ESI Current Monitoring for LC-MS Post-Column Dead Volume Detection

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Solution Overview

Problem

Automated analyzers with mass spectrometers and electrospray ionization sources face challenges in detecting post-column dead volumes, which can lead to errors and increased downtime, as traditional monitoring methods like pressure measurement are insufficient and may require external expertise, complicating maintenance and resource allocation.

Innovation Solution

Monitoring the electrospray ionization current of the ESI source allows for precise identification of post-column dead volumes by analyzing time series data, distinguishing it from other conditions such as column aging, and triggering targeted responses to reduce downtime and resource inefficiencies.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If traditional pressure measurement methods are used to monitor the LC stream, then the monitoring system is simple, but post-column dead volumes cannot be detected

Engineering Contradiction:
Improvedetection capabilityVSAvoidmonitoring system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent introduces an intermediary parameter (ESI current) that mediates between the LC stream state and the detection system. Instead of directly measuring physical parameters like pressure that fail to detect dead volumes, the system measures the ESI current which is affected by the chromatographic separation quality, thereby enabling indirect detection of post-column dead volumes through their impact on ionization efficiency

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces the mechanical pressure measurement system with an electrical measurement system (ESI current monitoring). This substitution allows detection of dead volumes by measuring electrical current variations in the electrospray ionization process, which are affected by changes in the LC stream caused by dead volumes, rather than relying on mechanical pressure sensors

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

2Reliability

If external service personnel are called to fix errors, then expert knowledge is available, but analyzer downtime increases

Engineering Contradiction:
Improveerror detection accuracyVSAvoidanalyzer downtime
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent enables the analyzer to perform self-diagnosis by automatically monitoring ESI current and detecting conditions such as post-column dead volumes. The system can identify problems and alert operators without requiring external service personnel, thereby reducing downtime while maintaining reliable error detection through automated condition monitoring and identification

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The patent implements a feedback mechanism where the monitored ESI current is continuously analyzed to provide information about the analyzer's state. This feedback loop enables real-time detection of conditions like dead volumes, allowing the system to alert operators promptly and enable quick response without waiting for external service intervention

Inventive Principle:
Principle #23Feedback

3Reliability

If comprehensive monitoring of all parameters is performed, then all conditions can be detected, but resource allocation becomes inefficient

Engineering Contradiction:
Improvecondition detection coverageVSAvoidmaintenance efficiency
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent extracts and focuses on a single critical parameter (ESI current) that contains information about multiple possible conditions including post-column dead volumes. Instead of monitoring all parameters comprehensively, the system extracts the key diagnostic information from the ESI current, enabling efficient detection of various conditions while maintaining productivity through targeted rather than exhaustive monitoring

Inventive Principle:
Principle #2Taking out (Extraction)

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 method enables swift and effective maintenance by less experienced personnel, reduces analyzer downtime, and optimizes resource allocation by providing precise insights into the analyzer's state, integrating seamlessly into existing workflows without affecting performance.

Implementation Method 1

a mass spectrometer (MS) with an electrospray ionization (ESI) source coupled to a liquid chromatography (LC) stream

Methodology Applied
Scientific EffectElectrospray ionization: Electrohydrodynamics

Data Source

PatentEP3786635B1Techniques for checking state of LC/ms analyzers
Publication Date: 2023.09.27 ROCHE DIAGNOSTICS GMBH
  • EP3786635B1 patent drawingFigure 1
  • EP3786635B1 patent drawingFigure 2
  • EP3786635B1 patent drawingFigure 3a~3b

AI summary

The present disclosure relates to an automated method of monitoring a state of an analyzer including a mass spectrometer (MS) with an electrospray ionization (ESI) source coupled to a liquid chromatography (LC) stream, the method comprising: monitoring an electrospray ionization current of the ESI source and identifying a condition of multiple conditions of the analyzer based on the monitored ionization current of the ESI source, one of the conditions being a presence of a dead volume in a liquid chromatography stream of the analyzer downstream of an LC column of the LC stream.