Thiết kế hệ lên men

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Chng 4

Thit k h ln men

I. H ln men thng khuy

Ni phn ng sinh hc (bioreactor) hay cn gi l h ln men(fermenter) l loi thit b m trong n s bin i ha sinh c tin hnh

bi cc t bo sng hoc cc thnh phn t bo in vivo (enzyme). Trongchng ny, ni phn ng sinh hc nui cy cc t bo sng c gi lh ln men phn bit cc ni phn ng sinh hc dng cho cc enzyme.

Trong phng th nghim, cc t bo thng c nui cy trong cc bnhtam gic trn my lc. Lc nh bnh tam gic rt hiu qu to ra dchhuyn ph t bo, tng cng s oxy ha thng qua b mt cht lng v trgip s chuyn khi (mass transfer) ca cc cht dinh dng m khng gynguy him cho cu trc t bo.

bt

vch ngn

un nnglm lnh

turbin dt

khng kh v trng

Hnh 4. 1. S h ln men dng cho sn xut penicillin.

i vi hot ng sn xut quy m ln, th h thng ln men thngkhuy (stirred-tank fermenter, STF) c s dng rng ri nht thit k

cho qu trnh ln men cng nghip. N c thc dng cho c hai trnghp ln men hiu kh (aerobic) v ym kh (anaerobic) trong mt phm virng cc loi t bo khc nhau bao gm vi sinh vt, ng vt v thc vt.

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Hnh 4.1 gii thiu s h ln men dng trong sn xut penicillin.Cng pha trn (mixing intensity) c th rt khc nhau bng cch chnloi cnh khuy (impeller) thch hp v cc tc khuy khc nhau. Vicsc kh v khuy chc trong h ln men rt tt cho nui cy dch huyn

ph t bo, s oxy ha, s pha trn mi trng v truyn nhit. STF cng cthc dng cho cc mi trng c nht cao. N l mt trong nhngh ln men quy m ln u tin c pht trin trong cng nghip dc.c im v tim nng ca STF c nghin cu rng ri. Do h ln menthng khuy thng c lm bng thp khng r v hot ng trong iukin n ha nn tui th ca thit b rt lu.

Nhc im ca h ln men thng khuy bt ngun tu im ca

n. B phn (cnh) khuy rt hiu qu trong vic pha trn cc thnh phnca h ln men, nhng li tiu th mt lng ln cng sut v c th gynguy him cho nhng h thng t bo nui cy mn cm vi lc trt (shearforce) nh t bo ng vt c v hoc t bo thc vt. Lc trt ca chtlng trong hn hp c to ra bi gradient tc ca cc thnh phn tc (hng tm v tip tuyn) ca cht lng khi ri khi vng cnh khuy.Khi cht lng ri khi vng trung tm, th tc ca n v tr trn v di

cnh khuy (c khong cch bng chiu rng cnh khuy) s gim khong85% v to ra mt vng trt cao. Khi t l chiu rng cnh khuy trnng knh ca n tng th profile tc t c dng c trng ca parabolm trnn t hn v n to ra lc trt t hn do gradient tc ln dnln. V th, bng cch tng chiu rng cnh khuy, c thng dng thnhcng STF trong nui cy t bo ng vt hoc t bo thc vt.

Nhiu h ln men quy m phng th nghim c lm bng thy tinh

c np bng thp khng r. Cc thng ln men ln hn c lm bng thpkhng r. T l chiu cao trn ng knh ca thng ln men (vessel) hocl 2/1 hoc l 3/1 v thng c khuy bng hai hoc ba turbine khuy(cnh khuy). Trc cnh khuy c gn trn np hoc ty ca thng

bng gi . T lng knh cnh khuy (DI) trn ng knh ca thng(DT) thng l t 0,3-0,4. Trong trng hp h ln men c hai cnh khuy,th khong cch gia cnh khuy th nht vi y ca vessel v khong

cch gia hai cnh khuy bng 1,5 ng knh cnh khuy. Khong cchny gim xung cn 1,0 so vi ng knh cnh khuy trong trng hp hln men c ba cnh khuy. Bn vch ngn (baffles) cch u nhau thng

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c thit k ngn cn s hnh thnh dng xoy lm gim hiu sut phatrn. Chiu rng ca vch ngn thng bng 1/10 ng knh ca thng(tank). trng hp h ln men hiu kh (aerobic fermenter), th mt b

phun ln (single orifice sparger) hoc mt b phun vng c s dng

sc kh cho h ln men. B phn phun c t v tr gia cnh khuycui cng v y ca vessel. pH trong h ln men c thc duy trbng cch dng dung dch m hoc b iu chnh pH (pH controller).Nhit c iu chnh bng h thng gia nhit v lm lnh tng.

1. H ln men dng nt (plug-flow fermenter, PFF) hoc m (batchfermenter)

Mt h ln men khuy l tng phi c kh nng pha trn tt sao chocc thnh phn ng nht trong mt kt cu mi thi im. Mt h lnmen l tng khc l h ln men dng nt, mt dng tng ng ca h lnmen m.

