Application

Microbial Strain and Fermentation Development

Strain engineering focuses on creating microbial strains that can efficiently produce the target product. Techniques from genetic modification and synthetic biology are applied to boost recombinant protein expression and overall performance. After a high-performing strain is achieved, process development shifts to refining the fermentation process to increase yield and efficiency.

Automated solutions significantly enhance microbial fermentation by enabling high-throughput screening, real-time data collection, and consistent process optimization. They allow researchers to test multiple conditions quickly (e.g., temperature, pH, and Dissolved Oxygen (DO)), while continuous monitoring and timely adjustments help maintain ideal fermentation parameters.

Bioprocess automation minimizes human error, standardizes workflows, and ensures reproducibility and scalability from lab to industrial scale.

How Hamilton Supports your Microbial Strain and Fermentation Development Workflows

Hamilton supports efficient and scalable strain and process development with automated solutions that streamline and standardize key steps, from strain engineering and early selection to process optimization and clone storage, while maximizing walk-away time and reproducibility. Our platforms integrate seamlessly with third-party devices, such as the 2mag 48-parallel bioreactor, to reduce bottlenecks in bioprocess development.

Strain development begins with genetic engineering and uses synthetic biology to construct microbial strains with enhanced functions. Genetic constructs carrying target genes are introduced into hosts through transformation or genome integration. Large, diverse strain libraries are generated to maximize the chances of finding strains with improved titer, yield, and productivity.

Hamilton’s customizable liquid handlers can facilitate this step through automated insert amplification, restriction digestion, ligation and assembly, downstream colony picking, and plasmid purification of transformed bacteria. Plasmids can be securely stored at –80 °C using our automated sample storage and management systems.

Once constructed, strain libraries go through high-throughput screening to find the candidates with the best productivity, growth, and stability.
Hamilton’s EasyPick automates clone selection directly from agar plates using customizable criteria such as colony size, shape, color, or position. Additionally, we provide automated solutions for genomic assays (e.g., Quantitative Polymerase Chain Reaction (qPCR), Next-Generation Sequencing (NGS)), protein quantification (e.g., Enzyme-Linked Immunosorbent Assay (ELISA), Liquid Chromatography–Mass Spectrometry (LC-MS)) and cell-based assays on dedicated or customized robotic platforms. For short or long-term preservation, strains can be securely stored using our automated sample storage and management systems.

After the initial screening, the top-performing strains are further developed under conditions that mimic industrial fermentation. This stage typically involves small-scale testing in bioreactors. This is where parameters such as dissolved oxygen, agitation, and feed strategies are tightly controlled to assess strain performance more closely in production environments. These insights are essential for successful scale-up.

To support this, Hamilton developed an automated solution for clone screening by integrating a 2mag 48-parallel bioreactor and third-party devices into the Hamilton Microlab STAR platform.

Each bioreactor is equipped with real-time monitoring and control of critical parameters such as pH, DO and Optical Density (OD), ensuring consistent cultivation conditions. With up to 48 independent bioreactors running in parallel, users can efficiently screen clones and perform complex, multi-factor DoE studies.

By combining high-throughput capability with precise control and advanced analytics, Hamilton’s bioreactor 48 DS on STARline enables teams to identify the best-performing strains and processes earlier, accelerate development timelines, and overcome scale-up challenges.
Once fermentation development is complete, the process moves to upstream optimization, where selected strains are further refined in larger bioreactors under scaled-up conditions. Take a look at the Upstream Bioprocessing Application Page.

Good to Know about Microbial Strain and Fermentation Development Workflows

This section provides a selection of additional resources related to the application described on this page. It includes helpful articles, videos, and blogs that offer deeper insights into the topic.

Useful Links

External resources not written by Hamilton but valuable for understanding the topic, such as industry guidelines, explanatory videos, or relevant tools.

Applying Design of Experiments in industrial bioprocess development - JPM Statistical Discovery	Watch Video
Bio-processing overview (Upstream and downstream process) - Animated Biology with Arpan	Watch Video
Boodhoo, K. V. K., Flickinger, M. C., Woodley, J. M., & Emanuelsson, E. A. C. (2022). Bioprocess intensification: A route to efficient and sustainable biocatalytic transformations for the future. Chemical Engineering and Processing - Process Intensification, 172, 108793.	Read Article

Scientific Articles

Peer-reviewed journal publications that feature Hamilton products, demonstrating their use in real-world research and application

Blums, K., Herzog, J., Costa, J., Quirico, L., Turber, J., & Weuster-Botz, D. (2025). Automation of RNA-Seq sample preparation and miniaturized parallel bioreactors enable high-throughput differential gene expression studies. Microorganisms, 13(4), 849.

Read Article

Hamilton Products in Action

A collection of videos showcasing Hamilton products in use, providing practical insights into their functionality and benefits.

