Week 1 HW: Final Project Ideas

HTBAA Homework #1 Due: Tuesday September 22, by 2:30p ET

For your first homework, propose and describe one idea for something you would like to biomanufacture. This could be medicine, material, food, energy, an art, design, or architectural artifact, or beyond. Draw from your own background and interests for inspiration.

The goal of this assignment is not to develop a complete or technically optimized manufacturing process. Instead, we want you to begin connecting four fundamental questions: What do you want to make? → What living system could make it? → How could automation help you make it? → What would it take to make it at a meaningful scale? Include in detail:

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

Describe the target product or output you would like to make. Why are you interested in making it? Your motivation might be utilitarian—for example, addressing a problem in health, sustainability, food, energy, or manufacturing—but it does not need to be. Your project might instead have a social, cultural, artistic, or personal motivation. Clearly articulate what you want to make, who or what it is for, and why you think it is interesting or important. I have a background in art; I’ve considered myself an artist for my whole life, and I still am deeply passionate (despite art recently becoming more of a hobby for me). In my experience as an artist, I’ve occasionally used plaster as a sculpting medium. Something really annoying about plaster is that it cannot be recycled/broken back down to its original form like clay can be. Instead, you are expected to “over-build,” meaning that you put down more plaster on your sculpture with the expectation you then break it away and shave it down to make your sculpture. Additionally, plaster comes in powdered form, that the artist then must mix with just the right amount of water. Too much or too little and the plaster won’t form/dry correctly. There is not an exact measurement for the plaster mixing that artists can use without it being an inconvenience, considering that once the plaster properly mixes (this takes 8-10 minutes), it is only usable for about 5 minutes before it fully dries and is no longer mouldable. This generates a large amount of waste. Throwing away plaster really isn’t great for the environment, especially since it doesn’t break down very easily, and it’s tough on your lungs since it gets into the air as a fine powder when you’re chiseling it down. Something such as cultured collagen or biomaterial could be an interesting replacement for sculpture/casting. This would be primarily for artists to use, but the public health benefit would also be notable. (2) What living system would you use? Propose at least one living-system manufacturing chassis that could produce your target—for example, a microbial, mammalian, or cell-free system. It could be a mammalian cell or microbial system producing structural biomaterials. I’ve seen that recombinant yeast has been used for collagen production. This collagen/gelatin could be purified and made mouldable for artists. At a high level, describe how the system would make your target product. What goes into the system? What biological process or processes occur? What comes out? I’ve never done anything like this, so I don’t know if this would actually work or not, but a basic description (I say basic because my knowledge on this topic is incredibly limited) of how it would work is that we have an isolated/engineered strain that expresses the collagen gene. Then it would be grown in a bioreactor, where the cells secrete/make collagen proteins. This protein is then harvested and purified so that it will be mouldable. You do not need to design the complete biological system yet. Make reasonable assumptions where necessary and identify them. (3) How would you use automation? Identify at least one automation technology that you would combine with your living system. This could include a large-scale Cloud Lab, a desktop liquid-handling robot such as an Opentrons, a programmable microfluidics platform such as Nuclera’s, or another automation technology. Describe what part of the biomanufacturing workflow you would automate and why. For example, you might automate liquid handling, culturing, assembly, screening, sampling, measurement, optimization, or another step. I’m not familiar with any of these automation technologies, so after some quick research, I think a desktop liquid-handling robot such as an Opentron would be useful. These robots could be used to automate strain screening. You would need many different trial batches for the screening to ensure you find the right strain for appropriate stiffness/plasticity of the collagen so that it can actually be used. (4) How much would you need to make, and how long would it take? Perform a back-of-the-envelope calculation estimating what it would take to manufacture your target at a meaningful scale. (a) How much? Define a scale relevant to your project and calculate approximately how much of your target product you would need to manufacture. For example, if you are producing a medicine, you might estimate the amount required to treat 1,000 people, everyone in Massachusetts, or everyone in the world. If you are producing a building material, you might calculate the amount required for one structure or an entire neighborhood. If you are producing an art or design artifact, define an appropriate scale yourself. Clearly show your calculation, including units, assumptions, and sources for important numbers. So, for the material to actually be useful, I would say you’d need enough to create a human-sized sculpture (since most famous sculptures are of humans). This would mean that, since the average volume of a person is about 70 liters, that would then necessitate about 50kg (given that the material is lighter than the material that makes up an actual person) of material for one completed piece of artwork. However, I’d also need to know the grams of collagen per liter culture. (b) How long? Using your proposed living system and automation technology, estimate how long it would take to manufacture that amount. Consider quantities such as production rate, yield, volume, number of parallel experiments or reactors, automation throughput, or whatever parameters are most appropriate for your system. You may discover that the automation technology you would use to prototype your system is very different from what you would use to manufacture at scale. If so, describe both. Again, we are looking for a reasonable engineering estimate. Show your assumptions and calculations. Once we know the grams of collagen per liter of culture, you can then calculate the actual time and amount needed using this equation: liters needed = target mass / titer; batch time = growth time + purification time. I have absolutely no idea how much time it would take to create an adequate amount of material to use for multiple sculptures, because I am unsure how long it would take to create enough collagen for one sculpture, or if it would even be useful/work. 5. What don’t you know yet? After completing your analysis, identify the 2–3 biggest technical unknowns, bottlenecks, or assumptions in your proposed biomanufacturing system. What would you need to learn, measure, or experimentally determine to know whether your idea could actually work? I don’t know how much collagen can actually be secreted per liter of culture. I’d need to have run actual test fermentations before scaling up, otherwise those calculations are meaningless. I know that collagen needs proper hydroxylation to fold and behave correctly. If I use yeast, I am unsure whether the hydroxylase enzymes will work well enough to get a material with the correct structural properties. I may have to end up using a more complex and slower mammalian system instead. I also have no clue how the collagen produced would behave/interact with its environment to be useful as a sculpting medium. It is important to consider the amount of time the material would take to settle/cure, how much it would shrink when it dries, and what it’s appearance (translucence) is like. I feel like I can’t know much or figure out much about the collagen without working on it hands-on through experimentation. Which means this could be potentially a very expensive endeavor.

