Membrane Eluent Generator for Reproducible Chromatography
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Solution Overview
Problem
Chromatographic separations face challenges in reproducibility due to human error in preparing chromatographic eluent solutions and contamination during storage, particularly in ion chromatography, where CO2 intrusion leads to carbonate contamination, and ionic constituents in eluents interfere with analyte measurement in detection methods like ESI-MS.
Innovation Solution
A gas permeable membrane-based eluent generator that introduces CO2, NH3, or gases derived from volatile acids or bases into the eluent precursor or eluent, forming eluents of precise and reproducible composition, suitable for chromatographic separations, allowing for the generation of acids, bases, and organic solvents in pre-selected proportions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If eluent solutions are prepared manually and stored for later use, then the separation process can be performed with necessary ionic constituents, but contamination occurs during storage (particularly CO2 intrusion leading to carbonate contamination) and reproducibility is compromised
Solution Approach 1:
The system performs preliminary action by generating the eluent composition in-situ within the chromatography system before analysis begins. The eluent generator creates precise compositions of volatile buffers and ionic constituents directly in the flow path, eliminating the need for advance preparation and storage that would expose solutions to CO2 contamination. This on-demand generation ensures reproducible eluent composition for each analysis.
Solution Approach 2:
The invention extracts the harmful factor of contamination by removing the eluent preparation step from the external environment where CO2 can intrude. By integrating the eluent generator within the sealed chromatography system, the solution is protected from ambient air and CO2 contamination throughout its entire lifecycle from generation to use.
2Reliability
If ionic constituents are included in the eluent to enable separation of amino acids, peptides, and proteins, then the separation process works effectively, but the ionic constituents significantly interfere with analyte measurement in ESI-MS detection
Solution Approach 1:
The system changes the chemical parameters of the eluent by using volatile buffers (such as ammonium carbonate, ammonium formate, or ammonium acetate) that can provide necessary ionic constituents for separation but are completely volatile. These buffers allow effective separation of amino acids, peptides, and proteins while being removable by evaporation before ESI-MS detection, thus eliminating interference with analyte measurement.
Solution Approach 2:
The invention exploits phase transitions by utilizing volatile buffers that transition from liquid phase in the chromatographic separation to gas phase through evaporation before mass spectrometry detection. This phase change removes the ionic constituents that interfere with ESI-MS while maintaining their functional role during the liquid-phase separation process.
3Adaptability or versatility
If conventional mechanical gradient pumps are used to perform gradient separations, then the system can handle multiple eluent components, but the complexity of preparation increases and gradient delay time is extended
Solution Approach 1:
The invention replaces the mechanical gradient pump system with an electrochemical eluent generator. Instead of mechanically mixing multiple eluent reservoirs through pumps and valves, the system uses electrochemical generation of ionic constituents from volatile buffers directly in the flow path. This substitution eliminates mechanical complexity and reduces gradient delay time by generating gradients in-situ without requiring physical mixing chambers or multiple pump systems.
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 solution enables precise and reproducible chromatographic separations by generating eluents that promote analyte dissociation, reducing background interference, and facilitating sensitive detection of analytes, with the ability to control pH and ionic strength independently, improving the reproducibility and efficiency of chromatographic analyses.
Implementation Method 1
A gas permeable membrane-based eluent generator that introduces CO2, NH3, or gases derived from volatile acids or bases into the eluent precursor or eluent
Implementation Method 2
introduces CO2, NH3, or gases derived from volatile acids or bases into the eluent precursor or eluent, forming eluents of precise and reproducible composition
Implementation Method 3
generating eluents that promote analyte dissociation, reducing background interference, and facilitating sensitive detection of analytes
Data Source
AI summary
There is provided a system for performing a chromatographic separation of an analyte, methods of using the system to separate at least one component of an analyte and an eluent generator of use in the system. An exemplary system comprises: (a) an eluent generator comprising: (i) a housing configured to be pressurizable by gas, comprising an annular void defined by the housing, and a gas inlet for the gas and a gas outlet for the gas in fluid communication with the annular void; (ii) a membrane permeable to the gas defining an eluent flow channel disposed within the annular void, the eluent flow channel having an eluent precursor fluid inlet and an eluent outlet; (iii) a source of gas in fluidic communication with the gas inlet; (iv) a source of the eluent precursor fluid; and (b) a chromatography column disposed downstream of and in fluidic communication with the eluent outlet.