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bioreactor studies of heterologous protein production by ...

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where 6 = p- - p' + pp*, which is always positive because p- 2 $. Eq. (4.5) shows<br />

that the concentration <strong>of</strong> plasmid-hx œlls inmases with culture the. Letting B = X /<br />

f and dividing Eq. (4.5) <strong>by</strong> Eq. (4.2), one obtains:<br />

Differentiaüng Eq. (4.6) and rearranging the resuit yields:<br />

Substimting Eq. (4.6) into Eq. (4.7) gives:<br />

dB<br />

According to Eq. (4.8), the slope <strong>of</strong> a plot <strong>of</strong> - venus B is:<br />

dt<br />

and the intercept <strong>of</strong> the plot is:<br />

C, =p--p++pp+ (4.9)<br />

b = pp* (4.10)<br />

According to Eq. (4.2), a semilogarithmic plot <strong>of</strong> X versus tirne t yields a dope oE<br />

C, = v+-p~'-D=-k~ (4.1 1)<br />

Solving Eq. (4.91, (4.10) and (4.1 1) for the spsinc growth rate <strong>of</strong> ped-beeg celis,<br />

the s w c growth rate <strong>of</strong> plasruid-free celis and probability <strong>of</strong> plasmid los gives:<br />

p+=C,+b+D (4.12)<br />

p-=C,+C,+D (4.13)

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