WE SOURCE and connect vision, funding, and expertise for large scale impact

As members, we address common challenges across the industry, extending the state of the art and speeding cultivated meat from lab bench prototype, to staple of the kitchen table.

Strategic Framework

North Stars

• Develop projects that provide immediate value to the cultivated meat industry, while systematically contributing to the vision of replacing live experiments with simulated ones

• Respond to the needs of members with bespoke projects and advice sufficient to advance their goals

• Provide thought leadership in terms of a technical modeling strategy, to guide member-companies to expert suppliers

• Ensure maximum confidentiality and trust is maintained at all times for member-companies

2020 - 2022 Multi-Scale Stir-TANK BIOREACTOR INITIATIVE

CMMC's modeling initiatives for 2022 include the multi-scale stir-tank bioreactor “proof of concept,” a modeling platform capable of simulating the internal environment of typical stir-tank bioreactors used to produce muscle cells. This model extends the capabilities of present-day CFD and agent-based methods, allowing companies to simulate experiments and thereby reduce the number of live experiments they must currently perform to scale their yield to cost-competitiveness with traditional agriculture.

Executive summary

Stir-tank bioreactors are the chief means of producing the cell mass required by cultivated meat to compete with traditional agriculture. Increasing the number of cells yielded by each bioreactor run is the primary path for companies to scale to cost-competitiveness. Significantly, there are many variables in a bioreactor system with the potential to influence yield positively or negatively. Many of these factors, and the relationships between them, are unknown to companies with respect to their cell lines. Increasing yield is often the result of trial and error, requiring hundreds of experiments, some of which cost tens or hundreds of thousands of USD per run, and days or weeks to complete, tying up equipment and gating the speed at which companies can learn. According to McKinsey, "For cultivated meat to deliver 10% of 2030 demand would require an estimated 300x increase in the world’s bioreactor capacity. Annual bioreactor production is $2.6B (2020)." 

The Multi-Scale Stir-Tank Bioreactor initiative aims to eliminate a significant portion of the costs and time associated with live experiments by uniting various computational methods together into a comprehensive simulation platform. This platform will allow companies to privately input the parameters of their own bioreactors, cells, and media, set the parameters of their desired experiment (for example, run time, the positioning of impellers, and their RPM), then run a virtual experiment and observe the results. Experiments take hours to complete, instead of days or weeks, and for a fraction of the cost. Widespread adoption of the MSST has the potential to greatly accelerate time to market for both cultivated meat companies, and their suppliers.

History (2020 - August 2022)

The MSST was conceived when, in 2019, twenty-three industry stakeholders, among them WildType, MOSA, Meatable, Merck KGaA Darmstadt, the Netherlands eScience Center, Penn State University, Tufts University, the Good Food Institute, and Biocellion SPC, met to form the CMMC's initial membership. Three areas of interest were identified: scaffolding, media composition, and bioprocess in bioreactors. Initial research suggested that of the three, the area of opportunity with the most urgency and relevance for modeling was the stir tank bioreactor. As the first commercial member of the CMMC, Merck KGaA Darmstadt asked the CMMC membership to develop a bioreactor proof of concept (POC) to validate the CMMC's ability to create value. Simultaneously, a grant proposal was submitted to the Good Food Institute proposing to model three novel bioreactor formats in addition to the stir tank. Both the POC and GFI grant aimed to understand the effect of shear stress on cells in each bioreactor, and compare the effect of various stir speeds on the rate of cell proliferation and death.

Because the POC was necessary to complete the GFI grant, it was decided that both projects would be combined under a single team responsible for execution. Members included Simon Kahan, as PI; Chris Clark as project manager; Jaro Camphuisen and Boris Aguilar as agent-based modelers (ABM), Greg Potter as biology consultant, and Jiajia Chen and Fernando Cantarero Rivera as Computational Fluid Dynamics (CFD) modelers. Initial experimental data and consulting came from a leading cultivated meat company who, for the sake of protecting proprietary information asked not to be disclosed as a partner. Work proceeded over the course of six months. The POC was built using Biocellion, Comsol, and Unity software. The current version of the demo can be found here.

After the POC was released, the CMMC community gathered to provide feedback and suggest next steps. The most important need identified by membership was validation of current results.

Current State 

At present, the CMMC’s 2021 modeling initiatives, including the GFI Novel Bioreactor Grant, the Multi-Scale Stir Tank Bioreactor, and IBIDI projects have concluded. The reports on these projects, including their final outcomes, can be found here.

At a glance, the GFI Novel Bioreactor Grant demonstrates the utility of using modeling approaches to evaluate the efficacy of novel bioreactor forms. 

The IBIDI project modeled sheer stress on single cells to determine their maximum tolerance. Companies interested in understanding their own cell-line’s range of tolerance can reproduce the experiments by Boston College in the IBIDI chamber. We use this data to calibrate models to specific member-company cell lines.

The Multi-Scale Bioreactor Model unites fluid flow and individual cell growth to understand how sheer stress inhibits proliferation. This model has the potential to replace live experiments for member-companies. Many of the proposed projects described herein look to extend the capability of the current model to bring it closer to this potential. 

Current Goals

The CMMC now aims to refresh its modeling initiatives for 2022 - 2023 with feedback from members. As our community has grown, we’ve brought in new modelers and companies with different interests and needs. At the same time, we aim to continue to invest in the progress we’ve made so far, particularly in extending the Multi-Scale Stir Tank Bioreactor model.

Project proposals are currently being accepted for the next round of modeling project work for 2022. These include:

• The suggested projects list contained in this document, and

• The CMMC Call for Proposals

The CMMC is adaptive to its members! We have begun a fresh round of conversations to evaluate potential project directions. 

Industry Insights: 

In the fall of 2021, the CMMC conducted an effort to understand how our current modeling efforts would support the industry. We learned a few key facts from these interviews.

1. The need to increase yield is the primary challenge facing most (but not all) companies

2. Many companies face a huge experimental space, with many unknown factors related to their cell-lines’ yield

3. Time is of the essence: many companies are faced with investor deadlines to prove the cost-effectiveness of their product

4. CFD is the most commonly applied modeling technique for most companies

5. A minority of companies have hired at least one computer modeling expert to support their efforts

6. Most companies indicated that they would adopt a simulated experimental approach, if a platform for one existed

7. Companies are reluctant to share data that may disclose their proprietary information, including process technology

8. Despite significant raises in 2021, companies are concerned with the additional cost required to develop modeling solutions, while acknowledging that the long-term savings compared to traditional live bioreactor runs may be worth the investment

Benchmarking and Collaborations

• As of August 2022, there are several efforts underway across the industry to use modeling for the benefit of the cultivated meat industry. UCLA, Tufts, and Penn State have focused on metabolic modeling, used primarily to optimize media composition. 

• Cultured Biosciences, a bioreactor outsourcing startup, is popular with companies looking to run a large number of experiments but lacking the physical capacity. These runs may take several months and cost north of $250k.

• CFD contract firms are currently supplying the industry by running experiments at need; these companies require significant input from customers and do not necessarily provide thought-partnership for their clients. In contrast, TTP, a firm of for-hire technologists, extend the capacity of companies to quickly address a challenge in a technology space (e.g. CFD modeling) albeit at significant cost; they are currently exploring inroads into the industry.