Automated Chromatographic Sample Dilution for Low-Carryover LC Analysis
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Solution Overview
Problem
Existing liquid chromatography (LC) systems face challenges such as operator error, imprecision, difficulty in handling hydrolytically unstable species, significant sample volumes, and carryover issues, particularly in monitoring batch reactor systems, which hinder real-time reaction adjustments.
Innovation Solution
A computer-implemented method for analyzing a product stream of a chemical reaction, involving withdrawal of a small volume of the product stream, mixing with a diluent, and transferring it to an LC device for real-time chemical profile development, with minimal carryover and automated adjustments to reaction conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If large sample volumes are used in automated LC dilution and injection systems, then the system can handle various sample types, but significant carryover from one sample to the next occurs
Solution Approach 1:
The sampling system is divided into multiple independent sampling ports (first sampling port, second sampling port) that can selectively access different locations in the reactor. This segmentation allows the system to withdraw small aliquots from specific zones without cross-contamination, enabling back-to-back sample analysis with minimal carryover while maintaining versatility across sample types.
Solution Approach 2:
The patent extracts only the necessary small volume of sample (less than 200 μL) from the product stream at specific locations rather than using large volumes. By extracting minimal aliquots through strategically positioned sampling ports, the system achieves sufficient analysis while minimizing carryover effects between consecutive samples.
2Ease of operation
If manual sample withdrawal and dilution steps are performed, then operator flexibility is maintained, but operator error and imprecision occur
Solution Approach 1:
The system performs automated sample withdrawal, dilution, and injection without requiring manual intervention. The automated sampler independently executes the complete LC analysis workflow, eliminating operator errors and imprecisions while maintaining operational flexibility through programmable control of sampling ports and flow rates.
Solution Approach 2:
Manual mechanical operations (sample withdrawal, dilution, injection) are replaced with an automated electronic control system. The automated sampler uses programmed instructions to control valve positioning, flow rates, and timing, substituting human operator skill with precise electronic control for reproducible results.
3Productivity
If real-time reaction adjustments are made based on LC data, then process optimization is achieved, but data time delay prevents accurate adjustments
Solution Approach 1:
The system performs preliminary sample withdrawal and preparation steps quickly and automatically upon detecting a sampling event. By pre-positioning sampling ports and preparing dilution solutions in advance, the system minimizes the time between reaction condition changes and data availability, enabling more responsive real-time adjustments.
Solution Approach 2:
The automated sampling system operates continuously or at frequent intervals without interruption to the reaction process. The sampler continuously monitors reaction conditions and immediately withdraws samples when adjustments are needed, eliminating the discontinuities and delays associated with manual sampling, thereby maintaining continuous useful action for real-time process optimization.
4Object-generated harmful factors
If small sample volumes are withdrawn for analysis, then carryover is minimized, but sufficient sample volume for accurate LC analysis may not be obtained
Solution Approach 1:
The system employs multiple sampling ports positioned at different locations within the reactor to access samples from specific local zones. By selecting appropriate sampling locations and using localized sampling, the system obtains representative aliquots that provide accurate chemical profiles while maintaining minimal sample volumes to prevent carryover.
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 real-time reaction condition adjustments with minimal sample volume and reduced carryover, improving accuracy and efficiency in LC analysis, especially for hydrolytically unstable species and heterogeneous reaction mixtures.
Implementation Method 1
Liquid chromatography (LC) is a chemical analysis method that utilizes the partition coefficients of the constituents of a mixture between a mobile phase and a stationary phase
Data Source
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AI summary
The present disclosure relates to a computer-implemented method for analyzing a product stream of a chemical reaction. The method includes withdrawing a portion of the product stream of the chemical reaction from a reactor, the portion of the product stream having a volume of less than about 200 µL. The method further includes mixing the portion of the product stream with a diluent to produce a sample and then transferring the sample to a liquid chromatography device. A measured chemical profile is then developed, via the liquid chromatography device, which can be used for process monitoring or real time decision making. In some embodiments, the method can include adjusting a reaction condition in the reactor based on differences between the measured chemical profile and a desired chemical profile.