Mass Spectrometer Calibration via Automated Downstream Dilution

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Solution Overview

Problem

Current mass spectrometer calibration methods require intensive manual intervention, leading to inefficiencies, errors, and increased costs due to the need for manual handling of volatile solvents and frequent maintenance of HPLC columns, which is laborious and time-consuming, especially in high-throughput applications.

Innovation Solution

An automated analytical system that uses a downstream pump to dilute and infuse a concentrated calibration solution into the mass spectrometer, bypassing the analytical fluidic system, allowing for automated calibration and adaptive adjustment of calibration conditions, minimizing manual intervention and reducing the risk of errors and system downtime.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If manual calibration procedures are used, then calibration can be performed with standard equipment, but user intervention time and risk of errors increase

Engineering Contradiction:
Improveuser intervention timeVSAvoidrisk of errors
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The system enables automated self-calibration through the downstream pump and mixing unit, which automatically prepare and deliver calibration solutions without user intervention. The mass spectrometer performs self-diagnosis and self-adjustment based on real-time analysis of calibration peaks, eliminating manual operation steps and reducing human error risk.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The patent replaces manual mechanical operations (pipetting, solution preparation, instrument adjustment) with an automated fluid delivery system comprising a downstream pump, mixing unit, and electronic control. This substitution transforms manual calibration into an automated process controlled by software algorithms that analyze mass spectra and adjust calibration parameters.

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

2Measurement precision

If concentrated calibration solutions are stored, then calibration accuracy can be maintained, but handling and storage risks of volatile solvents increase

Engineering Contradiction:
Improvecalibration accuracyVSAvoidhandling and storage risks
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The calibration solution is segmented into concentrated stock solution and diluent, stored separately in the fluid container. The downstream pump and mixing unit combine them in controlled ratios only when needed for calibration. This segmentation allows the concentrated solution to be stored safely in small quantities while maintaining calibration accuracy through precise automated mixing.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The mixing unit acts as an intermediary between the concentrated calibration solution and the mass spectrometer. It automatically prepares the required diluted calibration solution on-demand, eliminating the need to store large quantities of ready-to-use calibration solutions and reducing handling risks of volatile solvents.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Productivity

If HPLC columns are used for separation, then sample analysis can be performed, but frequent maintenance and backflushing requirements increase downtime

Engineering Contradiction:
Improvesample throughputVSAvoidmaintenance downtime
Core Design Contradiction:
ProductivityVSLoss of time

Solution Approach 1:

The calibration function is extracted from the analytical HPLC column path and performed separately through the downstream pump connected to the mass spectrometer. This allows calibration to be performed without interrupting or affecting the HPLC column, eliminating the need to stop sample analysis for column maintenance and backflushing.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The system performs preliminary calibration checks continuously in the background during sample analysis using the downstream pump. This preliminary action ensures calibration status is monitored without interrupting the main analytical workflow, and maintenance can be scheduled during planned downtime rather than causing unexpected interruptions.

Inventive Principle:
Principle #10Preliminary action

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 automated system ensures continuous analytical performance with reduced user intervention, minimizing errors and downtime, while also reducing the handling and storage risks associated with volatile solvents, and enabling flexible adaptation of calibration conditions.

Implementation Method 1

controlling the downstream pump in order to obtain at least one diluted composition by automatically mixing at least one concentrated composition with at least one diluent

Methodology Applied
Scientific EffectMixing:

Implementation Method 2

downstream pump fluidically connectable to the ionization source via the downstream valve... to infuse the at least one diluted composition into the ionization source

Methodology Applied
Scientific EffectPumping: Pump

Data Source

PatentUS20240385155A1Analytical system and method
Publication Date: 2024.11.21 ROCHE DIAGNOSTICS OPERATIONS INC
  • US20240385155A1 patent drawing
  • US20240385155A1 patent drawing
  • US20240385155A1 patent drawing

AI summary

An analytical system comprising a mass spectrometer and an ionization source. The analytical system further comprises an analytical fluidic system connectable to the ionization source for infusing samples into the mass spectrometer via the ionization source, a downstream pump fluidically connectable to the ionization source via the downstream valve, where the downstream pump is fluidically connected to a plurality of fluid containers comprising respective fluids, the fluids comprising a concentrated composition for calibrating the mass spectrometer and at least one diluent for diluting the at least one concentrated composition. The analytical system further comprises a controller configured to control the downstream pump to obtain at least one diluted composition by automatically mixing a concentrated composition with a diluent with a predetermined dilution factor, to infuse the diluted composition into the ionization source, to obtain a mass spectrum of the diluted composition and to execute a calibration of the mass spectrometer. A respective automated analytical method.