe~, suQh a~
gas and t~mperature probes (~ot show~), which are conn2Gted, ~ia el~ctrical leads 1}4, to a controller 112 which can co~rol the conc~ntration o oxygen, ~arbon disxide and other ga6es introduced into ~he diffu~ion apparatus as will hereinafter be described to automatically maintain the oxygen or carbon dioxide levels in the medium at a predetermined value.
wo 92/18228 pcr/us92to3199 .. --8--.
An additional probe 106 may be provided on return conduit 94 in order to sense variou6 condit:ion~ of the medium and cell mixt:ure. This probe, in turr~, may be connect2d to a control devia~ 108 (or alternativ~ly, control device 112) which d~vic~ control~ t:he ~rar~ous pumps for pH balan~ing the ga~ conce~trations in the medium/c~ll mixture. ~exlerally, the 6ystern i~ designed 80 that ~re~h ~e~ium iEi conE;tantly ~eing introduc:ed into the circulating 6y~ and t~e c:ul~ured cell pro~uct is co~ti~uously bei~g wi~hdrawn ~rom ~che system at ~ rate of circulation d~termined by the control device 1û8. An illustrative ~y6tem such as t:h~t illu~trated i~ Figure 1 i6 shown in detail in TJ,S. Patent Application 8erial ~o.
07~361,141 entitled "Continuous High Density Cell C:ultur~ 8~r~tem~ ~ile~ by ~3ric 9erry on June 1, 1g89, a~d licensed to ~he as~ig~se of the present invention.
8in~ the d4tails of thi~ sy~t~m are not importan~ for an u~derstanding of the operation of the ga~ di~fu ion apparatu~ o~ the pre~ent invention, th~y will ~ot b~
di~cussed further h~rein.
Figur~s 2 and 3 illustrate one embodiment o~ ~he ga6 diffusion apparatu~ 110 ~on6truct~d in accordance with the inve~tive principl~s dis~losed hera~n. ~s shown in Figure 2, the ~pparatus consists of a body 10 which is illustrated as hav~ng a cylindrical cross-sectio~, however, other cro~s-fiectional shape~ may be used in accordance with th~ prin~iples of the invention without altering the operation of the device. Body lo ~s fabricated from a material which is iner~ with respec~
to the liquid and gas flowing through it. A suitabl~
~ W0 92/18228 ~ ~ 6 ~ ~ PCr/U592/03199 ~9_ . .
material is ~las~, ~u~ other ma~erials may al60 3~e u~ed.
As will be disoussed in more detail ~elow, ~he i~ner wall 11 of body lo is 6peciaily treated so that it i6 "w~ttable" by the liquid flowing through th~ t. In ~he ca~e where body 10 i~; fa~ricated of glas~, i~er wall 11 may illustra~ively be plasma treated, ~cid ~leaned or ch~ically etch~d.
Body 10 i provided with a cover 12 which is clamped to body 10 ~y m~an6 of a ~la~i~g ring 14. Ri~g 14 i6 con~tructE~d with a plurality o~ ~hraad~d ~tud~ 16 mouslted thereon ~hic~ project through holes in ~ ver 12 into nuts 18 which c:an be threaded o~o the stud6 to attach cover 12 to ring ~4 . A 1 ip 13 of body 10 i~
ptured be~ween cover 12 and ~:ing 1~ to ho~d the a~se~bly together. Arl ~nul~r elastomerio cush~on 20 is provided between clamp~ng rirlg 1~ and body lip 13 to prevent da~age to bo~y lo ~ould the nut~ 18 b overtighte~d. In addi~ion, lip 13 iE; 6ealed to coVQr 12 by ~ s o~ ri~g 22 (show~ Fig. 33.
Attach~d to ~he underside of cover 12 i~ a ~preade:c plate 24, the pu~pose of which i~ to eve~ly dis~ribute liquid flowing i2lto the appa~a~us via inl~t 26, a~ will hereina~er ~e d~sc:ribed. Li3Euid moving ~hrough the ~pp~ratus leave6 by mean~ of exit 30.
Ring 14 i8 suppor~ed on a circular base 34 by means of three upright supports 36. The ends of support~ 36 have threaded holes 38 into which bolts 40 snd 42 can be ~crewed to fasten ~upports 36 to ring 1~ and base 34.
WO 9'~/18228 i . . PCI/US92/031~9 ~.~08~6~
The diffusion appara~u~ may al80 ~e ~ ed with ~ariou~ probes which project ~hrough the cover 12 in order to monitor variou~ co~dition~ of the ga6 and liquid i~ide ~ody lo. ~or example, a p~ probe.44 and an oxygen probe 4~ are illu~tr~t~d, how~ver o~her probe~
and metering devi~es may also be i~er~ed ~hrough cGver 12. 8uch probe~ may bæ sealed ~o c~ver 1~ by ~eans o~
cl~mp nut~ S5 or O-ri~gs ~4 (~æ ~how~ in ~igure 3) or ~y other means ~o tha~ they project into ~he body 1~.
Th~ operation of the diffu~ion ~ppara~u~ hown sch~m~tically in Figure 4. In thi~ ~gure, pro~e~ ~4 and ~ a~d the gtrU~ure surrcu~ding body 10 have b~Qn eliminatad to clari~y the drawing. During op~ration, ligu~d iB introduced i~to the deviae through i~let ~6 and flow~ i~to ~pace 70 be~wee~ the cov~r 12 ~nd ~pre~dar plat~ 2~. Due ~ocw~ ao~ surface t~nslon.~ffects, the liquid spread~ o~t ~venly acros6 tha e~ a plate 2 until it reac:he~ the g~p 50 be~cween th~ ~uter-periphery of plate 24 and ~ha ian2r wall 11 of body 10.
Gap 50 i8 0~ 6u~h a size that ~urface tea~ion of the liquid eauses it ~o bridge the gap an~ ~orm a thin film along the i~er wall.ll of body 10. T~e wi~th of gap 50 iE dspendent on the ~i~co~ity and compo~tion of the liquid with which the apparatu~ operat~ and may illu~tratively be in ~he range of .020-.0~0 inahe~. For example, gap 50 may be approximately 0.020 inches when ~he diffu~ion appara~u~ i~ u~ed with standard biological cell ~ulture médium of the type that may be u~ed in ~he cel} ~ulturing syst~m shown in Figure 1.
o 92/18228 ~ ~ ~ 8 ~ ~ ~ Pcr/us92/03199 .
