Lattice Light-Sheet Holography for Deeper, Faster 3D Imaging

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Solution Overview

Problem

Current microscopy techniques face limitations such as high excitation intensity, reduced penetration depth, complex optical setups, long image acquisition times, and high equipment costs, particularly in applications like live cell imaging and biological tissue imaging, where they result in low contrast and loss of three-dimensional imaging information.

Innovation Solution

Incoherent holographic microscopy lattice light-sheet (IHLLS) imaging using Fresnel incoherent correlation holography with a spatial light modulator to generate three-dimensional images, employing incoherent light sources and reducing the need for mechanical components by using a scanning geometry with two imaging planes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If light sheet microscopy is used to reduce excitation intensity, then photobleaching is reduced, but penetration depth is limited due to rapid dispersion in refractive tissue

Engineering Contradiction:
ImprovephotobleachingVSAvoidpenetration depth
Core Design Contradiction:
Object-affected harmful factorsVSLength of stationary object

Solution Approach 1:

The illumination is segmented into multiple Bessel beams arranged in a lattice pattern, where each beam maintains its shape over extended distances through self-reinforcement properties, enabling deeper penetration while keeping individual beam intensities low enough to avoid photobleaching

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent transitions from conventional planar light sheets to a three-dimensional lattice arrangement of Bessel beams, adding spatial dimensionality to the illumination pattern. This lattice structure propagates through the sample volume, extending penetration depth while maintaining low excitation intensity at any given point

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

2Length of stationary object

If additional optics are added to increase penetration depth in LLSM, then imaging depth improves to around 200 μm, but device complexity and cost increase significantly

Engineering Contradiction:
Improveimaging depthVSAvoidoptical setup complexity
Core Design Contradiction:
Length of stationary objectVSDevice complexity

Solution Approach 1:

The Bessel beams in the lattice structure are self-reinforcing, automatically maintaining their shape and intensity profile over extended propagation distances without requiring additional corrective optics or complex alignment mechanisms. The lattice geometry itself provides the necessary optical correction through its structured arrangement

Inventive Principle:
Principle #25Self-service

3Productivity

If conventional microscopy techniques are used to achieve high imaging speed, then image acquisition is fast, but excitation intensity is high causing photobleaching and tissue damage

Engineering Contradiction:
Improveimage acquisition speedVSAvoidphotobleaching and tissue damage
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The lattice light sheet illuminates different planes in rapid succession through the sample volume, creating a periodic illumination pattern that cycles through multiple focal planes. This allows high-speed volumetric imaging by sequentially sampling different planes at high temporal resolution while keeping instantaneous intensity low

Inventive Principle:
Principle #19Periodic action

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

IHLLS imaging provides improved spatial resolution, contrast, and reduced system complexity, enabling deeper penetration and faster image acquisition without mechanical movement, suitable for biological samples and tissues.

Implementation Method 1

modulating, by the modulator, the phase of the radiation to generate a plurality of beams

Methodology Applied
Scientific EffectDiffraction: Diffraction

Implementation Method 2

detecting, at a detection plane of a detector module, the plurality of beams. The method further includes generating, by the detector module, a signal indicative of an interference pattern of the plurality of beams

Methodology Applied
Scientific EffectInterference: Interference

Implementation Method 3

a convergent lattice of Bessel beams to generate the light sheet. In LLSM the excitation is confined to a plane defined by a lattice of intersecting Bessel beams that self-reinforce as they project through a target

Methodology Applied
Scientific EffectInterference: Interference

Data Source

PatentEP4100796B1Lattice light-sheet and fresnel incoherent correlation holography
Publication Date: 2025.08.06 THE BOARD OF TRUSTEES OF THE UNIV OF ILLINOIS
  • EP4100796B1 patent drawingFigure 1
  • EP4100796B1 patent drawingFigure 2
  • EP4100796B1 patent drawingFigure 3A

AI summary

A method and system for performing incoherent holographic microscopy imaging, including modulating radiation to form one or more beams and detecting the modulated one or more beams at a detector. The one or more beams include phase information that is detected at the detector and holographic information is determined from the detected modulated one or more beams. A processor is configured to receive the holographic information via a signal generated by the detector and the processor further generates a three-dimensional image of a target.