If you're reading up about how cultivated meat is made, you may wind up asking yourself (or perhaps Google) what is a bioreactor? In our burgeoning industry, it's the key piece of equipment we use to produce animal biomass – big batches of animal cells that form the basis of our slaughter-free meat.
Over the last few decades, variations of these sophisticated vessels have played an important role in producing items in your pantry and medicine cabinet, developing vaccines and facilitating advancements in everything from energy production to low footprint food. Below, for the cultivated meat curious, we explain what bioreactors are, and how different types of bioreactors produce revolutionary products that have and continue to change the world.
What is a bioreactor?
A bioreactor is a specialized vessel or tank used to grow either cells or other microorganisms for a wide variety of purposes, from producing ingredients for medicines to cultivating meat. Broadly, they can be lumped into two categories: fermenters (or fermentation tanks) and bioreactors for cell culture, which are the ones we talk about when we talk about cultivating meat.
Anyone who's visited a brewery has likely seen fermenters, big steel tanks affixed with pumps and sensors that are used to transform raw ingredients into beer by maintaining the environmental conditions necessary to keep yeast — a microorganism— happy, so that it can transform sugars into alcohol via the process of fermentation.
Beyond breweries, fermenters are used to treat wastewater, produce antibiotics, ethanol, flavor agents, preservatives, proteins, fats and other industry-spanning products by creating the environmental conditions needed for microorganism workhorses like fungus, yeast or bacteria to thrive and produce products or ingredients the world needs.
Bioreactors for Cell Culture
The other type of bioreactor is the kind we use to cultivate or to mass produce cells. Like fermentation tanks, their job is to maintain very specific environmental conditions for the ingredients inside, which in our case are animal cells.
Instead of triggering fermentation, the goal of a bioreactor for cell culture is to enable the cells inside to proliferate, or to grow and divide, as they would inside a living organism. To enable this process, the bioreactor's job is to mimic conditions these cells would experience in their natural environments, whether that's inside a cow or a chicken.
To do this, the bioreactor keeps the cells moving via specialized "agitators" that stir them through cell culture media, a water-based liquid enriched with vitamins, amino acids and other nutrients that provides cells with the conditions they need to survive.
(Some labs and companies use animal ingredients in their media, but we don't — ours is 100% animal free.) The bioreactor also maintains specific parameters like level of dissolved oxygen in the media, pH and temperature to ensure the environment is as natural for the cells as possible.
Sensors affixed to the bioreactor can track these parameters in real time, while pumps and aerators supply cells with the nutrients, supplements and gasses they need to thrive.
Some types of bioreactors also have special features to remove waste that cells naturally produce, mimicking the role of the liver and kidneys in an animal's body. Others use sophisticated filters to control ingredients coming in and waste and cellular biomass coming out.
When the cells reach an optimal density, they are "harvested" or removed and separated from any waste and lingering media. From there, scientists can use the mass of identical cells for a wide range of purposes, from mass producing vaccines to mass producing cultivated meat.
What is a bioreactor used for?
For the last century, bioreactors have played an increasingly important behind-the-scenes role in shaping our lives and charting our future. They produce products we depend on every day and are behind some of the most cutting-edge research and innovation in the worlds of agriculture, biofuel, biomaterials, medicine, and food production.
Fermentation tanks have long enabled the mass production of ethanol, lactic acid, and other compounds like acetone, and are responsible for most antibiotics on the market today. For years, the food industry has also used fermenters to mass produce specific molecules used to make vitamins, nutritional supplements and fortified processed foods. Building on this history, innovators today are using advanced forms of fermentation like "precision fermentation" to make cow-free dairy products, bee-free honey, and a range of other sustainable foods and ingredients. These products are made by "programming" or genetically modifying microorganisms like fungus to produce specific enzymes, proteins and other molecules found in high footprint foods, and then mass producing these products in a special fermenter.
Bioreactors for cell culture
While our friends in the world of animal-free dairy use precision fermentation to manufacture proteins from genetically-modified fungus or yeast, the cultivated meat industry uses cell culture bioreactors to produce batches of animal cells (to produce non-GMO batches of animal cells in our case), without ever slaughtering an animal. This biotechnology has its roots in the pharmaceutical industry, which develops vaccines and therapies by mass producing cells programmed to fight illnesses. Medical researchers have also used bioreactors to safely learn more about diseases, and understand how drugs, toxins and different therapies affect people and animals. In the world of food, meanwhile, we have been using bioreactors as a way of sustainably mass producing meat. As the world's population continues to grow and demand for meat increases, bioreactors present a compelling low footprint alternative to the complex supply chains used to raise, slaughter and transport traditionally-farmed meat.
