Tilted Reactor Rotation for Microwave Peptide Synthesis

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Solution Overview

Problem

Conventional vortex mixing in microwave-assisted solid phase peptide synthesis limits the maximum reaction vial size and volume due to space requirements, restricting the amount of resin and liquid that can be heated and mixed effectively.

Innovation Solution

An apparatus featuring a cylindrical reactor with alternating clockwise and anti-clockwise rotation around its central axis, allowing for larger reaction vials and greater volumes to be heated, while minimizing surface turbulence and splashing.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Volume of moving object

If vortex mixing is used for mixing resin beads and liquid solvent in microwave-assisted solid phase peptide synthesis, then effective mixing is achieved, but the maximum reaction vial size and volume are limited due to space requirements for circular oscillation

Engineering Contradiction:
Improvereaction vial volumeVSAvoidmixing effectiveness
Core Design Contradiction:
Volume of moving objectVSEase of operation

Solution Approach 1:

Instead of rotating the contents of the vial horizontally as in vortex mixing, the invention inverts the approach by tilting the entire vial at an angle (e.g., 45 degrees) and rotating it about its longitudinal axis. This inversion of the mixing geometry allows the vial to be much taller relative to its diameter, enabling significantly larger reaction volumes without requiring the wide clearance needed for horizontal vortex motion.

Inventive Principle:
Principle #13The other way round (Inversion)

Solution Approach 2:

The invention transitions from two-dimensional horizontal vortex mixing to three-dimensional mixing by tilting the vial and rotating it about its longitudinal axis. This dimensional change allows the mixing action to occur along the length of the tilted vial, utilizing the vertical dimension more effectively and accommodating larger reaction volumes within the microwave cavity.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

2Quantity of substance

If larger reaction vials are used to increase resin and liquid volume, then synthesis capacity is improved, but mixing effectiveness deteriorates due to insufficient agitation

Engineering Contradiction:
Improveresin and liquid volumeVSAvoidhomogeneity of mixture
Core Design Contradiction:
Quantity of substanceVSStability of the object's composition

Solution Approach 1:

By inverting the mixing geometry to rotate the tilted vial about its longitudinal axis, the invention achieves effective mixing of large volumes without requiring high-speed horizontal vortex motion. The tilted orientation ensures that reagents and resin beads are continuously redistributed along the length of the vial, maintaining homogeneity even in larger reaction volumes.

Inventive Principle:
Principle #13The other way round (Inversion)

Solution Approach 2:

The mixing is performed through periodic rotation of the tilted vial, which continuously redistributes the resin beads and liquid reagents. This periodic tumbling action ensures thorough mixing and prevents settling or aggregation, maintaining homogeneous composition throughout the reaction volume.

Inventive Principle:
Principle #19Periodic action

3Productivity

If conventional vortex mixing geometry is used, then mixing is achieved, but the microwave cavity volume utilization is reduced due to space requirements

Engineering Contradiction:
Improvesynthesis throughputVSAvoidmicrowave cavity volume utilization
Core Design Contradiction:
ProductivityVSVolume of stationary object

Solution Approach 1:

The invention inverts the conventional vortex mixing geometry by tilting the vial and rotating it about its longitudinal axis rather than horizontally. This allows the use of much taller, narrower vials that fit more efficiently into the microwave cavity volume, increasing the number of reactions that can be performed simultaneously or sequentially and improving overall synthesis throughput.

Inventive Principle:
Principle #13The other way round (Inversion)

Solution Approach 2:

By changing from horizontal to tilted-axis rotation, the invention utilizes the vertical dimension of the microwave cavity more effectively. This dimensional transition allows for better space utilization, enabling larger reaction volumes or multiple vials to be accommodated within the same cavity volume.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

Enables the use of larger reaction vials and greater volumes within the microwave cavity, enhancing mixing efficiency and utilization of the reactor volume, thereby improving the scalability and effectiveness of solid phase peptide synthesis.

Implementation Method 1

a porous frit associated with the outlet of the reactor, the porous frit preventing discharge of beads and allowing discharge of the solvent from the reactor

Methodology Applied
Scientific EffectFiltration: Filter (physical)

Implementation Method 2

means for concentric rotation of the reactor around the central axis in alternating clockwise and anti-clockwise directions

Methodology Applied
Scientific EffectCentrifugal force: Centrifugal Force

Implementation Method 3

mixing by the contents of the reactor by rotating the reactor around the central axis in alternating directions

Methodology Applied
Scientific EffectFluid mixing: Convection

Implementation Method 4

apparatus for microwave assisted solid phase synthesis

Methodology Applied
Scientific EffectMicrowave heating: Dielectric Heating

Data Source

PatentEP2890480B1APPARATUS AND METHOD FOR SOLID PHASE peptide SYNTHESIS
Publication Date: 2019.03.13 BIOTAGE INC
  • EP2890480B1 patent drawingFigure 1

AI summary

An apparatus for microwave assisted solid phase synthesis using solid-phase resin beads mixed with a liquid solvent comprises: - a generally cylindrical reactor (1) made of microwave transparent material and having a central axis, the reactor (1) having an inlet (5) and an outlet (6); - a porous frit associated with the outlet (6) of the reactor (1), the porous frit preventing discharge of beads and allowing discharge of the solvent from the reactor; and - means (4) for concentric rotation of the reactor (1) around the central axis in alternating clockwise and anti-clockwise directions. A method for microwave assisted solid phase synthesis using the apparatus is also disclosed.