Trong h ln men dng ng (tubular-flow fermenter), cht dinh dng(ccht) v t bo i vo mt u ca ng hnh tr v t bo s sinh trngtrong khi chng i qua ng ny. Do ng di v thiu b phn khuy nn

ngn cn s pha trn hon ton ca cht lng, v th tnh cht ca dng chythay i trong hai chiu tip tuyn v hng tm. Tuy nhin, s bin thintrong chiu hng tm nh hn chiu tip tuyn. Mt h ln men dng ngm khng c nhng bin thin hng tm th c gi l h ln men dngnt (PFF).

Thc t, h ln men PFF rt kh xy dng. Cho d h ln men PFFtrng thi n nh (steady state) c hot ng trong mt kiu lin tc, th

nng t bo ca h ln men m l tng sau thi gian t s ging nhnng t bo ca h ln men PFF trng thi n nh v tr chiu dc nim thi gian lu (residence time) bng t(Hnh 4.2). V th, s phn tchsau y ng dng cho c hai, h ln men m l tng v PFF trng thi nnh.

Nu mi trng lng c tip mu bng nui cy kt ht (seedculture), th t bo s bt u sinh trng theo hm m sau pha lag. Trongh ln men m, s thay i nng t bo bng tc sinh trng t bo:

XXX Cr

dt

dC== (4.1)

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V, CX, CS

CXoCso

fX

C fS

C pt

CXCs

to

F F

CX= CXoCs = Cso

(a)

t = to

(b)

Hnh 4.2. S (a) h ln men thng khuy m v (b) h ln men dng nt.

thu c phng trnh hiu sut ca ln men m, chng ta cn lytch phn phng trnh (4.1) sc:

0

000

ttdt

C

dC

r

dCt

t

C

C X

X

C

C X

XX

X

X

X

===

(4.2)

Cn lu rng, phng trnh (4.2) chc ng dng khi rX> 0. Vth, (trong phng trnh 4.2) khng phi l thi gian ca nui cy ban u

sau khi tip mu, m l thi gian t bo khi ng sinh trng, l giai onpha sinh trng bt u tng nhanh.

0t

Theo phng trnh (4.2), thi gian sinh trng tng m 0tt chnh l

din tch pha di ng cong X/r1 theo gia v (Hnh 4.3).ng cong lin tc hnh 4.3 c tnh ton bng phng trnh Monod vvng c mu ti bng

XC 0XC XC

0tt . Thi gian sinh trng tng m t khi c c

lng bng th ny v xc nh n th da vo ng cong ttheo

l n gin hn. Tuy nhin, biu din bng th s thun tin trong vic sosnh tim nng ca cc cu hnh h ln men khc nhau (sc tho lunsau). Lc ny ch lu rng, ng cong c mu ti dng ch U l c

trng ca ccphn ng xc tc tng:

XC

S + X X + X

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3

2

1Xr

1

0 2 4 6 8

CX

Hnh 4.3. th ca thi gian sinh trng tng m 0tt (vng ti). ng cong

lin tc biu din m hnh Monod vi max = 0,935/gi; g/L;71,0=SK

v;6,0=X/SY g/L;6,10 =XC g/L.100 =SC

Tc khi u ca phn ng xc tc tng chm do nng ca

X thp. Tc phn ng tng ln khi cc t bo sinh sn v sau stn tc ti a. Khi lng ccht gim v cc sn phm c c tchly, th tc phn ng gim xung gi tr thp hn.

Nu ng hc Monod (Monod kinetics) biu din thch hp tc sinh trng trong sut pha hm m, th chng ta c th thay th phngtrnh (3.11) chng 3 vo phng trnh (4.2) c c:

=

+ t

t

C

C XS

XSS dt

CC

dCCKX

X 00max

)(

(4.3)

Phng trnh (4.3) c th tnh c tch phn nu chng ta bit miquan h gia CSv CX. Ngi ta quan st thy rng s lng sinh khi t

bo c sn xut t l vi lng ccht gii hn c tiu th. Hiu sutsinh trng ( ) c nh ngha nh sau:X/SY

)( 0

0

SS

XX

S

X

X/S CC

CC

C

CY

=

= (4.4)

Thay phng trnh (4.4) vo phng trnh (4.3), tch phn ca phngtrnh tng hp ny sa ra mi quan h gia nng t bo v thi gian:

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( )S

S

SXSX

SXS

X

X

SXSX

SXS

C

C

YCC

YK

C

C

YCC

YKtt 0

00000

lnln1/

/

/

/max0

++

+

+= (4.5)

