Automated Quenched Flow Reactor HPLC Integration

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Solution Overview

Problem

Current methods for analyzing quenched flow reaction liquids using high-performance liquid chromatography (HPLC) are limited by manual intervention, leading to variability in reaction times, reduced throughput, and inconsistent analysis results due to the need for manual transfer of samples, which is particularly problematic when using fast Hydrogen Deuterium Exchange (HDX) techniques.

Innovation Solution

A fully automated system where a quenched flow reactor is directly connected to an HPLC apparatus, allowing for controlled and rapid transfer of the quenched flow reaction liquid, enabling precise reaction times of milliseconds and improved reproducibility through automated reagent release mechanisms and fluid communication.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If manual transfer of quenched flow reaction liquid to HPLC apparatus is used, then ease of operation is maintained, but productivity is reduced and measurement precision deteriorates due to variability in transfer time

Engineering Contradiction:
Improvemanual transfer operationVSAvoidthroughput of protein analysis
Core Design Contradiction:
Ease of operationVSProductivity

Solution Approach 1:

The patent merges the quenched flow reactor and HPLC apparatus into a single integrated system where the reaction chamber is directly connected to the HPLC injection port. This eliminates the manual transfer step while maintaining operational simplicity, thereby increasing throughput and reducing variability in analysis time.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent introduces an automated sample transfer mechanism as an intermediary between the quenched flow reactor and HPLC apparatus. This automated intermediary handles the sample transfer rapidly and consistently, improving productivity while maintaining ease of operation through automated control.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Device complexity

If manual transfer of quenched flow reaction liquid is used, then device complexity is reduced, but manufacturing precision deteriorates due to inconsistent transfer timing

Engineering Contradiction:
Improvesystem structureVSAvoidconsistency of analysis results
Core Design Contradiction:
Device complexityVSManufacturing precision

Solution Approach 1:

By merging the reactor and HPLC apparatus into one integrated system, the patent eliminates the manual transfer step that causes timing variability. The integrated design maintains relatively simple structure while achieving consistent analysis results through direct fluid communication between components.

Inventive Principle:
Principle #5Merging (Combining)

3Measurement precision

If fast reaction times of milliseconds are achieved, then measurement precision is improved for structural analysis, but device complexity increases due to need for rapid automated transfer

Engineering Contradiction:
Improvestructural information accuracyVSAvoidautomated transfer system
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent achieves millisecond reaction times by merging the reactor and HPLC apparatus into an integrated system with direct fluid communication. This eliminates the need for complex automated transfer mechanisms while enabling fast reaction times and high measurement precision for structural analysis.

Inventive Principle:
Principle #5Merging (Combining)

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 automated system increases throughput, reduces variability, and enhances the consistency of analysis results by allowing direct and controlled transfer of the quenched flow reaction liquid, achieving efficient and reproducible HPLC analysis with fast reaction times.

Implementation Method 1

mixing the first reagent and the second reagent in a reaction area

Methodology Applied
Scientific EffectMixing:

Implementation Method 2

allowing a reaction to take place between the first reagent and the second reagent in the reaction area for a predetermined reaction time

Methodology Applied
Scientific EffectChemical reaction: Reaction (physics)

Implementation Method 3

quenching the reaction in a quenching area to form a quenched flow reaction liquid

Methodology Applied
Scientific EffectQuenching:

Implementation Method 4

analysing the quenched flow reaction liquid by HPLC to form an HPLC analyte

Methodology Applied
Scientific EffectChromatography: Chromatography

Data Source

PatentUS11860139B2System and method for analysing the composition of a quenched flow reaction liquid
Publication Date: 2024.01.02 APPLIED PHOTOPHYSICS
  • US11860139B2 patent drawing
  • US11860139B2 patent drawing
  • US11860139B2 patent drawing

AI summary

The present invention relates to a system for analysing the composition of a quenched flow reaction liquid comprising a quenched flow reactor, and a high performance liquid chromatography (HPLC) apparatus; wherein the quenched flow reactor is in fluid communication with the HPLC apparatus.