Aplanatic Solid Immersion Lens for Cryogenic Super-Resolution

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Solution Overview

Problem

Conventional microscopy techniques face limitations in achieving high resolution at cryogenic temperatures due to the unsuitability of wet immersion fluids for low temperatures, which hinders the improvement of super-resolution microscopy.

Innovation Solution

The use of aplanatic solid immersion lenses in super-resolution microscopy at cryogenic temperatures, enhancing the numerical aperture and allowing for resolutions beyond the diffraction limit, particularly with single molecule localization techniques, and enabling correlative imaging with electron microscopy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If wet immersion objective lenses are used to improve resolution, then numerical aperture increases and resolution improves, but the immersion fluids are not suitable for cryogenic temperatures

Engineering Contradiction:
Improvespatial resolutionVSAvoidtemperature compatibility
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent changes the physical state parameter of the immersion medium from liquid to solid, enabling the system to function at cryogenic temperatures where liquid immersion fluids would freeze or become unsuitable. Solid immersion lenses maintain their optical properties at low temperatures while providing the necessary refractive index enhancement.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The solid immersion lens acts as an intermediary optical element between the objective lens and the sample, providing the refractive index enhancement normally achieved by immersion fluids without requiring temperature-compatible liquid media. The solid lens material (such as sapphire or diamond) serves as a mediator that enables high numerical aperture at cryogenic temperatures.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Adaptability or versatility

If solid immersion lenses are used to enable cryogenic imaging, then temperature compatibility is achieved, but the aplanatic design is required to maintain image quality

Engineering Contradiction:
Improvetemperature compatibilityVSAvoidlens geometry complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent employs a spherical or spheroidal geometry for the solid immersion lens, which naturally provides the aplanatic properties needed to eliminate spherical aberration and other optical distortions. The curved surface configuration is mathematically optimized to maintain focus and image quality across the field of view at cryogenic temperatures.

Inventive Principle:
Principle #14Spheroidality (Curvature)

3Reliability

If super-resolution microscopy is performed at cryogenic temperatures, then biological samples are preserved in near-native state, but resolution is limited by diffraction

Engineering Contradiction:
Improvesample preservation qualityVSAvoidspatial resolution
Core Design Contradiction:
ReliabilityVSMeasurement precision

Solution Approach 1:

The patent changes the refractive index parameter by introducing a solid immersion lens with high refractive index material, which increases the numerical aperture of the optical system. This parameter change allows the system to overcome the diffraction limit and achieve super-resolution while maintaining cryogenic sample preservation.

Inventive Principle:
Principle #35Parameter changes

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 approach enables image resolutions of a few tens of nanometers, facilitating high-throughput imaging and combining super-resolution optical microscopy with electron microscopy for biological samples preserved in a near-native state.

Implementation Method 1

The achievable spatial resolution therefore depends on optical parameters such as the numerical aperture of the objective lens, and this can be increased in various ways such as by using liquid immersion techniques in which a fluid of high refractive index is used to optically couple the objective lens and the sample to be imaged

Methodology Applied
Scientific EffectRefraction: Refraction

Implementation Method 2

The resolution of conventional microscopy is limited due to the diffraction of light, with the achievable spatial resolution being approximately determined by the Abbe diffraction limit

Methodology Applied
Scientific EffectDiffraction: Diffraction

Implementation Method 3

It is often desirable to carry out such super-resolution microscopy techniques at cryogenic temperatures, for example to enable accurate imaging of vitrified biological samples

Methodology Applied
Scientific EffectVitrification: Vitrification

Data Source

PatentEP3596534B1Super-resolution microscopy with an aplanatic solid immersion lens in a cryogenic environment
Publication Date: 2024.01.03 UNITED KINGDOM RESEARCH AND INNOVATION
  • EP3596534B1 patent drawingFigure 1
  • EP3596534B1 patent drawingFigure 2A~2B
  • EP3596534B1 patent drawingFigure 3

AI summary

We describe a super-resolution optical microscopy technique in which a sample is located on or adjacent to the planar surface of an aplanatic solid immersion lens and placed in a cryogenic environment.