Piston-Controlled Oligonucleotide Reactor for Uniform Reagent Flow

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Solution Overview

Problem

Current synthesizers and columns are not optimized for large-scale synthesis of long oligonucleotides, leading to issues such as reduced efficiency, increased undesired oligomers, fouling, clogging, and nonuniform distribution of reagents, resulting in high back pressures and incomplete synthesis.

Innovation Solution

A reactor system with a vessel, pistons, and a processor that measures load and adjusts piston position to maintain optimal pressure and flow dynamics, using flow distribution units and sensors to ensure uniform distribution of reagents and prevent fouling.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If large-scale synthesis of long oligonucleotides is performed using current synthesizers and columns, then the quantity of oligonucleotide produced increases, but the synthesis efficiency decreases and undesired oligomers increase

Engineering Contradiction:
Improvequantity of oligonucleotideVSAvoidsynthesis efficiency
Core Design Contradiction:
Quantity of substanceVSProductivity

Solution Approach 1:

The system divides the synthesis process into discrete cycles with automated piston control, segmenting the reaction chamber into controlled zones. The piston creates distinct regions for reagent delivery, reaction, and waste removal, enabling efficient large-scale synthesis while maintaining high productivity through systematic process segmentation.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The piston position is dynamically adjusted during synthesis cycles to optimize flow distribution and pressure control. The system transitions between different piston positions to accommodate varying synthesis stages, maintaining optimal hydrodynamics for both small-scale and large-scale operations, thereby preserving synthesis efficiency while increasing quantity.

Inventive Principle:
Principle #15Dynamics

2Length of moving object

If the oligonucleotide chain length increases, then the product length increases, but the overall synthesis efficiency decreases

Engineering Contradiction:
Improveoligonucleotide chain lengthVSAvoidoverall synthesis efficiency
Core Design Contradiction:
Length of moving objectVSProductivity

Solution Approach 1:

The system maintains continuous useful action through automated piston control that ensures uninterrupted reagent delivery and flow distribution throughout the synthesis cycles. The piston continuously adjusts to maintain optimal conditions for each synthesis step, enabling efficient synthesis of long oligonucleotides by eliminating idle time and maintaining constant productive operation.

Inventive Principle:
Principle #20Continuity of useful action

Solution Approach 2:

The system incorporates feedback mechanisms through sensors that monitor synthesis progress and piston position. This feedback enables real-time adjustments to maintain optimal synthesis conditions throughout extended synthesis cycles required for long oligonucleotides, preserving efficiency by preventing deviations that would reduce productivity.

Inventive Principle:
Principle #23Feedback

3Quantity of substance

If large quantities of materials are used in synthesis, then the scale of production increases, but fouling and clogging of fluid distributors and solid support increases

Engineering Contradiction:
Improvequantity of materialsVSAvoidsystem reliability
Core Design Contradiction:
Quantity of substanceVSReliability

Solution Approach 1:

The system extracts and removes waste products and byproducts efficiently through the piston-driven flow distribution system. By actively pumping out reaction byproducts and unreacted reagents after each cycle, the system prevents accumulation that would lead to fouling and clogging, maintaining reliability during large-scale synthesis with high material quantities.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The system uses pneumatic and hydraulic principles through the piston mechanism to control fluid flow and pressure distribution. The piston creates pressure gradients that ensure uniform reagent distribution while preventing localized over-pressurization that could cause clogging, and facilitates efficient waste removal, maintaining system reliability at large scale.

Inventive Principle:
Principle #29Pneumatics and hydraulics

4Stress or pressure

If high back pressure occurs during synthesis, then the pressure control becomes challenging, but part failures and incomplete synthesis increase

Engineering Contradiction:
Improveback pressureVSAvoidsynthesis completion
Core Design Contradiction:
Stress or pressureVSReliability

Solution Approach 1:

The piston position is dynamically adjusted to maintain optimal back pressure levels throughout the synthesis process. By transitioning between different positions, the system adapts to changing pressure requirements at different synthesis stages, preventing excessive back pressure that would cause part failures while ensuring sufficient pressure for complete synthesis reactions.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

Pressure sensors provide feedback on back pressure levels to the control system, which automatically adjusts piston position to maintain optimal pressure ranges. This feedback control prevents pressure-related failures and ensures complete synthesis by maintaining pressure within the optimal window throughout the synthesis cycles.

Inventive Principle:
Principle #23Feedback

5Quantity of substance

If columns are used for large scale synthesis, then the production capacity increases, but nonuniform packing of solid support causes void formation and flow channeling

Engineering Contradiction:
Improveproduction capacityVSAvoiduniformity of reagent distribution
Core Design Contradiction:
Quantity of substanceVSManufacturing precision

Solution Approach 1:

The system segments the flow distribution through the piston mechanism, creating multiple controlled flow paths that distribute reagents uniformly across the solid support. This segmentation approach prevents the formation of large voids and flow channeling that occur in traditional columns, maintaining manufacturing precision while enabling large-scale production capacity.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The piston-driven hydraulic system provides uniform pressure distribution across the solid support bed, preventing nonuniform packing and void formation. The controlled hydraulic pressure ensures even reagent flow distribution throughout the entire solid support volume, maintaining manufacturing precision at large production scales.

Inventive Principle:
Principle #29Pneumatics and hydraulics

6Device complexity

If nonuniform fluid distribution occurs throughout the solid support, then the synthesis process becomes complex, but yields are reduced

Engineering Contradiction:
Improvefluid distribution complexityVSAvoidsynthesis yield
Core Design Contradiction:
Device complexityVSProductivity

Solution Approach 1:

The piston-driven hydraulic system provides uniform fluid distribution throughout the solid support by controlling pressure and flow rates. This simplified hydraulic approach eliminates the need for complex multi-channel distribution systems, reducing device complexity while maintaining high synthesis yields through uniform reagent exposure of all solid support regions.

Inventive Principle:
Principle #29Pneumatics and hydraulics

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 system enhances the efficiency of large-scale oligonucleotide synthesis by maintaining uniform flow and pressure, reducing undesired products, and improving overall yield and quality of long oligonucleotides.

Implementation Method 1

a force measuring device coupled to the piston and configured to measure a load on the piston

Methodology Applied
Scientific EffectForce measurement: Force

Implementation Method 2

a piston driver coupled to the piston; and a processor operably coupled to the force measuring device and the piston driver, the processor configured to: measure a load on the piston using the force measuring device, and adjust a position of the piston using the piston driver based on measuring the load on the piston

Methodology Applied
Scientific EffectMechanical displacement: Displacement

Data Source

PatentUS12415172B2Systems and method for automated oligonucleotide synthesis
Publication Date: 2025.09.16 SYNTHEGO CORP
  • US12415172B2 patent drawing
  • US12415172B2 patent drawing
  • US12415172B2 patent drawing

AI summary

A reactor system is disclosed. The reactor system includes a vessel configured to contain a solid support, the vessel including: a vessel wall defining a reaction chamber, the reaction chamber having a first end and a second end opposite the first end; a piston operatively arranged at the first end and configured to translate within the reaction chamber; a force measuring device coupled to the piston and configured to measure a load on the piston; a piston driver coupled to the piston; and a processor operably coupled to the force measuring device and the piston driver, the processor configured to: measure a load on the piston using the force measuring device, and adjust a position of the piston using the piston driver based on measuring the load on the piston.