Key Facts about Microbial Fermentation

Microbial cells (bacteria, yeast) enable small scale microbial fermentation with rapid growth rates (doubling times of 20–60 min), achieve very high cell densities (>100 g/L dry cell weight), and tolerate higher shear than mammalian cells, but generate significant metabolic heat and oxygen demand. Their metabolism often leads to rapid pH shifts, foam formation, and accumulation of by-products such as acetate (bacteria) or ethanol (yeast), requiring Applikon bioreactors for precise aeration, mixing, and feeding strategies. 

Prokaryotic bacteria lack organelles and post-translational modifications, enabling simple media and high yields of recombinant proteins, enzymes, or biofuels. Yeasts offer eukaryotic folding but slower growth. These properties require robust bioreactors like Applikon MiniBio, autoclavable glass, single-use or stainless steel bioreactors. Applikon bioreactors enable optimum gas transfer (high kLa), precise temperature control, and flexible feeding for batch, fed-batch, or continuous fermentation.

Microbial cells

Key Parameters for Microbial Processes

Microbial fermentations rely on tight control of a few core parameters across all bioreactor types (Mini Bio, lab scale glass, single-use or stainless steel).

  • pH control

    Typically 5–7 for yeast and 6–7.5 for bacteria; controlled via acid/base addition.

  • Dissolved oxygen

    High oxygen transfer rates (OTR) with air or air/O₂ mixtures; kLa is key for scale-up.

  • Temperature

    From mesophilic (30–37°C) to thermophilic; fast metabolic heat removal.

  • Agitation and shear

    Higher impeller speeds for mass transfer, suitable for shear-tolerant strains.

  • Nutrient and feed strategy

    Carbon/nitrogen feeds to avoid overflow metabolism and by-products.

Standard Fermentation Workflow

A typical microbial fermentation follows a simple, reproducible sequence adaptable to batch, fed-batch, or continuous operation.

  1. Seed preparation

    Shake flask or small seed bioreactor for healthy inoculum.

  2. Inoculation

    Transfer to the Applikon production bioreactor at defined cell concentration.

  3. Fermentation phase

    Control pH, DO, temperature, antifoam; optional feeds

  4. Monitoring

    Biomass, product, substrates via off-/at-line analytics.

  5. Harvest

    Broth collection for downstream; BioSep enables continuous harvest at high densities (brief note: typically downstream equipment).

Bioreactor Types for Microbial Applications

Microbial fermentation works across all Applikon formats with tailored mixing, aeration, and controls.

Type Scale Key Use Cases Microbial-Specific Features
Applikon MiniBio glass small-scale bioreactor 0.25–1 L Strain screening, media optimization High kLa/OTR in low volume, antifoam integration, Peltier cooling and heating
Applikon glass autoclavable bioreactors for microbial fermentation 2–20 L Process development, scale-down models Multiple spargers, high agitation for O₂ demand, jacketed or single wall vessel
AppliFlex ST single‑use bioreactor for microbial fermentation 0.5–15 L Development & small production Robust mixing, foam control, no cross-contamination, cooling option available
Stainless-steel bioreactors for large-scale microbial fermentation and continuous perfusion from 20L to 5000L Pilot & large-scale production Consistent H/D design for optimum scale-up, high gas flow, heat exchange, CIP / SIP for fast cycles

Strategies for High-Density and Intensified Microbial Processes

Intensify microbial fermentation for maximum productivity in Applikon bioreactors. These transfer consistently from Applikon Mini bioreactor to production scale.

  1. High-density fed-batch

    Controlled feeds for high cell densities without by-products.

  2. Oxygen transfer enhancement

    O₂ enrichment, advanced spargers for peak demand.

  3. Temperature/induction profiles

    Optimized for expression systems (e.g., phase-specific induction).

Overview

Harnessing Microbial Potential with Applikon Bioreactors

In the field of industrial microbiology, bioreactor fermentation stands as a cornerstone technique for producing a broad spectrum of microbial products — from antibiotics and biofuels to food and beverages. The Applikon bioreactor portfolio is at the forefront of this domain, offering precision and control for cultivating bacteria, yeast, and fungi.