,., As previously mentioned, the inrler wall 11 o body 10 mu~t be ~r~ated to make it ~wet~ble" wi.th s:esp~c~ to the liguid ~o ~hat the liguid will ~low down the wall in a thi~, even l~yer. q~his tre~ t may be dorle i~ ~
convention~ ashio~, for example, ~y pl~sma tre~ g, chemically etchi~g or a::id ~tchi~g the i~sr surfac~ 11 of a glas~ body 10.
Wharl the liquid ~arges ~rom g~? 50 it ~orm~ ~ thin, ~ven ~ilm 72 over the ~ire ~ody wall 11. Thus, ~he surface area of the liquid is ~fecti~rely ~e ~res of the isuler wall 11. Thi~ area ~ ~p~ded by si~?ly mak~g thQ ~evice diameter l~rger. A large surface nreA/volurne r~tio i~ establiE~hed due to the t~ film 72 an~ the large l~urace area/volume ratio enha~ces diffus~o~ i~ a ~awn ma~er. The l~lL~id in ~he f~lm 72 run~ dow~ the wall 11 into a collecti2lg pool 74 whie~h forms i~ th~-botto~ part of body 10. ~he liguid i~ ~he ~ollect~g 3?ool t~ler~ s by meu~ of ~ lo~r eoci~ 30.
as to be diffused ~into ~ quid i6 i~trodu~ed in~o body 10 by ~san~ o~ ga6 inle~c 60 where i~ rapidly di~use~ i~tc~ ~ilm 72. Ul~dif~u~ed ga~ exits body 10 ~y ~ean6 of gas outle~ 62 80 tha~ g~s ~o~ti~ually eslt~rs ~nd exit6 t}le apparstu6 m~int~i~ing a ~on~tan~ g~s conce~trntios~ body which c~m be ~onitored by mQans of ~he aorementioned pro~es shown in Figure 3. ~ince liguid constantly ent~rs the apparatus at inlet 26 and exits, via ~xit 30, the entire de~rice ~an op~rate in a continuous fashion without arly movi~g parts or rotating seals that require maintenance.
W0~2/182~8 ~.~ . P~T/US92/031~9 ~
.
Fi~ld of_the Invention This i~vention relat~s to apparatus whi~h e~hanc~
the diffuæion of a g~ i~to a liquid ~nd more particularly ~o app~ratus, ~uch as oxygenators and aerator~, for diffusing oxygen into a liguid.
Bac~qround of the Inve tion There are presently many use~ for appara~u~ which enhances tha ~if~u6ioxl of gas into a ligu~d - ~or ~xa~ple, blood oxyge~ators, cell culture oxyge~a~ors and aerator6. ~nce ~iffu6io~ is ~ molecular pheno~
which oocur~ at the gas/l~quid inte~ac~, the ~ppara~u~
generally operate~ by i~crea~ing the i~terface area over which diffu~on take6 place or by ag~ta~ing ~he ga~liquid inter~a~e.
For exa~ple, an oxyge~ation method commonly u~ed in ~ell cultur~ng ~y~tems to introduce oxygen into liquid cell growth ~edium i~ to place the liguid m~dium in a long cylindrical container s~c:h as a ~ottle. The container is o~ly partially fille~ with the liquid BO
that a gas/liguid inter~ace i~ formed. Air is introdu~Qd int~ the container ~o that oxygen dif~u6es into the growth medium at the i~terfa~e. In order to enhance diffusion, the container is ~lowly rotated around its long axis by a mechanical device in order to agitate the gas~ uid inter~ace. One obvious problem with such an WO 92/l8222 1 0 8 6 6 ;~ Pcr/US92/03199 ~
arrangement is that it is not a continuou process and the m~dium must be ~ontinually removed and repla~sd in the con~ainer~. In addition, it is di~fic1llt to mo~itor the overall proc~ to determine when ~he proper l~el of gas di~fu~ion h~s occurred. Further, ~he ~utrie~t supply must be periodically repleni6hed through the labor-intensi~re proce~;s of diE;moun~ing, opening and reclosing ~he bo~tle, thereby furth~r ~xposir~g the eo~tQnt to ~ontami~ation.
In order to ~ercome the problems of ~on-~oIatinuouE;
operation and monitoring, other conven~ional apparatu6 is designed to increase the gas/liguid ~n~erface area.
One k2~0wn technigue involv0~ passing large ~umbers o~
very ~all gas bubbles through ~he l~quid. 8i~ce ~he bubble~ are small, their surfGce area to volu~e r~io is uite large as~d the large ~u~ober of bubble~ ~n~;ur~s that ~he cu~ulati~e ~urfai:e area of ~Q ga~ guid islg~rface i~ ~uite high a~d diffu~ion is ~er~by ~a~ced. qhis latter method is typically used in blood oxygerla~o~.
~uch a technique allows cor~tinuous opera~io~ in which the liquid can glow t;hrough ~he ~yst~m in a coatinuous ~tre~n. Howe~er, care ~ust be taken to remove gas bu~ble~ entrained in the blood prior to it~
reintroduction back into the p~ient in order to avQid problesns with emboli6m.
The second method of enhancing gas diffusion in a continuous sy6tem i6 to increa~e the ~urf ace area to volume ratio of the li~uid by 6preading ~he liquid in a thin film in an atmcsphere ~ontaining the gas. ~ common method of achieving a ~hin liguid ~ilm is to use stacked , ~ Wo ~2/182~8 ? ~ ~ ~ fi ~ ~; PCr/US92/03]99 trays. Each of the ~rays holds a ~hin lay~r of liguid and as the liguid flow~ through the tray, i.~ spills oler to the next lower tray in the stack. The process continues until the liquid rea~h~s the bot~:om of. ~he tray 2;tACl~. The eff~c~ive ~;ur~ace are~ o~ the tray stac~c can therefore be a large multiple of the ~;urface ~rea of each tray.
