Bulged Sample Vessel for Light Sheet Microscopy

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Solution Overview

Problem

Light sheet microscopy techniques face limitations in high-throughput analysis due to sample preparation complexities and incompatibility with standard sample holders like microtiter plates, resulting in reduced axial resolution and difficulty in analyzing multiple samples quickly.

Innovation Solution

The development of a light sheet microscopy arrangement featuring a sample vessel with a bulge that is partially transparent to illumination and detection light, allowing the objectives to access the sample with minimal aberrations, enabling the use of microtiter plates and facilitating high-throughput analysis by adapting the shape, position, and optical axes of the objectives to reduce aberrations.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If a flat bottom sample vessel is used, then the structure is simple, but the objectives cannot access the sample effectively and axial resolution is limited

Engineering Contradiction:
Improveaxial resolutionVSAvoidsample vessel structure
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent applies a bulge (convex curvature) to the bottom of the sample vessel to enable effective optical access. This curved structure allows the illumination and detection objectives to approach the sample from below, improving axial resolution by enabling thinner light sheets and better optical sectioning, while the curvature itself manages the complexity of the vessel design.

Inventive Principle:
Principle #14Spheroidality (Curvature)

2Ease of operation

If standard microtiter plates are used, then sample preparation is easy and high-throughput is enabled, but optical access is poor and aberrations occur

Engineering Contradiction:
Improvesample preparationVSAvoidoptical measurement quality
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent modifies only the local region where optical access is needed by adding a bulge to the bottom of the sample vessel. This localized modification enables effective optical access and reduces aberrations for fluorescence detection, while the rest of the vessel maintains the simple, standardized structure compatible with microtiter plate formats, thus preserving ease of operation and high-throughput capability.

Inventive Principle:
Principle #3Local quality

3Object-affected harmful factors

If the light sheet is illuminated at an angle to the detection direction, then light stress on the sample is reduced, but the geometry becomes more complex

Engineering Contradiction:
Improvelight stress and photobleachingVSAvoidoptical geometry
Core Design Contradiction:
Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The patent positions the illumination and detection objectives at different spatial locations and orientations (different dimensions) to achieve oblique illumination. The illumination objective is positioned to illuminate the sample from one direction while the detection objective is positioned to detect fluorescence from another direction, creating the desired angular relationship that reduces light stress while managing optical geometry through spatial arrangement.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

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 configuration allows for higher axial resolution, easier sample preparation, and the ability to use microtiter plates, thereby enhancing the efficiency of high-throughput analysis while minimizing aberrations and maintaining compatibility with standard sample holders.

Implementation Method 1

at least one bulge which is at least partially transparent to illumination light and detection light is formed at the covering for receiving the sample

Methodology Applied
Scientific EffectRefraction: Refraction

Data Source

PatentUS10620419B2Arrangement for light sheet microscopy
Publication Date: 2020.04.14 CARL ZEISS MICROSCOPY GMBH
  • US10620419B2 patent drawing
  • US10620419B2 patent drawing

AI summary

An arrangement for light sheet microscopy including: a sample vessel, for receiving a medium containing sample, having a covering and being oriented with respect to a planar reference surface; illumination optics with an illumination objective for illuminating the sample with a light sheet; and detection optics with a detection objective. The optical axis of the illumination objective and the light sheet lies in a plane that forms a nonzero illumination angle with the normal of the reference surface. The optical axis of the detection objective forms a nonzero detection angle with the normal of the reference surface. A bulge is formed at the covering for receiving the sample. The bulge has inner and outer interfaces. The optical axes of the illumination objective and detection objective form a minimal angle with the normals of the interfaces at least in the region where the optical axes pass through the interfaces.