Patent Analysis: Fork and Goode’s Novel Bioreactor System
Fork and Goode is a Brooklyn-based cultivated meat company developing large-scale cell culture systems for growing pork. This patent application, filed in August 2018, describes Fork and Goode’s novel bioreactor system aimed at providing a cheaper alternative to animal-derived serums and recombinant growth factors.
The bioreactor is designed to mimic the physiological system, whereby specialized cells are organized into organs (in the bioreactor, these are imitated by culturing tanks) that are connected via a network of cardiovascular and lymphatic vessels (in the bioreactor, these are imitated by tubes and membranes). These vessels allow for the circulation of nutrients and metabolites, and the removal of waste. The bioreactor design has many similarities to a patent application filed by Integriculture, the for-profit arm of the Shojin Meat Project based in Japan. The recently announced collaboration between Integriculture and Shiok Meats shows increased interest in systems like these.
In the bioreactor system, different cell types are cultured in separate tanks where gas, pH, and temperature can be independently controlled. These tanks can be connected in series, in parallel, or a combination of the two. At the start of the cultured process, basal media is added to the upstream tanks, which contain “feeder cells” such as liver and pancreatic cells. As the feeder cells are cultured, they produce cell-specific and tissue-specific growth factors, thereby creating a “conditioned medium.” The conditioned medium is circulated throughout the bioreactor system to destination tanks containing muscle, fat, endothelial, and cartilage cells. The target cells take cues from the growth factors in the conditioned medium to proliferate or differentiate.
Membranes between the tanks ensure that nutrients and metabolites, but not cells, can travel between tanks. Secondary feedlines also allow the addition of fresh medium, growth factors, and gases. Tanks can also be connected to a dialyser to filter waste, so that media can then be recycled back to the system. Media recycling would greatly reduce the total amount of fresh media needed, and hence the cost of production.
The main advantage of this bioreactor system is that it greatly reduces the need for exogenous growth factors, which are one of the major cost drivers for cultivated meat. Conventionally, growth factors are obtained through animal-derived serums, such as fetal bovine serum, or through costly recombinant production. Fork and Goode’s feeder cell system aims to be cheaper by requiring neither an animal-derived serum, nor recombinant growth factors.
However, many technical hurdles remain unsolved. For example, even if this bioreactor system eliminates the need for growth factors, further cost reductions in the basal medium are still required [1]. Another technical hurdle is how to make the feeder cells produce the desired growth factors. Given that the aim of the bioreactor system is to lessen the need for expensive growth factors, it is likely infeasible to provide the feeder cells themselves with expensive recombinant growth factors. However, there are a number of reasons that this may be an easier problem to solve. Firstly, the feeder cells themselves aren’t meant to be harvested and sold, and therefore don’t need to be cultured in as high of volumes as the target cells. They can also be re-used between batches. Furthermore, since cells don’t move between tanks, feeder cells can be genetically modified without introducing the need for the final product to be labeled as GMO. Finally, more work is needed to determine the optimal size for each of the bioreactor tanks, each of which can each be a different size. The optimal size depends on many factors, including cell type, species, the potential use of microcarriers, and the final cell density per unit volume. Larger tanks (e.g. 250,000L) can produce more material, but increase the risk of contamination, and the challenge of maintaining heterogenous nutrient concentrations.
Dr Bianca Le is a cell biologist and Founder of Cellular Agriculture Australia. You can connect with her on Twitter and LinkedIn.
Footnotes
[1] Specht, L. The Good Food Institute. 2020. https://www.gfi.org/files/sci-tech/clean-meat-production-volume-and-medium-cost.pdf
[2] Allan SJ, De Bank PA, Ellis MJ. 2019. Bioprocess Design Considerations for Cultured Meat Production With a Focus on the Expansion Bioreactor. Front. Sustain. Food Syst. https://www.frontiersin.org/articles/10.3389/fsufs.2019.00044/full