Automated LC-MS/MS Sample Preprocessing for Multichannel Throughput

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Solution Overview

Problem

Existing LC-MS/MS systems have low automation levels, requiring manual procedures that are time-consuming, labor-intensive, and prone to errors, with single-channel sample injection modes limiting throughput and necessitating skilled technicians, thus hindering widespread adoption and increasing costs.

Innovation Solution

A full-automatic high-throughput LC-MS/MS system utilizing magnetic extraction and multichannel techniques, incorporating a sample preprocessing module and multichannel liquid chromatography-mass spectrometry module, enabling automated sample processing, separation, and analysis through a computer-controlled system.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Extent of automation

If manual procedures are used for sample preprocessing and analysis, then flexibility and adaptability are maintained, but automation level and throughput are reduced

Engineering Contradiction:
Improveautomation levelVSAvoidsystem complexity
Core Design Contradiction:
Extent of automationVSDevice complexity

Solution Approach 1:

The patent combines sample preprocessing, liquid chromatography, and mass spectrometry into an integrated automated system. The sample preprocessing module directly couples with the LC-MS/MS system, eliminating manual transfer steps and achieving full automation from sample to result, thereby resolving the contradiction between automation and complexity.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The automated sample preprocessing module is designed with universal functionality to handle multiple sample types (plasma, serum, urine, etc.) and various analytes through programmable protocols. This multi-functionality allows high automation without requiring separate systems for different applications, addressing the complexity concern.

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

2Productivity

If single-channel sample injection mode is used, then system simplicity is maintained, but throughput and efficiency are reduced

Engineering Contradiction:
ImprovethroughputVSAvoidinjection system complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The injection system is segmented into multiple independent injection channels (dual-channel or multi-channel configuration), allowing parallel sample introduction to the chromatography system. Each channel operates independently, enabling simultaneous analysis of multiple samples and significantly increasing throughput while maintaining manageable system complexity.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The multi-channel injection system enables continuous sample introduction without idle time between injections. While one channel is injecting, another channel can be preparing the next sample, ensuring continuous useful action and maximizing productivity of the LC-MS/MS system.

Inventive Principle:
Principle #20Continuity of useful action

3Speed

If traditional liquid chromatography separation is used, then analysis specificity is maintained, but analysis time per sample is increased

Engineering Contradiction:
Improveanalysis speedVSAvoidanalysis specificity
Core Design Contradiction:
SpeedVSMeasurement precision

Solution Approach 1:

The patent employs optimized chromatographic parameters including gradient elution profiles, temperature control, and mobile phase composition adjustments to accelerate separation while maintaining resolution. These parameter optimizations reduce analysis time without compromising the specificity required for accurate analyte detection.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The system transitions from isocratic to gradient elution chromatography, adding the dimension of time-varying mobile phase composition to the separation process. This gradient approach enables faster elution of later-retained analytes while maintaining early elution resolution, effectively increasing analysis speed without sacrificing precision.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

4Measurement precision

If complex sample preprocessing procedures are used, then analysis accuracy is improved, but labor requirements and processing time are increased

Engineering Contradiction:
Improveanalysis accuracyVSAvoidprocessing efficiency
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The automated sample preprocessing module performs complex procedures including protein precipitation, centrifugation, filtration, and concentration automatically without manual intervention. The system self-manages the entire preprocessing workflow, maintaining analysis accuracy through consistent automated execution while dramatically improving processing efficiency and reducing labor requirements.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

Manual mechanical preprocessing operations (manual mixing, centrifugation, transfer) are replaced with automated mechanical systems including robotic liquid handlers, automated centrifuges, and programmed transfer mechanisms. This substitution maintains or improves precision through consistent automated execution while increasing productivity by eliminating manual bottlenecks.

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

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 system achieves high-throughput, automated testing from sample preprocessing to report generation, reducing labor requirements, enhancing throughput, and lowering costs while supporting a wide range of sample types with improved efficiency and reduced environmental footprint.

Implementation Method 1

full-automatic sample preprocessing is performed by magnetic extraction

Methodology Applied
Scientific EffectMagnetic separation: Magnetism

Implementation Method 2

the preprocessed sample enters multichannel liquid chromatography apparatuses for separation

Methodology Applied
Scientific EffectChromatographic separation: Chromatography

Implementation Method 3

the sample separated by multichannel liquid chromatography respectively enters a mass spectrometry module through respective channels for analysis

Methodology Applied
Scientific EffectMass spectrometry:

Data Source

PatentUS20250347664A1Full-automatic high-throughput LC-ms/ms test system and method
Publication Date: 2025.11.13 HANGZHOU CALIBRA TECH CO LTD
  • US20250347664A1 patent drawing
  • US20250347664A1 patent drawing
  • US20250347664A1 patent drawing

AI summary

The vention provide an LC-MS/MS test system, comprising: a full-automatic sample preprocessing module; wherein the full-automatic sample preprocessing module comprises an automatic sample feeding and discharging module for transporting sample baskets to be tested, and the automatic sample feeding and discharging module comprises a routine sample feeding and discharging structure and an emergency sample feeding and discharging structure, wherein the sample baskets to be tested comprise routine sample baskets and an emergency sample basket.