Solvent-Free Matrix Deposition for Imaging Mass Spectrometry

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Solution Overview

Problem

Conventional matrix deposition methods in imaging mass spectrometry rely on solvents, leading to issues like analyte spreading, low signal intensity, and irreproducibility, and lack solvent-free sublimation techniques and apparatus for uniform deposition across multiple samples.

Innovation Solution

The development of solvent-free matrix deposition apparatus and methods using sublimation techniques, which include a rotatable matrix and sample holding system for optimized sublimation-condensation positioning, allowing for uniform gas-phase molecular deposition on multiple samples simultaneously, minimizing analyte diffusion and contamination.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If spraying or spotting methods are used for matrix deposition, then the deposition process is simple and fast, but analyte spreading occurs leading to reduced signal intensity and resolution

Engineering Contradiction:
Improvedeposition speedVSAvoidspatial resolution
Core Design Contradiction:
ProductivityVSManufacturing precision

Solution Approach 1:

The patent employs sublimation of the matrix from solid to gas phase, allowing direct deposition onto the sample surface without passing through a liquid state. This phase transition eliminates solvent-mediated analyte spreading while maintaining efficient deposition, resolving the contradiction between deposition speed and spatial resolution

Inventive Principle:
Principle #36Phase transitions

Solution Approach 2:

The invention replaces mechanical spraying or spotting systems with a thermal field-based sublimation system. By using controlled heating to sublime the matrix and cooling the sample surface to condense the vapor, the system achieves precise spatial control without mechanical contact, thereby maintaining both speed and resolution

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

2Ease of operation

If solvents are used as media for matrix transfer, then the matrix can be easily applied to the sample surface, but lateral movement of analytes occurs reducing signal intensity and resolution

Engineering Contradiction:
Improvematrix application easeVSAvoidanalyte spatial localization
Core Design Contradiction:
Ease of operationVSManufacturing precision

Solution Approach 1:

The patent extracts and eliminates the solvent component from the matrix application process. By using pure solid matrix material that sublimates directly, the system removes the harmful lateral movement effect while maintaining ease of application through automated sublimation control, resolving the contradiction between operational ease and spatial precision

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention introduces a vapor phase as an intermediary between the matrix source and sample surface. The sublimated matrix molecules travel through the vacuum chamber as gas and condense on the cooled sample, providing a solvent-free transfer mechanism that preserves analyte spatial localization while maintaining ease of matrix application

Inventive Principle:
Principle #24Intermediary (Mediator)

3Device complexity

If conventional spraying and spotting techniques are used, then the equipment is simple, but irreproducibility and poor control of matrix/analyte incorporation occur

Engineering Contradiction:
Improveequipment simplicityVSAvoiddeposition reproducibility
Core Design Contradiction:
Device complexityVSReliability

Solution Approach 1:

The patent incorporates feedback control through temperature monitoring and adjustment of the sublimation source and sample stage. By controlling the thermal fields and monitoring deposition conditions, the system achieves high reproducibility of matrix/analyte incorporation ratios, resolving the contradiction between equipment simplicity and deposition reliability

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The invention controls deposition parameters such as sublimation temperature, sample stage temperature, and vacuum pressure to optimize and reproduce matrix deposition. By systematically controlling these parameters, the system achieves consistent matrix/analyte incorporation across multiple samples while maintaining relatively simple equipment architecture

Inventive Principle:
Principle #35Parameter changes

4Area of stationary object

If solvent-based matrix deposition is used, then the matrix can be applied to large or multiple samples, but analyte diffusion occurs reducing imaging quality

Engineering Contradiction:
Improvesample coverage areaVSAvoidimaging quality
Core Design Contradiction:
Area of stationary objectVSManufacturing precision

Solution Approach 1:

The patent uses sublimation-condensation phase transitions to deposit matrix uniformly across large sample areas. The gaseous matrix molecules diffuse in the vacuum chamber and condense on the cooled sample surface, providing uniform coverage without solvent-induced analyte diffusion, thus resolving the contradiction between sample coverage area and imaging quality

Inventive Principle:
Principle #36Phase transitions

Solution Approach 2:

The invention replaces solvent-based liquid transport with vapor-phase transport for matrix application. This substitution allows uniform matrix deposition over large areas through controlled vapor diffusion and condensation, eliminating analyte diffusion while maintaining broad sample coverage 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

This approach enhances spatial resolution, detection sensitivity, and reproducibility of molecular imaging by eliminating solvent-related issues, enabling precise and high-throughput matrix deposition on large or multiple samples with improved signal intensity and reduced contamination.

Implementation Method 1

gas-phase molecular solvent-free matrix deposition using sublimation techniques

Methodology Applied
Scientific EffectSublimation: Sublimation

Implementation Method 2

sublimation-condensation positioning, allowing for uniform gas-phase molecular deposition

Methodology Applied
Scientific EffectCondensation: Condensation

Data Source

PatentUS7880139B2Method and apparatus of uniform gas-phase molecular matrix deposition for imaging mass spectrometry
Publication Date: 2011.02.01 GEORGIA TECH RES CORP
  • US7880139B2 patent drawing
  • US7880139B2 patent drawing
  • US7880139B2 patent drawing

AI summary

Disclosed are apparatus and methods for depositing solvent-free molecules on surfaces of samples, with particular application to imaging mass spectrometry. A vacuum chamber is configured to have controllable matrix translation apparatus for controlling the position of one or more solvent-free matrices within the chamber. Sublimation apparatus is used to sublimate molecules from the solid phase matrices. One or more samples are placed separately from the solvent-free matrices within the chamber. Condensation apparatus individually cools the samples to deposit sublimated molecules on the samples. Controllable sample translation apparatus is used to control the position of the samples within the chamber. Rotatable sample holding apparatus may be used to hold and move the samples to allow deposition of molecules on multiple samples at substantially the same time. Rotatable matrix holding apparatus may also be used to hold and move a plurality of matrices to create a homogenous mixture of molecules that are deposited onto one or more samples. As surface characterization system may be used to monitor deposition of the molecules to determine their thickness and roughness. A computer may be configured to control the matrix translation apparatus, the sublimation apparatus, the condensation apparatus, and the sample translation apparatus to provide for automated deposition of solvent-free molecules on the samples.