~ ;till other gas dif~usios~ arra~ge~t~ utilize rotating parts such ~E; d~E; or oo~e~ ~ou~te~
atmo~phere oo~tai~ing the ga~. Llguid intro~luced o~o such a moving par~ forms a t:hin film due to the rotation.
Thi6 l~tter app~ratus ca.~ operate 6~ontinuou~ly, but require6 mechanical saal~; to gea1 ~he mo~ring parts and i~ ~hu~ p~one to geal ~ilure~;, con~mination, azld high ~ai~tsTl~ace co~t~.
Accordingly, it is ~ object of the pres~t inve~ion to provide a ga~ d~ffug~o~ apparaSu~ ~hich ean operate co~tinuously.
~ t is another object of the pr~ent inven~io~ to provide ~ ga6 diffu~ion apparatus which contai~ no moving mechanical part~.
It i~ still nnother obj~ct of the present t~ve~tion to provide a gas d~ffusion apparatus which c~n be easily molded ~rom a polymeric pla6tic material.
It is yet snother ob;ect of the pre6~nt invention to provide a gas di~fu~ion apparatu~ whi~h is suitable for use in cell culture apparatus.
It is a ~urther object of the pr~sent inven~ion to provide a gas di~fusion apparatus in which the chance of entraining gas bubbles into a li~ui~ is reduced.
w092~822~ ` . PCT/VS92/031ss ~10~6~ 4 .
~ yet a further object of the pre~e~t inv0ntion to proYide a gas diffu~ion apparatu~ which ifi ea~y to maintai~ and service.
= ary of the InvQn~ion The foregoing obj~ct~ are achieve~ ~nd ~he ~or~going pxoblQms ar~ ~olved in one illu~trative e~bodiment Df the invention in which a liguid is constrained to ~orm Is th~n l~yer o~ d flow down, the ver~ical wall~ o~ a cont~iner ~illed with ~e ga~. The thin li~uid layer i~
subjec~ to e~hanced gas diffu~ion.
More p~r~icularly, the li~uid is applied to a ~pread0r plate which extQnds towards, and forms ~ narrow gap wi~h, the ~ontainar w~lls. Th~ l~qu~d spre~ds out in a thin fil~ across the ~preader pl~te, fills ~he plate/w~ll gap a~d flows down along the co~t~i~er wall~
~nd QXit8 the co~ai~er at the co~ai~er bottom. The film on the ~ontainer w~116 is sufficiently thin that gaseou6 d~ffu~ion is greatly anha~c~d.
The device iE suitable for use in the continuous application ~ince the liquid can ~e continuou61y introduced at one e~d o~ the container a~d wi~hdrawn at ~he other. 8uffi~ient space ~ a~ail~ble i~ the container to mount probe6 to monitor ga6 eoncentration and o~her parameters.
' ~,7 WO 92/18228 ~ fi 5 ~ PCT/~S92/03199 ... . . .
:
~rief Des~rip~ion of the Drawinq6 Figure 1 i6 a bloc~ sc~ematic diagram of ~n illu~trative continuous cell culture ~y~tem in which the gas di~fu~io~ apparatus of the pr~sent inYention.can be u~ed.
Figure 2 i6 an axploded per~pe~tive ~iew of one embod~ment of the inventiv~ gas diffu6ion apparatu6.
Figure 3 i~ a partial cros~-6e~tional diagram of ~he ~mbodiment ~hown in e~plodod form in F~gure 2.
Figure 4 i~ a partial cros~-~ec~ional diagram of the embodiment shown in Figuras 2 and 3 illu6trating the liguid flow path.
Figure S i~ a partial ~ross-sectional diagram of an alternat~ve Q~bodiment of the invent~on.
F~gure ~ i~ a c~o~ eotional diagram of ~ fir~t alter~ative ~mbodi~ent of the ~preader plate~wall area of ~he inventive ga~ diffusion apparatus.
Figure 7 i6 a cro~ ectional diagram of a ~ec~d alternative embodiment of the spreader plate/wall ar~a of the inventiv2 ga~ diffusion apparatu~.
Figure 8 i~ a cro~s-sectional diagram of a ~hird alterna~ive embodiment of the s2reader plat~/wall area of the inventive gas diffu~ion apparatu6.
Figure 9 is a cros~-~ec~ional diagra~ of a fourth al~ernative embodi~ent of the spreader plate/wall area of the inventive gas diffusion apparatu~.
Figure 10 i6 a cro6s-~ectional diagram of a fifth alternative embodiment of the spreader plate/wall area of the inventive gas dif~u~ion apparatus.
:-Wo 92/18228 ~; Pcr/us92/03199 ~ ~ 0 8 ~
Figure 11 i6 a cro~;g-;ectiorlal diagr~n of a ~i~th al~ernative ~mbodiment of ~he spreader plate~wall area of the inventi~e gas diffu~ion apparatu~.
Detailed DQ~CriPtiOn of ~he Preferr~ EDbodiment~
Although the present iI~v~ntion ca~ b~ us~d ln ma:rly applicatio~ in which it i~; de ir~d to di:~u~e ga5 into a liquid, orl6 such ap~lication for which the ~:a~ention is particularly su~ted i~ ~ conti~uou~ c~ll culture ~ystem in which ox~en must be diffu~ed :;~to ~
contirluou~ly-~lowing l~quid cell culture ~nedium i~ oxder to induca enhanced cel 1 gro~,rth . For ex~mple, th2 inventive gas diffusion ~pparatus can be provided a6 part of a co~t~nuous cell ~ulture sy~t~m ~0 as shown in ~igure 1.
8ys~n ~0 i~ a clos~d-lo~p sy~em whi~h inaorpor~te~
a cell oul~ure ~s~sel 120, ~ gas dif~usio~ app~ra~us and r~ervoir 110 which may illu~ratavely be t~e i~Yentive appa~atus and a plurali~y o~ fluid co~duits which co~vey a conve~tional cell cul~ure medium b~t~een the variou6 ~lemen~ o~ the ~ystem. 6uch ~edium may, for exam~le, be a rea~ly-available, ~tandard ~iological medium for cell ~ultura. Cel} culturing actuslly ta~s plac~ in culture ve6sel 120 which i~ supplied with replac~mQ~t liquid medium ~rom apparatu6 110 ~ia conduit 88. As the medium i~ pas6ing through apparatu~ 110, oxygen i6 added by mean6 of gas difu~ion.
