Deep UV Laser Ablation for Single-Cell Biomolecule Sampling

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Solution Overview

Problem

Current methods for microdissection tissue sampling, such as infrared laser or near-ultraviolet laser ablation, are time- and labor-intensive and require additional extraction processes for high-precision chemical analyses at the single cell level, limiting their effectiveness in biomolecule isolation for applications like protein and DNA sequencing.

Innovation Solution

The use of a deep UV laser ablation device coupled with an electrospray ion source, which includes a pulsed nanosecond 193 nm laser and an electrospray emitter, allows for precise ablation and detection of protonated analyte molecules without fragmentation, enabling faster and more accurate sampling at the micrometer scale without the need for extraction.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If infrared laser or near-ultraviolet laser ablation is used for microdissection tissue sampling, then tissue sampling can be performed, but the process is time- and labor-intensive and requires additional extraction processes

Engineering Contradiction:
Improvesingle cell level analysis precisionVSAvoidtime-intensive extraction process
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent combines deep UV laser ablation with electrospray ionization in a single integrated system, eliminating the need for separate extraction processes. The ablation and ionization occur simultaneously, allowing direct analysis of tissue samples at the single-cell level without time-consuming intermediate extraction steps.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent removes the extraction step entirely from the workflow by using deep UV laser ablation to directly vaporize and ionize tissue molecules, which are then immediately analyzed by mass spectrometry. This eliminates the labor-intensive extraction process that is required by conventional infrared or near-UV laser methods.

Inventive Principle:
Principle #2Taking out (Extraction)

2Manufacturing precision

If conventional laser ablation methods are used, then tissue sampling is achieved, but fragmentation occurs and additional processing is required

Engineering Contradiction:
Improveablation precisionVSAvoidprocessing complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent changes the laser wavelength parameter from infrared or near-UV to deep UV (193 nm), which fundamentally alters the ablation mechanism. This wavelength produces cleaner ablation with minimal fragmentation, eliminating the need for additional processing steps to handle fragmented samples.

Inventive Principle:
Principle #35Parameter changes

3Productivity

If deep UV laser ablation is used, then faster and more precise sampling is achieved, but specialized equipment is required

Engineering Contradiction:
Improvesampling speedVSAvoidequipment complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent integrates multiple functions into a single system: the deep UV laser performs both ablation and the electrospray ionization source performs both ionization and direct injection into the mass spectrometer. This multi-functional integration achieves fast, precise sampling while managing equipment complexity through consolidation rather than addition of separate processing steps.

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

This approach provides higher resolution and faster sampling compared to existing methods, allowing for precise localization of biomolecules and enabling applications in clinical diagnostics, forensic genetics, and understanding neurological diseases, with the ability to perform single cell spatially resolved biochemistry.

Implementation Method 1

deep UV laser ablation

Methodology Applied
Scientific EffectLaser ablation: Laser Ablation

Implementation Method 2

193 nm laser

Methodology Applied
Scientific EffectPhotodissociation: Photodissociation

Implementation Method 3

electrospray ion source having an electrospray emitter

Methodology Applied
Scientific EffectElectrospray ionization: Electrohydrodynamics

Data Source

PatentUS11094518B2Devices and methods for deep UV laser ablation
Publication Date: 2021.08.17 BOARD OF SUPERVISORS OF LOUISIANA STATE UNIV & AGRI & MECHANICAL COLLEGE
  • US11094518B2 patent drawing
  • US11094518B2 patent drawing
  • US11094518B2 patent drawing

AI summary

Laser ablation devices and methods including laser ablation are provided. The ablation devices can include a deep UV laser. Dual-laser ablation devices are also provided. Biomolecules can be ablated using a combination of deep UV laser and nanoelectrospray, resulting in protonated sample molecules.