Scale‑up of CHO cell cultures: from 96‑well‑microtiter plates to stirred tank reactors across three orders of magnitude(Anne Neuss et al., Journal of Biological Engineering 2025)

Reliable estimation of substrate affinity remains a critical limitation in industrial bioprocess development, particularly for organisms such as Corynebacterium glutamicum where accurate kinetic parameters are required to manage substrate gradients and ensure robust large scale performance. Conventional approaches are analytically demanding and provide limited resolution at low substrate concentrations, restricting their applicability for process optimization. A multi scale screening concept combining microtiter based methods with the Kuhner microTOM and single cell analysis enables rapid and application relevant characterization of substrate affinity across different resolution levels.

Unraveling the potential and constraints associated with corn steep liquor as a nutrient source for industrial fermentations (Sekar Mayang W. Wahjudi et al., Biotechnology Progress 2023)

The high cost and compositional variability of conventional complex media remain critical constraints in industrial fermentation. Corn steep liquor offers a cost-efficient alternative but introduces uncertainty due to batch heterogeneity. Rapid and reliable evaluation of such substrates is essential to ensure consistent process performance. A scalable screening approach combining high-throughput cultivation with online metabolic monitoring enables early identification of suitable media compositions and limiting factors. The results in this publication demonstrate that corn steep liquor is a viable and economically attractive alternative to conventional media, provided that nutrient imbalances are addressed. The Kuhner microTOM enabled rapid, parallelized screening and sensitive detection of metabolic differences, significantly accelerating media optimization and improving process robustness under industrially relevant conditions.

Unraveling the impact of pH, sodium concentration, and medium osmolality on Vibrio natriegens in batch processes (Eva Forsten et al., BMC Biotechnology 2024)

The high growth rate of Vibrio natriegens offers clear advantages for accelerated bioprocessing, yet uncontrolled batch cultivation leads to substrate accumulation, overflow metabolism, and pH instability, limiting process robustness and scalability. Stable control of substrate availability at small scale is therefore essential to enable reproducible and transferable process conditions aligned with industrial requirements. The results in this study highlight the impact of controlled feeding strategies on process stability, yield, and scalability. The Kuhner microTOM enabled high-resolution monitoring of respiration activity, providing direct insight into metabolic state and enabling rapid adjustment of feeding conditions. Using the Kuhner microTOM reduces experimental effort, accelerates process optimization, and improves transferability to larger scales, supporting efficient integration of fast-growing organisms into industrial bioprocess development.

Small‑scale fed‑batch cultivations of Vibrio natriegens: overcoming challenges for early process development (Clara Lüchtrath et al., Bioprocess and Biosystems Engineering 2025)

The exceptional growth rate of Vibrio natriegens offers significant potential for intensified bioprocesses, yet uncontrolled batch conditions lead to pronounced overflow metabolism, mixed acid formation, and pH instability, limiting its applicability in early process development. Establishing controlled feeding strategies at small scale is therefore critical to enable robust and scalable processes while maintaining high metabolic efficiency. The Kuhner microTOM enabled noninvasive, high-resolution monitoring of respiration activity, providing a direct link between metabolic state and substrate availability. This capability supports rapid optimization of feeding strategies, reduces experimental effort, and facilitates reliable transfer from microtiter plate to larger scales, accelerating early-stage process development.

Inoculum cell count influences separation efficiency and variance in Amesplate incorporation and Ames RAMOS test(Eva Forsten et al., Elsevier 2023)

Reliable mutagenicity assessment remains essential for regulatory screening of chemicals and environmental samples, yet conventional Ames test formats rely on endpoint evaluation and exhibit high variability in miniaturized systems. Limited sensitivity at low concentrations and extensive manual workload constrain throughput and robustness. Continuous monitoring of respiratory activity provides a process-oriented alternative, enabling real-time detection of mutagenic effects while maintaining compatibility with established assay principles. The Kuhner microTOM enabled high-throughput implementation in 96-well format with consistent oxygen transfer resolution, providing a scalable platform for sensitive and efficient mutagenicity screening in industrial and environmental applications.