2. H ln men thng khuy lin tc (continuous stirred-tank fermenter-CSTF) l tng

Qun th t bo c th tip tc giai on sinh trng hm m trongmt thi gian di bng cch duy tr h thng nui cy lin tc. Hnh 4.4trnh by s h ln men thng khuy lin tc (CSTF). Bung sinh trng(thng ln men hay bnh nui) c kt ni vi bnh cha mi trng vtrng. Khi qu trnh sinh trng bt u th mi trng sch c cung cp

lin tc t bnh cha mi trng.H thng nui cy lin tc c th hot ng nh l mt chemostat (th

n nh ha tnh) hoc turbidostat (thn nh c). Trong chemostat tc dng chy c ci t mt gi trc bit v tc sinh trng canui cy s iu chnh tc dng chy ny. Ni chung, hot ngchemostat d dng hn turbidostat, do n c thc thc hin bng ccht my bm mt tc dng chy khng i, trong khi turbidostat ihi mt thit b cm quang (optical sensing device) v mt biu chnh(controller). Tuy nhin, turbidostat c gii thiu khi h ln men lin tccn c tin hnh cc tc pha long cao gn vi im ra tri(washout point), khi ta c th ngn cn s ra tri bng cch iu ha tc dng chy trong trng hp tht thot t bo thng qua dng chy ra ngoivt qu s sinh trng t bo trong h ln men.

CXi

CsiF

V, CX, CSCXCs

F

Hnh 4.4. S h ln men thng khuy lin tc (CSTF).

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Cn bng nguyn liu cho t bo trong CSTF (Hnh 4.4) c thcvit nh sau:

dt

dCVVrFCFC XXXXi =+

(4.6)

Trong : rXl tc sinh trng t bo trong h ln men vbiu din s thay i nng t bo trong h ln men theo thi gian.

dtdCX /

i vi CSTF hot ng trng thi n nh, th s thay i nng tbo theo thi gian l bng khng ( )0/ =dtdCX do cc t bo trong bnhnui ch sinh trng nhanh thay th nhng t bo b hao ht theo dngchy ra ngoi, v phng trnh (4.6) trthnh:

X

XX

mr

CC

F

Vi

== (4.7)

Phng trnh (4.7) cho thy thi gian lu cn thit (m) bng din tchhnh ch nht c chiu rng

iXXCC v chiu cao trn ng cong

theo CXr/1

Xr/1 X.

Hnh 4.5 biu din ng cong theo CXr/1 X. Din tch hnh ch nhtc t m trong hnh bng thi gian lu trong CSTF khi dng chy vo

l v trng. Minh ha thi gian lu bng th c th gip chng ta so snhhiu qu ca cc h ln men. H ln men c thi gian lu ngn hn (tti mt nng t bo nht nh) l hiu qu hn. Hot ng ti u ca hln men da trn s minh ha th ny sc tho lun trong phn tiptheo.

4

3

2

1

0 2 4 6

XC

Xr1

Hnh 4.5. Minh ha bng thc lng thi gian lu cho CSTF. ng biudin m hnh Monod vi max = 0,935/gi; 71,0=SK g/L; 0,6;

g/L; v

=X/SY

10=iS

C =iX

C 0.

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Nu dng chy vo l v trng ),0( =iX

C v t bo trong CSTF

ang sinh trng theo hm m )( XX Cr = th phng trnh (4.7) s tr

thnh:

Dm

11== (4.8)

Trong : Dc bit nh l tc pha long v c gi tr bngnghch o ca thi gian lu ( m ). V th, i vi CSTF trng thi n

nh c cht dinh dng v trng, th tc sinh trng c trng bngtc pha long. Mt khc, tc sinh trng c trng ca t bo cth c iu chnh bng cch thay i tc dng chy mi trng.

Nu tc sinh trng c thc biu din bng phng trnh Monod,th sau :

SS

S

m CK

CD

+=== max

1

(4.9)

T phng trnh (4.9), CS c thc tnh ton bng thi gian lu bit v cc thng sng hc Monod nh sau:

1max =

m

SS

KC (4.10)

Tuy nhin, cn ch rng phng trnh (4.10) ch c gi tr khi1max >m . Nu 1max


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Tng t:

+=

1max/

m

SSSPPiP

KCYCC

i (4.13)

Trong : CPl nng sn phm, CPil nng sn phm a vo.

Mt ln na, phng trnh (4.12) v (4.13) ch c gi tr khi1max >m .

Trong phn ny, chng ta t cn bng nguyn liu cho nng tbo v thu c cc phng trnh khc nhau cho CSTF. Cc phng trnhtng t cng c th thu c bng cch t cc cn bng nguyn liu cho

nng ccht v nng sn phm.

3. c lng cc thng sng hc Monod

ng thc tc sinh trng c trng v tc pha long ca CSTFtrng thi n nh (phng trnh 4.9) tin li trong nghin cu nh hngca cc thnh phn khc nhau ca mi trng ln tc sinh trng ctrng. Bng cch o nng c cht trng thi n nh vi cc tc

dng chy khc nhau, cc m hnh ng hc khc nhau c thc thnghim v gi tr ca cc thng sng hc c thc c lng. Sp xpli phng trnh (4.9) c th thu c mi quan h tuyn tnh nh sau:

maxmax

111

+=

S

S

C

K (4.14)

Trong :bng tc pha long (D) cho chemostat. Nu mt t bonht nh tun theo ng hc Monod, th th /1 theo sem li

gi trSC/1

max vKS (bng cch c phn b chn v dc ca ng thng).

th ny c u im cho thy mi quan h gia bin c lp (CS) v binph thuc . Tuy nhin, /1 s tin ti nu nng ccht gim dn

n trng lng vt qu mc o khi nng c cht thp v trnglng khng o khi cc nng ccht cao.

