Automated LCMS Sample Handling With Integrated Purification

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Solution Overview

Problem

Existing solutions for biological sample delivery in liquid chromatography-mass spectrometry (LCMS) analysis are inefficient and lack a single system capable of performing multiple operations such as sample drawing, purification, titer calculation, titer normalization, CQA pre-treatment, and injection signal, leading to complexity and vulnerability due to software integration issues.

Innovation Solution

An automated fluid handling system comprising an inlet tube, multi-position selector valves, syringe pumps, a purification column, titer detection system, and a pre-treatment unit, which collectively perform sample drawing, purification, titer calculation, normalization, and pre-treatment for LCMS analysis, using components like hollow membrane fiber filters and syringe pumps controlled by stepper motors.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If multiple separate systems are used for sample draw, purification, titer calculation, and CQA analysis, then each function can be performed with specialized equipment, but the overall system complexity increases and software integration becomes vulnerable

Engineering Contradiction:
Improvesystem reliabilityVSAvoidsystem complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent combines multiple separate systems (sample draw, purification, titer calculation, and CQA analysis) into a single integrated automated liquid handling system. This merging eliminates the need for multiple software APIs and handoffs between separate systems, thereby improving reliability while managing complexity through unified control.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The automated liquid handling system is designed to perform multiple functions including sample aspiration, purification, titer calculation, and CQA analysis within a single platform. This multi-functionality reduces dependency on multiple specialized systems and their interconnections, enhancing system reliability.

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

2Adaptability or versatility

If multiple software packages are integrated via APIs to achieve complete CQA analysis, then comprehensive analysis capability is achieved, but software updates can break integration and increase complexity

Engineering Contradiction:
Improveanalysis capabilityVSAvoidsoftware integration complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent integrates titer calculation and CQA analysis capabilities directly into the automated liquid handling system, eliminating the need for separate software packages and API integrations. This unified approach maintains comprehensive analysis capability while avoiding the complexity and fragility of multi-software integrations.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The system incorporates multiple analytical functions (titer calculation, normalization, and CQA analysis) within a single software platform, enabling comprehensive biotherapeutic analysis without requiring integration with multiple external software packages.

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

3Ease of operation

If automated liquid handler uses only micropipettes and well plates for CQA analysis, then the system is simple to operate, but it cannot provide complete CQA analysis including titer calculation and normalization

Engineering Contradiction:
Improveoperational simplicityVSAvoidanalysis capability
Core Design Contradiction:
Ease of operationVSAdaptability or versatility

Solution Approach 1:

The automated liquid handling system is designed to perform multiple functions including sample aspiration, purification, titer calculation, normalization, and CQA analysis within a single platform. This multi-functionality expands analysis capability while maintaining automated operation simplicity.

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

4Measurement precision

If different systems are used for titer calculation, titer normalization, and CQA pre-treatment, then each process can be optimized independently, but the overall workflow complexity increases

Engineering Contradiction:
Improvetiter measurement accuracyVSAvoidworkflow complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent combines titer calculation, titer normalization, and CQA pre-treatment into a single integrated automated liquid handling system. This unified approach maintains measurement precision through specialized algorithms while reducing workflow complexity by eliminating multiple system handoffs.

Inventive Principle:
Principle #5Merging (Combining)

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

Provides a single, efficient, and effective solution for real-time CQA analysis, simplifying the sample handling process and reducing software integration complexities by integrating these functions into a unified system.

Implementation Method 1

a first multi-position selector valve fluidly connected to a hollow membrane fiber filter; wherein the first multi-position selector valve comprise at least one inlet port for fluidic connection with the inlet tube

Methodology Applied
Scientific EffectFiltration: Filter (physical)

Implementation Method 2

a plurality of syringe pumps fluidly connected to a hollow membrane fiber filter; wherein each of the plurality of syringe pumps is configured to aspire and dispense a fluid

Methodology Applied
Scientific EffectMechanical pumping: Pump

Implementation Method 3

a titer detection system fluidly connected to the purification column, wherein the titer detection system is configured to determine titer concentration value of biological fluid sample

Methodology Applied
Scientific EffectDetection:

Data Source

PatentUS12422413B2Automated sample handling system for liquid chromatography-mass spectrometry
Publication Date: 2025.09.23 FIALAB INSTRUMENTS INC
  • US12422413B2 patent drawing
  • US12422413B2 patent drawing
  • US12422413B2 patent drawing

AI summary

Presented is an automated fluid handling system for handling a biological fluid sample prior to being delivered for liquid chromatography-mass spectrometry (LCMS) analysis. The automated fluid handling system includes two multi-position selector valves fluidly connected to a hollow membrane fiber filter. Multiple syringe pumps are fluidly connected to the hollow membrane fiber filter. A purification column is fluidly connected to an outlet port of a multi-position selector valve. The automated fluid handling system is capable of conducting multiple operations needed before the liquid chromatography-mass spectrometry (LCMS) analysis.