Device for respiration activity measurement enables the determination of oxygen transfer rates of microbial cultures in shaken 96-deepwell microtiter plates(Robert Dinger et al., Biotechnology and Bioengineering 2021)

Early bioprocess development requires high experimental throughput while maintaining process-relevant information for reliable strain and cultivation assessment. Although 96-deepwell microtiter plates enable efficient screening with low material consumption, oxygen transfer rate monitoring had previously been limited to shake flasks and smaller microtiter plate formats. The Kuhner microTOM extends online respiration monitoring to the 96-deepwell format, providing oxygen transfer information directly at the scale commonly used for high-throughput process development. The Kuhner microTOM therefore closes an important gap between conventional high-throughput microtiter plate screening and quantitative process monitoring. Its demonstrated precision and substantial gains in throughput and material efficiency provide a practical basis for faster and more resource-efficient early-stage bioprocess development, with clear potential for broader application in strain and process optimization.

Enhancing acetate-based biosurfactant production by Pseudomonas putida KT2440 through fermentation optimization (Michel et al. Microbial Cell Factories, 2026)

Discover how researchers optimized fed-batch fermentation of Pseudomonas putida for sustainable biosurfactant production using acetate as a carbon source. The study highlights improved feeding strategies, enhanced HAA yields, and the use of Kuhner microTOM technology for online oxygen transfer rate (OTR) monitoring.

Small‑scale fed‑batch cultivations of Vibrio natriegens: overcoming challenges for early process development (Clara Lüchtrath et al., Bioprocess and Biosystems Engineering 2025)

The exceptional growth rate of Vibrio natriegens offers significant potential for intensified bioprocesses, yet uncontrolled batch conditions lead to pronounced overflow metabolism, mixed acid formation, and pH instability, limiting its applicability in early process development. Establishing controlled feeding strategies at small scale is therefore critical to enable robust and scalable processes while maintaining high metabolic efficiency. The Kuhner microTOM enabled noninvasive, high-resolution monitoring of respiration activity, providing a direct link between metabolic state and substrate availability. This capability supports rapid optimization of feeding strategies, reduces experimental effort, and facilitates reliable transfer from microtiter plate to larger scales, accelerating early-stage process development.

Unraveling the impact of pH, sodium concentration, and medium osmolality on Vibrio natriegens in batch processes (Eva Forsten et al., BMC Biotechnology 2024)

The high growth rate of Vibrio natriegens offers clear advantages for accelerated bioprocessing, yet uncontrolled batch cultivation leads to substrate accumulation, overflow metabolism, and pH instability, limiting process robustness and scalability. Stable control of substrate availability at small scale is therefore essential to enable reproducible and transferable process conditions aligned with industrial requirements. The results in this study highlight the impact of controlled feeding strategies on process stability, yield, and scalability. The Kuhner microTOM enabled high-resolution monitoring of respiration activity, providing direct insight into metabolic state and enabling rapid adjustment of feeding conditions. Using the Kuhner microTOM reduces experimental effort, accelerates process optimization, and improves transferability to larger scales, supporting efficient integration of fast-growing organisms into industrial bioprocess development.

Experimental kS estimation: A comparison of methods for Corynebacterium glutamicum from lab to microfluidic scale (Heiko Steinhoff et al., Biotechnology and Bioengineering 2023)

Reliable estimation of substrate affinity remains a critical limitation in industrial bioprocess development, particularly for organisms such as Corynebacterium glutamicum where accurate kinetic parameters are required to manage substrate gradients and ensure robust large scale performance. Conventional approaches are analytically demanding and provide limited resolution at low substrate concentrations, restricting their applicability for process optimization. A multi scale screening concept combining microtiter based methods with the Kuhner microTOM and single cell analysis enables rapid and application relevant characterization of substrate affinity across different resolution levels.

Unraveling the potential and constraints associated with corn steep liquor as a nutrient source for industrial fermentations (Sekar Mayang W. Wahjudi et al., Biotechnology Progress 2023)

The high cost and compositional variability of conventional complex media remain critical constraints in industrial fermentation. Corn steep liquor offers a cost-efficient alternative but introduces uncertainty due to batch heterogeneity. Rapid and reliable evaluation of such substrates is essential to ensure consistent process performance. A scalable screening approach combining high-throughput cultivation with online metabolic monitoring enables early identification of suitable media compositions and limiting factors. The results in this publication demonstrate that corn steep liquor is a viable and economically attractive alternative to conventional media, provided that nutrient imbalances are addressed. The Kuhner microTOM enabled rapid, parallelized screening and sensitive detection of metabolic differences, significantly accelerating media optimization and improving process robustness under industrially relevant conditions.

