Improving Your Bacterial Production With BactoBox

Whether you are producing probiotics, live biotherapeutic products, plant growth-promoting bacteria, bacterial vaccines, or any other bacterial products, BactoBox helps you maximize the efficiency of your production equipment and shorten development cycles when transferring processes to shake flasks or bioreactors.

The Challenge: No Rapid Method Reliably Identifies Peak Cell Concentration

Your bacterial cells are your product. The goal of process development and production is to achieve the highest cell concentration in the shortest time with the greatest downstream survivability. Determining peak cell concentration in bacterial production is crucial yet challenging. Optical density is the most commonly used in-process control (IPC) method for this metric, but it is a proxy method for actual cell concentration and culture health. Optical density, and similar biomass probes, are heavily affected by changing cell morphologies, media composition, extracellular metabolites, and particulates in the fermentation media.

Using optical density, backscatter light, and similar approaches to assess peak cell concentration introduces several challenges:

• Various process conditions and strains can cause bacteria to produce metabolites or change morphology in the stationary phase, increasing optical density but not cell concentrations.
• Some strains rapidly die after entering the stationary phase, which optical density measurements do not detect.
• The optimal harvest window for downstream survivability might be just before the stationary phase, but offsets between optical density and CFUs make it difficult to pinpoint the growth curve position.
• Correlation to actual cell counts, such as CFUs, must be re-established whenever a process parameter is varied.
  

These challenges make process development difficult and hinder the achievement of consistent yield in production and process development.

The Solution: BactoBox Provides CFU Equivalents in 2 Minutes

BactoBox is essential for in-process control of bacterial fermentations, providing precise bacterial concentrations in just 2 minutes. Unlike OD600, BactoBox results are unaffected by changing process conditions, cell morphologies, or metabolite production.

In the example below, BactoBox accurately tracks CFUs and determined that growth stagnated after 7-8 hours. Optical density values continued to increase due to non-relevant metabolite production. The accuracy and transparency of BactoBox allow users to know precisely when to harvest for maximum yield, without needing a CFU calibration curve.

Beyond providing accurate cell counts, BactoBox also offers information about cell morphology. This is demonstrated in the last graph of the above figure, which depicts the amplitude, or size, of the cells at different sampling points. BactoBox accurately tracks cell counts for virtually any bacterial strain with precision superior to CFUs.

Reach Out to Learn More or Get a Trial

We invite you to discuss how BactoBox can enhance your development processes and improve the consistency of your bacterial production. Simply fill out the form below, and an SBT representative will contact you shortly.

Learn About a BactoBox Customer

Biose Industrie, a leading contract development and manufacturing organization (CDMO) specializing in live biotherapeutic products (LBPs), extensively utilizes BactoBox for their process development and production. Performing several thousand measurements annually with BactoBox, they effectively address the challenges of reliably producing high-quality bacteria. This advanced monitoring capability enhances their ability to maintain consistency and precision in bacterial cultivation, ensuring optimal outcomes in their biotherapeutic products.

In implementing BactoBox within Biose’s manufacturing process, Biose is readily embracing a new industrial standard for enumeration of microorganisms. The implementation of rapid viable cell counts in both process and release testing aims to shorten the journey from clinical trials to market authorization for Biose’s innovative live biotherapeutic companies. Read more about SBT and Biose's collaboration here.