Phng trnh (4.9) c th sp xp li a ra cc mi quan h tuyntnh ng dng thay cho phng trnh (4.14) nhm c lng tt hn ccthng s trong nhng trng hp nht nh:

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maxmax

SSS CKC += (4.15)

SS C

K

=max

(4.16)

Tuy nhin, gii hn ca php tnh gn ng ny ( xc nh ccthng sng hc) gp kh khn khi s dng CSTF. i vi trng hpvn hnh theo tng m, chng ta thm ch c th dng bnh tam gic lc trnmy lc vn hnh nhiu m vi cc iu kin khc nhau trong cng mtthi gian. Vn hnh theo tng m trong ni ln men c khuy cng khngkh khn lm, do khng c cc kt ni i vo v i ra (ngoi tr b phncung cp khng kh) v thi gian vn hnh ngn, t c nguy cca s nhim

bn h ln men.

vn hnh CSTF, chng ta cn c cc ngun cung cp dinh dngv tch tr sn phm c kt ni v trng vi h ln men. Tc ca ccdng chy vo v ra khi h ln men cn c kim sot mt cch chnhxc. Thnh thong, vic kim sot tc dng chy ra c th gp kh khndo s to bt v kt khi ca cc t bo. Do thi gian vn hnh t nht mt

vi ngy hoc thm ch c tun t ti trng thi n nh (cng gy ra sbin i tc pha long), cho nn lun c ri ro cao i vi h ln men dob nhim bn. Thng xuyn gp kh khn trong vic t ti trng thi nnh bi t bin ca t bo v kh nng thch nghi vi mi trng mi cachng.

Hn na, do hu ht cc h ln men quy m ln c tin hnh trongkiu tng m, cho nn cc thng sng hc c xc nh bi nghin cu

chemostat phi d bo c s sinh trng trong kiu ln men ny. Tuynhin, bng chng (kim tra v xc minh) m hnh ng hc v c lngcc thng sng hc bng cch vn hnh chemostat l phng php ngtin cy nht do iu kin mi trng khng thay i ca n.

Cc s liu ca vn hnh theo tng m c thc dng xc nhcc thng s ng hc, cho d n khng phi l phng thc c giithiu cao. Tc sinh trng c trng trong sut qu trnh vn hnh theotng m c thc c lng bng cch o dc ca ng cong nng t bo theo thi gian cc im khc nhau. Nng ccht cn thitc o cng cc im ni m dc c c. Sau cc th theocc phng trnh (4.14), (4.15) v (4.16) c thc xy dng xc nh

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cc thng sng hc. Tuy nhin, gi tr ca cc thng s thu c trongphng php ny cn thit c kho st cn thn xem chng c trongphm vi hp l cho cc t bo c kim tra hay khng.

4. Hiu sut ca CSTF

Thng thng, hiu sut ca h ln men c hiu nh l s lngsn phm c sn xut trn mt n v thi gian v th tch. Nu dngchy vo l v trng )0( =

iXC th hiu sut sinh khi t bo bng mXC / ,

chnh l dc ca ng thng OAB ca ng cong CX theo m (Hnh4.6).

10

8

6

4

2

0

XC

D0 2 4 6O

m

A

C B

Hnh 4.6. S thay i nng t bo v ccht nh l mt hm ca thi gian lu.

Hiu sut bng dc ca ng thng OAB. ng cong c v bng m hnhMonod vimax = 0,935/gi;KS= 0,71 g/L; YX/S= 0,6; v 10=

iSC g/L.

Hiu sut im A bng hiu sut im B. im A nng tbo ca dng chy ra thp nhng thi gian lu li ngn, v th mi trngc th chy qua d dng hn. Ngc li, im B nng t bo ca dngchy ra cao nhng thi gian lu li di v th ch c mt lng nh ca mitrng chy qua. im A l vng khng n nh v rt gn vi im ra triD, v v ch cn mt s dao ng nh trong thi gian lu cng c themli mt s thay i ln trong nng t bo. Khi dc ca ng thng

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tng ln th hiu sut s tng v di ca BA gim. dc ca ngthng st gi tr cc i khi n l ng tip tuyn ca ng cong CX.