Inoculum cell count influences separation efficiency and variance in Amesplate incorporation and Ames RAMOS test(Eva Forsten et al., Elsevier 2023)

Reliable mutagenicity assessment remains essential for regulatory screening of chemicals and environmental samples, yet conventional Ames test formats rely on endpoint evaluation and exhibit high variability in miniaturized systems. Limited sensitivity at low concentrations and extensive manual workload constrain throughput and robustness. Continuous monitoring of respiratory activity provides a process-oriented alternative, enabling real-time detection of mutagenic effects while maintaining compatibility with established assay principles. The Kuhner microTOM enabled high-throughput implementation in 96-well format with consistent oxygen transfer resolution, providing a scalable platform for sensitive and efficient mutagenicity screening in industrial and environmental applications.

Device for respiration activity measurement enables the determination of oxygen transfer rates of microbial cultures in shaken 96-deepwell microtiter plates(Robert Dinger et al., Biotechnology and Bioengineering 2021)

Early bioprocess development requires high experimental throughput while maintaining process-relevant information for reliable strain and cultivation assessment. Although 96-deepwell microtiter plates enable efficient screening with low material consumption, oxygen transfer rate monitoring had previously been limited to shake flasks and smaller microtiter plate formats. The Kuhner microTOM extends online respiration monitoring to the 96-deepwell format, providing oxygen transfer information directly at the scale commonly used for high-throughput process development. The Kuhner microTOM therefore closes an important gap between conventional high-throughput microtiter plate screening and quantitative process monitoring. Its demonstrated precision and substantial gains in throughput and material efficiency provide a practical basis for faster and more resource-efficient early-stage bioprocess development, with clear potential for broader application in strain and process optimization.

Early bioprocess development using Komagataella phaffii: application scenarios for the microTOM mini bioreactor system (David Wollborn et al., Journal of Biological Engineering, 2026)

Early bioprocess development for Komagataella phaffii requires rapid discrimination of strain, medium, carbon source and cultivation conditions while maintaining sufficient process information for subsequent development. Conventional microtiter plate screening provides high-throughput but limited insight into oxygen demand and metabolic activity. The Kuhner microTOM extends this scale by providing online oxygen transfer rate information across 96 individual wells, enabling data-rich screening with direct relevance to aerobic process performance. The combination of high throughput and well-resolved OTR information supports faster strain and media selection, more informed feeding strategies and earlier identification of oxygen transfer constraints. This provides a practical basis for more robust process development and can reduce the number of experiments required before progression to larger-scale cultivation.

Metabolic studies of Ogataea polymorpha using nine different corn steep liquors (Sekar Mayang W. Wahjudi et al., BMC Biotechnology 2025)

The increasing demand to replace costly complex media components with sustainable alternatives highlights corn steep liquor as a promising nutrient source, yet its inherent batch variability challenges process consistency in industrial fermentations. Reliable identification of performance-limiting factors is therefore essential to enable its robust application. A respiration-based fingerprinting approach using the Kuhner microTOM allowed rapid differentiation of media performance and detection of growth limitations under varying conditions.

Primary high-throughput screening of engineered phytases by online monitoring of the oxygen transfer rate of Komagataella phaffii (Sarah Luise Straaten, Marie Zöllner, Eva Forsten, Sekar Mayang W. Wahjudi et al., Straaten et al. BMC 2025)

The fast growth kinetics of Vibrio natriegens create strong potential for intensified bioprocesses, yet conventional batch cultivation leads to rapid substrate excess, overflow metabolism, and unstable pH conditions, limiting reproducibility and scalability. Reliable control of substrate availability at small scale remains a critical requirement for early process development. Controlled feeding strategies combined with real-time physiological readouts provide a route to stabilize metabolism and align small-scale conditions with industrially relevant operation. The Kuhner microTOM enabled high-resolution monitoring of respiration activity, allowing precise alignment of substrate supply with cellular demand. This capability accelerates process development, reduces experimental iterations, and supports reliable transfer to larger scales, providing a practical framework for integrating fast-growing organisms into industrial workflows.

