Electron Microscopy Grid Functionalization With Temporary Reaction Chambers

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current methods for sample preparation in electron microscopy, such as pin-printing and plasma treatment, face challenges including low throughput, cross-contamination, limited flexibility in functionalization types, and inefficiencies in sample preparation and data acquisition.

Innovation Solution

A method for regioselective functionalization of electron microscopy grids involves creating temporary reaction chambers on the grid surface, where different modification solutions can be applied to achieve specific functionalizations without cross-contamination, allowing for multiple analytes to be deposited on a single grid.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If pin-printing methods are used for sample deposition, then sample deposits can be made on the EM grid, but cross-contamination occurs between different deposits and a large part of the grid surface remains unused

Engineering Contradiction:

Improvenumber of sample depositsVSAvoidcross-contamination between deposits

Core Design Contradiction:

Quantity of substanceVSReliability

Solution Approach 1:

The EM grid surface is divided into multiple distinct quadrants or regions separated by physical barriers (hydrophobic walls or raised structures). Each quadrant can independently receive different sample deposits without cross-contamination, allowing multiple samples to be processed on a single grid while maintaining spatial separation and preventing mixture between deposits.

Inventive Principle:

Principle #1Segmentation

2Adaptability or versatility

If plasma treatment is used for surface functionalization, then the EM grid surface can be modified, but the type of functionalization is severely limited

Engineering Contradiction:

Improvetype of functionalizationVSAvoidfunctionalization method flexibility

Core Design Contradiction:

Adaptability or versatilityVSEase of manufacture

Solution Approach 1:

The patent introduces intermediate functional layers or coating materials that can be applied to the EM grid surface through conventional methods. These intermediate layers serve as mediators that enable diverse functionalizations (including peptides, DNA, oligonucleotides, and other biomolecules) without requiring advanced plasma treatment equipment, thus expanding functionalization versatility while maintaining ease of manufacture.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Productivity

If multiple samples are deposited on a single EM grid, then throughput is increased, but cross-contamination risk increases and washing steps become difficult

Engineering Contradiction:

Improvethroughput of samplesVSAvoidcross-contamination between samples

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The EM grid is segmented into multiple isolated compartments using hydrophobic walls or physical barriers. Each compartment can hold a different sample independently, allowing multiple samples to be processed simultaneously on one grid. The barriers prevent cross-contamination while enabling washing steps to be performed on the entire grid or individual compartments, thus increasing throughput without compromising reliability.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

Different regions or quadrants of the EM grid are given different local properties through selective functionalization or sample deposition. Each region maintains its unique characteristics (hydrophobicity, charge, or specific binding properties) while being part of the same grid structure, allowing diverse samples to be processed simultaneously with appropriate local conditions for each.

Inventive Principle:

Principle #3Local quality

4Productivity

If the EM grid surface is fully utilized with multiple functionalizations, then productivity increases, but the complexity of preventing cross-contamination and defining functionalization boundaries increases

Engineering Contradiction:

Improvesurface coverage of gridVSAvoidfunctionalization boundary definition

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The grid surface is divided into clearly defined quadrants or regions separated by physical barriers (hydrophobic walls, raised structures, or patterned coatings). These segments provide natural boundaries that simplify the definition of functionalization zones and prevent cross-contamination. The segmented structure allows full surface utilization while reducing the complexity of managing functionalization boundaries through intuitive spatial organization.

Inventive Principle:

Principle #1Segmentation

Data Source

PatentUS20250037963A1Methods for regioselective functionalizing a surface of an electron microscopy grid

Publication Date: 2025.01.30 INTERUNIVERSITAIR MICRO ELECTRONICS CENT (IMEC VZW)

AI summary

The invention provides a method for regioselective functionalizing a surface of an electron microscopy grid (10), therefore:a) providing a surface (20) of an electron microscopy grid (101);b) providing a plurality of wall systems (30A, 30B) on the surface of an electron microscopy grid, thereby forming a plurality of temporary reaction chambers (40A, 40B);c) providing a modification solution (50) in each temporary reaction chambers (40A, 40B);d) modifying the parts of the surface (21A, 21B) in the temporary reaction chambers (40A, 40B) with the modification solution(s) (50, 50A, 50B);e) removing the modification solution(s) (50, 50A, 50B) from the temporary reaction chambers (40A, 40B);f) removing the plurality of wall systems (30A, 30B) from the surface (20).The invention further provides in an electron microscopy grid to be regioselective functionalised and an apparatus for regioselective functionalizing a surface of an electron microscopy grids.