GREEN CHEMISTRY
More sophisticated approaches can be introduced during the final phase. This might include automation for lifecycle processes such as loading, extraction and sterilisation, thereby demonstrating the ability to run with a reduced workforce.
Design rules, drawn from the benchscale metabolic model combined with a fluidic model of the system, should be used to drive bioreactor design. Simply taking a large, stirred tank and modelling the fluidics in detail is unlikely to deliver performance improvements during scale-up. It will only mitigate the limitations intrinsic to that design.
Achieving the efficient transport of gases, nutrients and waste products often leads to novel reactor geometries. This is particularly true for cell culture processes, which are based on a scaffold and may require mechanical stimulus. The requirements
1: BioProcess International, Biden Pledges $ 2 Billion to Launch US Biomanufacturing Initiative. https:// www. bioprocessintl. com / global-markets / biden-pledges-2-billion-tolaunch-us-biomanufacturing-initiative 2: UK Government, National Vision for Engineering Biology. https:// www. gov. uk / government / publications / national-visionfor-engineering-biology / national-vision-forengineering-biology 3: Japan Science and Technology Agency( JST), Japanese News on Biomanufacturing, 25 June 2024. https:// sj. jst. go. jp / news / 202406 / n0625-02k. html
4: Stepan Company, Rhamnolipid Biosurfactants Featured in Chemical Engineering News. https:// www. stepan. com / content / stepan-dot-com / en / news-events / news---events / rhamnolipid-biosurfactantsfeatured-in-chemical-engineering-news. html 5: Evonik, First Product from World’ s First Industrial-Scale Rhamnolipid Biosurfactant Plant. https:// personal-care. evonik. com / en / evonik-manufactures-first-product-fromworlds-first-industrial-scale-rhamnolipidbiosurfactant-plant-233324. html 6: Holiferm, Secures £ 18.5 Million to Scale Up to 15 KTA Production Capacity. https:// holiferm. com / holiferm-news / holiferm-
for the lifecycle processes and monitoring sensors also contribute design rules for the reactor geometry.
Once these design rules are identified, fluidic modelling develops in tandem with the design. Simple models are usually sufficient to assess high-level design options and select a preferred architecture. Then, computational fluid dynamics( CFD) of sub-sections aids component-level design. When the design is complete, the CFD of the whole system enable final optimisation and prototype validation.
Standard bioreactor designs( such as open geometry and impellers which provide indirect control of the flow field) can require complicated CFD. However, a system design driven by design rules is more likely to have a geometry where flows are controlled more directly, which in turn makes fluidic modelling more straightforward.
Step 3: System modelling & digital twins
In the final stage, system modelling and digital twins are used to monitor performance, support control and diagnose issues. A key part of design validation and verification is to check that low-level measurands( such as species concentrations) are performing as expected, as well as ensuring highlevel metrics( like productivity) are performing well.
This is where sensor technology comes to the fore. While bioreactors typically use simple sensors to assess pH, dissolved oxygen and CO 2
, electrochemical sensors are emerging for glucose and lactate.
This technology is well established for monitoring a whole range of metabolic species in medical applications, but the
secures-18-5-million-to-scale-up-to-15kta- production-capacity-from-rhapsody-venture- partners-and-clean-growth-fund / 7: MarketsandMarkets, Biosurfactant Market – Press Release. https:// www. marketsandmarkets. com / PressReleases / biosurfactant. asp 8: A. Das et al., Bioresour. Technol., 2022, 344, 126195. https:// www. sciencedirect. com / science / article / abs / pii / S0960852421014012 9: Y.-H. Du et al., Bioengineering, 2022, 9, 473. 10: SkyQuest, Synthetic Biology Market Report, October 2024. https:// www. skyquestt. com / report / synthetic-biology-market transition to bioreactor applications has been slow for commercial reasons. Similarly, there are well-established medical biosensor technologies that could be used to monitor proteins and antibodies from bioreactor samples, such as enzyme-linked immunosorbent assays.
Fingerprinting technologies like Raman spectroscopy take these capabilities further, offering ways to sense more subtle properties such as cell viability. This would likely involve microfluidic sampling, which indicates how sensing requirements can influence bioreactor design. Sensing over a range of positions, rather than at a single point or port of the bioreactor, also has significant design implications.
The time is right
Companies that harness engineering biology for speciality chemical production will earn a firm position in a market that is forecast to hit $ 110 billion by 2032 at a compound annual growth rate of 25.5 %. 10 They will also move the needle on Green Chemistry for the chemicals industry and downstream industries that rely on speciality chemicals.
To achieve this, manufacturers will have to implement technologies that maintain efficient and effective production of chemicals as engineering biology processes are scaled. Strategic planning, with expert multi-disciplinary input, will be essential.
As governments follow through on their infrastructure commitments for engineering biology, it will become easier to derive a good return from investment in these production capabilities. Manufacturers that have already optimised the unit economics of core processes and overcome other scale-up challenges will be the first to benefit. ●
J j
Matthew Fagg
MARKETING MANAGE
SAGENTIA INNOVATION matthew. fagg @ sagentiainnovation. com www. sagentiainnovation. com
MAY / JUN 2025 SPECCHEMONLINE. COM
75