V th, gi tr hiu sut cc i bng dc ca ng OC . Hiu sut cci st c im D.

iu kin hot ng t hiu sut cc i CSTF c thc lngtheo th bng cch dng ng cong theo CXr/1 X. Hiu sut cc i c

th thu c khi thi gian lu l ti thiu. V thi gian lu bng din tchca hnh ch nht vi chiu rng CX v chiu cao trn ng cong

theo CXr/1

Xr/1 X, cho nn n st ti thiu khi l ti thiu (Hnh 4.7).Xr/1

4

3

2

1

02 4 6

XC

Xr

1

Hnh 4.7. Minh ha bng th CSTF vi hiu sut cc i. ng lin tc biudin cho m hnh Monod vi max = 0,935/gi; KS = 0,71 g/L; YX/S = 0,6;

g/L; v10=iS

C 0=iX

C .

iu cn lu l iu chnh cc phng trnh cho nng t bo vthi gian lu sao cho hiu sut t bo t cc i. Hiu sut t bo choCSTF trng thi n nh vi cht dinh dng v trng l:

SS

XS

X

m

X

CK

CCr

C

+== max

(4.17)

Hiu sut t cc i khi =XX dCdr / 0, sau khi thay th

vo phng trnh (4.17), ly tch phn theo CSXXSS YCCC i //= X v t

phng trnh tng hp bng 0, chng ta thu c nng t bo ti ucho hiu sut cc i nh sau:)( ,optXC

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1/, +=

iSSXoptX

CYC (4.18)

Trong :

S

SS

K

CKi

+= (4.19)

V:SX

XSS

Y

CCC

i

/

= nn nng ccht ti u (CS, opt) s l:

1, += iS

optS

CC (4.20)

Thay phng trnh (4.20) vo phng trnh (4.17) thu c mtthi gian lu ti u (m,opt) nh sau:

)1(max,

=

optm (4.21)

5. So snh nui cy ca h ln men m v h ln men thng khuy lin tc

Nh cp, thi gian lu cn thit nui cy m hoc PFF trngthi n nh t ti mt nng t bo nht nh l:

+=

X

X

C

C X

X

b r

dC

t0

0 (4.22)

Trong : t0 l thi gian cn thit t ti pha sinh trng theo hmm. Din tch bn di ca ng cong theo CXr/1 X, gia v CiXC X l

bng 1tb nh c trnh by hnh 4.3.

Mt khc, thi gian lu CSTF c biu din bi phng trnh(4.17) bng din tch hnh ch nht vi chiu rng

iXXCC , v chiu cao

.Xr/1

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V ng cong theo CXr/1 X c dng hnh ch U nn chng ta c th

c mt vi nhn xt cho h ln men n nh sau:

- Hu ht cc h ln men sn xut l mt CSTF hot ng vi nng t bo m gi tr ca l ti thiu (Hnh 4.8 a) do n i hi thi

gian lu ngn nht.

Xr/1

- Nu nng cui cng ca t bo c hng ti trong pha tnh,th h ln men m l chn la tt hn CSTF, v thi gian lu cn thit chonui cy m (Hnh 4.8 b) l ngn hn ca CSTF.

ba

Xr

1

Xr

1

XC XC

Hnh 4.8. Minh ha bng th thi gian lu c yu cu (vng ti) cho: (a)

CSTF v (b) h ln men m.

II. Thu hi t bo

i vi hot ng lin tc ca PFF v CSTF, cc t bo tht thotcng vi dng chy ra (outlet) hn ch hiu sut ca h ln men. V th,hiu sut c thc ci thin bng cch thu hi (recycling) t bo t dngchy ra a trli h ln men.

1. Thu hi tbo PFF

PFF i hi s hin din ban u ca t bo trong dng chy vo

(inlet) nh l mt h ln men mi hi a mu vo ban u. Phng thckinh t nht cung cp t bo trong dng chy vo l thu hi mt phn ca

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dng chy ra a trli dng chy vo vi (hoc khng c) thit b tch rit bo.

Hnh 4.9 m t s thu hi t bo PFF. Khng ging nh CSTF,PFF khng i hi thit b tch ri t bo thu hi, v s hin din ca n

khng lm tng ng k hiu sut ca h ln men.Phng trnh hiu sut ca PFF vi ng hc Monod c thc vit

nh sau:

+

==+

=+

fX

X

fX

X

C

C XS

XSS

C

C X

Xp

CC

dCCK

r

dC

RFR

V

'' max

)(

1)1(

(4.23)

Trong : p l thi gian lu da trn tc dng chy ca ton bh thng. Thi gian lu thc t trong h ln men ln hn p do tc dng

chy tng ln nhthu hi t bo.

RF

(1 +R)F

CXR,Csf

CXCs

CXiCsi

CXf

Csf

F B

CXL= 0Csf

L

Hnh 4.9. S thu hi t bo PFF.

