Integrated LCMS Sample Handling for Purification and Titer Normalization

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Solution Overview

Problem

Existing solutions for biological sample delivery for LCMS analysis are limited in providing a single, easy-to-use, efficient, and effective solution that integrates sample drawing, purification, titer calculation, titer normalization, CQA pre-treatment, and injection signal for LCMS, often requiring multiple systems and software integration that is prone to failure.

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 enables sample drawing, purification, titer calculation, normalization, and pre-treatment for LCMS analysis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If multiple separate systems and software packages are used for sample draw, purification, titer calculation, and LCMS analysis, then each individual function can be performed, but the overall system complexity increases and software integration becomes unreliable

Engineering Contradiction:
Improvefunctional capabilityVSAvoidsystem complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent combines multiple separate systems (sample draw, purification, titer calculation, and LCMS analysis systems) into a single integrated automated sample handling system. The system uses a unified hardware platform with integrated fluid handling, purification columns, and detection capabilities, eliminating the need for multiple separate systems and their associated software integration issues.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The automated sample handling system is designed to perform multiple functions within a single platform, including sample aspiration, filtration, purification, titer calculation, and direct injection into LCMS. The system can handle different sample types and perform various operations using the same hardware infrastructure, providing universal functionality without requiring separate specialized systems.

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

2Adaptability or versatility

If multiple software packages with APIs are integrated to achieve complete CQA analysis, then comprehensive analysis capability is provided, but software updates can break integration and maintenance complexity increases

Engineering Contradiction:
Improveanalysis capabilityVSAvoidsoftware integration stability
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The patent replaces the software-based integration approach with a hardware-based integrated system. Instead of using multiple software packages connected via APIs, the system uses a unified hardware platform with embedded control that directly manages all sample handling operations, eliminating software integration vulnerabilities and update-related compatibility issues.

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

3Extent of automation

If automated liquid handlers using micropipettes and well plates are used for CQA analysis, then automation is achieved, but the system requires multiple separate systems for different operations

Engineering Contradiction:
Improveautomation levelVSAvoidnumber of systems
Core Design Contradiction:
Extent of automationVSDevice complexity

Solution Approach 1:

The patent merges the functions of multiple automated systems (sample draw, purification, titer calculation, and injection systems) into a single automated sample handling platform. The system uses integrated fluid handling mechanisms, purification columns, and detection systems all controlled by a unified automation platform, reducing the number of separate systems while maintaining high automation levels.

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

The system provides a single, efficient, and effective solution for handling biological samples, ensuring real-time CQA analysis and seamless integration of multiple operations required for LCMS, reducing complexity and software integration issues.

Implementation Method 1

a hollow membrane fiber filter

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 displacement pumping: Pump

Implementation Method 3

at least one purification column fluidly connected to an outlet port of the second multi-position selector valve

Methodology Applied
Scientific EffectChromatography: Chromatography

Data Source

PatentUS20250383325A1Automated sample handling system for liquid chromatography-mass spectrometry
Publication Date: 2025.12.18 FIALAB INSTRUMENTS INC
  • US20250383325A1 patent drawing
  • US20250383325A1 patent drawing
  • US20250383325A1 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.