Investigation into struvite precipitation: A commonly encountered problem during fermentations on chemically defined media(Thomas Steimann et al., Biotechnology and Bioengineering 2023)

Precipitation phenomena in chemically defined mineral media remain a critical constraint in high cell density fermentations, particularly under elevated pH conditions. The formation of poorly soluble salts reduces macronutrient availability, introduces variability, and increases operational risks such as fouling and inconsistent medium composition. Addressing this challenge requires a process-oriented understanding of nutrient accessibility rather than nominal concentrations, combined with scalable tools that enable rapid screening of relevant parameter spaces. These findings highlight the necessity of integrating precipitation and dissolution dynamics into media design. The Kuhner microTOM enabled high-throughput, quantitatively reproducible identification of limiting conditions and kinetic effects, reducing development time while improving robustness.

Scale‑up of CHO cell cultures: from 96‑well‑microtiter plates to stirred tank reactors across three orders of magnitude(Anne Neuss et al., Journal of Biological Engineering 2025)

Reliable estimation of substrate affinity remains a critical limitation in industrial bioprocess development, particularly for organisms such as Corynebacterium glutamicum where accurate kinetic parameters are required to manage substrate gradients and ensure robust large scale performance. Conventional approaches are analytically demanding and provide limited resolution at low substrate concentrations, restricting their applicability for process optimization. A multi scale screening concept combining microtiter based methods with the Kuhner microTOM and single cell analysis enables rapid and application relevant characterization of substrate affinity across different resolution levels.

Predicting high recombinant protein producer strains of Pichia pastoris MutS using the oxygen transfer rate as an indicator of metabolic burden (David Wollborn et al., Scientific reports 2022)

Efficient identification of high-producing clones remains a critical bottleneck in recombinant protein process development with Pichia pastoris, where large clone libraries require extensive analytical effort. Conventional screening approaches rely on protein quantification, limiting throughput and delaying decision-making. A process-relevant alternative is the use of respiration-based indicators to directly capture metabolic burden during induction, enabling rapid differentiation of production phenotypes under industrially relevant conditions. The results of this study demonstrate that respiration-based screening significantly accelerates early-stage process development by reducing analytical workload and enabling robust clone selection. The Kuhner microTOM enabled high-resolution oxygen transfer monitoring in standard deepwell microtiter formats, extending this approach to scalable high-throughput environments. This contribution translates into faster strain selection, improved process robustness, and reduced development costs, with clear potential for broader application across recombinant production systems.

Phosphate limitation enhances malic acid production on nitrogen‑rich molasseswith Ustilago trichophora
(Luca Antonia Grebe et al., Biotechnology for Biofuels and Bioproducts 2024)

The growing demand for efficient phosphate recovery from plant-based side streams requires high-performance phytase variants, while conventional screening of large mutant libraries remains labor-intensive and slow. Early-stage identification of productive and active clones is therefore a critical bottleneck. A high-throughput strategy based on respiratory activity monitoring enables direct assessment of production performance during cultivation, combining rapid discrimination of non-performing strains with activity-based selection under process-relevant conditions. The combined strategy enables simultaneous evaluation of protein production and enzymatic performance, providing a scalable solution for enzyme engineering workflows. The Kuhner microTOM was central to this advancement by enabling parallelized, high-resolution monitoring in microtiter plate format, thereby substantially reducing experimental effort and enabling faster, more robust process development.

Development of an itaconic acid production process with Ustilaginaceae on alternative feedstocks (Paul-Joachim Niehoff et al., BMC Biotechnology 2023)

The economic viability of bio-based itaconic acid production remains constrained by substrate costs and process robustness. Conventional processes based on refined sugars and filamentous organisms impose limitations in oxygen transfer, process stability, and feedstock flexibility. A process concept based on Ustilaginaceae and alternative substrates from the food industry enables cost reduction while maintaining competitive performance. Central to this approach is rapid, data-driven strain and substrate evaluation combined with controlled nitrogen limitation. The results demonstrate that alternative feedstocks can match or exceed conventional performance while reducing raw material costs. The Kuhner microTOM enabled rapid identification of suitable strains, substrates, and operating windows, significantly accelerating process development. This high-throughput capability supports robust scale-up and facilitates economically viable industrial implementation.

