Liquid-Immersed Imaging for Rapid Biological Sample Archiving

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Solution Overview

Problem

The preparation, imaging, and archiving of biological samples often occur under time pressure, with delays in sample preparation cascading through the workflow and risking degradation, particularly in histopathology, where rapid and efficient processing is crucial for maintaining cellular fidelity and reducing delays in decision-making.

Innovation Solution

An imaging device with an optical system positioned in a liquid container filled with an imaging reagent, allowing biological samples on a sample carrier to be imaged while submerged in the reagent, which maintains sample fidelity and avoids drying, followed by archival storage with a mounting reagent after imaging.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If biological samples are prepared for long-term archiving with mounting reagents, then sample conservation and fidelity are improved, but processing time is significantly increased (days required)

Engineering Contradiction:
Improvesample conservationVSAvoidprocessing time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The workflow is segmented into two distinct phases: rapid imaging phase using water-based reagents, and subsequent archiving phase using mounting reagents. This allows imaging to occur before full archival processing, reducing the time-critical imaging step from days to minutes while maintaining sample fidelity through the transition between phases.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Imaging is performed as a preliminary action before the sample is fully processed for long-term archiving. The sample is imaged in a water-based environment first, then subsequently mounted in archival reagents. This preliminary imaging captures the sample state before archival processing begins, eliminating the need to wait days for mounting completion.

Inventive Principle:
Principle #10Preliminary action

2Reliability

If biological samples remain wet during imaging, then optical aberrations are reduced, but sample drying and degradation occur during conventional preparation

Engineering Contradiction:
Improveoptical qualityVSAvoidsample degradation
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The refractive index parameter of the imaging medium is changed to match water (approximately 1.33), eliminating optical aberrations typically caused by mounting reagents. This parameter change allows the sample to remain in a water-based environment during imaging, maintaining both optical quality and sample hydration without the need for conventional drying and mounting steps.

Inventive Principle:
Principle #35Parameter changes

3Duration of action of stationary object

If conventional mounting reagents are used for archiving, then long-term sample preservation is achieved, but optical aberrations and imaging quality deteriorate

Engineering Contradiction:
Improvearchival storage durationVSAvoidimaging fidelity
Core Design Contradiction:
Duration of action of stationary objectVSMeasurement precision

Solution Approach 1:

The process is segmented into imaging and archiving as separate sequential steps. Imaging occurs first in a water-based environment optimized for optical quality, then the sample is transferred to mounting reagents for long-term storage. This segmentation allows each step to be optimized independently: imaging for optical fidelity and archiving for long-term preservation.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Imaging is performed as a preliminary step before the sample is mounted in archival reagents. By capturing images while the sample is still in the water-based environment, the system preserves imaging quality without requiring the sample to be in the final archival state, thereby avoiding the optical aberrations that would result from using mounting reagents during imaging.

Inventive Principle:
Principle #10Preliminary 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

Enables rapid and efficient imaging of biological samples with high fidelity, reducing degradation and optical aberrations, and allows for immediate archival storage without compromising sample quality.

Implementation Method 1

the imaging reagent has a refractive index that is similar to at least one of water, the material of the sample carrier, and the material of a front lens of the optical system of the imaging device

Methodology Applied
Scientific EffectRefraction: Refraction

Data Source

PatentEP4610711A1Imaging device and biological sample processing arrangement
Publication Date: 2025.09.03 LEICA BIOSYSTEMS NUSSLOCH GMBH
  • EP4610711A1 patent drawingFigure 1
  • EP4610711A1 patent drawingFigure 2
  • EP4610711A1 patent drawingFigure 3

AI summary

In a first aspect, an imaging device (100, 200) for imaging biological samples (110) is provided. The imaging device (100, 200) comprises an optical system (102) for imaging a biological sample (110) arranged on a sample carrier (108) and a liquid container (104) at least partially filled with an imaging reagent (106). A focus plane of the optical system (102), in particular of an objective (112) of the optical system (102), is arranged in the liquid container (104). In a further aspect, a biological sample processing arrangement (300) comprising the imaging device (100, 200) is provided.