Gradient Delay Reduction in Liquid Chromatography via Flow Rate Control
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Solution Overview
Problem
Current chromatographic systems experience significant gradient delays due to low flow rates, leading to extended analysis times and reduced efficiency in sample detection, particularly in high-performance liquid chromatography (HPLC) with nanoflow columns, where delays can result in 20 minutes of non-detection time due to the dead volume between pumps and the column inlet.
Innovation Solution
A device and method that utilize a control system to manage fluid flow rates and concentration gradients by determining a fast period and a slow period, allowing for the formation of concentration gradients within the fluid conveying means, which reduces gradient delays by using the inherent delay volumes to store and generate gradients efficiently, enabling faster elution and separation processes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If gradient elution is performed at low flow rates to improve separation quality, then separation efficiency is improved, but gradient delay time increases significantly
Solution Approach 1:
The system pre-forms the concentration gradient in the fluid conveying means before the actual separation process. By preparing the gradient profile in advance in the connecting volume, the system eliminates the delay that would normally occur when trying to establish the gradient at the column inlet during low-flow separation.
Solution Approach 2:
The fluid conveying means (connecting volume between pump and column) serves as an intermediary element that stores and delivers the pre-formed gradient. This intermediate volume acts as a buffer that decouples gradient formation from the low-flow separation process, allowing the gradient to be ready for immediate delivery without causing delay.
2Loss of time
If the dead volume between pumps and column inlet is reduced to decrease gradient delay, then gradient delay is reduced, but the system becomes more sensitive to flow rate variations and harder to operate
Solution Approach 1:
The system changes the operational parameters by forming the gradient at a different flow rate than the separation flow rate. The control system adjusts pump flow rates dynamically - using higher flow rates for gradient formation in the connecting volume, then switching to lower flow rates for separation at the column, optimizing both speed and stability.
3Measurement precision
If multiple pumps are used to generate solvent gradients, then gradient control is improved, but device complexity increases
Solution Approach 1:
The system makes the fluid conveying means serve multiple functions: it acts as both the connection pathway and as a gradient formation chamber. This multi-functional use of existing components eliminates the need for additional gradient formation devices, reducing overall system complexity while maintaining precise gradient control through the control system.
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
This approach significantly reduces analysis time while maintaining separation quality, allowing detectors to receive more sample data efficiently, with the ability to operate at fast total flow rates four to one hundred times slower rates, and ensuring safe operating pressures to prevent mechanical breakdown.
Implementation Method 1
The pump means propels a first solvent and a second solvent to form a range of mixtures having a different concentration of the first solvent and the second solvent over time
Implementation Method 2
The movement of the first solvent and second solvent define a total flow rate capable of being changed over time
Implementation Method 3
reduces gradient delays by using the inherent delay volumes to store and generate gradients efficiently
Implementation Method 4
The compounds held in the mixture, the mobile phase, exhibit different affinity for the stationary phase. The compounds are thus retained or allowed to pass at different rates as the mobile phase moves
Data Source
AI summary
Embodiments of the present invention feature methods and apparatus for performing chromatographic separations. The invention feature methods and control means in the form of computer programs and software that control the formation of a concentration gradient at two or more total flow rates, with an elution period occurring in a slow flow rate and at least other portions of the gradient occurring during a fast total flow rate.