Sub-micrometer Elemental Image Analysis by Mass Spectrometry

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Solution Overview

Problem

Current laser ablation methods for sample analysis are limited by physical constraints on sample size, destructive nature, and reduced sensitivity due to poor ion introduction into the mass spectrometer vacuum, particularly in the analysis of biological samples.

Innovation Solution

The use of a primary ion beam for sub-micron sampling and ionization in a vacuum, combined with time-of-flight mass spectrometry for temporal separation of charged particles based on mass and/or mass-charge ratio, allowing for elemental isotopic analysis of two-dimensional substrates like biological tissue slices or elementally-coded standards.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If laser ablation is used for sample analysis, then elemental information can be obtained, but the sample size is limited by physical constraints and the analysis precision is reduced

Engineering Contradiction:
Improveelemental analysis precisionVSAvoidsample segment size
Core Design Contradiction:
Measurement precisionVSLength of moving object

Solution Approach 1:

The patent replaces laser ablation (optical system) with ion beam sputtering (mechanical/particle system) for sample analysis. This substitution enables sub-micrometer sampling precision and sub-micron depth control, overcoming the physical wavelength limitations of laser methods while maintaining elemental analysis capability through mass spectrometry detection.

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

Solution Approach 2:

The patent changes the fundamental operating parameters by transitioning from atmospheric pressure laser ablation to vacuum-based ion beam sputtering. This parameter change enables precise control of sampling depth at sub-micron levels and allows for non-destructive or minimally destructive analysis by controlling ion beam energy and exposure time.

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If laser ablation is used for sample analysis, then elemental composition can be measured, but the analysis is destructive and prevents re-analysis

Engineering Contradiction:
Improveelemental composition measurementVSAvoidsample integrity
Core Design Contradiction:
Measurement precisionVSStability of the object's composition

Solution Approach 1:

The patent applies partial action by using low-energy ion beam sputtering that removes only atomic layers (sub-nanometer to nanometer depths) rather than vaporizing the entire sample thickness. This controlled partial removal enables multiple sequential scans of the same sample area, allowing re-analysis and repeated measurements without destroying the sample.

Inventive Principle:
Principle #16Partial or excessive action

Solution Approach 2:

The patent employs periodic scanning of the ion beam across different sample areas or repeated scanning of the same area with controlled low energy doses. This periodic action allows systematic data collection over time while preserving sample integrity, enabling both dynamic processes monitoring and repeated analytical measurements.

Inventive Principle:
Principle #19Periodic action

3Measurement precision

If ablation and ionization at atmospheric pressure is used, then sample analysis can be performed, but sensitivity is reduced due to poor ion introduction into vacuum

Engineering Contradiction:
Improvedetection sensitivityVSAvoidion introduction efficiency
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent transitions from atmospheric pressure operation to vacuum environment for the entire analysis process. This creates an inert environment that allows efficient ion generation, transport, and detection without atmospheric interference. The vacuum conditions enable direct introduction of sputtered ions into the mass spectrometer, dramatically improving sensitivity and detection limits for elemental analysis.

Inventive Principle:
Principle #39Inert atmosphere (Inert environment)

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 precise, non-destructive analysis of sub-micron sample segments with enhanced sensitivity, enabling multiple scans and integration of elemental data from continuous ion introduction, improving the resolution and accuracy of elemental composition analysis.

Implementation Method 1

sub-micrometer segments of the two dimensional analyte matrix are samples for their elemental ions using a primary ion beam or charged particle beam. Application of the beam to a particular segment of the analyte results in the secondary ionization of the elemental constituents therein.

Methodology Applied
Scientific EffectIonization: Ionisation

Implementation Method 2

characterizing the ablated products using an ICP-MS (inductively coupled plasma mass spectrometer)... operating a mass spectrometer to measure and quantify the elemental isotopic constituents... using a mass analyzer that provides for temporal separation of charged particles within a flow of charged particles, based on mass and/or mass-charge ratio

Methodology Applied
Scientific EffectTime of flight: Time of Flight

Data Source

PatentUS9312111B2Apparatus and method for sub-micrometer elemental image analysis by mass spectrometry
Publication Date: 2016.04.12 THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIV
  • US9312111B2 patent drawing
  • US9312111B2 patent drawing
  • US9312111B2 patent drawing

AI summary

A mass spectrometer system having: a primary ion source capable of irradiating a segment on a planar sample with a beam of primary ions, an orthogonal ion mass-to-charge ratio, the analyzer being configured to separate secondary elemental atomic ions according to their mass-to-charge ratio by time of flight; an ion detector for detecting secondary elemental atomic ions and producing mass spectra measurements; and a synchronizer. In the system, the beam of primary ions scans across the planar sample in two dimensions and the synchronizer associates the mass spectra measurements with positions on the planar sample.