Waveguide Cell Imaging for Wide-Field Secretion Detection

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Solution Overview

Problem

Existing methods for observing cell secretions are inefficient, high-cost, and low-throughput, necessitating a more efficient and cost-effective system for high-throughput sample processing.

Innovation Solution

A method utilizing a microscope with a waveguide for total internal reflection illumination, optimized to maintain a sufficient signal-to-noise ratio at lower magnifications, and incorporating a total internal reflection angle adjustment chamber to suppress background signals, allowing for higher sample capacity and reduced costs.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If high magnification is used to observe single cells and secretions, then measurement precision is improved, but productivity decreases due to limited field of view

Engineering Contradiction:
Improvedetection sensitivityVSAvoidnumber of samples measured
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The patent changes the magnification parameter from conventional high magnification (60x or higher) to low magnification (less than 60x, preferably 10x or lower). This parameter change allows a wider field of view to be captured, enabling simultaneous observation of multiple cells and secretions, thereby increasing productivity while maintaining detection sensitivity through optimized optical path design and waveguide configuration

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If conventional observation systems are used, then measurement precision is maintained, but loss of time increases due to sequential processing of samples

Engineering Contradiction:
Improvedetection sensitivityVSAvoidprocessing time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent segments the observation field into multiple regions that can be simultaneously captured in a single wide-field image. By using low magnification with a wide field of view, multiple cells and their secretions are observed concurrently rather than sequentially, significantly reducing processing time while maintaining detection sensitivity through optimized optical path design and waveguide configuration

Inventive Principle:
Principle #1Segmentation

3Productivity

If wide area observation is attempted with low magnification, then productivity is improved, but measurement precision deteriorates due to reduced signal-to-noise ratio

Engineering Contradiction:
Improvenumber of samples measuredVSAvoidsignal-to-noise ratio
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent introduces a waveguide as an intermediary component between the light source and the sample. The waveguide generates total internal reflection light that provides uniform illumination across the wide field of view, enabling low magnification observation while maintaining sufficient signal-to-noise ratio for detecting cell secretions. The waveguide acts as a mediator that distributes light evenly across the observation area

Inventive Principle:
Principle #24Intermediary (Mediator)

4Measurement precision

If total internal reflection illumination is used, then measurement precision is improved, but device complexity increases due to waveguide requirements

Engineering Contradiction:
Improvedetection sensitivityVSAvoidoptical system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The waveguide structure utilizes total internal reflection, a natural optical phenomenon, to generate uniform illumination without requiring complex external illumination systems. The waveguide itself serves as both the light guiding structure and the illumination source through total internal reflection, simplifying the overall optical system while maintaining high detection sensitivity

Inventive Principle:
Principle #25Self-service

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 the analysis of more samples in a shorter time and at a lower cost while maintaining sensitivity, by optimizing the system to reduce background noise and increase sample capacity.

Implementation Method 1

excitation of the fluorescence is carried out by means of total internal reflection illumination; the total internal reflection illumination is carried out using a waveguide; the waveguide is configured to limit the irradiation angle of the total internal reflection illumination

Methodology Applied
Scientific EffectTotal internal reflection: Total Internal Reflection

Implementation Method 2

a liquid, a solid, or a gel having a refractive index similar to that of the solution containing the target is provided in an upstream portion of the waveguide

Methodology Applied
Scientific EffectRefraction: Refraction

Implementation Method 3

the observation of the target is carried out using fluorescence; excitation of the fluorescence is carried out by means of total internal reflection illumination

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentEP4682514A1Method for analyzing cells and cell-related materials, and system
Publication Date: 2026.01.21 LIVE CELL DIAGNOSIS LTD
  • EP4682514A1 patent drawingFigure 1
  • EP4682514A1 patent drawingFigure 2
  • EP4682514A1 patent drawingFigure 3

AI summary

An object of the present invention is to provide a more efficient, high-throughput system that is able to process more samples in a shorter time and at a lower cost, when observing living cells. The relationship between an objective lens and S/N ratio in the imaging of single-cell secretions was verified through theory and experimentation, and developed a system for observing a wide area without degrading the S/N ratio. Even at a magnification lower than the magnification conventionally considered to be necessary for observing the targets, observation at a sufficient sensitivity and S/N ratio is possible by appropriately setting measurement conditions, and, therefore, it has become possible to significantly increase the number of samples that can be measured in one measurement. Moreover, by irradiating light using a waveguide equipped with a total internal reflection angle adjustment chamber, the S/N ratio was furthered improved.