Mass Spectrometry Screening With Isotopic MRM Quantification

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Direct acoustic ionization mass spectrometry is inefficient for obtaining specific, quantitative results due to the lack of separation methods, leading to detector saturation and requiring additional time-consuming preparation steps for dilution and reanalysis, which are prone to errors.

Innovation Solution

A sample processing system that combines direct sampling with a quantitative mass analyzer using label-free multiple reaction monitoring (MRM) of natural isotopic abundance, allowing for high-throughput quantitative analysis without physical dilution, by performing mass screening and subsequent quantitative analysis using product and isotopic ion transitions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If direct acoustic ionization mass spectrometry is used for high-throughput screening, then screening throughput is improved, but quantitative accuracy deteriorates due to detector saturation and lack of separation

Engineering Contradiction:
Improvescreening throughputVSAvoidquantitative accuracy
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent segments the analytical process into two distinct stages: (1) high-throughput screening using direct acoustic ionization mass spectrometry for rapid identification, and (2) targeted quantitative analysis using LC-MS/MS for precise measurement. This segmentation allows each method to operate in its optimal performance range without compromise

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces an intermediary decision-making step where screening results guide whether samples proceed to quantitative analysis. Samples that screen positive or require quantification are selectively transferred to the LC-MS/MS system, creating an efficient workflow that optimizes both throughput and accuracy

Inventive Principle:
Principle #24Intermediary (Mediator)

2Use of energy by moving object

If samples are concentrated for direct acoustic ionization mass spectrometry, then ionization efficiency is improved, but additional preparation steps are required for dilution and reanalysis

Engineering Contradiction:
Improveionization efficiencyVSAvoidpreparation time
Core Design Contradiction:
Use of energy by moving objectVSLoss of time

Solution Approach 1:

The patent merges the advantages of concentrated sample analysis (high ionization efficiency) with automated sample transfer capabilities. The Acoustic Droplet Ejection system automatically handles sample transfer and the workflow integrates screening and quantification steps, eliminating manual dilution and reanalysis while maintaining high ionization efficiency in the screening stage

Inventive Principle:
Principle #5Merging (Combining)

3Measurement precision

If manual dilution and reanalysis steps are performed, then quantitative results can be obtained, but operational errors and time consumption increase

Engineering Contradiction:
Improvequantitative resultsVSAvoidoperational error rate
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent replaces manual mechanical operations (pipetting, dilution, transfer) with automated Acoustic Droplet Ejection technology. This substitution eliminates human error in sample handling while maintaining the necessary quantitative analysis steps, thereby improving both reliability and throughput

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

Solution Approach 2:

The system implements self-service through automated sample transfer and workflow management. The Acoustic Droplet Ejection system automatically identifies, transfers, and prepares samples for analysis without human intervention, reducing operational errors and increasing reproducibility

Inventive Principle:
Principle #25Self-service

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

Enables accurate and efficient quantification of analytes without reanalysis or dilution, reducing errors and operational time, and extending the dynamic range of the mass analyzer for analyzing samples with varying concentrations.

Implementation Method 1

ionizing the sample; monitoring, by mass spectrometry, at least one product ion transition for the at least one analyte and at least one isotopic ion transition for the at least one analyte

Methodology Applied
Scientific EffectIonization: Ionisation

Implementation Method 2

acoustic radiation pressure to eject droplets from a sample plate

Methodology Applied
Scientific EffectAcoustic radiation pressure: Acoustic Radiation Pressure

Data Source

PatentUS20240420939A1Ultra high throughput screening combined with definitive testing in a single sample preparation step
Publication Date: 2024.12.19 DH TECH DEVMENT PTE
  • US20240420939A1 patent drawing
  • US20240420939A1 patent drawing
  • US20240420939A1 patent drawing

AI summary

The presently claimed and described technology provides a sample processing system comprising at least one sample introduction device, wherein the at least one sample introduction device is configured to receive a sample; a mass analyzer coupled to the sample introduction device; a control system configured to at least control the at least one sample introduction device and/or the mass analyzer, wherein the mass analyzer is configured to perform a first mass analysis on the sample, wherein the first mass analysis is mass screening for an analyte of interest in the sample, and wherein if the analyte of interest is detected in the sample, the mass analyzer is configured to perform a second mass analysis, wherein the second mass analysis is a quantitative analysis, comprising: ionizing the sample; monitoring, by mass spectrometry, at least one product ion transition for the at least one analyte and at least one isotopic ion transition for the at least one analyte; determining intensity and/or abundance of the at least one product ion transition and/or the at least one isotopic ion transition; and quantifying the at least one analyte present in the sample using the intensity and/or abundance of the at least one product ion transition and/or isotopic ion transition.