Adaptive Immersion Medium Mixing for Aberration-Free Microscopy

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Solution Overview

Problem

The mismatch between the refractive index of the immersion medium and the sample in microscopy leads to aberrations, particularly in live cell microscopy, where the refractive index of the sample is often unknown, limiting the optical performance and imaging quality.

Innovation Solution

A system for dynamically adjusting the refractive index of the immersion medium by mixing two components with different refractive indices, allowing for continuous adaptation to match the sample's refractive index, using a media supply unit, image acquisition, evaluation, and control units to determine and set the optimal mixing ratio based on image data.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Device complexity

If water immersion objectives are used with a fixed refractive index of n = 1.33, then the optical arrangement is simple and cost-effective, but aberrations occur due to refractive index mismatch between the immersion medium and the sample

Engineering Contradiction:
Improveoptical arrangement complexityVSAvoidimaging quality
Core Design Contradiction:
Device complexityVSManufacturing precision

Solution Approach 1:

The patent implements a dynamic refractive index adjustment system where the immersion medium's refractive index can be continuously varied by mixing different components (e.g., water and glycerol) in different ratios. This dynamic adaptation allows the system to match the unknown refractive index of live cell samples, eliminating spherical aberrations while maintaining optical simplicity and avoiding the need for complex adaptive optics

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The system changes the physical parameter (refractive index) of the immersion medium by controlling the mixing ratio of its components. By adjusting this parameter in real-time based on sample characteristics, the system optimizes imaging quality without requiring complex optical corrections or expensive adaptive optics components

Inventive Principle:
Principle #35Parameter changes

2Manufacturing precision

If adaptive optics are used to compensate for refractive index mismatch, then imaging quality improves, but the system becomes complex and expensive

Engineering Contradiction:
Improveimaging qualityVSAvoidsystem complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent replaces complex mechanical adaptive optics systems (such as deformable mirrors) with a simpler fluid mixing system. Instead of mechanically adjusting optical elements to compensate for aberrations, the system directly adjusts the refractive index of the immersion medium through controlled mixing of components, achieving the same correction effect with much lower complexity and cost

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

Solution Approach 2:

Rather than using adaptive optics to correct wavefront distortions, the system changes the fundamental optical parameter (refractive index) of the immersion medium to match the sample. This parameter change approach eliminates the need for complex correction mechanisms while achieving equivalent or superior imaging quality

Inventive Principle:
Principle #35Parameter changes

3Productivity

If oil immersion objectives are used to maximize numerical aperture, then spatial resolution and light collection efficiency improve, but spherical aberrations increase when penetrating deeper into the sample

Engineering Contradiction:
Improvespatial resolutionVSAvoidoptical penetration depth quality
Core Design Contradiction:
ProductivityVSManufacturing precision

Solution Approach 1:

The system dynamically adjusts the refractive index of the immersion medium to match both the cover glass and the sample interior. This dynamic matching allows the system to achieve high numerical aperture for spatial resolution while simultaneously eliminating spherical aberrations that would otherwise limit penetration depth, enabling high-quality imaging throughout the sample volume

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The patent uses a composite immersion medium formed by mixing multiple components (e.g., water and glycerol) to achieve a refractive index that simultaneously matches both the cover glass and the sample. This composite approach allows optimization of both spatial resolution (through high numerical aperture) and penetration depth quality (through refractive index matching)

Inventive Principle:
Principle #40Composite materials

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 significantly enhances imaging quality by reducing aberrations, increasing penetration depth, and providing a cost-effective solution compared to adaptive optics, while also allowing for the creation of a refractive index map for future measurements.

Implementation Method 1

The first medium component has a first refractive index, the second medium component has a second refractive index, and the two refractive indices differ from one another. The mixing device is designed for setting a mixing ratio of the two medium components... a resulting refractive index of the medium is adapted

Methodology Applied
Scientific EffectRefraction: Refraction

Data Source

PatentEP3462225B1Immersion device for dynamic adaptation of a medium to a sample
Publication Date: 2022.11.02 CARL ZEISS MICROSCOPY GMBH
  • EP3462225B1 patent drawingFigure 1a~1c
  • EP3462225B1 patent drawingFigure 2
  • EP3462225B1 patent drawingFigure 3

AI summary

The invention relates to an arrangement for supplying media (6) serving as immersion media and comprises a media supply unit (1) for the controlled supply of a medium (6) or a mixture into a contact area (7) between an optical lens (8) and a sample carrier (11) on which a sample (14) is arranged or can be arranged in an object space (13). Furthermore, an image acquisition unit (16) is provided for acquiring image data based on detection radiation (DB) obtained from the object space (13) along a detection beam path extending through the contact area (7). According to the invention, an evaluation unit (17) is provided which is configured to determine current image parameters based on acquired image data, to compare these with target image parameters, and, depending on the comparison, to determine a desired mixing ratio of at least two components (K1, K2) of the medium (6).A mixing device (2) for controlled adjustment of the mixing ratio of the components (K1, K2) of the medium (6) to be introduced into the contact area (7) and a control unit (18) for controlling the mixing device (2) depending on the determined desired mixing ratio are parts of the arrangement. The invention further relates to a method for adjusting optical parameters of a medium (6).