Real-time molecular visibility for p-coumaric acid bioproduction

Real-time molecular visibility for p-coumaric acid bioproduction

Advanced biologics, precision fermentation, synthetic biology, and bio-based manufacturing are pushing biological systems into increasingly complex production environments. Yet most bioprocesses still operate with limited real-time visibility.

Critical molecular changes often remain invisible between intermittent measurements. By the time data arrives, process deviations may already have impacted performance. Despite advances in biomanufacturing, many processes still operate as black boxes.

InSpek is building a real-time molecular visibility layer designed to change that.

Using Raman-on-chip sensing powered by photonic integrated circuits (PICs), InSpek enables continuous molecular monitoring directly inside bioprocesses. This significantly reduces dependence on manual sampling and offline analysis while enabling continuous process visibility

This application study demonstrates how InSpek’s sensing platform was used to monitor p-coumaric acid (p-CA) fermentation in real time, transforming a difficult-to-observe biological process into a continuously visible system.

The Challenge. Bioprocesses generate complexity faster than conventional monitoring can follow

p-Coumaric acid is a high-value aromatic compound used in pharmaceuticals, food ingredients, biomaterials, cosmetics, and specialty chemicals. Industrial production increasingly relies on engineered Saccharomyces cerevisiae fermentation systems.

EXPLAINER: Engineered Saccharomyces cerevisiae fermentation systems are fermentation processes that use genetically modified yeast strains, specifically Saccharomyces cerevisiae, to produce a desired molecule or biological product. It’s a species of yeast commonly known as ‘baker's yeast’, and has been used for centuries to produce bread, wine and beer.

In biotech, it’s one of the most widely used microorganisms because it is well understood, easy to cultivate, scalable, and it is genetically programmable.

But producing p-coumaric acid through fermentation is difficult to optimize, and the process presents several challenges:

• p-CA does not dissolve easily in the fermentation liquid
• high concentrations can slow down or stress the yeast
• the biological process changes continuously during fermentation
• production performance is highly sensitive to process conditions and feeding strategies

Successfully scaling these fermentation processes requires continuous visibility into:

• how nutrients are being consumed
• how target molecules are being produced
• how the biology changes over time whether the process remains stable

Current monitoring methods are not designed for this level of real-time process control. Many fermentation processes still rely on offline HPLC analysis, which means that samples must be taken manually, results arrive with delays, data points are limited and then teams cannot react immediately to process changes

This creates a major visibility problem. Without continuous molecular monitoring teams will struggle to fully understand what is happening inside the reactor. If these process deviations go unnoticed for a long period of time it can increase the economic risk of batch loss.

You cannot optimize or control a process you cannot continuously see.

The InSpek Approach. Continuous molecular monitoring directly inside the process

To address this challenge, InSpek deployed its real-time molecular monitoring platform directly inside the fermentation process.

By using Raman-on-chip sensing technology, the system continuously tracked key molecules throughout fermentation using a compact photonic sensing platform designed for bioprocess environments.

The goal was to create continuous visibility into how the process evolved over time.During fed-batch fermentations using engineered yeast, InSpek continuously monitored several important metabolites, including:

• p-coumaric acid
• glucose
• ethanol
• glycerol
• acetic acid

This allowed teams to observe, in real time:

• how nutrients were being consumed
• how target molecules were being produced
• how the biological system changed throughout the process

Instead of relying on occasional analytical snapshots, the platform generated continuous molecular insight into the fermentation process.

From Sparse Sampling To Continuous Process Intelligence

Across four fermentation runs, InSpek’s platform continuously collected real-time molecular data throughout the process. The data was then compared with traditional HPLC measurements to validate monitoring performance and build predictive process models.

The project demonstrated that Raman-on-chip sensing could successfully operate directly inside complex fermentation environments while continuously tracking multiple metabolites in real time.

More importantly, it showed the value of continuous molecular visibility.

Traditional offline workflows provide only a limited number of measurements per day. Continuous monitoring creates a much richer understanding of how the process evolves over time, enabling:

• earlier detection of process changes
• better visibility into biological behavior
• richer datasets for optimization and modeling
• faster and more informed process development

Instead of reacting to delayed analytical results, teams gain continuous insight into the state of the bioprocess as it happens.

Results. Supporting faster optimization and more controllable bioprocesses

The monitoring framework supported fed-batch fermentation strategies associated with a 2.3x increase in p-coumaric acid production compared with traditional batch fermentation approaches.

Beyond the production improvement itself, the project demonstrated how continuous molecular monitoring can help make bioprocesses more visible, understandable, and controllable.

Real-time process visibility

Multiple metabolites were continuously monitored directly inside the fermentation process, providing ongoing insight into how the biology evolved over time.

Richer process data

Continuous monitoring generated far more process data than traditional offline measurements, helping teams better understand and optimize fermentation performance.

Faster process development

Reducing dependence on delayed lab analysis enabled faster learning, quicker iteration, and more efficient process optimization.

Earlier detection of process changes

Real-time visibility into metabolic shifts created the potential for faster operational responses and improved process stability.

Support for modern biomanufacturing strategies

The platform aligns with the industry shift toward continuous, data-driven bioprocessing and modern Process Analytical Technology (PAT) approaches.

The future of biomanufacturing requires continuous visibility

Biomanufacturing processes are becoming increasingly complex, but the tools used to monitor them have not kept up. AI-driven optimization, automation, and future autonomous bioprocess control all depend on one foundational requirement: continuous, high-quality process data.

Today, most bioprocesses still lack that level of real-time visibility.

InSpek is building the infrastructure to change that. The company’s vision goes beyond individual sensors. The goal is to provide continuous multi-parameter molecular visibility and richer process intelligence that help teams better understand, monitor, and optimize biological manufacturing processes. The sensor is the starting point. The larger opportunity is turning bioprocesses from black boxes into visible, controllable, and data-driven systems.

Looking ahead

InSpek is continuing to expand its platform across bioprocessing applications, including:

• advanced metabolite monitoring
• multi-parameter sensing
• scalable inline deployment
• AI-assisted process modeling
• future closed-loop optimization systems

As biomanufacturing scales in complexity, continuous molecular visibility will become foundational infrastructure.

InSpek’s mission is to provide the eyes, the data, and the intelligence layer required to make bioprocesses controllable at scale.

Research Context

The work presented in this application study reflects ongoing development and validation activities performed under controlled fermentation conditions.

The results demonstrate the potential of continuous molecular monitoring for bioprocess visibility and optimization, while ongoing work continues to expand model robustness, process integration, and application scalability across broader biomanufacturing environments.