Bioprocess Development in Shaken Systems

Shaken systems, encompassing shake flasks and microtiter plates, have long underpinned early‐stage bioprocess development by offering a simple, low‐cost platform for parallel cultivation and screening. Advances over the past decade have focused on miniaturisation, real‐time monitoring and controlled feeding to mimic large‐scale stirred tank reactors more accurately. Enzyme‐based substrate delivery and ready‐made fed-batch media now allow gradual nutrient release, preventing oxygen limitation and pH drift while achieving higher cell densities and improved product folding. Concurrently, non-invasive optical sensors and fluorescence spectroscopy have been integrated into microtiter plates to track biomass, metabolite consumption and product formation with high temporal resolution. These developments have accelerated strain characterisation, media optimisation and induction profiling, reducing reliance on labour-intensive stirred-tank experiments. The global significance of shaken systems extends from academic research to industrial biomanufacturing, facilitating rapid biotherapeutic screening, enzyme discovery and process scale-up in an era of increasing demand for agile and sustainable bioprocesses.

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Bioprocess Development in Shaken Systems publication trend

The graph below shows the total number of articles in bioprocess development in shaken systems across all publications each year (not limited to Nature Index journals).

Technical terms

Shake flask: A glass or disposable vessel agitated on a rotary shaker to cultivate microorganisms under aerobic conditions.

Microtiter plate: A flat plate with multiple wells used for parallel miniaturised cultivations and assays.

Fed-batch cultivation: A process mode in which substrates are added gradually to control growth rate and avoid substrate inhibition.

Oxygen transfer rate (OTR): The rate at which oxygen dissolves into culture medium, influencing aerobic growth and productivity.

2D fluorescence spectroscopy: An optical technique that records fluorescence across excitation and emission wavelengths for real-time monitoring of cellular metabolites and products.

Enzymatic substrate delivery: A method using enzymes to release substrates such as glucose gradually into the culture medium, enabling controlled fed-batch growth in shaken systems.

References

1. Assessing the capabilities of 2D fluorescence monitoring in microtiter plates with data-driven modeling for secondary substrate limitation experiments of Hansenula polymorpha. Journal of Biological Engineering (2023).
2. Thermal segment microwell plate control for automated liquid handling setups. Lab on a Chip (2024).
3. Enzyme controlled glucose auto-delivery for high cell density cultivations in microplates and shake flasks. Microbial Cell Factories (2008).
4. The fed-batch principle for the molecular biology lab: controlled nutrient diets in ready-made media improve production of recombinant proteins in Escherichia coli. Microbial Cell Factories (2016).