Sample Dilution via Flow Splitting in Liquid Chromatography

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Solution Overview

Problem

High pressure liquid chromatography (HPLC) systems require sample dilution before injection, but manual dilution is impractical due to distance and risk of contamination, and existing automated systems are complex and prone to human error.

Innovation Solution

A method and system for diluting samples in a liquid chromatography system by separating the mobile phase flow into two channels with different flow rates, allowing for controlled dilution at the injection point, reducing the need for multiple valves and minimizing contamination risks.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If manual sample dilution is performed by a technician, then the dilution can be customized, but it causes significant delay and risk of contamination due to distance and human error

Engineering Contradiction:
Improvedilution accuracyVSAvoiddilution time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The HPLC system performs sample dilution automatically through integrated fluid channels and valves, eliminating the need for external technician intervention. The system self-regulates flow rates and mixing ratios, ensuring consistent accuracy while reducing time loss.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

An automated fluid handling system acts as an intermediary between sample injection and chromatography separation, performing dilution operations programmatically. This intermediary mechanism eliminates human error while maintaining precise control over dilution parameters.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Adaptability or versatility

If sample dilution is performed manually, then flexibility in dilution ratio is available, but contamination risk and human error increase

Engineering Contradiction:
Improvedilution flexibilityVSAvoidcontamination risk
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The system automatically manages sample dilution through programmed flow rate control, eliminating human contact with samples and preventing contamination. The self-service mechanism maintains flexibility by allowing dynamic adjustment of dilution ratios through software control.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

Manual mechanical dilution operations are replaced by an automated electronic control system that manages fluid flow through programmed valve actuation and flow rate regulation. This substitution eliminates human error while preserving adaptability through software-configurable parameters.

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

3Productivity

If existing automated dilution systems are used, then technician availability is reduced, but device complexity increases with multiple valves

Engineering Contradiction:
Improvesystem efficiencyVSAvoidvalve configuration
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The sample injection and sample dilution functions are merged into a single integrated operation. The same fluid handling mechanism that delivers the sample also performs dilution by controlling flow rates through existing channels, eliminating the need for separate dilution valves and reducing overall system complexity.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The fluid handling system is designed to perform multiple functions: sample loading, sample injection, and sample dilution. By making the system universal, fewer dedicated components are needed, reducing device complexity while maintaining high productivity through automated operation.

Inventive Principle:
Principle #6Universality (Multi-functionality)

4Stability of the object's composition

If strong solvent samples are injected directly, then sample focus is maintained, but sample retention at the column head is prevented

Engineering Contradiction:
Improvesample focusVSAvoidsample retention
Core Design Contradiction:
Stability of the object's compositionVSReliability

Solution Approach 1:

The system changes the concentration parameter of the sample by performing controlled dilution with mobile phase. This parameter change reduces the strong solvent concentration to a level that allows proper sample retention at the column head while maintaining adequate sample focus for separation.

Inventive Principle:
Principle #35Parameter changes

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 efficient, controlled sample dilution at the point of injection, reducing delays and errors, and allowing for a wide range of dilution ratios to ensure sample retention at the chromatographic column, even when samples are in strong solvents.

Implementation Method 1

The flow of mobile phase in the first fluid channel displaces the sample in the first fluid channel

Methodology Applied
Scientific EffectFluid flow displacement: Advection

Implementation Method 2

The sample exiting the first fluid channel and the mobile phase exiting the second fluid channel are combined at a location of injection into the system flow to thereby generate a diluted sample in the system flow. A dilution ratio of the diluted sample is responsive to the first flow rate and the second flow rate

Methodology Applied
Scientific EffectFluid mixing: Advection

Data Source

PatentEP2990790B1Injector sample dilution for a liquid chromatography system
Publication Date: 2024.04.24 WATERS TECHNOLOGY CORP
  • EP2990790B1 patent drawingFigure 1
  • EP2990790B1 patent drawingFigure 2A
  • EP2990790B1 patent drawingFigure 2B

AI summary

Described are a method and a system (70) for diluting a sample at a location of injection in a liquid chromatography system. The method includes loading a sample (54) into a first fluid channel (56), separating a flow of a mobile phase (78) into a first flow in the first fluid channel (56,57) and a second flow in a second fluid channel (82), and combining the sample that is displaced from the first fluid channel and the mobile phase exiting the second fluid channel at the location of injection into the system flow (79) to thereby generate a diluted sample in the system flow. The dilution ratio of the diluted sample is responsive to the flow rates of the first and second flows. Advantageously, the flow rates can be changed by changing the flow restriction of one of the fluid channels. Thus providing the proper flow restriction enables a user to obtain a desired dilution ratio. Fig. 6B