~O ~2/18228 2 ~ 9 8 6 6 ~ P~r/US92103199 More particula~ly, outlet port 8~ of alppara~u~i llO
i~ connected ~o the inlet port 86 o~ the culture ve~el 120 ~ia f luid supply co~duit 88 . Outlet por~ 90 of cell cultur~ vas~el 120 i~, in turn, in fluid co1~iG~tion with an inlet port 92 cf 2~ppal:a~u~; llO via fluid return conduit 9~. A pump ~16 i6 po~itior~ed alo~g fluid supply conduit 88 to co~tinuously p~mp ~luid mediuM from apparatus llO through culturE~ ~re~s~l 120 a~d ba k to appar~tu6 llO .
I~ ~rder to add ~luid ~e~ium to ~he appara~us, a ~utrie~t ~upply line 98 i6 con~ectad to ~he fluid sup~?ly co~duit 88 be~woen pump 96 a~d t~ulture Ye~sel 120 so that addi~ional medium and nutrie~ts may be a~ded~ to ~lu~d supply cc~nduit 8~. A separat0 pump lO0 is provided for pu~p~ng ~he nut:rie~ts into the s~luid ~upply co~uit 88 via ~upply line 98.
Apparatu~ 110 i8 al~o provide~ with ~ ~roduct withdr~wal co~duit 102 conn~ted to a wi~hdr~wnl ~u~p 104 ~or r~ovi~g ~luid medium and ~ul~ured cells down~tre~m from the culture ve~el, preferably ~o~inuously.
~ a~ di~fusion app~ratu~ lla is provided for continuou6 ~e~upply af oxygen ~nd for carbon ~iox~de rff~oval or add~tion to ~he culture ~alum. ~ptionally, gas ~if~usion apparatu~ 110 may i~clude probe~, suQh a~
gas and t~mperature probes (~ot show~), which are conn2Gted, ~ia el~ctrical leads 1}4, to a controller 112 which can co~rol the conc~ntration o oxygen, ~arbon disxide and other ga6es introduced into ~he diffu~ion apparatus as will hereinafter be described to automatically maintain the oxygen or carbon dioxide levels in the medium at a predetermined value.
wo 92/18228 pcr/us92to3199 .. --8--.
An additional probe 106 may be provided on return conduit 94 in order to sense variou6 condit:ion~ of the medium and cell mixt:ure. This probe, in turr~, may be connect2d to a control devia~ 108 (or alternativ~ly, control device 112) which d~vic~ control~ t:he ~rar~ous pumps for pH balan~ing the ga~ conce~trations in the medium/c~ll mixture. ~exlerally, the 6ystern i~ designed 80 that ~re~h ~e~ium iEi conE;tantly ~eing introduc:ed into the circulating 6y~ and t~e c:ul~ured cell pro~uct is co~ti~uously bei~g wi~hdrawn ~rom ~che system at ~ rate of circulation d~termined by the control device 1û8. An illustrative ~y6tem such as t:h~t illu~trated i~ Figure 1 i6 shown in detail in TJ,S. Patent Application 8erial ~o.
07~361,141 entitled "Continuous High Density Cell C:ultur~ 8~r~tem~ ~ile~ by ~3ric 9erry on June 1, 1g89, a~d licensed to ~he as~ig~se of the present invention.
8in~ the d4tails of thi~ sy~t~m are not importan~ for an u~derstanding of the operation of the ga~ di~fu ion apparatu~ o~ the pre~ent invention, th~y will ~ot b~
di~cussed further h~rein.
Figur~s 2 and 3 illustrate one embodiment o~ ~he ga6 diffusion apparatu~ 110 ~on6truct~d in accordance with the inve~tive principl~s dis~losed hera~n. ~s shown in Figure 2, the ~pparatus consists of a body 10 which is illustrated as hav~ng a cylindrical cross-sectio~, however, other cro~s-fiectional shape~ may be used in accordance with th~ prin~iples of the invention without altering the operation of the device. Body lo ~s fabricated from a material which is iner~ with respec~
to the liquid and gas flowing through it. A suitabl~
~ W0 92/18228 ~ ~ 6 ~ ~ PCr/U592/03199 ~9_ . .
material is ~las~, ~u~ other ma~erials may al60 3~e u~ed.
As will be disoussed in more detail ~elow, ~he i~ner wall 11 of body lo is 6peciaily treated so that it i6 "w~ttable" by the liquid flowing through th~ t. In ~he ca~e where body 10 i~; fa~ricated of glas~, i~er wall 11 may illustra~ively be plasma treated, ~cid ~leaned or ch~ically etch~d.
Body 10 i provided with a cover 12 which is clamped to body 10 ~y m~an6 of a ~la~i~g ring 14. Ri~g 14 i6 con~tructE~d with a plurality o~ ~hraad~d ~tud~ 16 mouslted thereon ~hic~ project through holes in ~ ver 12 into nuts 18 which c:an be threaded o~o the stud6 to attach cover 12 to ring ~4 . A 1 ip 13 of body 10 i~
ptured be~ween cover 12 and ~:ing 1~ to ho~d the a~se~bly together. Arl ~nul~r elastomerio cush~on 20 is provided between clamp~ng rirlg 1~ and body lip 13 to prevent da~age to bo~y lo ~ould the nut~ 18 b overtighte~d. In addi~ion, lip 13 iE; 6ealed to coVQr 12 by ~ s o~ ri~g 22 (show~ Fig. 33.
Attach~d to ~he underside of cover 12 i~ a ~preade:c plate 24, the pu~pose of which i~ to eve~ly dis~ribute liquid flowing i2lto the appa~a~us via inl~t 26, a~ will hereina~er ~e d~sc:ribed. Li3Euid moving ~hrough the ~pp~ratus leave6 by mean~ of exit 30.
Ring 14 i8 suppor~ed on a circular base 34 by means of three upright supports 36. The ends of support~ 36 have threaded holes 38 into which bolts 40 snd 42 can be ~crewed to fasten ~upports 36 to ring 1~ and base 34.
