Bioprocess Engineering

Summary

Bioprocess engineering is an interdisciplinary science that combines the disciplines of biology and engineering. It is associated primarily with the commercial exploitation of living things on a large scale. The objective of bioprocess engineering is to optimize either growth of organisms or the generation of target products. This is achieved mainly by the construction of controllable apparatuses. Both government agencies and private companies invest heavily in research within this area of applied science. Many traditional bioprocess engineering approaches (such as antibiotic production by microorganisms) have been advanced by techniques of genetic engineering and molecular biology.

Definition and Basic Principles

Bioprocess engineering is the use of engineering devices (such as bioreactors) in biological processes carried out by microbial, plant, and animal cells to improve or analyze these processes. Large-scale manufacturing involving biological processes requires substantial engineering work. Throughout history, engineering has helped develop many bioprocesses, such as the production of antibiotics, biofuels, vaccines, and enzymes on an industrial scale. Bioprocess engineering plays a role in many industries, including the food, microbiological, pharmaceutical, biotechnological, and chemical industries.

Background and History

People have been using bioprocessing for making bread, cheese, beer, and wine—all fermented foods—for thousands of years. Brewing was one of the first applications of bioprocess engineering. However, it was not until the nineteenth century that the scientific basis of fermentation was established, with the studies of French scientist Louis Pasteur, who discovered the microbial nature of beer brewing and winemaking.

During the early part of the twentieth century, large-scale methods for treating wastewater were developed. Considerable growth in this field occurred toward the middle of the century when the bioprocess for large-scale production of the antibiotic penicillin was developed. The World War II goal of industrial-scale production of penicillin led to the development of fermenters by engineers working together with biologists from the pharmaceutical company Pfizer. The fungus Penicillium grows and produces antibiotics much more effectively under controlled conditions inside a fermenter.

Later progress in bioprocess engineering has followed the development of genetic engineering, which raises the possibility of making new products from genetically modified microorganisms and plants grown in bioreactors. Just as past developments in bioprocess engineering have required contributions from a wide range of disciplines, including microbiology, genetics, biochemistry, chemistry, engineering, mathematics, and computer science, future developments are likely to require cooperation among scientists in multiple specialties.

How It Works

Living cells may be used to generate a number of useful products: food and food ingredients (such as cheese, bread, and wine), antibiotics, biofuels, chemicals (enzymes), and human healthcare products such as insulin. Organisms are also used to destroy or break down harmful wastes, such as those created by the 2010 oil spill in the Gulf of Mexico, or to reduce pollution.

A good example of how bioprocess engineering works is the development of a bioprocess using bacteria for the industrial production of the human hormone insulin. Without insulin, which regulates blood sugar levels, the body cannot use or store glucose properly. The inability of the body to make sufficient insulin causes diabetes. In the 1970s, the U.S. company Genentech developed a bioprocess for insulin production using genetically modified bacterial cells.

The initial stages involve genetic manipulation (in this case, transferring a human gene into bacterial DNA). Genetic manipulation is done in laboratories by scientists trained in molecular biology or biochemistry. After creating a genetically engineered bacterium, scientists grow it in small tubes or flasks and study its growth characteristics and insulin production.

Once the bacterial growth and insulin production characteristics have been identified, scientists increase the scale of the bioprocess. They use or build small bioreactors (1–10 liters) that can monitor temperature, pH (acidity-alkalinity), oxygen concentration, and other process characteristics. The goal of this scale-up is to optimize bacterial growth and insulin production.

The next step is another scale-up, this time to a pilot-scale bioreactor. These bioreactors can be as large as 1,000 liters and are designed and built by engineers to study the response of bacterial cells to large-scale production. During a scale-up, decreased product yields are often experienced because the conditions in the large-scale bioreactors (temperature, pH, aeration, and nutrient supply) differ from those in small, laboratory-scale systems. If the pilot-scale bioreactors work efficiently, engineers will design industrial-scale bioreactors and supporting facilities (air supply, sterilization, and process-control equipment).

