Imaging System with Tilted Optics for High-Resolution Volumetric Analysis

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Solution Overview

Problem

Current imaging systems face limitations in achieving high-throughput, high-resolution, three-dimensional imaging of biological samples, particularly due to sterical constraints and reflections when trying to image from above through small vessels like 96-well microplates, which restricts the use of high numerical aperture objectives and results in low throughput or low spatial resolution.

Innovation Solution

The imaging system employs a sample moving unit with detection and illumination optics tilted at specific angles relative to the movement direction, allowing for optical sectioning and volumetric imaging by intersecting planes, enabling high-throughput imaging with improved spatial resolution through the use of multiple detection and illumination optics and light sheet illumination.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If imaging is performed from above through small vessels like 96-well microplates, then accessibility to sample is improved, but spatial resolution deteriorates due to sterical constraints and reflections

Engineering Contradiction:
Improveaccessibility to sampleVSAvoidspatial resolution
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent transitions from vertical imaging (through the well) to oblique/directional imaging by tilting the detection optic at angles between 20°-70° relative to the sample movement direction. This dimensional change in optical path allows high numerical aperture objectives to be used without suffering from the sterical constraints and reflections that plague top-down imaging through small vessels.

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

2Measurement precision

If high numerical aperture objectives are used, then spatial resolution is improved, but device complexity increases due to sterical constraints

Engineering Contradiction:
Improvespatial resolutionVSAvoiddevice complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The system employs a moving sample configuration where the sample carrier translates through the illumination and detection optics. This dynamic arrangement replaces the need for complex, fixed high-NA objective positioning mechanisms, allowing standard objectives to achieve high resolution through the motion-based optical sectioning approach.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The imaging system uses multiple detection optics (at least two, preferably three or four) arranged at different angles around the sample path. This segmentation of the detection function allows each optic to capture images from its specific angular perspective, and computational fusion of these segmented views reconstructs high-resolution three-dimensional images without requiring a single complex high-NA objective.

Inventive Principle:
Principle #1Segmentation

3Productivity

If high throughput imaging is achieved, then productivity is improved, but spatial resolution deteriorates

Engineering Contradiction:
ImprovethroughputVSAvoidspatial resolution
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The system implements continuous imaging during sample translation through the use of light sheet illumination that continuously illuminates the sample volume, combined with continuous detection by the tilted optics. This continuous acquisition during motion enables high throughput without sacrificing resolution, as images are captured throughout the entire sample transit rather than requiring sequential positioning.

Inventive Principle:
Principle #20Continuity of useful action

Solution Approach 2:

By tilting the detection optic to enclose an angle of 20°-70° with the movement direction, the system creates an oblique detection geometry that captures spatial information along the motion trajectory. This angular dimension, combined with the temporal dimension of continuous acquisition during sample movement, enables simultaneous high throughput and high resolution through four-dimensional data acquisition (three spatial dimensions plus time).

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 high-throughput, high-resolution three-dimensional imaging of biological samples, overcoming the limitations of existing systems by enabling imaging from above through small vessels and improving spatial resolution through the combination of images from multiple detection optics.

Implementation Method 1

at least one illumination optic including an illumination optical axis that encloses a second angle with the movement direction within a range of 70° to 110°

Methodology Applied
Scientific EffectLight sheet illumination: Light

Implementation Method 2

at least one detection optic including a detection optical axis that encloses a first angle with the movement direction within a range of 20° to 70°

Methodology Applied
Scientific EffectOptical detection: Light

Data Source

PatentUS20240402475A1Imaging system and method
Publication Date: 2024.12.05 LEICA MICROSYSTEMS CMS GMBH
  • US20240402475A1 patent drawing
  • US20240402475A1 patent drawing
  • US20240402475A1 patent drawing

AI summary

An imaging system for imaging a sample includes a sample moving unit configured to move the sample in a sample space along a movement direction. The imaging system further includes at least one detection optic including an optical axis enclosing a first angle with the movement direction within a range of 20° to 70°, the optical axis of the at least one detection optic and the movement direction defining a first plane; and at least one illumination optic including an optical axis that encloses a second angle with the movement direction within a range of 70° to 110°, and that encloses a third angle with the optical axis of the at least one detection optic within a range of 70° to 110°, the optical axis of the at least one illumination optic and the movement direction defining a second plane, the first and second planes intersecting and being different.