How does a bioreactor work?
So how exactly does a cell culture bioreactor work? There are many types of bioreactors, ranging from the small (think water bottle-sized) to the very large (up to 20,000 liters). Some are basic "off-the-shelf" models, while others, like ours, are customized and include patented technology. No matter the model, though, all bioreactors follow a similar process:
- First, cells must be sourced and cultivated in small flasks containing cell culture media, which provides cells with a nutrient-rich environment in which they can comfortably proliferate.
- When the cells begin to outgrow the flasks, they are transferred to a larger home, which might be a larger flask or small bioreactor. This process of "sizing up" is known as a "seeding train" and ensures that the cells are always growing under optimal conditions.
- Before the cells enter a bioreactor, the vessel is programmed to meet specific parameters and media is added.
- When conditions are right, cells are introduced to the bioreactor and allowed to proliferate – either on scaffolds if they are the type of cells that like to adhere to surfaces, or in suspension, like our cells, which proliferate happily as they float through the moving media. Conditions are constantly monitored for the duration of the bioreactor "run" or cycle. Depending on the design of the bioreactor and the process used to cultivate the cells, other steps may be taken to maintain optimal conditions.
- When the cells reach an optimal density, they are "harvested" or removed and cleaned, or separated from the media and waste that may have accumulated during the run. Scientists can then use the cells for a range of purposes. In our case, we use the biomass to make chicken strips, kebabs and other familiar types of meat.
Types of bioreactor processes
- Batch: The most basic type of bioreactor process is a batch process, which is a "closed" process akin to popping something in the oven, leaving it there until the timer dings, and then taking it out. It involves inserting media and cells into a bioreactor, allowing them to proliferate without any meddling, and then harvesting them after the run. This is the simplest type of bioreactor process, but comes with challenges. As the cells proliferate, they consume growth media and produce waste, which inhibits their ability to proliferate. If the waste is left in the bioreactor and fresh nutrients aren't added, the cells' growth potential is limited.
- Fed-Batch: A fed-batch process improves on the batch process by "feeding" cells with fresh nutrients throughout the bioreactor run, resulting in better conditions for proliferation and higher cell densities. This process, however, does not remove waste, which can still present challenges for scaling.
- Continuous: Continuous processes improves the fed-batch process by both continuously feeding the cells fresh media, while continuously draining waste materials through technology that mimics the role of kidneys and liver in an animal. This type of process, which we use and have further optimized, yields the highest cell densities (more biomass per run) than any other type of bioreactor process.
Believer's bioreactor process
At Believer, we use a continuous process to make our cultivated meat. To reduce our raw material costs (with the goal of keeping costs down for consumers), we designed our bioreactors to recycle waste materials filtered out through perfusion. Our media rejuvenation process purifies bioreactor waste, and reinserts it into the vessel as fresh media.
Along with other patented improvements we've developed throughout our seed train (our process of scaling up from flasks to larger bioreactors) our rejuvenation process has enabled us to drastically cut costs and maximize cell densities. Currently, we're working with engineers to build scaled up copies of our bioreactors at our first commercial-scale facility, which is under construction in North Carolina. Once completed, this facility will be capable of producing more than 22 million pounds of food a year.
Innovating the future with bioreactors
In a world of limited resources, bioreactors are becoming an increasingly important tool for innovators looking for sustainable ways to meet growing demand for everything from food to building materials — all without having to chop trees, raise or slaughter animals, or to drive the planet closer to climate doom.
Advanced fermentation techniques and cell cultivation are allowing us to imagine a world in which leather and fur, pet food and chicken strips are made without ever harming an animal. They are advancing medical research and carving a path to a future in which we can all feel confident that the products we use and consume are ethically produced and environmentally friendly.
So what is a bioreactor? Yes, it is a vessel used to cultivate cells and microorganisms for a range of purposes, but it's really so much more. It is a feat of engineering that has already given us so much and that holds the potential to vastly reshape our lives and our world.