Optimal operation of tangential flow MF has been investigated by several researchers.6,7 A typical flux-versus-trans-membrane pressure (TMP) relationship is shown in Figure 2. In general, this can be typified by
two regimes: i) a pressure-dependent regime in which an increase in TMP results in an increase in flux, and ii) a pressure-independent
regime in which increases in TMP do not further increase flux. As a general rule, it is recommended to operate at the transition
between these regimes to maximize flux while not permitting the TMP to rise to a level that would cause increased pore plugging
and fouling of the membrane. A similar relationship exists for the cross-flow velocity at a given TMP, the effect of which
also levels off at a certain point. Because TMP and cross-flow velocity are interdependent, one can maintain constant TMP
operation only by manipulating back-pressure on the membrane to vary the cross-flow velocity as the operation proceeds and
Figure 2. Typical flux-versus-trans-membrane pressure profile for cross-flow microfiltration
Microfiltration membranes used for cell culture harvest are often plagued with the problem of membrane fouling (i.e., irrecoverable
declines in membrane flux). The operating conditions for the MF operation and the cleaning regimen for the membranes after
use are both significant ways to address this issue. Another important variable is the membrane chemistry, with more hydrophilic
membranes generally being less susceptible to significant fouling.
Optimizing MF Harvest Operations
The development of an MF harvest process has been outlined as a step-by-step process.7 Two important determinants for using MF systems for mammalian cell culture harvest are the flux and the product yield. The
flux determines the surface area of membrane needed to process the cell culture broth, which has significant economic implications,
because too high a flux can foul the membrane and shorten membrane lifetime.
The measurements of flux versus TMP and cross-flow rate curves at various concentrations at laboratory scale typically are
the first series of experiments that are conducted. An easy way to carry out these experiments is to operate under total recycle
mode in which the permeate is fed back into the load tank to maintain a constant concentration level. Steady state flux can
then be measured over a few different cross-flow velocities to produce the flux versus TMP plot shown earlier in Figure 2.
In these initial experiments, the broth should be concentrated to a degree which will be representative of the final desired
concentration. Various membranes can be screened to identify ones that are optimal for the application because both the chemistry
and the pore size play an important role in determining flux and flux decay characteristics. It is usual to operate at the
transition point between the zones of increasing flux versus TMP and the zone of TMP-independent flux to maximize flux and
minimize detrimental effects of fouling and pore plugging.