Week 1 HW: Final Project Ideas

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(1) What you would like to biomanufacture and why?

I would like to biomanufacture cultivated meat because of its potential to be healthier, more humane, and sustainable than conventional meat production. The goal of the project is to explore the four key challenges/research pillars for tangible scalability and sustainability of cultivated meat production:

  1. cell line development
  2. serum-free media
  3. edible scaffoldings
  4. bio-process design

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(2) What living system would you use?

I will start this project by evaluating the usage of

  • Bovine satellite cells (BSCs) o The starting muscle stem/progenitor cells that can proliferate and later differentiate into muscle cells

  • Fetal bovine serum (FBS) o A mixture of growth factors, proteins, hormones, lipids, and other components that promote cell proliferation in cell culture media o Note: I would also explore serum-free/animal-free alternatives that are currently being researched

  • Basal culture medium + nutrients o Provides water, salts, amino acids, glucose, vitamins, and other ingredients needed for celluluar metabolism and growth

  • Growth factors/signaling molecules o Encourages proliferation and/or differentiation of the BSCs

  • Edible scaffolding materials o Provides a three-dimensional structure for the cells to attach and grown on so that they organize into tissue rather than just a mass of cells o Specifically, will look at edible scaffolding that support cells derived from bovine, porcine, piscine, and chicken cells lines  e.g. textured soy protein, pea protein, wheat glutenim, sorghum protein, konjac glucomannan, alginate k-carrageenan ,broccoli florets, pork skin gelatin, fish skin gelatin, peanut wire drawing protein

This system would produce proliferated and differentiated muscle cells organized into edible tissue, i.e. structured cultivated meat

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(3) How would you use automation?

An automation technology that I would combine with the cultivated meat production system is an automated bioreactor control and monitoring system to assist with the scalability of the production. The BSC/FBS/culture-medium/scaffold system could be combined with a controlled, automated bioreactor to automate the following parts of the workflow:

  • monitoring environmental conditions: temperature, pH, dissolved oxygen, carbon dioxide, agitation/mixing
  • replenishing nutrient and media levels: automated replenishment of fresh culture medium and nutrients, removal of metabolic waste, and automated sampling

(4) How much would you need to make, and how long would it take?

A 2024 review identified 20,000+ L stirred-tank reactors used in many industrial cultivated meat technoeconomic analyses and bioprocess literature. In those analyses the scale of production is on the order of 10,000 metric tons of cultivated meat per year, which accounts for 0.014% of global beef production [Ref4.2]. Although, this scale is larger than a pilot/small commercial scale estimate, it provides a scale relevant to the real-world global demand and production capability for existing beef products.

Using a target production volume of 1,000 metric tons of cultivated meat per year, the required cell mass, bioreactor volume, media, and facility scale can be estimated as follows:

Assuming a production facility operates 330 days/year:

1,000 metric tons/year = 10^6 kg/year 
        = 10^6 kg/330 days 
        ~ 3,030 kg/day

Thus 3 metric tons of cultivated mass would need to be produced every day

Note: A conventional laboratory cell culture produces approximately 10 to 30 x 10^6 cells per T175 flask per harvest [Ref 4.4][Ref 4.5].

This corresponds to roughly tens to hundreds of milligrams of wet cell biomass (see calculation below). A kilogram-scale cultivated-meat process requires ~ 1011 cells, while a 1,000-ton/year process requires ~1017 cells/year [Ref4.4]. High density bioreactor cultures would be the practical approach to pursue for scalable production of cultivated meat.

Using a mammalian-cell wet mass approximation of 3.5ng/cell, the conventional T175 flask contains about 35-100mg of wet cellular biomass at harvest. It is not practical to use the T175 flasks at scale because it means that approximately 10,000 T175 flask-equivalents would be needed to produce 1kg of wet cellular biomass. Thus, cultivated-meat production needs to transition from surface-area-based laboratory culture to high-density suspension culture in bioreactors.

Using a conventional seed bioreactor allows for growing cells in a liquid volume that reaches approximately 2 to 5 x 106 cells per mL [Ref 4.7] including some industrial mammalian-cell processes that can reach 10 to 15 106 cells per mL [Ref 4.6]. Thus, a 10-L bioreactor culture at a production density of 5x10^6 cells/mL gives

10L x 5x10^6 cells/mL = 10,000 mL x 5 x 10^6 cells/mL 

      = 5x10^10cells

5x10^10 cells x 3.5ng/cell ~ 

      175 grams of wet cellular biomass

Higher density 10-L cultures , e.g. 10^7 cells/mL, would produce

10^11 cells ~ 

      350g of wet cellular biomass

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(5) What don’t you know yet?

The 2-3 biggest unknowns, bottlenecks, and assumptions in my proposed manufacturing system are the production costs and output estimates at varying scales of production, the economic viability of existing input materials at large production scale, and the quality of the cultivated meat at large production scale.

Existing analyses provide rough estimates of production considerations for production scales on the order 10,000 metric tons of cultivated meat per year where medium cost is estimated at $1.40/L [Ref4.2]. This would result in a cultivated meat cost that is approximately $35/kg. The analysis notes that the cost of the medium would need to be less than $0.75/L [Ref4.2] for the cultivated meat cost to be less than $10/kg. The analysis also notes that the economics of small-scale production makes media prices extremely unfavorable.

Another analysis identified that medium, bioreactors, and labor account for more than 80% of production costs in a large-scale model [Ref5.1]

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