All these stages are part of upstream processing. An important part of bioprocess engineering is the product recovery process, or so-called downstream processing. Product recovery from cells can often be very difficult. It involves laboratory procedures such as mechanical breakage, centrifugation, filtration, chromatography, crystallization, and drying. The final step in bioprocess engineering is testing the recovered product, in which animals are often used.

Applications and Products

A wide range of products and applications of bioprocess engineering are familiar, everyday items.

Foods, Beverages, Food Additives, and Supplements. Living organisms play a major role in the production of consumables. Foods, beverages, additives, and supplements traditionally made by bioprocess engineering include dairy products (cheeses, sour cream, yogurt, and kefir), alcoholic beverages (beer, wines, and distilled spirits), plant products (soy sauce, tofu, sauerkraut), and food additives and supplements (flavors, proteins, vitamins, and carotenoids).

Traditional fermenters with microorganisms are used to obtain products in most of these applications. A typical industrial fermenter is constructed from stainless steel. Mixing the microbial culture in fermenters is achieved by mechanical stirring, often with baffles. Airlift bioreactors have also been applied in the manufacturing of food products such as crude proteins synthesized by microorganisms. Mixing and liquid circulation in these bioreactors are induced by the movement of an injected gas (such as air).

Biofuels. Bioprocess engineering is used in the production of biofuels, including ethanol (bioethanol), oil (biodiesel), butanol, biohydrogen, and biogas (methane). These biofuels are produced by the action of microorganisms in bioreactors, some of which use attached (immobilized) microorganisms. Cells, when immobilized in matrices such as agar, polyurethane, or glass beads, stabilize their growth and increase their physiological functions. Many microorganisms exist naturally in a state similar to immobilization, either on the surface of soil particles or in symbiosis with other organisms.

Environmental Applications. Bioprocess engineering plays an important role in removing pollution from the environment. It treats wastewater and solid wastes, soil bioremediation, and mineral recovery. Environmental applications are based on the ability of organisms to use pollutants or other compounds as their food sources. One of the most important and widely used environmental applications is the treatment of wastewater by microorganisms. Microbes eat organic and inorganic compounds in wastewater and clean it simultaneously. In this application, microorganisms are placed inside bioreactors (known as digesters) specifically designed by engineers. Engineers have also developed biofilters, which are bioreactors for removing pollutants from the air. Biofilters remove pollutants, odors, and dust from the air using microorganisms. In addition, the mining industry uses bioprocess engineering for extracting minerals such as copper and uranium through the use of bacteria. Microbial leaching uses leaching dumps or tank bioreactors designed by engineers.

Enzymes. Enzymes are used in the health, food, laundry, pulp and paper, and textile industries. They are produced mainly from fungi and bacteria using bioprocess engineering. One of these enzymes is glucose isomerase, important in the production of fructose syrup. Genetic manipulation provides the means to produce many different enzymes, including those not normally synthesized by microorganisms. Fermenters for enzyme production are usually up to 100,000 liters in volume, although very expensive enzymes may be produced in smaller bioreactors, usually with immobilized cells.

Antibiotics and Other Healthcare Products. Most antibiotics are produced by fungi and bacteria. Industrial production of antibiotics usually occurs in fermenters (stirred tanks) of 40,000- to 200,000-liter capacity. The bioprocess for antibiotics was developed by engineers during World War II, although it has undergone some changes since the 1980s. Various food sources, including glucose and sucrose, have been adopted for antibiotic production by microorganisms. The modern bioprocess is highly efficient (90 percent). Process variables such as pH and aeration are controlled by computer, and nutrients are fed continuously to sustain maximum antibiotic production. Product recovery is also based on continuous extraction.

The other major healthcare products produced with the help of bioprocess engineering are steroids, bacterial vaccines, gene therapy vectors, and therapeutic proteins such as interferon, growth hormone, and insulin. Steroids are important hormones that are manufactured by the process of biotransformation, in which microorganisms are used to chemically modify an inexpensive material to create a desired product. Healthcare products are produced in traditional fermenters.