WO 9'~/18228 i . . PCI/US92/031~9 ~.~08~6~
The diffusion appara~u~ may al80 ~e ~ ed with ~ariou~ probes which project ~hrough the cover 12 in order to monitor variou~ co~dition~ of the ga6 and liquid i~ide ~ody lo. ~or example, a p~ probe.44 and an oxygen probe 4~ are illu~tr~t~d, how~ver o~her probe~
and metering devi~es may also be i~er~ed ~hrough cGver 12. 8uch probe~ may bæ sealed ~o c~ver 1~ by ~eans o~
cl~mp nut~ S5 or O-ri~gs ~4 (~æ ~how~ in ~igure 3) or ~y other means ~o tha~ they project into ~he body 1~.
Th~ operation of the diffu~ion ~ppara~u~ hown sch~m~tically in Figure 4. In thi~ ~gure, pro~e~ ~4 and ~ a~d the gtrU~ure surrcu~ding body 10 have b~Qn eliminatad to clari~y the drawing. During op~ration, ligu~d iB introduced i~to the deviae through i~let ~6 and flow~ i~to ~pace 70 be~wee~ the cov~r 12 ~nd ~pre~dar plat~ 2~. Due ~ocw~ ao~ surface t~nslon.~ffects, the liquid spread~ o~t ~venly acros6 tha e~ a plate 2 until it reac:he~ the g~p 50 be~cween th~ ~uter-periphery of plate 24 and ~ha ian2r wall 11 of body 10.
Gap 50 i8 0~ 6u~h a size that ~urface tea~ion of the liquid eauses it ~o bridge the gap an~ ~orm a thin film along the i~er wall.ll of body 10. T~e wi~th of gap 50 iE dspendent on the ~i~co~ity and compo~tion of the liquid with which the apparatu~ operat~ and may illu~tratively be in ~he range of .020-.0~0 inahe~. For example, gap 50 may be approximately 0.020 inches when ~he diffu~ion appara~u~ i~ u~ed with standard biological cell ~ulture médium of the type that may be u~ed in ~he cel} ~ulturing syst~m shown in Figure 1.
o 92/18228 ~ ~ ~ 8 ~ ~ ~ Pcr/us92/03199 .
,., As previously mentioned, the inrler wall 11 o body 10 mu~t be ~r~ated to make it ~wet~ble" wi.th s:esp~c~ to the liguid ~o ~hat the liguid will ~low down the wall in a thi~, even l~yer. q~his tre~ t may be dorle i~ ~
convention~ ashio~, for example, ~y pl~sma tre~ g, chemically etchi~g or a::id ~tchi~g the i~sr surfac~ 11 of a glas~ body 10.
Wharl the liquid ~arges ~rom g~? 50 it ~orm~ ~ thin, ~ven ~ilm 72 over the ~ire ~ody wall 11. Thus, ~he surface area of the liquid is ~fecti~rely ~e ~res of the isuler wall 11. Thi~ area ~ ~p~ded by si~?ly mak~g thQ ~evice diameter l~rger. A large surface nreA/volurne r~tio i~ establiE~hed due to the t~ film 72 an~ the large l~urace area/volume ratio enha~ces diffus~o~ i~ a ~awn ma~er. The l~lL~id in ~he f~lm 72 run~ dow~ the wall 11 into a collecti2lg pool 74 whie~h forms i~ th~-botto~ part of body 10. ~he liguid i~ ~he ~ollect~g 3?ool t~ler~ s by meu~ of ~ lo~r eoci~ 30.
as to be diffused ~into ~ quid i6 i~trodu~ed in~o body 10 by ~san~ o~ ga6 inle~c 60 where i~ rapidly di~use~ i~tc~ ~ilm 72. Ul~dif~u~ed ga~ exits body 10 ~y ~ean6 of gas outle~ 62 80 tha~ g~s ~o~ti~ually eslt~rs ~nd exit6 t}le apparstu6 m~int~i~ing a ~on~tan~ g~s conce~trntios~ body which c~m be ~onitored by mQans of ~he aorementioned pro~es shown in Figure 3. ~ince liguid constantly ent~rs the apparatus at inlet 26 and exits, via ~xit 30, the entire de~rice ~an op~rate in a continuous fashion without arly movi~g parts or rotating seals that require maintenance.
W0~2/182~8 ~.~ . P~T/US92/031~9 ~
2~0~6a ~
Fig. 5 shows an alternative embodiment of the pr2sent inven~ion in which the ~preader pla~e 24 i6 fabricated in th~ ~hape of a di~k rather ~.han the annular ~hape ~hown in ~igur~ 2 and 3. In thi~ odimen~, p~
probe ~4 and oxyg~n probe 46 ~xtend through both ~o~er 12 and ~pr~ader p~at~ 24. Prcbes ~4 an~ ~6 are pro~id~d with adapter ~ub~ 100 and 112, r~pectiv~ly. ~dapter ~ube 100 seals to the top of cover 12 by ~e~s of thr-~aded ring 102 a~d 0-rir~g 104. A spac~r 106 and 0-ring 108 8e~1 adaptQr tu~e 100 again~t ~h2 bottom o cover 12. ~preader pl~te 24 i8 held against ~pacer 106 by threaded ring 110. ~imi~arly, adapter tub~ 112 ~eal~
to the top of co~er 12 by means o~ thr~aded ring 11~ and 0-ring 116. A spacer 118 and 0-ring 120 Eeal 3dspter tube 112 again~t the bottom of co~er 12. 6preader plate 24 is h*ld ~gai~st spa~er 118 by threaded ri~g 122. In any ca~e, the probes 4~ and 46 must be sealed ~gainst ~preader plate 44 80 that ~o liquid runs down the prob~s.
In the embodiment ~how~ in Figure 5, ligu~d inl~t 26 is loc~ted in th~ ce~ter of ~h~ appara~us; ~his location ha~ the adva~tage that liquid introdu~Qd i~to inlet 26 will ~pread more uni~ormly over plate ~4. To accGmmodate ~he new location of liguid inl~t 26, gas inlet 60 may be mo~ed to the 6ida and mu~t al60 pass through plate 24. ~as outl~t 62 (not 6hown in Figure 5) may al~o b~ placed in an o~f-~enter location.
