AEMS-DMS Setting Selection for High-Throughput OPI Analysis

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Solution Overview

Problem

Current techniques for coupling acoustic droplet ejectors with differential mobility spectrometry in mass spectrometry face challenges such as determining optimal compensation voltage settings, requiring substantial modifications to the ion source and limiting high-throughput analysis due to differences in solvent flow rates and short sampling times.

Innovation Solution

A method and system that operate an acoustic ejection mass spectrometer with a differential mobility spectrometer, using pseudo-continuous and discontinuous sample ejection modes to evaluate and select optimal separation voltage and compensation voltage pairs for ion selection, eliminating the need for pre-optimization and reducing hardware modifications.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional infusion approaches are used to determine DMS settings, then compensation voltage values can be determined, but the solvent flow rate difference (10 μL/min vs 300 μL/min) invalidates the CoV values for OPI operation

Engineering Contradiction:
ImproveCoV determination accuracyVSAvoidapplicability to OPI operation
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent changes the operating parameters of the ion source to match OPI conditions (300 μL/min carrier fluid flow) during CoV determination, rather than using conventional infusion parameters (10 μL/min). This ensures the determined CoV values are valid for actual OPI-DMS-MS operation.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The system performs self-optimization by automatically determining CoV values under actual operating conditions without requiring separate infusion optimization steps. The OPI-DMS-MS system itself is used to generate the optimization data, eliminating the need for external infusion equipment and parameter translation.

Inventive Principle:
Principle #25Self-service

2Productivity

If ADE-OPI sampling is used for high throughput analysis, then sample analysis speed increases, but the short sampling duration (<1 second) makes it difficult to determine appropriate DMS settings

Engineering Contradiction:
Improvesample analysis throughputVSAvoidsampling event duration
Core Design Contradiction:
ProductivityVSLoss of time

Solution Approach 1:

The patent performs preliminary determination of DMS settings (CoV values) before actual high-throughput analysis. By establishing optimal CoV values in advance under representative conditions, the system prepares all necessary parameters beforehand, allowing rapid analysis without real-time optimization during each short sampling event.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The system maintains continuous carrier fluid flow (300 μL/min) through the OPI during both optimization and analysis phases, ensuring consistent operating conditions. This continuity allows the pre-determined CoV values to remain valid throughout high-throughput operation without requiring re-optimization between samples.

Inventive Principle:
Principle #20Continuity of useful action

3Reliability

If conventional LC-MS separation is used to avoid isobaric interferences, then compound separation based on mobility is achieved, but sample run time increases and system complexity increases

Engineering Contradiction:
Improveisobaric interference resolutionVSAvoidsystem complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent combines the open port interface (OPI) with the differential mobility spectrometer (DMS) in a single integrated configuration. This merging eliminates the need for separate LC separation systems while achieving equivalent interference resolution through DMS's mobility-based filtering, thereby reducing overall system complexity.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent replaces the mechanical LC separation system with a field-based DMS separation system. Instead of using physical column chromatography to separate compounds, the system uses electric fields to separate ions based on their mobility characteristics, eliminating moving mechanical parts and simplifying the system architecture.

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

4Adaptability or versatility

If substantial modification of the ion source is made to incorporate DMS, then DMS can be integrated with OPI, but the complexity of determining DMS settings increases

Engineering Contradiction:
ImproveDMS integration with OPIVSAvoidion source modification complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent designs the ion source to serve multiple functions: it handles both conventional infusion mode and OPI mode with carrier fluid flow, and provides the same CoV determination capability for both modes. This universal design eliminates the need for separate ion source configurations for different operating modes, reducing modification complexity.

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

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 efficient determination of optimal DMS settings for high-throughput analysis without substantial hardware alterations, improving sensitivity and selectivity by generating consistent ion signals and reducing interference, thus enhancing the analytical capabilities of acoustic ejection mass spectrometry systems.

Implementation Method 1

an acoustic droplet ejection device that is configured to allow for variation and selection of several different droplet ejection modes

Methodology Applied
Scientific EffectAcoustic radiation pressure: Acoustic Radiation Pressure

Implementation Method 2

DMS can be incorporated in a mass spectrometer downstream of the ion source and OPI device, and can achieve separations on the millisecond time scale

Methodology Applied
Scientific EffectIon mobility separation: Electrophoresis

Data Source

PatentUS20240379338A1Optimization of DMS separations using acoustic ejection mass spectrometry (AEMS)
Publication Date: 2024.11.14 DH TECH DEVMENT PTE
  • US20240379338A1 patent drawing
  • US20240379338A1 patent drawing
  • US20240379338A1 patent drawing

AI summary

Disclosed are methods and systems that provide for the analysis of one or more analytes of interest in an acoustic ejection mass spectrometer (AEMS) system that incorporates an open port interface (OPI) and differentiation mass spectrometry (DMS) that allows for operation of the system in a pseudo-continuous mode to scan and determine optimal DMS settings for the one or more analytes of interest, and for operation of the system in a discontinuous mode to analyze for the presence of the one or more analytes of interest in a sample.