Biomass Production.Biomass is used as a fuel source, as a source of protein for human food or animal feed, and as a component in agricultural pesticides or fertilizer. Baker's yeast biomass is a major product of bioprocess engineering. It is required for making bread and other baked goods, beer, wine, and ethanol. Yeast is produced in large aerated fermenters of up to 200,000 liters. Molasses is used as a nutrient source for the cells. Yeast is recovered from the fermentation liquid by centrifugation and then is dried. People also use the biomass of algae. Algae are a source of animal feed, plant fertilizer, chemicals, and biofuels. Algal biomass is produced in open ponds, in tubular glass, or in plastic bioreactors.

Animal and Plant Cell Cultures. Bioprocess engineering incorporating animal cell culture is used primarily for the production of healthcare products such as viral vaccines or antibodies in traditional fermenters or bioreactors with immobilized cells. Antibodies, for example, are produced in bioreactors with hollow-fiber immobilized animal cells. Plant cell culture is also an important target of bioprocess engineering. However, only a few processes have been successfully developed. One successful process is the production of the pigment shikonin in Japan. Shikonin is used as a dye for coloring food and has applications as an anti-inflammatory agent.

Chemicals. The chemical industry is continuously trending toward using bioprocess engineering instead of pure chemistry to produce a variety of chemicals, such as amino acids, polymers, and organic acids (citric, acetic, and lactic). Some chemicals (citric and lactic acids) are used as food preservatives. Many chemicals are produced in traditional fermenters by the action of microbes.

Careers and Course Work

There is an increasing demand for students trained in bioprocess engineering who can convert discoveries in biology into industrial applications. Young specialists in bioprocess engineering have many career options. Their work may be in biological process development, manufacturing operations, environmental bioremediation, food technology, or therapeutic stem cell research. They may also develop and manufacture gene therapy vectors, vaccines, or renewable biofuels.

Bioprocess engineering is widely used in industry. Many educational institutions offer bioprocess courses for undergraduates and degrees or concentrations in bioengineering or bioprocess engineering. Several community colleges offer associate degrees and certificate programs that typically prepare students to work in industry. Most of these programs are interdisciplinary. Graduates of these programs will have the knowledge and internship experience to enter directly into the bioprocess engineering workforce. Advanced degrees such as a master's or doctorate are necessary to obtain top positions in academia and industry in the bioprocess engineering area. Some universities, such as Cornell University, offer graduate programs in bioprocess engineering.

The basic courses for students interested in a career in bioprocess engineering are microbiology, plant biology, organic chemistry, biochemistry, agriculture, bioprocess engineering, and chemical engineering. Students must master basic engineering calculations and principles and understand physical and chemical processes, including material and energy balances, reactor engineering, fluid flow and mixing, heat and mass transfer, filtration and centrifugation, and chromatography.

Careers in the bioprocess engineering field can take different paths. Biotechnological, microbiological, chemical, and biofuel companies are the biggest employers. People interested in research in bioprocess engineering can find jobs in government laboratories and universities. In universities, bioprocess engineers may divide their time between research and teaching.

Social Context and Future Prospects

The role of bioprocess engineering in industry is likely to expand because scientists can increasingly manipulate organisms to expand the range and yields of products and processes. Developments in this field continue rapidly.

Bioprocess engineering can potentially be the answer to several problems faced by humankind. One such problem is climate change, caused by rising carbon dioxide levels and other greenhouse gases. A suggested method of addressing this issue is carbon dioxide removal, or sequestration, based on bioprocess engineering. This bioprocess uses microalgae (microscopic algae) in photobioreactors to capture the carbon dioxide discharged into the atmosphere by power plants and other industrial facilities. Photobioreactors are closed systems of transparent tubes where microalgae are cultivated and monitored under illumination.

The healthcare industry is another area where bioprocess engineers will likely be active. For example, as pharmaceutical applications are found for stem cells, a bioprocess must be developed to produce a reliable, plentiful source of stem cells so these drugs can be produced on a large scale. The process for growing and harvesting cells must be standardized so that the cells have the same characteristics and behave predictably. Bioprocess engineers must take these processes from laboratory procedures to industrial protocols.

In general, the future of bioprocess engineering is bright, although questions and concerns, primarily about using genetically modified organisms, have arisen. Public education in such a complex area of science is important to counter public mistrust of bioprocess engineering, which is beneficial in most applications.

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