Early bioprocess development using Komagataella phaffii: application scenarios for the microTOM mini bioreactor system (David Wollborn et al., Journal of Biological Engineering, 2026)

Early bioprocess development for Komagataella phaffii requires rapid discrimination of strain, medium, carbon source and cultivation conditions while maintaining sufficient process information for subsequent development. Conventional microtiter plate screening provides high-throughput but limited insight into oxygen demand and metabolic activity. The Kuhner microTOM extends this scale by providing online oxygen transfer rate information across 96 individual wells, enabling data-rich screening with direct relevance to aerobic process performance. The combination of high throughput and well-resolved OTR information supports faster strain and media selection, more informed feeding strategies and earlier identification of oxygen transfer constraints. This provides a practical basis for more robust process development and can reduce the number of experiments required before progression to larger-scale cultivation.

Small‑scale fed‑batch cultivations of Vibrio natriegens: overcoming challenges for early process development (Clara Lüchtrath et al., Bioprocess and Biosystems Engineering 2025)

The exceptional growth rate of Vibrio natriegens offers significant potential for intensified bioprocesses, yet uncontrolled batch conditions lead to pronounced overflow metabolism, mixed acid formation, and pH instability, limiting its applicability in early process development. Establishing controlled feeding strategies at small scale is therefore critical to enable robust and scalable processes while maintaining high metabolic efficiency. The Kuhner microTOM enabled noninvasive, high-resolution monitoring of respiration activity, providing a direct link between metabolic state and substrate availability. This capability supports rapid optimization of feeding strategies, reduces experimental effort, and facilitates reliable transfer from microtiter plate to larger scales, accelerating early-stage process development.

Scale‑up of CHO cell cultures: from 96‑well‑microtiter plates to stirred tank reactors across three orders of magnitude(Anne Neuss et al., Journal of Biological Engineering 2025)

Reliable estimation of substrate affinity remains a critical limitation in industrial bioprocess development, particularly for organisms such as Corynebacterium glutamicum where accurate kinetic parameters are required to manage substrate gradients and ensure robust large scale performance. Conventional approaches are analytically demanding and provide limited resolution at low substrate concentrations, restricting their applicability for process optimization. A multi scale screening concept combining microtiter based methods with the Kuhner microTOM and single cell analysis enables rapid and application relevant characterization of substrate affinity across different resolution levels.

Primary high-throughput screening of engineered phytases by online monitoring of the oxygen transfer rate of Komagataella phaffii (Sarah Luise Straaten, Marie Zöllner, Eva Forsten, Sekar Mayang W. Wahjudi et al., Straaten et al. BMC 2025)

The fast growth kinetics of Vibrio natriegens create strong potential for intensified bioprocesses, yet conventional batch cultivation leads to rapid substrate excess, overflow metabolism, and unstable pH conditions, limiting reproducibility and scalability. Reliable control of substrate availability at small scale remains a critical requirement for early process development. Controlled feeding strategies combined with real-time physiological readouts provide a route to stabilize metabolism and align small-scale conditions with industrially relevant operation. The Kuhner microTOM enabled high-resolution monitoring of respiration activity, allowing precise alignment of substrate supply with cellular demand. This capability accelerates process development, reduces experimental iterations, and supports reliable transfer to larger scales, providing a practical framework for integrating fast-growing organisms into industrial workflows.

Predicting high recombinant protein producer strains of Pichia pastoris MutS using the oxygen transfer rate as an indicator of metabolic burden (David Wollborn et al., Scientific reports 2022)

Efficient identification of high-producing clones remains a critical bottleneck in recombinant protein process development with Pichia pastoris, where large clone libraries require extensive analytical effort. Conventional screening approaches rely on protein quantification, limiting throughput and delaying decision-making. A process-relevant alternative is the use of respiration-based indicators to directly capture metabolic burden during induction, enabling rapid differentiation of production phenotypes under industrially relevant conditions. The results of this study demonstrate that respiration-based screening significantly accelerates early-stage process development by reducing analytical workload and enabling robust clone selection. The Kuhner microTOM enabled high-resolution oxygen transfer monitoring in standard deepwell microtiter formats, extending this approach to scalable high-throughput environments. This contribution translates into faster strain selection, improved process robustness, and reduced development costs, with clear potential for broader application across recombinant production systems.