Fundamentals Typical Unit Operations

Comprehensive descriptions of the basic unit operations commonly used in the production of biotechnology products are available in the literature (14). This section focuses on the typical unit operations currently used for production of biological molecules in cell culture and the technologies used for the purification of pharmaceutical proteins. For each of these operations, laboratory and pilot scale experiments provide the basis for scale-up, particularly to define the expected range of process operating parameters. 

Commercial manufacturing operations in biotechnology usually employ bioreactors or fermentors for product expression. In this discussion, the term fermentor will refer to bacterial or fungal processes and the term bioreactor to animal cell cultures. While extensive description of the operation 

Coagulation factors Recombinate (F VIII) Hemophilia rCHO, bleed-feed 

Enzymes Pulmozyme (Dnase I) Cystic fibrosis rCHO, suspension 

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The reactor effluent usually contains a mixture of reactants and products. It is fed into a separation section where the products are separated by some means from the reactants. Because of their economic value, reactants are recycled back to upstream units toward the reactor. The products are transported directly to customers, are fed into storage tanks, or are sent to other units for further processing. The separation section uses one or more of the fundamental unit operations distillation, evaporation, filtration, crystallization, liquid-liquid extraction, adsorption, absorption, pressure-swing adsorption, etc. In this book we typically use distillation as the separation method because of its widespread use and our considerable experience with it. Everyone is a victim of his or her experience. Our backgrounds are in petroleum processing... 

The objective of this entry is to introduce the readers to the fundamental principles of gas-to-liquid mass transfer, as well as its major applications. Therefore, the first section of the entry is on the three fundamental mechanisms of gas-to-liquid mass transfer the film theory, the penetration theory, and the surface renewal theory followed by the applications of gas-to-liquid mass transfer in unit operations that are widely used in various chemical processes. There is a vast pool of reported literature on different aspects of gas-to-liquid mass transfer processes, all of which is impossible to be included in this entry. Therefore, only typical gas-to-liquid mass transfer processes are presented here. 

A fundamental requirement of distillation, as well as all other separations unit operations, is that intimate contact must occur between the phases at each stage in a cascade. In continuous distillation, this means intimate contact between the vapor and liquid phases in each stage. Typical equipment to achieve this requirement is a sieve tray. 

The campaigns in the FCPI are typically operated on a train/stream approach where a solid key reagent is introduced and a crystalline product is obtained. The average characteristics of a production campaign are presented in Table 13.4. Unit operations such as reaction, distillation, liquid-liquid extraction and crystallization are fundamental procedures in a multi-purpose train. A conventional batch vessel is able to perform all these operations, allowing flexibility and versatility in the production. 

Radar level transmitters and gauges use electromagnetic waves, typically in the microwave bands to make a continuous liquid and some solid level measurements. The radar sensor is mounted on the top of the vessel and is aimed down, perpendicular to the liquid surface. Most tank-farm gauges are operated on the FMCW principle (Figure 3.121). Other gauges and transmitters, particularly the lowest-cost units, are operated on the pulse principle. Both principles are fundamentally based on the time of flight from the sensor to the level of the surface to be measured. In the FMCW method, this time of flight is tracked on a carrier wave in the pulse method, it is the echo return. 

The steady-state model used in RTO typically is obtained either from fundamental knowledge of the plant or from experimental data. It utilizes the plant operating conditions for each unit such as temperature, pressure, and feed flow rates to predict properties such as product yields (or distributions), production rates, and measurable product characteristics (e.g., purity, viscosity, and molecular weight). The economic model involves the costs of raw materials, values of products, and costs of production as functions of operating conditions, projected sales figures, and so on. An objective function is specified in terms of these quantities in particular, operating profit over some specific period of time can be expressed as... 

Much of the fundaments we know about surface forces are based on experiments with the SFA. With the SFA, surface forces are measured between two atomically smooth mica surfaces. Distance is measured interferometrically, which allows absolute determination of separation distance with a resolution of typically 0.1 nm (with down to 25 pm achievable). Its absolute force sensitivity is not as high as in several other methods, but in terms of the usually more relevant force per unit area, its sensitivity is excellent. Lateral (friction) forces can be measured in addition to normal standard force versus distance measurements and have contributed much to our understanding of lubrication by thin films. Additional information such as refractive index and contact area can be obtained. The main reason for the limited number of groups using this instrument is the difficult operation of such a system that needs a very experienced and skillful expert. The large interaction areas demand a contamination-free surface preparation and can lead to significant hydrodynamic forces in highly viscous media, which could make equilibrium measurements hard to achieve. 

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