<h5 id="101-historical-perspective">10.1 Historical Perspective</h5> <ul> <li>The discovery of penicillin by Alexander Fleming in 1928 marked the beginning of understanding the significance of products from biological systems.</li> <li>The need to enhance the production of penicillin led to the emergence of bioprocessing, which involves biological or living systems or their components and chemical engineering processes to obtain desired products at a commercial level.</li> <li>Bioprocesses are carried out in vessels called fermenters or bioreactors at an industrial or commercial stage.</li> <li>The advent of recombinant DNA technology has led to the extensive employment of microbes for the production of various biological materials for the welfare of mankind.</li> <li>Bioprocessing involves a systematic process using the culture of biological entities, such as the Penicillium species, to increase the production of useful products.</li> </ul> <p>======</p> <h5 id="102-instrumentation-in-bioprocessing-bioreactor-and-fermenter-design">10.2 Instrumentation in BiopRocessing: Bioreactor and Fermenter Design</h5> <ul> <li>A bioreactor is a sterile, engineered vessel used for cultivating cells under aseptic conditions with appropriate nutritional and environmental requirements.</li> <li>It should provide a sterile environment, adequate air supply, uniform mixing, temperature maintenance, and monitoring of environmental process parameters.</li> <li>Components of a typical bioreactor include: agitator shaft, sparger, baffle, jacket, sensitivity probes for temperature and pH, and a digital controller.</li> <li>The agitator shaft ensures homogenous conditions for better nutrient and oxygen transport, while the sparger supplies sterilized air.</li> <li>The baffle prevents vortex formation, the jacket maintains temperature, and the sensitivity probes monitor temperature and pH.</li> <li>The digital controller manages process parameters, maintaining desired temperature, pH, and other conditions through water bath circulation and addition of acid or base as needed.</li> </ul> <p>======</p> <h5 id="1021-types-of-bioreactors">10.2.1 Types of bioreactors</h5> <ul> <li>Stirred tank reactors are conventional bioreactors with an agitator shaft for mixing nutrients, oxygen, and cells. The impeller’s design, shape, and size vary for different bioprocesses.</li> <li>Air-lift reactors use an air draft tube to create motion for mixing nutrients and oxygen. The fluid broth and cells move up and down inside the reactor vessel, ensuring adequate mixing.</li> <li>Bubble column reactors utilize air bubbles produced through a sparger jet for mixing nutrients and oxygen. They offer a low shear environment, which may be crucial for some cells, and have high oxygen transfer rates per unit of power input.</li> </ul> <p>======</p> <h5 id="103-operational-stages-of-bioprocess">10.3 Operational Stages of Bioprocess</h5> <ul> <li>A bioprocess consists of upstream and downstream processing stages.</li> <li>Upstream bioprocessing includes: <ol> <li>Optimization of nutritional conditions in artificial media.</li> <li>Sterilization of media, bioreactor, and other equipment.</li> <li>Production of pure, active, and healthy inoculums.</li> </ol> </li> </ul> <p>======</p> <h5 id="1031-upstream-processing">10.3.1 Upstream processing</h5> <ul> <li>Microfiltration, Ultrafiltration, and Reverse Osmosis are pressure-driven membrane separation processes.</li> <li>Microfiltration: 0.01-10 µm, <1000,000 Da, retains suspended materials like bacteria.</li> <li>Ultrafiltration: 0.01-0.1 µm, 300-300,000 Da, retains biological, colloids, and macromolecules.</li> <li>Reverse Osmosis: 0.001 µm or <1 µm, <300 Da, retains all suspended and dissolved materials.</li> <li>Osmosis is the movement of water molecules from pure water to saline water due to osmotic pressure.</li> <li>Reverse Osmosis (RO) works by applying pressure onto a salt-containing phase, driving water molecules in the reverse direction.</li> <li>RO requires pressure slightly larger than the osmotic pressure as solvent flux takes place against the concentration gradient.</li> <li>Dialysis is used for the removal of low-molecular weight solutes, such as organic acids (MW=100-500 Da) and inorganic ions (MW=10-100 Da) from a solution through a selectively permeable membrane.</li> <li>Dialysis retains high molecular weight molecules and equalizes chemical potentials of diffusing compounds on both sides of a membrane.</li> </ul> <p>======</p> <h5 id="104-bioprocessing-and-biomanufacturing-of-desired-products">10.4 BiopRocessing and BiomanufactURing of Desired Products</h5> <ul> <li>Ethanol, L-glutamic acid, lysine, organic acids, enzymes, and bioactive molecules are some of the many compounds produced through bioprocessing and biomanufacturing.</li> <li>Microorganisms such as Saccharomyces cerevisiae, Corynebacterium glutamicum, Aspergillus niger, Lactobacillus sp., and Bacillus spp. are used in the bioprocessing of these compounds.</li> <li>Enzymes like lipases, pectinases, and proteases are produced commercially through bioprocessing and are used in various industries such as detergent, food, and leather.</li> <li>Vitamins $B_{12}$ and riboflavin are commercially produced by fermentation using microorganisms like Propionibacterium freudenreichii, Pseudomonas denitrificans, Bacillus megaterium, Streptomyces olivaceus, and Ashbya gossypii.</li> <li>Vaccines, specifically the diphtheria toxoid vaccine, are produced through bioprocessing using microbial cultures like Corynebacterium diphtheria.</li> <li>Plant cell and tissue culture are used in bioprocess for commercial production of biochemicals such as pigments, quinone derivatives, plant alkaloids, etc. The bioprocess for the production of dye shikonin was commercially developed using cell culture of plant species Lithospermum erythrorhizon.</li> </ul> <p>======</p>