AIRLAB-MS Gas Confinement for Ambient Mass Spectrometry

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Solution Overview

Problem

Current techniques for ambient mass spectrometry imaging of live cells face challenges in achieving high transfer efficiency and reproducibility due to low concentrations of molecular species in complex biological samples, with existing methods reporting low transfer efficiency and significant sample losses.

Innovation Solution

The implementation of an ambient infrared (IR) laser ablation mass spectrometry (AIRLAB-MS) system, which includes an infrared microscope, a continuous flow probe coupled to a mass spectrometer, and a gas confinement device, enhances transfer efficiency by confining the laser ablation plume and optimizing solvent droplet size and flow, achieving transfer efficiencies of ~50% to 100%.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional mass spectrometry imaging techniques (MALDI, SIMS) are used, then chemical information with high molecular specificity can be obtained, but vacuum is required which makes them unsuitable for analysis of living systems

Engineering Contradiction:
Improvemolecular specificityVSAvoidsuitability for living systems
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent introduces an intermediary gas phase interface that mediates between the laser ablation source and the mass spectrometer detector. This interface allows atmospheric pressure operation while maintaining the vacuum requirements of the mass spectrometer, enabling analysis of living systems without compromising molecular specificity.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces the mechanical vacuum system with a gas-phase interface that uses controlled atmospheric pressure. This substitution allows the system to operate at atmospheric pressure for living system analysis while still achieving the necessary vacuum conditions for mass spectrometry detection through the intermediary interface.

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

2Adaptability or versatility

If laser ablation techniques are used for ambient mass spectrometry imaging, then analysis of living systems becomes possible, but transfer efficiency is low and significant sample loss occurs

Engineering Contradiction:
Improveanalysis of living systemsVSAvoidsample loss
Core Design Contradiction:
Adaptability or versatilityVSLoss of substance

Solution Approach 1:

The gas-phase interface acts as an intermediary that efficiently transfers ablated material from the atmospheric pressure ablation zone to the vacuum mass spectrometer. This intermediary system recovers and directs sample material, reducing loss while maintaining the ability to analyze living systems.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The system incorporates feedback mechanisms that monitor and optimize the transfer of ablated material through the gas-phase interface. This feedback control adjusts parameters to maximize sample transfer efficiency and minimize sample loss during living system analysis.

Inventive Principle:
Principle #23Feedback

3Measurement precision

If conventional MALDI technique is used, then chemical images can be generated for fixed tissue samples, but external matrix molecules must be applied which are usually denaturing

Engineering Contradiction:
Improvechemical imaging capabilityVSAvoiddenaturing effect
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent extracts and eliminates the need for external matrix molecules from the analysis process. By using laser ablation of the sample itself followed by gas-phase ionization and transfer, the system achieves chemical imaging without introducing denaturing matrix substances to the sample.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent substitutes the chemical matrix-assisted ionization mechanism with a physical laser ablation and gas-phase ionization mechanism. This substitution eliminates the need for external matrix molecules and their denaturing effects while maintaining chemical imaging capability.

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 AIRLAB-MS system provides high reproducibility with standard deviations of less than 10% and significantly improves the transfer efficiency of laser-ablated material to the mass spectrometer, enabling detailed analysis of biological samples with enhanced spatial and temporal resolution.

Implementation Method 1

a laser positioned to emit light through an objective lens of the microscope

Methodology Applied
Scientific EffectLaser ablation: Laser Ablation

Implementation Method 2

a gas confinement device with a plurality of vents positioned to direct a gas to confine a plume generated by the laser

Methodology Applied
Scientific EffectGas flow confinement: Convection

Implementation Method 3

a continuous flow probe positioned between the sample and the objective lens and coupled to a spectrometer

Methodology Applied
Scientific EffectMaterial transfer:

Data Source

PatentUS10714326B2Laser ablation spectrometry system
Publication Date: 2020.07.14 RGT UNIV OF CALIFORNIA
  • US10714326B2 patent drawing
  • US10714326B2 patent drawing
  • US10714326B2 patent drawing

AI summary

This disclosure provides systems, methods, and apparatus related to laser ablation spectrometry systems. In one aspect, a system comprises a microscope, a laser, a continuous flow probe, and a gas confinement device. The laser is positioned to emit light through an objective lens of the microscope. The continuous flow probe is coupled to a spectrometer. An end of the continuous flow probe is positioned proximate a sample and between the sample and the objective lens. The gas confinement device defines a gas inlet, a chamber, a platform, a wall surrounding the platform, a plurality of vents, and a plurality of channels. Each of the plurality of vents is positioned to direct a gas substantially parallel to the platform, and each of the plurality of vents is defined in the wall. The plurality of channels is operable to provide fluid communication between the chamber and the plurality of vents.