Light Sheet Microscope With Overlapping Line Foci for Fast 3D Imaging

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Solution Overview

Problem

Existing imaging systems for biological samples face limitations in speed, resolution, and mechanical complexity, particularly due to the use of high-speed moving parts and F-theta scanning mechanisms, which hinder efficient data acquisition and increase costs.

Innovation Solution

A light sheet microscope that utilizes multiple collimated light sources to create overlapping line foci, employing Scheimpflug optics and a pixelated detector for error correction, with few moving parts, allowing for three-dimensional imaging with enhanced resolution and contrast.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If F-theta scanning mechanisms are used to scan a single focused laser into the sample, then image clarity and resolution are improved, but the speed of data acquisition is limited and mechanical complexity increases

Engineering Contradiction:
Improveimage resolutionVSAvoidmechanical complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces the mechanical F-theta scanning system with a stationary optical system that uses a light sheet approach. Instead of moving mirrors to scan the laser beam, the system uses a stationary laser source combined with a stationary objective lens to illuminate the sample, eliminating high-speed moving parts while maintaining resolution through optical means.

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

Solution Approach 2:

The patent segments the illumination into a light sheet that can be scanned laterally across the sample using a movable component, separating the illumination function from the detection function. This allows the objective lens to remain stationary while still achieving comprehensive coverage of the sample volume.

Inventive Principle:
Principle #1Segmentation

2Measurement precision

If F-theta scanning mechanisms are used to scan a single focused laser into the sample, then image clarity is improved, but the speed of mirror movement directly determines image acquisition speed, limiting the time scale of effects that can be captured

Engineering Contradiction:
Improveimage clarityVSAvoidimage acquisition speed
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent replaces the mechanical scanning system with a stationary optical system that illuminates the sample with a light sheet. This eliminates the speed limitation imposed by moving mirror mechanics, allowing for rapid capture of dynamic processes without being constrained by the acceleration and deceleration requirements of high-speed mirrors.

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

Solution Approach 2:

The light sheet illumination provides continuous coverage of the sample volume without the start-stop nature of scanned beam illumination. This allows for continuous acquisition of images at high speed, capturing rapid temporal changes without interruption or mechanical latency.

Inventive Principle:
Principle #20Continuity of useful action

3Measurement precision

If a single focused laser is scanned into the sample, then subsurface structure imaging is achieved, but mechanical complexity and cost increase

Engineering Contradiction:
Improvesubsurface structure imaging capabilityVSAvoidcost
Core Design Contradiction:
Measurement precisionVSEase of manufacture

Solution Approach 1:

The patent replaces expensive high-speed mechanical scanning components with a simpler stationary optical system. The light sheet approach uses standard optical components arranged in a fixed configuration, significantly reducing the cost of the instrument while maintaining the capability to image subsurface structures through the light sheet illumination technique.

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

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 system achieves high-resolution, three-dimensional imaging with reduced mechanical complexity, cost-effectiveness, and ease of use by using overlapping line foci and error correction techniques, enabling precise imaging of subsurface structures without high-speed moving parts.

Implementation Method 1

at least two optical subassemblies which focus the at least two beams of light into at least two straight lines

Methodology Applied
Scientific EffectOptical focusing: Focusing

Implementation Method 2

The excitation may cause the biological sample to emit fluorescence

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS12352941B2Light sheet microscope with line focus
Publication Date: 2025.07.08 MILTENYI BIOTEC BV & CO KG
  • US12352941B2 patent drawing
  • US12352941B2 patent drawing
  • US12352941B2 patent drawing

AI summary

A light sheet microscope for imaging biological materials uses a plurality of light beams, focused to an overlapping line to excite a fluorescent material within the biological sample. The laser-induced fluorescence image is then analyzed and displayed.