Figure~ 6-11 show al~ernative embodiments of ~he spreader plate edge~wall area 52 shown in Figure 3. For example, in ~igure 6, ~he edge of ~he spreader plate 24 is provided with a ~mall dam 80 which aid~ in maintaining ~ i~W~ 92/18228 ~ ~ 0 8 ~ 5 ~ PCr/US92/03199 -13- .
a thin "pool" of liquid on the top of spreader plate 24 60 that the liquid will ~pread more evenly over pla~e 24. During operation, liquid will spill o~er ~he top of dam ~0 into gap 50 and the appara~us would perform sub~tantially a~ previou~ly described.
Figure 7 ~how~ an additional embodiment i~ which dam 80 has bsen exte~ded i~ heigh~ ~o orm a ~arrow gap 82 bQtween the upper e~d of dam 80 and cover 12. In this csse gap 5D i6 le~ ~ri~ieal ~inc~ gap ~2 (which may be smaller than gap 50) control~ ~he release of liquid from 6preader plate 24.
An additional ~mbodiment is ~hown in Figure 8 in which a knie edge 84 i6 pro~ided a~ the outer periphery of pl~te 24 ~o prosride ~he cleararl~e in gap 50 between plate 2~ and the wall 11 o~ bo~ 10.
Anoth~r embod~ment ~ show~ in Fi~ure 9 in which a drip lip 86 i8 provt~ed along the outer periphery of the lower edg~ of ~pread~r pla~e 24. Lip a6 preY~rlt~ uid pa6sing through gap 50 from running alor~g the bo~tom surface of plate 24 and dripping from plate 2~ directly i~to the pool of liguid a~ the bottom of the appar~tu6.
A further embodims~t is shown in Figure 10, in which the radius of the curved upper lip of ~ody 10 is increased and the di~meter of plate 2~ is i~creased from tha point where body 10 is 6ealed b~ O-ring 22 located in circular s~otch lS ~o that the outer edge of spreader plate 24 fi~ into the 6pace between the ~ur~red wall portion and the cover 12 as shown. In this embodiment, liguid spills off the edge of plate 24 against ~he WO 92/18228 Pcr/us~2/03199 ~i 2108~6~ -14-curved portion 86 of body 10 and ~hen run~ along ~he curved portion and down the in~ide wall o~ body 10 a6 schematically illustrated by arrow 100.
Anoth~r ambodiment is ~hown in Figure 11, which 2mbodimQnt utili~e~ a ~l~ghtly di~erQnt ~ody wall configuration. In particular, ~otch 15 in cov~r 12 ( ~hc>w~ in Figure lC ) has been eliminated a~d a corresponding cir::ular notch 19 has ~en molded i~to the top edg~ of body 10 to r~ceiYe tha ~eali~g 0-ring 22.
I~ ad~ition, the upp~r in~ida wall of body 10 ha~ a ~apered rection 102 which provides a 61a~ted sur*ace.
8prsader plate 24 has a tongue 108 which extend6 int~
the ~ap 106 b~tween the body 10 and cover pla~e 12 ~ormed by 0-ri~g 22. Bpreader plate 2~ ha~ circul~r rlot~hes 102 and 104 cut into its unders~de. ~lotch 102 re~lirect~ ~
liquid flowi~g along the ~ders~de o~ tongue lQ8 to provide b~th vertical &nd horizo~tal flow ~:ontrol.
~otch 104 ~cts as a drip gap to pr~ven~ 1i5ruid ~rom running ~long the under~ide of ~preader plate 24 ~d dropping off directly into the liquid po41 in the dQvice.
Although only a ~ew e~odime~t~ of ~he inve~tive apparatus have been desc:ribed, many modifiGatio~s a~d changes will be immediately apparent ~o those skilled in the art. These mc)difica~io~s ~nd ol:her obvious ch~ges are intendQd tc) be covered by the following claims, W~at is claimed is.
Fig. 5 shows an alternative embodiment of the pr2sent inven~ion in which the ~preader pla~e 24 i6 fabricated in th~ ~hape of a di~k rather ~.han the annular ~hape ~hown in ~igur~ 2 and 3. In thi~ odimen~, p~
probe ~4 and oxyg~n probe 46 ~xtend through both ~o~er 12 and ~pr~ader p~at~ 24. Prcbes ~4 an~ ~6 are pro~id~d with adapter ~ub~ 100 and 112, r~pectiv~ly. ~dapter ~ube 100 seals to the top of cover 12 by ~e~s of thr-~aded ring 102 a~d 0-rir~g 104. A spac~r 106 and 0-ring 108 8e~1 adaptQr tu~e 100 again~t ~h2 bottom o cover 12. ~preader pl~te 24 i8 held against ~pacer 106 by threaded ring 110. ~imi~arly, adapter tub~ 112 ~eal~
to the top of co~er 12 by means o~ thr~aded ring 11~ and 0-ring 116. A spacer 118 and 0-ring 120 Eeal 3dspter tube 112 again~t the bottom of co~er 12. 6preader plate 24 is h*ld ~gai~st spa~er 118 by threaded ri~g 122. In any ca~e, the probes 4~ and 46 must be sealed ~gainst ~preader plate 44 80 that ~o liquid runs down the prob~s.
In the embodiment ~how~ in Figure 5, ligu~d inl~t 26 is loc~ted in th~ ce~ter of ~h~ appara~us; ~his location ha~ the adva~tage that liquid introdu~Qd i~to inlet 26 will ~pread more uni~ormly over plate ~4. To accGmmodate ~he new location of liguid inl~t 26, gas inlet 60 may be mo~ed to the 6ida and mu~t al60 pass through plate 24. ~as outl~t 62 (not 6hown in Figure 5) may al~o b~ placed in an o~f-~enter location.
Figure~ 6-11 show al~ernative embodiments of ~he spreader plate edge~wall area 52 shown in Figure 3. For example, in ~igure 6, ~he edge of ~he spreader plate 24 is provided with a ~mall dam 80 which aid~ in maintaining ~ i~W~ 92/18228 ~ ~ 0 8 ~ 5 ~ PCr/US92/03199 -13- .
a thin "pool" of liquid on the top of spreader plate 24 60 that the liquid will ~pread more evenly over pla~e 24. During operation, liquid will spill o~er ~he top of dam ~0 into gap 50 and the appara~us would perform sub~tantially a~ previou~ly described.
