Automated Liquid Chromatography Mobile Phase Preparation

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Solution Overview

Problem

Existing liquid chromatography systems require users to manually calculate and blend solvents to achieve specific pH and salt concentrations, which is cumbersome and lacks automation for varying proportions over the course of elution.

Innovation Solution

A method and device that calculate pH and salt concentrations using user-determined gradient functions, controlling the proportions of acids, bases, salts, and solvents to prepare a liquid mixture for precise mobile phase conditions in liquid chromatography systems, utilizing a computer program and mixer control unit to automate the process.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Extent of automation

If users manually calculate and blend solvents to achieve specific pH and salt concentrations, then they can obtain the required mobile phase composition, but the process is cumbersome and lacks automation

Engineering Contradiction:
Improveautomation of mobile phase preparationVSAvoidease of mobile phase preparation
Core Design Contradiction:
Extent of automationVSEase of operation

Solution Approach 1:

The system performs self-service by automatically calculating the required solvent proportions and controlling the blending process without user intervention. The computer program calculates pH and salt concentration at any time from a gradient function, then automatically controls the proportional blending of solvents, making the system serve itself rather than requiring manual user operation.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The patent replaces manual mechanical blending operations with an automated computer-controlled system. The mechanical act of manually calculating and mixing solvents is substituted by a computer program that performs calculations and an automated blending system that controls solvent proportions, eliminating the need for manual mechanical operations.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Measurement precision

If users blend multiple solvents to create mobile phases of particular pH and salt concentrations, then they can achieve the desired composition, but they must know the pH and salt concentrations of individual solvents and their mixing results

Engineering Contradiction:
Improveprecision of pH and salt concentration controlVSAvoidcomplexity of calculation and blending process
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The computer program acts as an intermediary between the user's desired pH/salt concentration specifications and the actual solvent blending process. It calculates the required proportions of each solvent based on the gradient function and desired final composition, mediating the complex calculations and control decisions so users only need to specify the target parameters without needing to know individual solvent properties or mixing mathematics.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The system changes the approach from manually tracking multiple parameters (individual solvent pH, salt concentrations, mixing ratios) to a single parameter-driven approach where the user specifies the desired final pH and salt concentration, and the system automatically adjusts all other parameters (solvent proportions) to achieve the target composition.

Inventive Principle:
Principle #35Parameter changes

3Adaptability or versatility

If solvent proportions are kept constant, then the mobile phase composition remains stable, but the system cannot vary proportions over the course of elution to optimize separation

Engineering Contradiction:
Improveability to vary solvent proportions during elutionVSAvoidstability of mobile phase composition
Core Design Contradiction:
Adaptability or versatilityVSStability of the object's composition

Solution Approach 1:

The patent implements dynamics by enabling the mobile phase composition to change over time during the elution process. The gradient function allows solvent proportions to be dynamically adjusted at different time points, transforming the static composition into a dynamic one that adapts to the separation requirements at each stage of the chromatographic run.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The system employs periodic action by varying the solvent proportions at different time intervals during elution. The gradient function specifies different mixing ratios at different time points, creating a periodic or sequential variation in composition that optimizes separation at each stage while maintaining overall process control.

Inventive Principle:
Principle #19Periodic action

Data Source

PatentUS9643103B2Process for preparing liquid mixtures of known pH and salt concentration
Publication Date: 2017.05.09 WATERS TECHNOLOGY CORP
  • US9643103B2 patent drawing
  • US9643103B2 patent drawing
  • US9643103B2 patent drawing

AI summary

A method of preparing a liquid mixture for use in a liquid chromatography system is provided. The mixture comprises one or more acids, one or more bases, one or more salts, and one or more solvents, and the method comprises the steps of: i) calculating pH and/or salt concentration at a particular time t from a user-determined gradient function; and ii) based on the values obtained in step (i), calculating percent acid, percent base, percent salt and percent solvent in the liquid mixture at time t. A liquid chromatography system incorporating such method is also provided.