Testing catalysts in flow: The enginzyme approach

EnginZyme's purpose is to reduce the environmental impact of the chemical industry by making it easier and more cost effective for companies to use enzymes to create new products, reduce waste streams or otherwise make their operations more efficient. Our main technology is EziG™, a universal enzyme immobilization material that eliminates several common issues with enzyme immobilization and is workable for all enzyme types. Here is a practical look at how we apply the technology using custom reactors as we set out to solve a specific problem.

EziG is based on the immobilization of enzymes on porous supports. This allows us to re-use these enzymes many times over, creating catalysts that can stay on-stream from hours to weeks or even months by engineering increasingly stable enzymes and optimizing process conditions. Immobilization also eases downstream processing of the products created from the target reactions.

During the initial R&D phase, we focus on developing highly active immobilized catalysts with good selectivity. This optimization can be performed relatively quickly in batches by scanning over many catalyst candidates using short reaction times. We like to use small batch reactors and agitate the reaction mixture to suspend our EziG catalyst and ensure good mixing, as shown in the figure below.

This configuration uses a small amount of support suspended in a large volume of the reaction mixture. By sampling carefully over time, we can follow the progress of the reaction — and even decide to replace the entire reaction mixture to test how well the catalyst can be reused.

This process is merely the beginning. Once a promising subset of catalysts has been identified, we proceed to the next phase of R&D.

A bridge between the R&D and pilot phase

Although small-scale batch tests are great at finding exciting catalyst candidates, they are not so great at predicting how a scaled-up system will behave. By running our target reactions in a packed-bed flow reactor, we can evaluate how well our catalysts would perform in a fully scaled-up system, while keeping the process on a practical level in a lab environment.

This allows us to accomplish two main tasks. First, we can assess the stability and reproducibility of catalyst performance over extended periods under industrially relevant conditions. Second, we can map the reaction kinetics of the system across a range of conditions — varying temperature, feedstock composition and extent of reaction. Our process engineering team uses the resulting information to make changes to the system's design and improve the process before piloting, which can mitigate the risks of scale-up.

The catalyst particles are stationary in a fixed-bed reactor, and the liquid flows through the bed, as shown above. Suppose the catalyst is perfectly stable and all other experimental parameters are constant. In that case, the product concentration we measure at the reactor outlet should be stable over time. This allows us to study the stability of the catalyst efficiently.

We can also decide to change parameters, such as flow rate, and see how this affects the performance of the packed bed. Or we can stack packed beds in series and sample the reaction mixture as it passes from bed to bed, allowing us to follow the reaction profile over the bed.

EziFlow: flow chemistry made easy

EziFlow is the name we gave to the family of packed-bed reactor systems we developed to evaluate catalyst performance in flow. A typical EziFlow system has four independent channels, allowing researchers to assess the stability of multiple catalysts, or the effect of different conditions on a single catalyst simultaneously and over extended periods. Similar commercial reactors exist, but we evaluated them for our applications, and feel confident that EziFlow is the most customisable, flexible, and cost-effective solution for our needs.

Reactors tailored to our specific needs

Since we build our systems in-house, we can design highly customized reactors, improving cost efficiency. For example, we don't need to build our test systems from materials with high chemical resistance, since we operate under relatively benign conditions. More importantly, because we design to our exact needs, our systems make the most out of the lab space we have. EnginZyme is a fast-growing start-up, and the time, effort and disruption involved in expanding lab space could hamper our ability to grow at a steady, sustainable pace. Striking a balance between how fast we can grow and how often we need to expand our labs is one of the things that makes our company a lean, agile and reliable long-term partner.

Modular and adaptable

Our engineers can also take direct feedback from researchers and quickly implement changes or repairs to the system without any administrative overhead. Such speed of delivery would be tough with a third-party contractor, as most commercially available reactors are not highly customisable, and even the most professional contractor will have other customers to serve.

Thanks to EziFlow’s proprietary modular design, our engineers can quickly design and integrate new elements, for example, a cooling jacket to run a target reaction at low temperature. Such adaptability is crucial to our process engineering team — they need to make frequent changes to the design of a reactor to optimize process conditions.

Automated and seamlessly integrated

Our multichannel reactor systems are integrated with robotic autosamplers that collect samples according to carefully orchestrated schedules set by our researchers. We go beyond that essential labor-saving aspect by integrating the entire control system and autosampler with our laboratory information management system (LIMS). This allows us to reliably connect timestamped sampling data and process conditions from the control system with compositional data coming from our analytical processes. All of this improves the reliability and accuracy of data collection and frees up researchers to do more valuable work. Because the software for the reactors is written specifically for our LIMS system, we can easily integrate new sensors into the EziFlow control unit, keeping the design adaptable and flexible.

The future of flow chemistry

A final, more holistic benefit of having built EziFlow systems is that developing the competence needed to succeed has forced us to take foundational steps in developing an in-house engineering team focused on the design, construction and operation of more fully functional process systems. The expertise this team has acquired allows us to explore more widely and develop processes further before we commit to a pilot run with an external partner. Operating a small reactor over an extended period can generate sufficient material to allow a thorough in-house optimization of downstream processes before piloting.

Ultimately, our ability to rapidly deliver breakthrough technology depends on the tools we have available to us. By bringing this core competence in-house, we ensure that every stage in our innovation pipeline achieves the same standards of high automation, responsiveness and scalability.