Nu hiu sut sinh trng l khng i th:

)(1 ''

XX

X/S

SS CCY

CC = (4.24)

Thay phng trnh (4.24) vo trong phng trnh (4.23) cho CS v lytch phn ta s c kt qu sau:

f

f

S

S

SXSX

SXS

X

X

X/SSX

X/SSp

CC

YCCYK

C

C

YCCYK

R

'

/''

/'''

max lnln11 ++

++=+

(4.25)

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Trong : v c thc c lng t s cn bng t bo v

ccht im phi trn ca dng chy vo v dng chy thu hi nh sau:

'XC

'SC

R

RCCC Ri

XX

X+

+=

1

' (4.26)

R

RCCC Ri

SS

S+

+=

1' (4.27)

Nng t bo ca dng chy ra, c thc c lng t ton b scn bng t bo nh sau:

[ ])(1

fiif SSX/SXX CCYCC += (4.28)

Nng t bo ca dng chy thu hi c thc c lng t scn bng t bo trn b lc nh sau:

fR XXC

R

RC

+=

1 (4.29)

Trong : l t l x (bleeding) c nh ngha nh sau:

F

B= (4.30)

Hnh 4.10 trnh by hiu qu ca tc thu hi (R) trn thi gian luca h thng PFF c thu hi. Lu rng thi gian lu c tnh ton datrn tc dng chy vo, l thi gian lu thc s ca h ln men. Thi

gian lu thc t trn h thng PFF l khng quan trng bi v n s gimxung khi tng tc thu hi.

Khi = 1, tc x s bng tc dng chy, v tc dng chyca phn c lc L l bng 0, v th dng chy thu hi khng c lc.Thi gian lu s l v hn nuR bng 0 v gim r rt khiR tng ln. Trongtrng hp ny t l thu hi ti u c thtrong khong 0,2.

Mt ng cong khc trong hnh 4.10 l cho FB /= = 1,8. Thi

gian lu cn thit c th gim bng cch tp trung dng chy thu hi t 25-40% khi R trong khong 0,2-1,0. Khi R 1,2, th mt on ca ng

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cong c biu din bng du chm, bi v kh c th gim t l thu hixung di 0,2 khi= 0,8.

= 1

= 0,80,0 0,2 0,4 0,6 0,8 1,0

8

6

4

2

0

F

Vp =

Hnh 4.10.nh hng ca tc thu hi (R) v t l x ( FB /= ) ln thi gian

lu (p = V/Fgi) ca h thng PFF c thu hi. ng cong c v bng m hnhMonod vi max = 0,935/gi;KS= 0,71 g/L; YX/S= 0,6; = 10 g/L; = 1,3 g/L;

v = 0.iS

CfS

C

iXC

Vic phn tch trong phn ny v cc phn sau cng c thc ngdng trong cc b lng t bo nh l mt b phn phn tch t bo. Dngchy ra ca b lng t bo s bng F = B+L v nng ca n s l

.)/(ff XX

CCFB =

2. Thu hi tbo CSTF

Hiu sut t bo trong CSTF tng ln cng vi vic tng tc phalong v t n gi tr cc i. Nu tc pha long tng ln qu im cci, th hiu sut ca h ln men s gim t ngt v t bo s bt u b phalong do tc sinh sn t bo km hn s hao ht t bo dng chy ra.Mt phng thc ci thin hiu sut h ln men l thu hi t bo bng cchtch ri t bo khi dng chy sn phm bng h lc dng chy ngang

(cross-flow filter unit) (Hnh 4.11).

Nng cao ca t bo (c duy tr bng cch thu hi t bo) s lmtng hiu sut t bo khi tc sinh trng t l tng ng vi nng t

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bo. Tuy nhin, phi c gii hn trong vic tng hiu sut t bo vi victng nng t bo bi v trong mi trng c nng t bo cao, th tc chuyn khi cht dinh dng s b gim do vic dn vo mt ni qung v gy kt khi ca t bo. Vic duy tr nng qu cao ca t bo

cng khng c li bi v b phn lc s thng xuyn b hng hn trnghp nng t bo cao.

CXiCsi

F

V

CXL= 0Csf

L

CXfCsf

B

Hnh 4.11. S thu hi t bo CSTF.

Nu tt c t bo c thu hi trli trong h ln men, th nng tbo s tng lin tc theo thi gian v trng thi n nh s khng bao gitc. V th, hot ng ca CSTF c s thu hi trng thi n nh,chng ta cn c mt dng x (Hnh 4.11). Phng trnh cn bng nguynliu cho t bo trong h ln men c b phn thu hi t bo c dng nh sau:

dt

dCVCVBCFC XXXXi =+ (4.31)

Cn lu rng, tc dng chy thc ti vo v i ra khi b phnlc khng quyt nh hon ton n s cn bng tt c nguyn liu. i viCSTF trng thi n nh c s thu hi t bo v cht dinh dng v trng,th:

==

m

D (4.32)

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Lc ny D thay cho D v bng tc sinh trng c trng. Khit bo khng c thu hi, v th= .1=D

Nu tc sinh trng c th biu din bng ng hc Monod, ththay th phng trnh (3.11) chng 3 vo phng trnh (4.32) ta c:

=

maxm

SS

KC (4.33)

CS ch c ngha khi .max >m Nng t bo trong h ln men c

thc tnh ton t gi tr ca CSnh sau:

)(/ SSSXX CCYC i = (4.34)

Hnh 4.12 cho thy nh hng ca t l x ln hiu sut t bo i vim hnh Monod. Khi b gim xung t 1 (khng thu hi) ti 0,5 th hiusut t bo c tng ln gp i.

