Application of process analytical technology for real-time monitoring of synthetic co-culture bioprocesses

Nicole A Dambruin ¹, Jack T Pronk ¹, Marieke E Klijn ²

⁰Department of Biotechnology, Delft University of Technology, Van Der Maasweg 9, Delft, 2629, HZ, The Netherlands.

Analytical and Bioanalytical Chemistry +

|

June 6, 2025

View abstract on PubMed

Summary

Synthetic microbial co-cultures improve bioprocesses using division-of-labor. Process Analytical Technology (PAT) enables real-time monitoring for precise population control, enhancing stability and scalability.

Area Of Science

Biotechnology and Synthetic Biology
Microbial Engineering
Process Engineering

Background

Synthetic microbial co-cultures leverage division-of-labor for enhanced bioprocess performance by segregating metabolic pathways.
Maintaining optimal relative abundance of microbial partners is critical for co-culture efficiency.
Existing genetic engineering strategies for population control can impose metabolic burdens, impacting performance.

Purpose Of The Study

To review Process Analytical Technology (PAT) methods for real-time monitoring of synthetic microbial co-cultures.
To explore how PAT can enable precise population control strategies.
To assess the potential of PAT for improving the stability and industrial scalability of co-cultures.

Main Methods

Review of established and emerging PAT techniques for monitoring co-cultures.
Analysis of methods including direct biomass measurements and metabolite tracking (soluble and volatile).
Discussion of advantages, limitations, and applications of various PAT approaches.

Main Results

PAT offers real-time monitoring capabilities essential for controlling co-culture composition.
Both direct and indirect (metabolite-based) PAT methods can be employed.
PAT provides a foundation for developing effective population control strategies.

Conclusions

Leveraging PAT for real-time population control is key to enhancing synthetic co-culture performance.
Precise control through PAT can improve the stability, efficiency, and industrial scalability of bioprocesses.
PAT represents a significant advancement for the practical application of synthetic microbial co-cultures.

Keywords:

Industrial biotechnology Microbiology Process analytical technology Process control Real-time monitoring Synthetic co-culture