Figure 7 ~how~ an additional embodiment i~ which dam 80 has bsen exte~ded i~ heigh~ ~o orm a ~arrow gap 82 bQtween the upper e~d of dam 80 and cover 12. In this csse gap 5D i6 le~ ~ri~ieal ~inc~ gap ~2 (which may be smaller than gap 50) control~ ~he release of liquid from 6preader plate 24.
An additional ~mbodiment is ~hown in Figure 8 in which a knie edge 84 i6 pro~ided a~ the outer periphery of pl~te 24 ~o prosride ~he cleararl~e in gap 50 between plate 2~ and the wall 11 o~ bo~ 10.
Anoth~r embod~ment ~ show~ in Fi~ure 9 in which a drip lip 86 i8 provt~ed along the outer periphery of the lower edg~ of ~pread~r pla~e 24. Lip a6 preY~rlt~ uid pa6sing through gap 50 from running alor~g the bo~tom surface of plate 24 and dripping from plate 2~ directly i~to the pool of liguid a~ the bottom of the appar~tu6.
A further embodims~t is shown in Figure 10, in which the radius of the curved upper lip of ~ody 10 is increased and the di~meter of plate 2~ is i~creased from tha point where body 10 is 6ealed b~ O-ring 22 located in circular s~otch lS ~o that the outer edge of spreader plate 24 fi~ into the 6pace between the ~ur~red wall portion and the cover 12 as shown. In this embodiment, liguid spills off the edge of plate 24 against ~he WO 92/18228 Pcr/us~2/03199 ~i 2108~6~ -14-curved portion 86 of body 10 and ~hen run~ along ~he curved portion and down the in~ide wall o~ body 10 a6 schematically illustrated by arrow 100.
Anoth~r ambodiment is ~hown in Figure 11, which 2mbodimQnt utili~e~ a ~l~ghtly di~erQnt ~ody wall configuration. In particular, ~otch 15 in cov~r 12 ( ~hc>w~ in Figure lC ) has been eliminated a~d a corresponding cir::ular notch 19 has ~en molded i~to the top edg~ of body 10 to r~ceiYe tha ~eali~g 0-ring 22.
I~ ad~ition, the upp~r in~ida wall of body 10 ha~ a ~apered rection 102 which provides a 61a~ted sur*ace.
8prsader plate 24 has a tongue 108 which extend6 int~
the ~ap 106 b~tween the body 10 and cover pla~e 12 ~ormed by 0-ri~g 22. Bpreader plate 2~ ha~ circul~r rlot~hes 102 and 104 cut into its unders~de. ~lotch 102 re~lirect~ ~
liquid flowi~g along the ~ders~de o~ tongue lQ8 to provide b~th vertical &nd horizo~tal flow ~:ontrol.
~otch 104 ~cts as a drip gap to pr~ven~ 1i5ruid ~rom running ~long the under~ide of ~preader plate 24 ~d dropping off directly into the liquid po41 in the dQvice.
Although only a ~ew e~odime~t~ of ~he inve~tive apparatus have been desc:ribed, many modifiGatio~s a~d changes will be immediately apparent ~o those skilled in the art. These mc)difica~io~s ~nd ol:her obvious ch~ges are intendQd tc) be covered by the following claims, W~at is claimed is.
Claims
Serial No.: PT/US92/03199 -2-1. (Amended) Apparatus for diffusing gas into a liquid, said apparatus comprising:
a container having wettable walls oriented to cause the liquid to flow along said walls;
[means for spreading said liquid in a thin layer over said walls;]
a spreader plate having a surface and a periphery which approaches said walls or form a gap having a width between said periphery and said walls;
means for introducing the liquid onto said surface;
means for mounting said plate relative to said container walls to cause the liquid to flow over said surface towards said periphery and to form a gap width sufficiently small that surface tension in the liquid causes the liquid to bridge said gap and form a continuous film of liquid in said gab, which continuous film flows in a thin layer along said walls; and means for introducing said gas into said container in contact with [so that said gas diffuses into] said thin layer of liquid.
4. (Amended) Apparatus for diffusing gas into a liquid according to Claim [3] 1 wherein said gap [has a] width is [substantially in the range of] between approximately 0.051 to 0.102 centimeters (.020-.040) inches.
Serial No.: PT/US92/03199 -3-5. (Amended) Apparatus for diffusing gas into a liquid according to Claim [3] 1 wherein said gap has a width of approximately 0.05 centimeters (.020 inches).
6. (Amended) Apparatus for diffusing gas into a liquid according to Claim 1 wherein said walls have a substantially vertical orientation and said container has a top and a bottom and said liquid [is introduced into] introducing means is located at the top of said container.
7. (Amended) Apparatus for diffusing gas into a liquid according to Claim 6 wherein said [spreading means] spreader comprises a flat plate having a flat surface which extends perpendicularly to said walls, 10. (Amended) Apparatus for diffusing gas into a liquid according to Claim [9] 1 further comprising means located below said liquid introducing means for removing said liquid from said container [so that liquid flows continuously through said container].
Serial No.: PT/US92/03199 -4-11. (Amended) Apparatus for diffusing gas into a liquid comprising:
a container having vertically-oriented wettable walls, said container having a top and a bottom;
a spreader plate having a surface with a peripheryl[, said surface being mounted];
means for introducing the liquid onto said surface;
means for mounting said surface horizontally in said container and located near said container top with said plate periphery extending towards said container walls to cause said liquid to spread across said surface towards said walls and to form a gap [therewith] between said surface periphery and said walls, said gap having a width sufficiently small that surface tension in the liquid causes the liquid to bridge said gap and form a continuous film of liquid in said gap, which continuous film flows in a thin layer [means for introducing said liquid onto said surface, said liquid spreading across said surface towards said walls, flowing into said gap and] down said walls;
means for introducing said gas into said container [so that] to cause said gas [diffuses] to diffuse into said [thin layer] continuous film of liquid;
means for removing gas from said container [so that] to cause said gas [flows] to flow through said container; and Serial No.: PCT/US92/03199 -5-means located near said container bottom for removing said liquid from said container [so that] to cause said liquid [flows] to flow continuously through said container.