AI

Feel free to use AI and our learning tools to be shared in recitation to assist you, but remember that you will present in class, so make sure you have a solid understanding of your responses.

Please also cite your AI client and prompts.

Readings:

Asin-Garcia, E., Fawcett, J. D., Batianis, C., & Martins dos Santos, V. A. P. (2025). A snapshot of biomanufacturing and the need for enabling research infrastructure. Trends in Biotechnology, 43(5), 1000–1014. https://doi.org/10.1016/j.tibtech.2024.10.014 Averesch, N. J. H., Berliner, A. J., Nangle, S. N., Zezulka, S., Vengerova, G. L., Ho, D., Casale, C. A., Lehner, B. A. E., Snyder, J. E., Clark, K. B., Dartnell, L. R., Criddle, C. S., & Arkin, A. P. (2023). Microbial biomanufacturing for space-exploration—what to take and when to make. Nature Communications, 14, 2311. https://doi.org/10.1038/s41467-023-37910-1 Karim, A. S. & Jewett, M. C. (2021). “Toward sustainable, cell-free biomanufacturing.” Current Opinion in Biotechnology 69, 136–144. DOI: 10.1016/j.copbio.2020.12.012. Petzold, C. J., & Mukhopadhyay, A. (2025). From bench to biofactory: High-throughput technologies and automated workflows to accelerate biomanufacturing. Current Opinion in Biotechnology, 94, 103320. https://doi.org/10.1016/j.copbio.2025.103320 Yap, W. S., Choudhury, D., & Suntornnond, R. (2023). Towards biomanufacturing of cultured meat. Trends in Biotechnology, 41(3), 292–294. https://doi.org/10.1016/j.tibtech.2023.01.014 Ye, J.-W., Lin, Y.-N., Yi, X.-Q., Yu, Z.-X., Liu, X., & Chen, G.-Q. (2023). Synthetic biology of extremophiles: A new wave of biomanufacturing. Trends in Biotechnology, 41(3), 342–357. https://doi.org/10.1016/j.tibtech.2022.11.010 Zhang, Y.-H. P., Sun, J., & Ma, Y. (2017). Biomanufacturing: History and perspective. Journal of Industrial Microbiology & Biotechnology, 44, 773–784. https://doi.org/10.1007/s10295-016-1863-2 Readings Folder: https://drive.google.com/drive/folders/1wX9w_MaJ3TFwHMyPp51b2vJ4mxkUNibf?usp=sharing