Fixed bed reactors are a practical tool for working with immobilized heterogeneous reagents and catalysts in continuous flow because of their simplicity. However, this technology has certain limits. The reactor’s volume cannot be adjusted to account for a change in packing media volume brought on, for instance, by reagent consumption or support swelling.
In recent years, Vapourtec has focused heavily on continuous flow peptide synthesis, developing a packed bed flow reactor that would automatically adjust its capacity to suit variations in the volume of the packed material. Vapourtec has named this reactor Variable Bed Flow Reactor (VBFR). The VBFR has applications far beyond peptide synthesis, for which it was originally designed.
Applications for the VBFR
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The VBFR is a fascinating novel reactor with numerous potential applications in chemical synthesis that have yet to be investigated. Vapourtec envisions uses in the following areas:
- Use of heterogeneous reagents in continuous flow (for example, the synthesis of organometallic reagents)
- Use of immobilized heterogeneous catalysts on supports that are prone to swelling (e.g., polystyrene resins)
- Solid phase synthesis
- Purification by catch and release
- Peptide synthesis
- Oligonucleotide synthesis
- Glycan assembly
Variable Bed Flow Reactor Features
- Four sizes available; 6.6 mm, 10 mm, 15 mm and 35 mm bore reactor
- Measurement of volume change with a resolution of 0.5 ul (6.6 mm bore reactor)
- Maximum working pressure 20 bar (6.6 mm bore reactor)
- VBFR can interface to Vapourtec’s R-Series software, and changes in volume can be logged and charted
- Glass, PTFE, PFA, and Kalrez fluid contact – resistant to strong acids and bases
- Fully automatic volume change
- Can be heated and cooled, 150 °C to -20 °C
- Working volume range from 0.3 ml to 20 ml
How Does the VBFR Work?
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The VBFR system consists of three key components:
Reactor
A reactor made of a thick-walled glass tube with a fixed plunger at the bottom and a moving plunger at the top. Frits linked to each plunger limit the packing media within the reactor and diffuser plates, ensuring that the flow through the frits is homogeneous. The upper moveable plunger is powered by a motor to contain and compact the packing media.
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Reactor Mount
The reactor and motor assembly are positioned inside a heat exchanger. The heat exchanger is housed within a reactor mount, which is affixed to the front of the Vapourtec E-Series or R-Series system in the same way as all other Vapourtec reactors.
Reactor Compression Controller
The reactor compression controller is a control box that senses the compression of the packing material and adjusts it continuously to obtain the appropriate compression. The reactor compression controller has a manual user interface that allows users to specify the reactor size (6.6, 10, or 15) as well as the desired level of packing.
In addition to the manual control interface, the R-Series software may control the reactor compression controller. The R-Series software will log the change in reactor volume. Changes within the reactor can be tracked in real time.
The VBFR allows for 100-fold packing modifications. This allows massive solid particles like magnesium turnings to be handled just as easily as little squidgy packings like ChemMatrix resins.
Once the chosen packing material has been added to the reactor, the procedure is as follows:
- Connect fluid and sensors to the reactor
- Start pumping solvent
- Set the appropriate reactor size and desired packing density
- Start the controller
- The reactor’s upper plunger will automatically move to limit the packing until the necessary packing density is reached
- The user can now specify upper and lower limits for the top plunger movement
- After the limitations are set, the operation is fully automatic. If the mass is introduced to the packing media, or if a solvent causes the packing material to swell, the plunger will move to increase reactor volume while maintaining the required packing density. If a reagent is removed from the reactor, such as peptide aggregates on a resin, the controller will reduce the reactor capacity. There will be no cavities or channeling as long as the packing material is kept at the predetermined packing density.
Four Different Sizes of VBFR are Available
Vapourtec has made four different sizes of VBFR available to help with reaction tuning and scale-up. The four sizes are recognized by the reactor's internal diameter in millimeters. Available sizes include 6.6 mm, 10.0 mm, 15.0 mm, and 35.0 mm.
6.6 mm Diameter Reactor
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- Working volume: 0.03 ml to 4.0 ml
- Temperature range: Ambient to 100 °C
- Maximum operation pressure: 20 bar
- Suitable for 50 mg to 400 mg of resin
10.0 mm Diameter Reactor
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- Working volume: 0.12 ml to 9.5 ml
- Temperature range: Ambient to 100 °C
- Maximum operation pressure: 15 bar
- Suitable for 100 mg to 800 mg of resin
15.0 mm Diameter Reactor
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- Working volume: 0.4 ml to 21.0 ml
- Temperature range: Ambient to 100 °C
- Maximum operation pressure: 10 bar
- Suitable for 250 mg to 2 grams of resin
35.0 mm Diameter Reactor
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- Working volume: 5.0 ml to 115.0 ml
- Temperature range: Ambient to 100 °C
- Maximum operation pressure: 5 bar
- Suitable for 1 gram to 10 grams of resin
What Else Will Users Need to Use the New VBFR?
- Users require either a Vapourtec E-Series or R-Series flow chemistry system
- Also needed is a Vapourtec reactor compression controller module
- The reactor must be installed in a Vapourtec reactor mount that includes the heat exchanger
- To obtain sub-ambient conditions, a Vapourtec chilled gas generator is required, as well as access to dry ice and a source of dry compressed air or nitrogen