Downstream phases

In the development of new products, optimization of the fermentation medium for titer only often ignores the consequences of the medium properties on subsequent downstream processing steps such as filtration and chromatography. It is imperative, therefore, that there be effective communication and understanding between workers on the upstream and downstream phases of the produc t development if rational trade-offs are to be made to ensure overall optimahty of the process. One example is to make the conscious decision, in collaboration with those responsible for the downstream operations, whether to produce a protein in an unfolded form or in its native folded form the purification of the aggregated unfolded proteins is simpler than that of the native protein, but the refolding process itself to obtain the product in its final form may lack scalabihty. 

Since the SF is a ratio of ratios, any measure of composition (mole fraction, mass fraction, concentration, etc.) can be used in Equation 7.1 as long as one consistently uses the same measure for both upstream and downstream phases in contact with the membrane. Locally within a module, the ratio of compositions leaving the downstream face of a membrane equals the ratio of the transmembrane fluxes of A vs. B. Local fluxes of each component are determined by relative transmembrane driving forces and resistances acting on each component. The ratio of the feed compositions in the denominator provides a measure of the ratio of the respective driving forces for the case of a negligible downstream pressure. This form normalizes the SF to provide a measure of efficiency that is ideally independent of the feed composition. 

Figure 2 illustrates the enormous importance of the biphase technique for homogeneous catalysis the aqueous catalyst solution is charged in the reactor with the reactants A and B, which react to form the solvent-dissolved reaction products C and D. C and D are less polar than the aqueous catalyst solution and are therefore simple to separate from the aqueous phase (which is recycled directly into the reactor) in the downstream phase separator (decanter). 

Vapor permeation and pervaporation are membrane separation processes that employ dense, non-porous membranes for the selective separation of dilute solutes from a vapor or liquid bulk, respectively, into a solute-enriched vapor phase. The separation concept of vapor permeation and pervaporation is based on the molecular interaction between the feed components and the dense membrane, unlike some pressure-driven membrane processes such as microfiltration, whose general separation mechanism is primarily based on size-exclusion. Hence, the membrane serves as a selective transport barrier during the permeation of solutes from the feed (upstream) phase to the downstream phase and, in this way, possesses an additional selectivity (permselectivity) compared to evaporative techniques, such as distillation (see Chapter 3.1). This is an advantage when, for example, a feed stream consists of an azeotrope that, by definition, caimot be further separated by distillation. Introducing a permselective membrane barrier through which separation is controlled by solute-membrane interactions rather than those dominating the vapor-liquid equilibrium, such an evaporative separation problem can be overcome without the need for external aids such as entrainers. The most common example for such an application is the dehydration of ethanol. 

When recycling material to the reactor for whatever reason, the pressure drop through the reactor, phase separator (if there is one), and the heat exchangers upstream and downstream of the reactor must be overcome. This means increasing the pressure of any material to be recycled. 

The vapor pressure of a crude oil at the wellhead can reach 20 bar. If it were necessary to store and transport it under these conditions, heavy walled equipment would be required. For that, the pressure is reduced (< 1 bar) by separating the high vapor pressure components using a series of pressure reductions (from one to four flash stages) in equipment called separators , which are in fact simple vessels that allow the separation of the two liquid and vapor phases formed downstream of the pressure reduction point. The different components distribute themselves in the two phases in accordance with equilibrium relationships. 

The method implies injection of a mixture of 3 radioactive tracers each being distributed into one of the 3 phases. The tracers must show such differences in the emitting y-radiation energy spectra that they can be simultaneously detected by on line y-spectrometry. Candidate tracers are Br-82 as bromobenzene for oil, Na-24 or La-140 for water, and Kr-85 for gas. The tracers are injected simultaneously at a constant rate into the flow in the pressurised pipe, and the concentration is detected as series of instantaneous measurements taken downstream as illustrated in figure 2. 

Immunoaffinity chromatography utilizes the high specificity of antigen—antibody interactions to achieve a separation. The procedure typically involves the binding, to a soHd phase, of a mouse monoclonal antibody which reacts either directly with the protein to be purified or with a closely associated protein which itself binds the product protein. The former approach has been appHed in the preparation of Factor VIII (43) and Factor IX (61) concentrates. The latter method has been used in the preparation of Factor VIII (42) by immobilization of a monoclonal antibody to von WiHebrand factor [109319-16-6] (62), a protein to which Factor VIII binds noncovalenfly. Further purification is necessary downstream of the immunoaffinity step to remove... 

Cavitation and Flashing From the discussion on pressure recoveiy it was seen that the pressure at the vena contracta can be much lower than the downstream pressure. If the pressure on a hquid falls below its vapor pressure (p,J, the liquid will vaporize. Due to the effect of surface tension, this vapor phase will first appear as bubbles. These bubbles are carried downstream with the flow, where they collapse if the pressure recovers to a value above p,. This pressure-driven process of vapor-bubble formation and collapse is known as cavitation. 

Pipe Lines The principal interest here will be for flow in which one hquid is dispersed in another as they flow cocurrently through a pipe (stratified flow produces too little interfacial area for use in hquid extraction or chemical reaction between liquids). Drop size of dispersed phase, if initially very fine at high concentrations, increases as the distance downstream increases, owing to coalescence [see Holland, loc. cit. Ward and Knudsen, Am. In.st. Chem. Eng. J., 13, 356 (1967)] or if initially large, decreases by breakup in regions of high shear [Sleicher, ibid., 8, 471 (1962) Chem. Eng. ScL, 20, 57 (1965)]. The maximum drop size is given by (Sleicher, loc. cit.)... 

FIG. 22-86 Process scheme for protein extraction in aqueous two-phase systems for the downstream processing of intracellular proteins, incorporating PEG and salt recycling. RepHnted from Kelly and Hatton in Stephanopoulos (ed), op. cit. adapted from Qre-oe and Kula, op. cit.]... 

Entrained Sohds Bubble Columns with the Sohd Fluidized by Bubble Action The three-phase mixture flows through the vessel and is separated downstream. Used in preference to fluidized beds when catalyst particles are veiy fine or subject to disintegration in process. 

When there is a choice, design for no flashing. When there is no choice, locate the valve to flash into a vessel if possible. If flashing or cavitation cannot be avoided, select hardw are that can withstand these severe conditions. The dowmstream line will have to be sized for tw o phase flow. It is suggested to use a long conical adaptor from the control valve to the downstream line. 

It is not a bad idea for the process engineer to familiarize himself with compressor surge controls. The interaction of the compressor surge controls with downstream process control valves can become a problem area later, and this study phase is not too early to put such items on a checklist. An LNG plant example comes to mind where such an operating problem existed. 

Pipe with high resistivity lining that contains semiconductive or nonconductive flammable liquids should be blown down with nitrogen rather than air. To avoid pinhole damage, the flow rate during blow-down should be no higher than normal liquid flow rate. Also, the possible hazards created in downstream tanks by charged, two-phase flow should be considered (5-2.5.4). 

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