The Applikon Mini bioreactor combines precision control with flexibility, allowing researchers and industrial biotechnologists to fine-tune environmental parameters to meet the specific needs of various microbial strains. It generates precise and valuable data on extremely small bench space, providing the foundation for large-scale production.

Step-by-Step

Detailed Fermentation Process

The microbial fermentation process in the Applikon bioreactor follows a carefully orchestrated sequence, from preparation through to monitoring — each step optimized for maximum yield and reproducibility.

  • Scalability

    Scalability

    Seamless scale-up from research to production scale. Applikon’s portfolio scales from mini bioreactors with 50 mL working volume to large-scale stainless steel bioreactors with 5000 L volume.

  • Flexibility

    Flexibility

    Accommodates a wide range of microbial types and fermentation strategies, including aerobic or anaerobic organisms, bacterial and yeast cultures for diverse bioprocess applications.

  • Control & Precision

    Control & Precision

    Advanced control systems enable precise manipulation of environmental conditions, enhancing microbial productivity and product consistency across all fermentation modes.

  • Efficiency

    Efficiency

    Optimized for high-density cultures and high-yield product recovery, providing a cost-effective solution for microbial fermentation from screening to production.

CTA Background

Looking for the Right Bioprocess Solution?

Our specialists support you throughout the entire bioprocess lifecycle — from system selection and application design to implementation, optimization, and long-term operation. We work closely with you to ensure reliable, compliant, and scalable solutions tailored to your requirements.

Talk to Our Experts
Contact Form EN

FAQ - Microbials Culture

The right choice depends on your scale and application. The Applikon MiniBio (0.25–1 L) is ideal for strain screening and media optimisation at small scale — offering high kLa and integrated antifoam control. Autoclavable glass bioreactors (2–20 L) are well suited for process development and scale-down models. The AppliFlex ST (0.5–15 L) is a single-use system that eliminates cross-contamination risks, making it a practical choice for development and smaller production runs. For pilot and large-scale production, stainless steel bioreactors from 20 L to 5,000 L are available — with CIP/SIP for fast turnaround between batches. Resea Biotec is happy to help you select the right system for your process.

Microbial cultures — particularly bacteria and yeast — grow rapidly and generate significant metabolic heat alongside high oxygen demand. Applikon bioreactors are designed specifically for these conditions: optimised gas transfer with high kLa values, aeration using air or air/O₂ mixtures, and agitation systems engineered for efficient mass transfer. Temperature is controlled precisely via heating/cooling jackets or Peltier elements at smaller scales. This keeps pH shifts, foam formation, and by-product accumulation — such as acetate in bacteria or ethanol in yeast — reliably under control throughout the fermentation.

Yes — this is one of the core strengths of the Applikon platform. A consistent height-to-diameter (H/D) design across all bioreactor sizes ensures that mixing behaviour, gas transfer, and control characteristics remain comparable as you scale up. Process parameters developed in the MiniBio at 50 mL working volume can be reliably transferred to stainless steel bioreactors of up to 5,000 L — without the need for extensive re-optimisation. This saves development time, reduces costs, and gives you confidence that the results achieved at research scale will be reproducible in full production.

Applikon bioreactors at Resea Biotec support the production of a broad range of microbial products — including recombinant proteins and enzymes for pharmaceutical and industrial applications, biotherapeutics such as vaccines and antibody fragments, antibiotics and secondary metabolites, biofuels and bio-based chemicals, as well as food ingredients and beverage components. Both prokaryotic bacteria such as E. coli and eukaryotic yeasts like Saccharomyces cerevisiae or Pichia pastoris are routinely cultivated in Applikon glass and stainless steel bioreactors — from the MiniBio through to 5,000 L production systems.

In fast-growing microorganisms such as E. coli, uncontrolled glucose supply can trigger overflow metabolism — recognised by acetate accumulation in bacteria or ethanol formation in yeast — which impairs cell growth, product yield, and process stability. Applikon bioreactors address this through precise fed-batch strategies with controlled carbon and nitrogen feeding, coupled with real-time monitoring of biomass, substrates, and metabolites. The Livit Flex control system enables automated feed regulation that keeps metabolism within the optimal zone — supporting cell densities above 100 g/L dry cell weight without compromising product quality. Explore our bundle solutions for complete fermentation workflows.