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Intensification Boost for Enzymatic Liquid/Gas Processes by means of Continuous Flow Processing

BACKGROUND

O2-dependent biotransformation reactions have proven difficult in fine chemical manufacturing due to the mass transfer limitations of supplying O2 to the enzymatic reaction, hence affecting the level of efficiency achieved. Previous research has shown that enzymatic processes involving gases have a high potential for process intensification by implementing continuous flow processing technology.

TECHNOLOGY

In a cooperation between acib and Microinnova Engineering GmbH, with more than 15 years of experience in flow chemistry it has been proven that process intensification can be applied using continuous flow processing. This technology offers a comprehensive solution with a pressurized system that results in a significantly higher level of dissolved oxygen. A continuous flow reactor pressurized to 34 bar enables biotransformation to be conducted in a single liquid phase and significant increase of enzymatic activity was detected already at 10 bar. For glucose oxidase, the intensification factor for enzyme activity was up to 2.5 and amino acid oxidase showed an intensification factor up to 6 for the enzyme activity. High product concentration has been demonstrated with the concentration being 6 to 10 times higher at 34 bars compared to atmospheric pressure. See also Bolivar J.M., Mannsberger A., Thomsen M.S, Tekautz G., Nidetzky B. (2019) Biotechnology and Bioengineering, 116(3), 503–514.

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Corning and Microinnova Celebrate Opening of Advanced-Flow™ Reactor Qualified Lab

Corning Incorporated and Microinnova recently celebrated the opening of the Corning® Advanced-Flow™ Reactors (AFR) Application Qualified Lab (AQL) at their facility near Graz. Application qualified labs enable AFR customers to effectively access continuous-flow demonstrations, experimental trials, feasibility testing, and chemical reaction process development.

Corning currently has one other AQL in Europe at the University of Liège, which opened in 2017, as well as several operational AQLs worldwide that support the business. These regional facilities provide customers with convenient access to AFR Technology.

Microinnova is an innovation-based company focused on process development, design, and the realization of continuous pilot lines and manufacturing plants. Based on their critical parameter approach, Microinnova intensifies synthesis, as well as work-up and formulation processes using a wide range of different technologies leading to high-performance processes.

Microinnova has recently established a fluorine lab at their facility in Graz and are utilizing Corning’s G1 Silicon Carbide (G1 SiC) reactors to process highly toxic and corrosive chemicals in an inherently safer, more efficient way that can help customers in pharmaceutical, fine and specialty chemicals industries create a better end product.

“We’ve worked closely with Microinnova over the last few years, and the core values of innovation and commitment to inherently safer continuous flow chemistry really makes this collaboration a great fit for both companies,” said Alessandra Vizza, regional business director, Corning® Advanced-Flow Reactors. “Corning’s equipment and materials enable more stable reactions and can reduce inherent risks associated with handling/processing hazardous chemicals – which is really what the core of AFR Technology is all about.”

The location of this laboratory will help Microinnova provide broader reach to their customer base within the pharmaceutical, fine and specialty chemicals industries in Europe.

“We operate to strengthen our capabilities in the fields of fast, exothermic or highly corrosive processes for development as well as for manufacturing plant realization as a system integrator,” said Dr. Dirk Kirschneck, strategic director, Microinnova. “Based on the strong collaboration between the two companies since 2007, we are looking forward to continuing to work with Corning on future programs as one of their Application Qualified Labs.”

In addition to its AQLs, a critical part of the AFR business’ model for more than a decade has been its commitment to educating the regions where it operates.

“In Europe, we’re actively trying to educate both at the academic and industrial level on the value of continuous flow technology,” Alessandra said. “We’re hopeful that our broad product offerings as well as collaborations with companies like Microinnova will help us in this effort.”

 

 

Modular Plants: Speed as the Key Success Factor for Chemical Businesses in the Future

We expect that speed and flexibility will be success factors for chemical businesses in the future. The example of Ryan Air illustrates the importance of focusing on value generation for the customers and how innovation in a business model can achieve it.

Modular plants offer the best processing solution giving both flexibility and speed; ownership may not be key in the future. To facilitate thisdesign modification between the modules and within the modules should be enabled with other aspects considered such as engineered spaces and access for maintenance and modificationsModule Type Package (MTP), a technology offered by Microinnova, enables a Plug-and-Play solution for processing plants (like USB for computers)It is important to also consider the changeover possibilitiesphysical movement and how the infrastructure is designed so that the equipment fits the processFurthermore, we also supply plant virtualization where we engage in the pre-testing of process conditions using digital twins/model predictive control, documentation of modifications with an implemented as-built/modified documentation, PAT and pre-HAZOP scenariosMoreover, we expect that some plants will consist mainly of pre-designed and pre-built package units in the future with a predicted 60-80% of the modules being pre-designed. An exception to this being specific reactors addressing a certain set of critical parameters that are designed bespoke for an individual process. A similar shift has been observed in the automotive industry, where cars are designed based on a platform concept. 

Learn more about how your chemical business can benefit from modular plants! »

 

Modular plants offer the best processing solution giving both flexibility and speed

 

Late-stage Fluorination by means of Continuous Manufacturing

Microinnova presents a new approach to execute fluorination reactions in a safe manner with conventional equipment on manufacturing scale. These processes can be realized by continuous fluorination reagent generators on manufacturing scale. Dr. Lorenzo Orsini, previously the former R&D director of Miteni has joined the continuous manufacturing team of Microinnova. Bringing with him, a historical global reference within the field of fluorine chemistry. With Lorenzo Orsini on board, Microinnova is able to offer a wide range of possibilities to develop bespoke fluorination processes. 

With a focus on high value, efficient and scalable applications, our fluorination solutions can provide easy-to-implement options for your manufacturing facility. Having a wider portfolio will allow the evaluation of novel synthetic strategies by considering all the possible advantages of a late-stage fluorination. The second important focus is on providing solutions that significantly simplify the safety risk management compared to a more common fluorine chemistry approach by replacing possibly hazardous processes with “in situ” reactivity. These processes can be realized by continuous fluorination units, which provide the desired reagents on demand at manufacturing scale. The on-site fluorination units can often be easily implemented in existing plant setups with an aim to provide more options and make hazardous chemistry safer, so that it can be transferred to medium level manufacturing infrastructures. This approach is more cost effective compared to the other commonly known techniques. 

Get in touch with our team to find out how to improve your fluorination capabilities! »

 

These processes can be realized by continuous fluorination reagent generators on manufacturing scale.

 

Capacity Boost by Batch-to-Conti Debottlenecking

Space economy is a typical issue fodebottlenecking projects. Since a continuous approach reduces mass and heat transfer distances up to a factor of 100, these solutions can easily be integrated into an existing batch environment. A number of different strategies can reduce or replace batch processing times. For example, a batch processing step can be translated into a continuous plant skid

In some cases, the mixing operation or even the reaction itself can be executed while filling the reactor. Reagents, especially hazardous ones, can be synthesized in situ. Large savings can be achieved in the field of acid-base-reactions, since they are characterized by a strong heat release. These kinds of processes can reduce residence times from hours to minutes, since they are limited by the heat exchange which can easily be controlled in a continuous device. Mobility of skids enables a flexible use in connection with different plants. Optimizing mass and heat transfer is an important factor in reducing the costs per kilogram, leading to an increased competitiveness.

Space economy is a typical issue for debottlenecking projects. Since a continuous approach reduces mass and heat transfer distances up to a factor of 100, these solutions can easily be integrated into an existing batch environment. A number of different strategies can reduce or replace batch processing times. For example, a batch processing step can be translated into a continuous plant skid.