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Solutions for the Top 3 Challenges for Microbial Strain and Fermentation Development Workflows

Consistent Scale-Up

Challenge: Transitioning microbial bioprocessing from laboratory to industrial scale presents challenges in maintaining process efficiency and product quality. Factors such as oxygen transfer, nutrient distribution, and heat dissipation can vary significantly across different scales, potentially impacting microbial growth, metabolic activity, and overall product yield.

Solution: The Hamilton bioREACTOR 48 DS offers a powerful solution to the challenges of scaling microbial bioprocesses from lab to industrial production. By enabling high-throughput experimentation under controlled and monitored conditions, researchers can efficiently screen multiple strains, media compositions, and process parameters in parallel, facilitating rapid strain and process development. Users can perform complex, multi-factor Design of Experiments (DoE) studies for process optimization.
Its ability to closely mimic conditions of larger-scale bioreactors—such as mixing, oxygen transfer, and pH control—provides valuable, scalable insights early in development. Integrated real-time monitoring and bioprocess automation enhance data quality and reproducibility, reducing variability and streamlining scale-up. Hamilton’s mini-parallel bioreactors de-risk scale-up, shorten timelines, and lower costs by enabling faster, more informed decision-making at the bench scale.

Precise Monitoring and Control

Challenge: Successful microbial bioprocessing relies on the precise monitoring and control of key parameters such as temperature, pH, dissolved oxygen, and nutrient availability. These variables directly influence microbial growth, metabolic activity, and product formation. Slight changes can lower process efficiency, reduce yields, or result in unwanted by-products. It is important to maintain optimal conditions to ensure microbial viability, maximized product yield, and to achieve reproducible results at any scale.

Solution: Hamilton’s bioREACTOR 48 DS tackles these challenges with 48 single-use microbioreactors that feature integrated pH and DO sensors for continuous online monitoring. Real-time tracking and control of key parameters help ensure consistent and reproducible processes. The system’s high-throughput design allows researchers to screen multiple strains, media types, and conditions at once, closely simulating large-scale bioreactor performance with fine-tuned control of mixing, oxygen transfer, and nutrient flow.

Advanced bioprocess automation and continuous online monitoring reduce variability and accelerate process optimization, helping you de-risk scale-up and shorten development timelines. The system also supports automated microbial fermentation, streamlining workflows from strain development through production.

Ensuring Process Reproducibility Across Batches

Challenge: Microbial bioprocessing often suffers from inconsistencies across batches due to variability in materials, protocols, and operator handling. Manual steps, differing techniques, and inconsistent timing can lead to fluctuating results, hindering comparability and delaying process development.

Solution: Workflow Harmonization Through Automation. Hamilton’s automated platforms ensure reproducibility by standardizing protocols. This reduces operator-dependent variation and automates repetitive steps. From liquid handling to cultivation and sample processing, automation brings consistency to every run. This enables reliable comparison of conditions, faster iteration, and robust, repeatable results that scale confidently from development to production.

What is Automated Microbial Fermentation?

Automated microbial fermentation uses advanced technology to grow microorganisms, such as bacteria, yeast, or fungi, under precisely controlled and continuously monitored conditions, with minimal manual intervention. It streamlines microbial cultivation by automating media handling, sampling, and environmental control, reducing variability and improving reproducibility.

What are the Most Common Microbial Strains?

Many industries rely on fermentation processes that use specific microbial strains specific to their production goals, substrate preferences, and product profiles. The choice of microorganism has a significant impact on yield, process efficiency, and product quality.

Food and Beverage Industry

Yeasts are the primary microorganisms, with Saccharomyces cerevisiae being the most dominant in beer, wine, and bread production due to its robust ethanol fermentation capabilities and distinctive flavor profile. Lactic acid bacteria (LAB), such as Lactobacillus and Streptococcus species, are widely used in dairy fermentations (e.g., yogurt, cheese) due to their ability to produce lactic acid, which improves texture and enhances preservation.

Pharmaceutical Industry

In the pharmaceutical industry, microbial strains producing antibiotics, enzymes, and vaccines are key. Streptomyces species are successful producers of antibiotics like streptomycin and tetracycline. Recombinant strains like Escherichia coli and Saccharomyces cerevisiae are extensively engineered for the production of therapeutic proteins and vaccines.

Biofuel Industry

For bioethanol, Saccharomyces cerevisiae remains the workhorse due to its high ethanol tolerance and efficient fermentation. In advanced biofuels, engineered strains of Zymomonas mobilis and Clostridium species are employed for their ability to ferment pentoses and produce butanol or other higher alcohols.

Chemical and Bioproduct Industry

Microbial strains capable of producing organic acids, bioplastics, and specialty chemicals are utilized. Corynebacterium glutamicum is widely used for amino acid production. Pseudomonas and Ralstonia species are harnessed for biopolymer precursors and biodegradation pathways.