Optical Vacuum Cryo-Stage for Correlative Microscopy

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Solution Overview

Problem

Current cryo-stages for correlative light and electron microscopy face challenges such as specimen drifting due to liquid nitrogen shaking, damage to objective lenses at low temperatures, and contamination during specimen transfer between microscopes, limiting the accuracy and reliability of high-resolution fluorescent imaging.

Innovation Solution

An optical vacuum cryo-stage with a vacuum chamber, anti-contamination system, and adaptable interfaces for various microscope configurations, which maintains a vacuum environment for refrigeration and uses a heat conductive system to manage temperature and contamination, allowing for precise and contamination-free imaging and transfer of specimens.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Temperature

If liquid nitrogen flow refrigeration is used in cryo-stage, then refrigeration effect is achieved, but specimen drifting occurs due to liquid nitrogen shaking

Engineering Contradiction:
Improverefrigeration effectVSAvoidspecimen stability
Core Design Contradiction:
TemperatureVSReliability

Solution Approach 1:

The patent replaces the mechanical liquid nitrogen flow refrigeration system with a vacuum-based refrigeration system. The vacuum environment eliminates liquid nitrogen shaking, thereby preventing specimen drifting while maintaining the refrigeration effect through vacuum insulation and controlled cooling mechanisms.

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

Solution Approach 2:

The patent introduces a vacuum environment as an inert atmosphere to replace liquid nitrogen flow. This vacuum environment provides thermal insulation while eliminating the harmful shaking effects of liquid nitrogen, thus stabilizing the specimen during cryo-fluorescent imaging.

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

2Temperature

If liquid nitrogen flow refrigeration is used in cryo-stage, then refrigeration effect is achieved, but objective lens damage occurs in low temperature condition

Engineering Contradiction:
Improverefrigeration effectVSAvoidlens damage
Core Design Contradiction:
TemperatureVSObject-affected harmful factors

Solution Approach 1:

The patent segments the imaging system into two distinct environmental zones: a vacuum-cryo environment for the specimen stage and a normal temperature environment for the objective lens. This segmentation allows the specimen to be cooled effectively while protecting the objective lens from low temperature damage.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces a vacuum chamber as an intermediary between the cryo-stage and the objective lens. This vacuum chamber acts as a thermal barrier, allowing refrigeration to be applied to the specimen while preventing extreme cold from reaching and damaging the objective lens.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Adaptability or versatility

If specimen transfer between light microscope and electron microscope is performed, then correlative imaging is achieved, but contamination occurs during transfer

Engineering Contradiction:
Improvecorrelative imaging capabilityVSAvoidspecimen contamination
Core Design Contradiction:
Adaptability or versatilityVSObject-affected harmful factors

Solution Approach 1:

The patent designs a universal vacuum cryo-stage that can accommodate both light microscopy and electron microscopy specimen holders. This multi-functional design allows specimens to be imaged in both modalities without transfer, eliminating contamination risks while maintaining correlative imaging capabilities.

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

Solution Approach 2:

The patent merges the light microscopy and electron microscopy imaging capabilities into a single vacuum-based platform. By combining both imaging modalities in one system, the patent eliminates the need for specimen transfer between separate microscopes, thereby preventing contamination while achieving correlative imaging.

Inventive Principle:
Principle #5Merging (Combining)

4Productivity

If integrated light and electron microscope system is used, then simultaneous imaging is achieved, but working distance limitation reduces imaging resolution

Engineering Contradiction:
Improvesimultaneous imaging capabilityVSAvoidfluorescent image resolution
Core Design Contradiction:
ProductivityVSManufacturing precision

Solution Approach 1:

The patent employs a dynamic, modular vacuum cryo-stage design that can adapt to different imaging configurations. This allows the system to optimize the working distance for fluorescent imaging while maintaining the capability for simultaneous or sequential electron microscopy imaging, thereby resolving the resolution limitation.

Inventive Principle:
Principle #15Dynamics

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

The optical vacuum cryo-stage effectively prevents specimen drifting and lens damage, reduces contamination, and enables flexible, high-resolution imaging across different microscope setups, enhancing the accuracy and reliability of correlative light and electron microscopy.

Implementation Method 1

an optical vacuum cryo-stage for correlative light and electron microscopy comprises a vacuum chamber

Methodology Applied
Scientific EffectVacuum: Vacuum

Implementation Method 2

uses a heat conductive system to manage temperature

Methodology Applied
Scientific EffectThermal conduction: Conduction (thermal)

Implementation Method 3

maintain a low temperature environment surrounding the freezing specimen for adsorbing and condensing the contamination in vacuum chamber

Methodology Applied
Scientific EffectAdsorption: Adsorption

Implementation Method 4

maintain a low temperature environment surrounding the freezing specimen for adsorbing and condensing the contamination in vacuum chamber

Methodology Applied
Scientific EffectCondensation: Condensation

Implementation Method 5

optical vacuum cryo-stage for correlative light and electron microscopy

Methodology Applied
Scientific EffectFreezing: Freezing

Data Source

PatentUS9899184B2Optical vacuum cryo-stage for correlative light and electron microscopy
Publication Date: 2018.02.20 INSTITUTE OF BIOPHYSICS CHINESE ACADEMY OF SCIENCES
  • US9899184B2 patent drawing
  • US9899184B2 patent drawing

AI summary

An optical vacuum cryostage for correlative light and electron microscopy comprises a vacuum chamber, an anti-contamination system adapter interface, an electron microscope specimen holder adapter interface, an upper optical window, a lower optical window, a vacuum pumping system adapter interface and a vacuum valve, wherein the anti-contamination system adapter interface is arranged in one end of the vacuum chamber, the electron microscope specimen holder adapter interface is arranged in the other end of the vacuum chamber, the upper optical window is arranged on the upper wall of the vacuum chamber, the lower optical window is arranged on the lower wall of the vacuum chamber and opposite to the upper optical window.