Electrospray-Assisted Laser Desorption Ionization for Tissue Analysis
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Solution Overview
Problem
Current mass spectrometry techniques face challenges in conducting direct, rapid, and accurate protein analysis on tissue sections without sample preparation, as they require tedious sample preparation and are limited by low ionization efficiency and sensitivity, especially for spatial analysis of proteins in organs or tissues.
Innovation Solution
An electrospray-assisted laser desorption ionization device that combines electrospray ionization and laser desorption techniques, allowing for ionization of proteins directly on solid samples under atmospheric pressure, eliminating the need for sample preparation and enhancing ionization efficiency by forming multiple-charged liquid drops that occlude and ionize analytes as they travel towards a mass analyzer.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If laser desorption is used to analyze proteins directly on tissue sections, then spatial analysis capability is improved, but ionization efficiency remains extremely low
Solution Approach 1:
The patent combines laser desorption ionization (LDI) with electrospray ionization (ESI) techniques to create a hybrid ionization method. The electrospray component generates charged droplets that enhance ionization of desorbed proteins, while the laser provides spatially resolved desorption. This merging allows direct tissue section analysis with improved ionization efficiency.
Solution Approach 2:
The patent introduces an electrospray medium as an intermediary substance between the laser and the protein sample. The electrospray droplets act as a mediator that facilitates charge transfer to desorbed proteins, enabling efficient ionization without requiring direct contact between the laser and protein molecules.
2Reliability
If electrospray ionization is used to ionize proteins, then ionization efficiency is improved, but sample preparation becomes tedious and time-consuming
Solution Approach 1:
The patent applies electrospray ionization directly to the tissue section surface without requiring preliminary extraction or solution preparation of proteins. The electrospray medium is applied directly to the intact tissue section, and laser desorption immediately follows to ionize and desorb proteins in their native spatial context.
Solution Approach 2:
The patent eliminates the extraction step by taking out the intermediate step of protein extraction and solution preparation. Instead of extracting proteins from tissue and preparing them in solution, the method directly ionizes proteins on the tissue section surface using the combined electrospray-laser approach.
3Measurement precision
If traditional mass spectrometry is used for protein analysis, then detection sensitivity is poor, but device complexity remains manageable
Solution Approach 1:
The patent merges electrospray ionization and laser desorption ionization systems into a unified mass spectrometry platform. This combination enhances detection sensitivity by improving ionization efficiency and enabling direct analysis of complex biological samples, while the integrated design manages device complexity through coordinated operation of the two ionization methods.
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 efficient and accurate mass spectrometric analysis of proteins on unprocessed tissue sections with improved sensitivity and spatial resolution, reducing operational complexity and time, and allowing for the detection of macromolecules with extensive molecular weight range, suitable for medical and biotechnological applications.
Implementation Method 1
Laser desorption mass spectrometer performs laser desorption (LD) by utilizing a transmission mechanism that is capable of transmitting laser beams in a vacuum environment. By irradiating laser beams at the surface of a tissue section, the protein molecules at the site of impact absorb the energy of the laser beams to thereby directly desorb from the surface of the tissue section in the form of ions carrying electric charges.
Implementation Method 2
The electrospray ionization device 11 performs an electrospray ionization procedure to ionize the proteins in the protein solution. When in use, an electric field, for instance, a 2-5 kV voltage difference, is established between the open end 111 of the capillary 112 and the entrance side 121 of a mass analyzer 12. The protein solution forms a Taylor cone 2 that is filled with electric charges as it passes through the open end 111 of the capillary 112 due to the combined effect of the electric field present between the open end 111 of the capillary 112 and the entrance side 121 of the mass analyzer 12 and the surface tension of the protein solution.
Implementation Method 3
As the charged droplets travel through the air from the open end 111 of the capillary 112 toward the entrance side 121 of the mass analyzer 12, the liquid portion of the charged droplets vaporize such that the charged droplets dwindle in size, causing the multivalent electrons to attach to the protein molecules to form ionized protein molecules with relatively lower m/z values.
Data Source
AI summary
An electrospray-assisted laser desorption ionization device includes: an electrospray unit including a nozzle; a voltage supplying member disposed to establish between the nozzle and a receiving unit a potential difference such that liquid drops of the electrospray medium formed at the nozzle are laden with charges, and such that the liquid drops are forced to leave the nozzle toward the receiving unit along a traveling path; a laser desorption unit adapted to irradiate a sample such that, upon irradiation, analytes contained in the sample are desorbed to fly along a flying path which intersects the traveling path so as to enable the analytes to be occluded in the liquid drops, and such that as a result of dwindling in size of the liquid drops when moving along the traveling path, charges of the liquid drops will pass on to the analytes occluded therein to form ionized analytes.