10

8

6

4

2

0

XDC

Khng thu hi

= 0,05

0,0 0,5 1,0 1,5 2,0

D

Hnh 4.12. nh hngca t l x ln hiu sutt bo (DCX).

III. Cc h ln men khc

Nhiu h ln men khc c xut v th nghim. Cc h lnmen ny c thit k ci thin hoc nhc im ca h ln men thngkhuy (tiu th cng sut ln) hoc cc yu cu c bit ca mt qu trnh

ln men nht nh nh: sc kh tt hn, chuyn nhit hiu qu, tch hoc gili t bo, bt ng t bo, gim bt thit b v gi thnh ca sn phm, vthng khng c thit k cho quy m ln.

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Cc h ln men thng c phn loi da trn cscc kiu bnhnui ca chng nh l thng, ct, hoc cc h ln men vng (loop). C haih ln men thng v ct c xy dng trn csbnh nui hnh tr. C th

phn loi da theo t l chiu cao (H) trn ng knh (D) nh sau:

H/D < 3 cho h ln men thng.H/D > 3 cho h ln men ct.

H ln men vng l h ln men thng hoc ct c vng lu thng chtlng, (c th l ng thng gi (draft) gia hoc l mt ci vng gn bnngoi h ln men).

C th phn loi cc h ln men theo mt cch khc da trn csccthnh phn ca h ln men c phi hp nh th no: bi kh nn, bi b

phn chuyn ng chc bn trong, hoc bi bm cht lng bn ngoi. Cch ln men tiu biu trong mi loi c trnh by bng 4.1, v cc u imv nhc im ca ba loi h ln men cbn c trnh by bng 4.2.

Bng 4.1. Phn loi cc h ln men.

Ngun trn scp

Loi bnhnui Kh nn Cc b phn chuyn

ng bn trongBm bn ngoi

Thng - Thng khuy -

Ct Ct bong bng

Ct hnh nn

Nhiu giai on

(hoc t)

Khay sng (ry)

m nhi

Vng p lc khng khy ln theo chuk

Vng chn vt Vng tia

1. H ln men ct (column fermenter)

H ln men n gin nht l h ln men ct bong bng (cn gi l hln men thp-tower fermenter), thng bao gm mt bnh tr di, c b

phn phun kh di y (Hnh 4.13 a-c). Cc thnh phn ca h ln menc trn bng cch tng s lng bong bng ln, cng l yu t c thcung cp oxygen cn thit cho t bo. Khi cc t bo lng xung, nng

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cao ca t bo c thc duy tr phn thp hn ca ct m khng c btk mt thit b no tch ri chng.

Tuy nhin, h ln men ct bong bng thng b hn chtrng hpln men hiu kh v vic tng cc bong bng khng th cung cp mt s pha

trn y cho s sinh trng ti u. Ch c phn thp hn ca ct c thduy tr nng t bo cao dn n s ln men ban u nhanh c tip theobi s ln men chm hn do cc ccht mong mun b gim i. Khi nng t bo tng ln trong h ln men, cn c lu tc khng kh cao duy trdch huyn ph t bo v s pha trn. Tuy nhin, lu tc khng kh tng lnc th gy ra s to bt nhiu v vic duy tr cc bong bng kh trong ctdn n lm gim hiu sut ca h ln men. Khi bong bng tng ln nhiutrong ct chng c th kt thnh mt khi nhanh chng lm gim tc

chuyn oxygen. V th, cc h ln men ct c th khng thay i c vhn ch mt phm vi kh hp cc iu kin hot ng.

Bng 4.2. u im v nhc im ca cu hnh ba h ln men cbn.

Loi u im Nhc im

Thngkhuy

1. Linh hot v d thch ng2. Phm vi mt pha trn rng

3. C th s dng mi trng c nht cao

1. Tiu th cng sut ln2. Gy tn hi cho cc tbo mn cm vi lc trt

3. Gi thnh thit b cao

Ctbongbng

1. Khng c cc b phn chuyn ng

2. n gin

3. Gi thnh thit b thp4. Nng t bo cao

1. Pha trn km

2. To bt d tha

3. Gii hn i vi hthng c nht thp

Lcykhngkh

1. Khng c cc b phn chuyn ng

2. n gin

3. Hiu sut ht kh cao

4. Chuyn nhit tt

1. Pha trn km

2. To bt d tha

3. Gii hn i vi hthng c nht thp

khc phc nhc im ca h ln men ct, mt vi kiu thit kkhc c xut. H ln men ct hnh chp ngc (Hnh 4.13 b) c th

Cng ngh tbo 53


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duy tr lu tc khng kh cao trn mt n v din tch phn thp hn cah ln men m c nng t bo cao. Mt vi khay sng lc c thc ci t trong ct (Hnh 4.13 c) tng hiu qu tip xc kh-cht lngv ph v s kt khi ca bong bng kh. tng cng s pha trn mkhng c cc phn chuyn ng bn trong, dch ln men (mi trng) c thc bm ra ngoi v quay vng (tun hon) bng cch dng mt bm chtlng bn ngoi (Hnh 4.13 d v e).

