Microscopic Sample Preparation via Suction and Evaporation

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Solution Overview

Problem

The existing blotting process for preparing microscopic samples is inconsistent and non-repetable due to calibration issues, material quality variations, and user skill factors, limiting the quality and consistency of plunge-frozen vitrified samples for electron microscopy and other cryo-techniques.

Innovation Solution

An apparatus using suction force to remove excess fluid from samples, followed by a gas stream for evaporation, allowing precise control of fluid removal and enabling repeatable, high-quality plunge-frozen samples, and incorporating optical methods for thickness measurement.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If blotting process is used to remove excess liquid from sample, then liquid removal is achieved, but consistency and repeatability of sample preparation deteriorates

Engineering Contradiction:
Improveconsistency of sample preparationVSAvoidcalibration and operational complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent replaces the mechanical blotting process with a pressure-controlled liquid removal system. Instead of using blotting paper and manual mechanical pressure, the invention uses a pressure chamber that applies controlled negative pressure to draw excess liquid through a membrane support, eliminating the need for mechanical calibration of blotting force and paper positioning.

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

Solution Approach 2:

The invention employs pneumatic pressure control to remove excess liquid from the sample. A pressure chamber applies controlled negative pressure (vacuum) to the sample assembly, causing excess liquid to be drawn through the membrane support in a controlled manner, replacing the variable mechanical blotting process with repeatable pneumatic control.

Inventive Principle:
Principle #29Pneumatics and hydraulics

2Productivity

If manual blotting is performed, then excess liquid is removed, but user skill dependency increases leading to variability

Engineering Contradiction:
Improveautomation of liquid removalVSAvoiduser skill requirement
Core Design Contradiction:
ProductivityVSEase of operation

Solution Approach 1:

The system performs self-regulated liquid removal through automated pressure control. The pressure chamber and control system automatically manage the liquid removal process without requiring user intervention for blotting paper exchange, force calibration, or timing, making the process independent of user skill while maintaining high productivity.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The invention changes the control parameter from manual mechanical force to automated pressure control. By using programmable pressure parameters (negative pressure magnitude and duration), the system achieves consistent liquid removal without requiring user skill, and allows easy adjustment of parameters for different sample types.

Inventive Principle:
Principle #35Parameter changes

3Manufacturing precision

If blotting paper is used for liquid removal, then excess liquid is absorbed, but paper quality variations affect results

Engineering Contradiction:
Improvecontrol of liquid removal amountVSAvoidmonitoring and replacement of blotting paper
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The invention uses a disposable membrane support that replaces the blotting paper function. The membrane support is a standardized, replaceable component that provides consistent liquid removal properties without requiring monitoring of saturation levels or quality variations inherent in natural blotting paper materials.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

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 method ensures consistent and repeatable sample preparation with minimized contamination, allowing for high-resolution imaging in cryo-electron microscopy, fluorescence microscopy, and other techniques.

Implementation Method 1

a suction means configured to create a suction force to draw excess liquid through the sample support

Methodology Applied
Scientific EffectSuction: Suction

Implementation Method 2

subsequently create a stream of gas in the vicinity of the sample in order to remove any remaining liquid on the sample by means of evaporation into the stream of gas

Methodology Applied
Scientific EffectEvaporation: Evaporation

Implementation Method 3

the water can be turned into a glass-like form, in a process known as vitrification

Methodology Applied
Scientific EffectVitrification: Vitrification

Implementation Method 4

Because the freezing happens very quickly, ice crystals do not form and the resulting water has a glass-like 'vitrified' property

Methodology Applied
Scientific EffectRapid freezing: Freezing

Data Source

PatentEP3018467B1Microscopic sample preparation
Publication Date: 2021.06.02 LINKAM SCIENCTIFIC INSTR
  • EP3018467B1 patent drawingFigure 1
  • EP3018467B1 patent drawingFigure 2(a)~2(b)
  • EP3018467B1 patent drawingFigure 3(a)

AI summary

An apparatus for removing fluid from a microscopic sample comprises a humidity chamber configured to control the humidity therein, and a sample clamp disposed within the humidity chamber and configured to clamp a sample support, which is loaded, or adapted to be loaded, with a microscopic sample. The apparatus further comprises suction means configured to create suction at least adjacent to the sample to thereby remove fluid therefrom.