Automated MALDI Ion Imaging Parameter Tuning

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Solution Overview

Problem

Current ion imaging methods for biological tissues require trial-and-error to determine optimal parameters for MALDI, leading to sample wastage and inefficiency due to non-orthogonal tuning parameters like laser shots per pixel and energy, which can result in suboptimal signal generation and increased analysis time.

Innovation Solution

A method involving automatic testing of a sample's parameters, such as laser shots and energy per pixel, to determine optimal settings using a sacrificial area, allowing for precise adjustment and application of these settings to the rest of the sample for improved ion imaging.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If trial and error method is used to determine optimal MALDI parameters, then the system can find suitable settings for each sample, but sample wastage increases and analysis time is extended

Engineering Contradiction:
Improveoptimal parameter determinationVSAvoidanalysis time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent applies preliminary action by performing a rapid parameter screening step before the main ion imaging acquisition. The system automatically tests multiple parameter combinations (laser shots per pixel, laser energy, delay time) on a test region to identify optimal settings in advance, preventing sample wastage and time loss during the main analysis phase.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The system implements self-service through automated parameter optimization. The mass spectrometer automatically varies parameters, evaluates signal quality metrics (S/N ratio, ion intensity), and selects optimal settings without operator intervention. This eliminates the manual trial-and-error process and reduces both time and sample consumption.

Inventive Principle:
Principle #25Self-service

2Quantity of substance

If too many laser shots per pixel are used, then more analyte ions can be generated, but the sample/matrix burns through quickly reducing signal quality and increasing analysis time

Engineering Contradiction:
Improveanalyte ion signalVSAvoidsample/matrix consumption
Core Design Contradiction:
Quantity of substanceVSLoss of energy

Solution Approach 1:

The patent applies dynamics by making the number of laser shots per pixel a variable parameter that is automatically optimized for each sample and imaging region. Rather than using a fixed high number of shots, the system dynamically adjusts this parameter based on real-time signal quality assessment, preventing sample burnout while maintaining adequate ion signal generation.

Inventive Principle:
Principle #15Dynamics

3Quantity of substance

If laser energy per shot is increased to improve ion signal, then analyte ion generation improves, but sample damage increases and optimal parameters become harder to determine

Engineering Contradiction:
Improveanalyte ion signalVSAvoidsample damage
Core Design Contradiction:
Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The system implements feedback by continuously monitoring signal quality metrics (S/N ratio, ion intensity, peak shape) during the parameter optimization process. The automated tuning algorithm uses this feedback to identify the optimal laser energy level that maximizes ion signal while preventing sample damage, eliminating the need for operator guesswork and reducing harmful sample effects.

Inventive Principle:
Principle #23Feedback

4Measurement precision

If manual parameter tuning is performed to optimize each sample, then signal quality can be maximized, but operator time and expertise requirements increase

Engineering Contradiction:
Improvesignal qualityVSAvoidoperator time and expertise
Core Design Contradiction:
Measurement precisionVSEase of operation

Solution Approach 1:

The patent applies self-service by implementing automated parameter tuning that performs independently without operator intervention. The system automatically acquires test spectra, evaluates multiple parameter combinations, and selects optimal settings based on predefined quality metrics. This eliminates the need for operator expertise in manual tuning while maintaining high signal quality.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The patent replaces the manual mechanical tuning process with an automated electronic control system. The mass spectrometer's control software automatically varies laser parameters, acquires data, and optimizes settings, substituting operator manual adjustment with an automated computational system that reduces both time and expertise requirements.

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 optimizes analytical ion signals by determining the best parameters for each sample, reducing wastage and analysis time while enhancing signal quality, thereby improving the efficiency of ion imaging processes.

Implementation Method 1

Matrix Assisted Laser Desorption Ionisation ('MALDI') is a destructive ionisation process

Methodology Applied
Scientific EffectMatrix Assisted Laser Desorption Ionisation:

Data Source

PatentUS9673029B2Automated tuning for MALDI ion imaging
Publication Date: 2017.06.06 MICROMASS UK LTD
  • US9673029B2 patent drawing
  • US9673029B2 patent drawing

AI summary

A method of ion imaging is disclosed comprising testing a first portion of a sample by automatically varying one or more parameters of a laser or other ionization device and manually or automatically determining from the first portion one or more optimum or preferred parameters of the laser or other ionization device. A second portion of the sample is then analyzed using the one or more optimum or preferred parameters.