Khng kh

(a) (b) (c) (d) (e)

Hnh 4.13. Cc h ln men ct: (a) ct bong bng (bubble column), (b) ct hnhnn (tapered column), (c) ct bong bng c khay sng lc (sieve-tray bubblecolumn), (d) ct bong bng c khay sng lc vi bm bn ngoi, (e) ct nhi(packed-bed) vi bm bn ngoi.

2. H ln men vng (loop fermenter)

H ln men vng l h ln men thng (tank fermenter) hoc ct

(column fermenter) c vng lu thng cht lng, n c th l mt ng thnggi gia hoc l mt ci vng bn ngoi. Ty thuc vo s lu thngcht lng c to ra nh th no, m h ln men c phn loi thnh bakiu: lc y khng kh (air-lift), vng khuy (stirred loop) v vi phun (jetloop) (Hnh 4.14).

S lu thng cht lng ca h ln men dng lc y nhvo vic phunkhng kh to ra s khc nhau v mt gia phn giu bong bng cacht lng trong tm ng (riser) v phn c rt ht bong bng nng hn

ca cht lng trong y thng (downcomer) (Hnh 4.14 a). S pha trn v luthng cht lng trong thng ln men c thc tng cng bng cch gnthm mt b phn bm bn ngoi (Hnh 4.14 b). Tuy nhin, vic b sung

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bm lm gim u im ca h ln men nhlc y khng kh l hiu sutnng lng thp v n gin.

H ln men p lc chu k ICI (Imperial Chemical Industries Ltd.,England) l mt h ln men dng lc y khng kh vi mt vng bn ngoi

(outer loop) c pht trin cho ln men hiu kh i hi c s chuyn nhit.Mi trng v khng kh c a vo trong cc phn cao hn v thp hn(Hnh 4.14 c). Khng kh phc v cho hai mc ch: cung cp oxygen cn thitcho s sinh trng ca t bo v to ra s lu thng t nhin ca cht lngtrong h ln men thng qua mt ci vng. B phn trao i nhit lm lnhmi trng lng c ci t vo trong ci vng . H ln men ny cchng minh l to ra mt tc hp th oxygen cao trn mt n v th tch.

Khng kh

(a) (b) (c)

Hnh 4.14. Cc h ln men vng: (a) lc y khng kh, (b) lc y khng kh cbm bn ngoi, (c) p lc chu k ICI.

IV. Cc k hiu

B tc chy ca dng x, m3/s

t l x, c nh ngha nhB/F

PC nng sn phm

iPC nng sn phm a vo

CS nng ccht'SC nng ccht im phi trn ca dng chy vo v dng chy

thu hi

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0SC nng ccht ti thi im t0

fSC nng ccht sau khi ra khi h ln men

iSC nng ccht a vo

optSC , nng ccht ti uCX nng t bo

'XC nng t bo im phi trn ca dng chy vo v dng chy thu

hi

0XC nng t bo ti thi im t0

fXC nng t bo sau khi ra khi h ln men

iXC nng t bo a vo

LXC nng t bo thu hi qua lc

RXC nng t bo ca dng chy thu hi

optXC , nng t bo ti u

D tc pha long, s-1

F tc dng chy, m3/s

m thi gian lu, s

optm, thi gian lu ti u, s

p thi gian lu da trn tc dng chy ca ton b h thng

b thi gian lu cn thit nui cy m hoc PFF trng thi n nh

t ti mt nng t bo nht nhKS h s h thng

L tc dng chy qua lc, m3/s

tc sinh trng c trng, s-1 hoc kg/m3/s

max tc sinh trng cc i

R tc thu hi

rX tc sinh trng t boV th tch lm vic ca h ln men, m3

YP/S hiu sut sn phm/ccht

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YX/S hiu sut sinh trng/ccht

X t bo trn cstrng lng kh

Ti liu tham kho/c thm

1. Asenjo JA and Merchuk JC.1995. Bioreactor System Design. MarcelDekker, Inc.New York, USA.

2. Atkinson B and Mavituna F. 1991. Biochemical Engineering andBiotechnology Handbook. 2nd ed. Stockton Press, New York, USA.

3. Flickinger MC and Drew SW. 1999. Encyclopedia of BioprocessTechnology: Fermentation, Biocatalysis and Bioseparation. John Wiley & Sons,New York, USA.

4. Lee JM. 2001. Biochemical Engineering.Prentice Hall, Inc. USA.

5. Shuler ML and Kargi F. 2002. Bioprocess Engineering-Basic Concepts.2nd ed.Prentice Hall, Inc. NJ, USA.

6. Vogel HC and Todaro CL. 1997. Fermentation and BiochemicalEngineering Handbook (Principles, Process Design, and Equipment). 2nd ed.NoyesPublications. New Jersey, USA.

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