Flow-Through Peptide Synthesis With Heated Recirculation
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Solution Overview
Problem
Existing solid phase peptide synthesis (SPPS) processes face inefficiencies in terms of process efficiency, environmental impact, and scalability, particularly in batch reactors, which require longer lead times, excessive solvent and reagent use, and lack real-time monitoring capabilities.
Innovation Solution
A flow-through process and system for SPPS involving cyclic addition of amino acids to a resin-packed column, with heating applied before passage through the column, recirculation of the amino acid mixture, and real-time monitoring using detectors, reducing the need for excess reagents and solvents, and enabling scalability across different scales.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Device complexity
If batch reactors are used for SPPS, then the synthesis can be performed with simple equipment, but the lead time is longer and scalability optimization is more time-consuming
Solution Approach 1:
The patent implements continuous flow-through synthesis where amino acids are continuously added to the resin column without interruption. This eliminates the batch processing steps of charging, reacting, draining, and recharging, thereby reducing lead time while maintaining equipment simplicity through a straightforward flow-through configuration.
Solution Approach 2:
The patent extracts and eliminates unnecessary intermediate steps from batch processing by implementing a direct flow-through approach. The continuous flow system removes the need for repeated charging and draining operations, directly addressing the time loss issue without complicating the equipment design.
2Device complexity
If batch reactors are used for SPPS, then the process can be performed with conventional equipment, but excess solvents and reagents are used due to PAT limitations
Solution Approach 1:
The patent incorporates real-time monitoring with detectors that provide feedback on reaction progress. This allows precise control of reagent addition, enabling the system to stop adding reagents when the reaction is complete, thereby minimizing solvent and reagent consumption while using conventional equipment.
Solution Approach 2:
The flow-through system uses stoichiometric or near-stoichiometric amounts of reagents rather than the excessive amounts required in batch processing. The continuous flow allows precise metering of reagents, eliminating the need for excess reagents to drive the reaction to completion.
3Device complexity
If batch reactors are used for SPPS, then the synthesis steps can be performed sequentially, but real-time monitoring of reaction progress is not possible
Solution Approach 1:
The patent integrates detectors in the flow path that continuously monitor reaction progress in real-time. The feedback from these detectors allows for real-time adjustment of the synthesis process, enabling precise control and monitoring without complicating the overall process architecture.
4Productivity
If flow-through reactors are used for SPPS, then real-time monitoring and faster kinetics are achieved, but the system complexity increases
Solution Approach 1:
The patent segments the flow-through system into simple, modular components: a resin column, a pump, and detectors. This segmentation allows the system to achieve continuous flow and real-time monitoring capabilities while keeping each component simple and easy to implement, thereby managing overall system complexity.
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
The process achieves efficient peptide synthesis with reduced reagent and solvent use, faster kinetics, and real-time monitoring, while being environmentally friendly and scalable from lab to commercial scales.
Implementation Method 1
heating is applied to the amino acid mixture before they are passed through the column
Data Source
AI summary
Processes and systems related to solid phase peptide synthesis are described. The processes include a flow-through process comprising cyclic addition of amino acids to a column packed with resin, wherein each cycle includes the combination of the amino acids with one or more reagents to provide an activated amino acid mixture, and wherein heating is applied to the amino acid(s) before they are passed through the column and wherein the amino acids are re-circulated at least once over the column packed with resin. Systems for such processes are also described.