Spherical Dielectric Optical Probe for Multiplexed Cell Tracking

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Solution Overview

Problem

Conventional fluorescence markers suffer from photobleaching, limited color range, and inability to label multiple cells simultaneously, restricting their use in analyzing complex tissues and tracing cancer metastasis.

Innovation Solution

A method utilizing a broadband light source and thin-film interference theory to analyze spherical dielectric materials, allowing for high-accuracy measurement and simultaneous labeling of multiple cells by analyzing the interference spectrum of reflected light.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If fluorescence markers are used for labeling cells, then the labeling process is simple and easy to use, but the signal fades over time due to photobleaching and the emission spectrum is broad, limiting the number of colors that can be used simultaneously

Engineering Contradiction:
Improveease of useVSAvoidsignal stability
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The patent changes the fundamental optical parameter from fluorescence emission to thin-film interference reflection. The spherical dielectric particles utilize interference effects in the visible spectrum (400-700 nm) to produce stable, non-fading colors that encode multiple parameters including cell size, particle diameter, and refractive index, thereby resolving the photobleaching issue while maintaining ease of use

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention utilizes color changes through thin-film interference rather than fluorescence emission. By controlling the thickness and refractive index of dielectric layers, different interference colors are produced that correspond to different cell parameters, enabling long-term stable tracking and multiplexed labeling without signal fading

Inventive Principle:
Principle #32Color changes

2Ease of operation

If fluorescence markers with broad emission spectrum are used, then the labeling process is simple, but the number of colors available for simultaneous labeling is limited to 3-5

Engineering Contradiction:
Improvelabeling simplicityVSAvoidnumber of labelable cells
Core Design Contradiction:
Ease of operationVSAdaptability or versatility

Solution Approach 1:

The patent transforms the optical mechanism from broad-spectrum fluorescence to narrow-band thin-film interference, where the reflected color is determined by precise control of layer thickness and refractive index. This enables generation of many distinct, well-separated colors from a single broadband light source, allowing simultaneous labeling of hundreds or thousands of cells with different gene expressions

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The spherical dielectric particles serve multiple functions: they act as optical markers for cell labeling, size standards for measurement calibration, and encoding elements for multiparameter analysis. A single particle system provides size information, gene expression information through color coding, and serves as a reference standard, thereby enabling high-throughput analysis of thousands of cells simultaneously

Inventive Principle:
Principle #6Universality (Multi-functionality)

3Ease of operation

If conventional fluorescence markers are used, then the method is straightforward, but the ability to trace cells over long periods is compromised due to signal fading

Engineering Contradiction:
Improvemethod simplicityVSAvoidtracking duration
Core Design Contradiction:
Ease of operationVSDuration of action of moving object

Solution Approach 1:

The patent changes the optical mechanism from fluorescence to thin-film interference, which does not suffer from photobleaching. The interference-based color encoding remains stable over time, enabling long-term tracking of cell fate and metastasis while maintaining procedural simplicity through passive optical detection

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention replaces the short-lived fluorescent signal with durable, non-fading interference colors. The spherical dielectric particles themselves serve as stable, long-lasting optical markers that maintain their encoding properties throughout the entire observation period, enabling tracking from hours to months without signal degradation

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

4Productivity

If fluorescence markers are used for analyzing complex tissues, then the current methodology is sufficient, but it cannot label and track hundreds or thousands of individual cells simultaneously

Engineering Contradiction:
Improveanalysis throughputVSAvoidmultiplexing capability
Core Design Contradiction:
ProductivityVSAdaptability or versatility

Solution Approach 1:

The patent changes from broad-spectrum fluorescence to narrow-band interference colors, enabling dense spectral multiplexing. By controlling particle diameter and layer thickness, hundreds of distinct color codes can be generated within the visible spectrum, allowing simultaneous tracking of thousands of cells with different gene expressions in complex tissue environments

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention replaces the mechanical limitation of sequential fluorescence filtering with optical interference-based color encoding. The thin-film interference structure inherently provides narrow, well-defined spectral peaks that can be rapidly detected and decoded, enabling high-throughput simultaneous analysis of multiple parameters across thousands of cells without the need for sequential scanning

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

This method provides high accuracy in measuring cell sizes, enabling the analysis of thousands of cells at once, with increased intensity and stability of the reflected light, facilitating the tracing of cancer metastasis and diverse cell gene analysis.

Implementation Method 1

an optical probe based on thin-film interference which occurs in a spherical dielectric material

Methodology Applied
Scientific EffectThin-film interference: Interference

Implementation Method 2

measuring an interference spectrum of reflected light from the spherical dielectric material

Methodology Applied
Scientific EffectLight reflection: Reflection

Data Source

PatentUS10598589B2Optical probe based on thin-film interference
Publication Date: 2020.03.24 RES & BUSINESS FOUND SUNGKYUNKWAN UNIV
  • US10598589B2 patent drawing
  • US10598589B2 patent drawing
  • US10598589B2 patent drawing

AI summary

The present disclosure relates to a method of analysis by an optical marker, including: irradiating a broadband light source onto a spherical dielectric material; measuring an interference spectrum of reflected light from the spherical dielectric material; and analyzing the reflected light using thin-film interference theory.