Microreactors in bioprocessing

Microreactors are miniaturized reactor systems engineered for use in chemical synthesis, analytics, and diagnostic screenings, and they are slowly entering into pharmaceutical research and manufacturing.

By utilizing microfluidic principles, microreactors are able to create environments within 10-500 µm channels where chemical/biological reactions can occur. Operating at this scale allows for tight process control and the ability to separate out and study a single reaction, eliminating compounding factors and unnecessary byproducts.

Key advantages of microreactors

Microreactors operate at significantly smaller scales than traditional macroscale batch reactors, making it easier to observe physical changes and reactions. Their spectroscopic techniques furthermore enable in-line optical monitoring.

In this section, we look at four primary advantages of microreactor systems.

1.    Tightly controlled environment

Reactions occurring within the microreactor are near ideal due to the highly predictable laminar flow conditions, allowing for precise system modelling, monitoring, and control. The fast mixing and mass transfer of microreactors additionally makes them invaluable tools for developing optimized process conditions for large-scale reactions.

Compared to batch reactors, microreactors have a significantly larger surface area to volume ratio which allows for increased heat transfer efficiency. This gives scientists and engineers precise control over temperature so they can easily suppress undesired by-products and focus on the single reaction being studied.

2.    Perfusion systems

Continuous processing is preferable to batch processing whenever feasible, and microreactors are perfusion systems by design. Microreactors are able to maintain favorable conditions with enhanced mass transfer, and channels can be designed to continuously introduce nutrients and remove waste products.

As is the case with macro-scale processes, removing batched media exchanges allows for higher yields and tighter process control. Further, perfusion processes are lower-cost than batch processes as there are fewer waste solutions – a factor which is compounded by advantages at the micro-scale.

3.    Scale-out capabilities

Microreactors can easily and quickly be scaled out (also known as numbering up) by connecting identical reactors either in parallel or in series. This allows for continuous operation of the whole system, as a broken reactor can simply be swapped out for an identical replacement. Most importantly, scaling out a system ensures that identical chemistry will occur at any scale, from research to production. This means significant time savings when moving from R&D to larger-scale manufacturing and avoidance of scale-up challenges inherent in batch processing.

While they are great for scale-out, microreactors cannot scale up very far. The microscale channels can possibly increase to the millimeter-scale, but increasing the channel diameter causes the laminar flow to become turbulent flow that can no longer be precisely controlled.

4.    Safe and low-cost

The minimal amount of reagents, buffers, and other solutions required by microreactors makes them inherently safer than batch processes. For example, a batch process requiring an extreme pH would involve large amounts of acids, bases, and/or buffers at concentrations that can be harmful to operators. Microreactors use significantly smaller quantities, and are most often made of glass that can easily withstand these extreme environments.

These low volumes of solutions also present significant cost savings to the user, and are more environmentally friendly due to less waste.

Microreactors in pharma

Perfusion cell cultures in microreactors are slowly being adopted in pharmaceutical research and process development, especially for smaller scale-processes which only require between milliliters and one liter yields.

The simplicity of scale-out creates environments with more system uptime and greater capacity utilization than traditional batch processes. Additionally, it requires a much lower upfront capital expenditure, with the ability to add more microreactors to the process only as necessary. And due to their ability to easily handle extreme conditions, microreactors are a useful tool for fermentation processes where yeast or bacterial cultures often require harsher conditions than mammalian cells.

The tight process control and ability to closely manipulate the microreactor system enables researchers and manufacturers to culture only the desired products, eliminating many of the unnecessary byproducts. This simplifies the downstream processes, requiring fewer filtration and purification steps to isolate the product. These conditions also represent a “best case” scenario for the batch process – which, if the microreactor process is later developed for a macro-scale batch, represents the ideal process parameters.