Microfluidic EM Grid Preparation Device

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Solution Overview

Problem

Conventional methods for preparing electron microscopy samples are prone to user variation, contamination, and exposure to air, leading to irreproducibility and poor signal-to-noise in image resolution.

Innovation Solution

A microfluidic sample preparation device that seals the EM grid and automates the delivery of samples and stains, using integrated channels and platforms to minimize exposure to air and reduce user variability, allowing for high throughput and reproducible sample preparation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If conventional hand-based preparation methods are used, then ease of operation is maintained, but manufacturing precision and reliability deteriorate due to user variation and contamination

Engineering Contradiction:
Improvesample preparation precisionVSAvoidpreparation system complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The system performs sample preparation automatically without requiring manual intervention at critical steps. The microfluidic device self-regulates fluid flow, mixing, and grid processing, eliminating user variation while maintaining operational simplicity through automated workflows

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

Manual mechanical operations (hand pipetting, blotting, grid handling) are replaced by an integrated microfluidic system that uses controlled fluid flow, pressure gradients, and automated mechanical movements to achieve precise sample preparation with superior reproducibility

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

2Object-affected harmful factors

If open environment preparation is used, then ease of operation is maintained, but object-affected harmful factors increase due to contamination and air exposure

Engineering Contradiction:
Improvecontamination and air exposureVSAvoidoperation simplicity
Core Design Contradiction:
Object-affected harmful factorsVSEase of operation

Solution Approach 1:

The system creates a controlled, sealed environment for sample preparation that protects air-sensitive samples from oxidation and contamination. The closed microfluidic pathways and enclosed grid processing chambers eliminate exposure to atmospheric contaminants while maintaining automated operation

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

Solution Approach 2:

The microfluidic system acts as an intermediary between the sample and the external environment, providing controlled interfaces that allow automated processing while isolating sensitive samples from harmful atmospheric exposure through sealed fluid pathways

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If automated microfluidic system is used, then manufacturing precision and reliability improve, but device complexity increases

Engineering Contradiction:
Improvepreparation reproducibilityVSAvoidsystem structural complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

Multiple discrete preparation steps (sample loading, mixing, staining, grid processing) are merged into a single integrated microfluidic device with interconnected channels and chambers. This consolidation improves reliability through standardized automated processing while managing complexity by combining functions in one compact system

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The microfluidic device is designed as a universal platform that can handle multiple sample types and preparation protocols through programmable fluid control. The same physical infrastructure supports various experimental conditions, improving reliability through consistent hardware while reducing the need for multiple specialized devices

Inventive Principle:
Principle #6Universality (Multi-functionality)

4Manufacturing precision

If conventional blotting methods are used, then device complexity is minimized, but manufacturing precision deteriorates due to variability in liquid removal

Engineering Contradiction:
Improveliquid removal consistencyVSAvoidfluid control system complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

Manual blotting operations are replaced by controlled hydraulic and pneumatic systems within the microfluidic device. Pressure gradients and flow control mechanisms precisely regulate liquid removal from samples and grids, eliminating variability associated with hand-based techniques while using integrated fluid control infrastructure

Inventive Principle:
Principle #29Pneumatics and hydraulics

Data Source

PatentUS10788404B2Microscope sample preparation device
Publication Date: 2020.09.29 FLORIDA STATE UNIV RES FOUND INC
  • US10788404B2 patent drawing
  • US10788404B2 patent drawing
  • US10788404B2 patent drawing

AI summary

A sample preparation device for electron microscopy (EM) that is configured to eliminate user-to-user variations and environment contaminations, which are often present in the conventional method of sample preparation. The device not only provides a means for evenly and reproducibly delivering a fluid or sample to an EM grid, but also provides a means for sealing the EM grid in an air-tight chamber and delivering air-sensitive samples to the EM grid. The platform may comprise readily fabricated glass chips with features integrated to preserve the integrity of the sample grid and to facilitate its extraction. The methods may eliminate the element of user dependent variability and thus improve the throughput, reproducibility and translation of these methods.