17. (Amended) Apparatus for diffusing gas into a liquid according to claim 11 wherein said r introducing] means for introducing the liquid onto said surface comprises a pipe located at said disk center.
18. (Amended) Apparatus for diffusing gas into a liquid according to claim 11 wherein said gap is [substantially in the range] between approximately 0.051-0.102 centimeters (.020-.040 inches).
19. (Amended) Apparatus for diffusing gas into a liquid according to claim 11 wherein said gap is approximately 0.051 centimeters (.020 inches).
Add the following new claim:
20. (New) Apparatus or diffusing gas into a liquid according to claim 1 wherein said plate is mounted so as to be substantially immobile relative to said container walls when said apparatus is operating.
a container having wettable walls oriented to cause the liquid to flow along said walls;
[means for spreading said liquid in a thin layer over said walls;]
a spreader plate having a surface and a periphery which approaches said walls or form a gap having a width between said periphery and said walls;
means for introducing the liquid onto said surface;
means for mounting said plate relative to said container walls to cause the liquid to flow over said surface towards said periphery and to form a gap width sufficiently small that surface tension in the liquid causes the liquid to bridge said gap and form a continuous film of liquid in said gab, which continuous film flows in a thin layer along said walls; and means for introducing said gas into said container in contact with [so that said gas diffuses into] said thin layer of liquid.
4. (Amended) Apparatus for diffusing gas into a liquid according to Claim [3] 1 wherein said gap [has a] width is [substantially in the range of] between approximately 0.051 to 0.102 centimeters (.020-.040) inches.
Serial No.: PT/US92/03199 -3-5. (Amended) Apparatus for diffusing gas into a liquid according to Claim [3] 1 wherein said gap has a width of approximately 0.05 centimeters (.020 inches).
6. (Amended) Apparatus for diffusing gas into a liquid according to Claim 1 wherein said walls have a substantially vertical orientation and said container has a top and a bottom and said liquid [is introduced into] introducing means is located at the top of said container.
7. (Amended) Apparatus for diffusing gas into a liquid according to Claim 6 wherein said [spreading means] spreader comprises a flat plate having a flat surface which extends perpendicularly to said walls, 10. (Amended) Apparatus for diffusing gas into a liquid according to Claim [9] 1 further comprising means located below said liquid introducing means for removing said liquid from said container [so that liquid flows continuously through said container].
Serial No.: PT/US92/03199 -4-11. (Amended) Apparatus for diffusing gas into a liquid comprising:
a container having vertically-oriented wettable walls, said container having a top and a bottom;
a spreader plate having a surface with a peripheryl[, said surface being mounted];
means for introducing the liquid onto said surface;
means for mounting said surface horizontally in said container and located near said container top with said plate periphery extending towards said container walls to cause said liquid to spread across said surface towards said walls and to form a gap [therewith] between said surface periphery and said walls, said gap having a width sufficiently small that surface tension in the liquid causes the liquid to bridge said gap and form a continuous film of liquid in said gap, which continuous film flows in a thin layer [means for introducing said liquid onto said surface, said liquid spreading across said surface towards said walls, flowing into said gap and] down said walls;
means for introducing said gas into said container [so that] to cause said gas [diffuses] to diffuse into said [thin layer] continuous film of liquid;
means for removing gas from said container [so that] to cause said gas [flows] to flow through said container; and Serial No.: PCT/US92/03199 -5-means located near said container bottom for removing said liquid from said container [so that] to cause said liquid [flows] to flow continuously through said container.
17. (Amended) Apparatus for diffusing gas into a liquid according to claim 11 wherein said r introducing] means for introducing the liquid onto said surface comprises a pipe located at said disk center.
18. (Amended) Apparatus for diffusing gas into a liquid according to claim 11 wherein said gap is [substantially in the range] between approximately 0.051-0.102 centimeters (.020-.040 inches).
19. (Amended) Apparatus for diffusing gas into a liquid according to claim 11 wherein said gap is approximately 0.051 centimeters (.020 inches).
Add the following new claim:
20. (New) Apparatus or diffusing gas into a liquid according to claim 1 wherein said plate is mounted so as to be substantially immobile relative to said container walls when said apparatus is operating.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US68717191A | 1991-04-18 | 1991-04-18 | |
| US07/687,171 | 1991-04-18 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2108665A1 true CA2108665A1 (en) | 1992-10-19 |
Family
ID=24759380
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002108665A Abandoned CA2108665A1 (en) | 1991-04-18 | 1992-04-17 | Apparatus for diffusing gas into a liquid |
Country Status (3)
| Country | Link |
|---|---|
| EP (1) | EP0580802A1 (en) |
| CA (1) | CA2108665A1 (en) |
| WO (1) | WO1992018228A2 (en) |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2563390A (en) * | 1951-08-07 | Carbonating apparatus | ||
| FR319059A (en) * | 1902-02-25 | 1902-11-03 | Ruelf | Automatic arrangement for the production of mineral waters, sparkling wines, 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 |
| CH259133A (en) * | 1945-04-07 | 1949-01-15 | Coca Cola Co | Apparatus intended for carbonation and the flow of beverages. |
| 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 (en) * | 1979-03-20 | 1980-10-17 | Carboxyque Francaise | Neutralising alkaline effluent with carbon di:oxide gas - which is contacted by descending, turning film of effluent |
| US4788020A (en) * | 1982-12-10 | 1988-11-29 | General Atomics | Method for effecting mass transfer |
-
1992
- 1992-04-17 CA CA002108665A patent/CA2108665A1/en not_active Abandoned
- 1992-04-17 WO PCT/US1992/003199 patent/WO1992018228A2/en not_active Application Discontinuation
- 1992-04-17 EP EP92917314A patent/EP0580802A1/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| WO1992018228A3 (en) | 1992-12-10 |
| EP0580802A1 (en) | 1994-02-02 |
| WO1992018228A2 (en) | 1992-10-29 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |