Gel Sample Observation via Flat Substrate Contact

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Solution Overview

Problem

Existing methods for observing 3D-cultured cellular aggregates in hanging drops face challenges with automation and high-definition imaging due to optical aberrations caused by refractive-index differences between the hanging drop and the objective lens, particularly when air is involved, and previous solutions do not adequately address these issues.

Innovation Solution

A sample observation method involving a gel-like transparent sample that is brought into contact with a transparent flat surface section of a substrate, allowing light to be collected by an objective lens with a pressing force to ensure an effective contact area for high-definition imaging, reducing refractive-index differences and aberrations.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If a hanging drop is observed by means of a microscope with a dry objective lens, then the observation can be performed without immersion liquid, but optical aberrations occur due to refractive-index difference between the hanging drop and air

Engineering Contradiction:

Improveease of observationVSAvoidimage definition

Core Design Contradiction:

Ease of operationVSMeasurement precision

Solution Approach 1:

The patent introduces a flat bottom section as an intermediary medium between the hanging drop and the objective lens. This flat bottom section eliminates the curved surface interface that causes refraction, providing a direct optical path while maintaining the hanging drop configuration for automation compatibility.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Measurement precision

If the hanging drop is gelled and immersed in liquid to reduce refractive-index difference, then optical aberrations are suppressed, but the original optical performance of the microscope cannot be obtained due to remaining refractive-index difference between liquid and gel

Engineering Contradiction:

Improveimage definitionVSAvoidoptical system complexity

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent extracts the problematic curved surface interface by using a flat bottom section. This removes the source of refraction-related optical aberrations while preserving the hanging drop structure, eliminating the need for immersion liquids and maintaining the microscope's original optical performance.

Inventive Principle:

Principle #2Taking out (Extraction)

3Measurement precision

If hanging drops are formed by inverting droplets as in PTL 1, then observation can be performed, but accurate array arrangement cannot be achieved making automation difficult

Engineering Contradiction:

Improveobservation capabilityVSAvoidautomation of preparation

Core Design Contradiction:

Measurement precisionVSExtent of automation

Solution Approach 1:

The patent inverts the conventional approach: instead of inverting droplets to form hanging drops (PTL 1), it forms hanging drops by dispensing them in an array format directly into the multiwell plate (PTL 2), and then adds the innovation of a flat bottom section to enable high-definition observation. This resolves both the automation issue and the optical aberration issue.

Inventive Principle:

Principle #13The other way round (Inversion)

4Extent of automation

If the transverse section of wells is gradually narrowed downward with a flat bottom surface as in PTL 3, then automation of observation is achieved and influence of aberrations is reduced, but the contact area may be insufficient for effective light flux passage

Engineering Contradiction:

Improveautomation of observationVSAvoidcontact area between sample and substrate

Core Design Contradiction:

Extent of automationVSArea of stationary object

Solution Approach 1:

The patent applies local quality by creating a specific flat bottom section with sufficient area optimized for light flux passage. The well structure combines the narrowed transverse section for automation/beneficial positioning with a localized flat bottom area large enough to ensure effective optical contact between the hanging drop and the substrate.

Inventive Principle:

Principle #3Local quality

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 high-definition observation and image acquisition of cellular aggregates with reduced optical aberrations, facilitating automation and maintaining the original optical performance of the microscope.

Implementation Method 1

the curved surface shape of the hanging drop acts as a lens due to the refractive-index difference between the hanging drop and a substance (for example, air when a dry objective is used) that is interposed between the hanging drop and an objective lens, and optical aberrations occur

Methodology Applied

Scientific EffectRefraction: Refraction

Data Source

PatentUS10895728B2Observation method and holder for gel-like transparent sample which encloses an observation target

Publication Date: 2021.01.19 EVIDENT CORP

AI summary

Provided is a sample observation method including: bringing a gel-like transparent sample that encloses an observation target into contact with a transparent flat surface section of a substrate; and collecting light from the observation target by means of an objective lens via the substrate, in a state in which a pressing force is made to act in a direction in which the sample and the flat surface section relatively approach each other, until the contact area between the sample and the flat surface section comes to have a size allowing an effective light flux for the objective lens of a microscope to pass therethrough.