Cell Autofluorescence Analysis for Metabolic Status Classification

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Solution Overview

Problem

Existing methods for acquiring cell information through autofluorescence struggle to discriminate between cells with different metabolic activities and types, as they require cell fixation and are not suitable for continuous measurement or individual cell analysis, limiting the ability to determine metabolic status and cell type accurately.

Innovation Solution

A method that involves changing the metabolic status of cells by adding or removing reagents, such as D-glucose and antimycin A, to alter autofluorescence luminance, allowing for the acquisition of information on metabolic pathways and cell type classification using autofluorescence emitted from cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If cell fixation is performed for autofluorescence measurement, then measurement reliability is improved, but cell viability is lost and continuous measurement becomes impossible

Engineering Contradiction:

Improvemeasurement reliabilityVSAvoidcontinuous measurement capability

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent changes the measurement parameter from fixed cells to live cells by controlling metabolic status dynamically. It measures autofluorescence intensity changes in response to metabolic inhibitors (like antimycin A) and substrates (like glucose) added to the culture medium, enabling continuous monitoring of cell metabolic state without fixation.

Inventive Principle:

Principle #35Parameter changes

2Productivity

If bulk measurement of cell population is performed, then measurement efficiency is improved, but individual cell discrimination capability is lost

Engineering Contradiction:

Improvemeasurement efficiencyVSAvoidindividual cell discrimination capability

Core Design Contradiction:

ProductivityVSMeasurement precision

Solution Approach 1:

The patent segments the cell population into individual cells for measurement. By using automated microscopy and image analysis, it captures and analyzes autofluorescence signals from individual cells within the population, enabling both high-throughput measurement and individual cell discrimination through automated processing of multiple cell images.

Inventive Principle:

Principle #1Segmentation

3Adaptability or versatility

If reagent addition is performed on solid culture medium, then metabolic status changing capability is improved, but measurement flexibility is reduced and reagent addition timing is constrained

Engineering Contradiction:

Improvemetabolic status changing capabilityVSAvoidreagent addition flexibility

Core Design Contradiction:

Adaptability or versatilityVSEase of operation

Solution Approach 1:

The patent transitions from static solid culture medium to dynamic liquid culture medium for reagent addition. This allows flexible timing of reagent addition (metabolic inhibitors or substrates) during the measurement process, enabling dynamic control of cell metabolic status and multiple sequential measurements with different metabolic conditions.

Inventive Principle:

Principle #15Dynamics

4Device complexity

If single time point autofluorescence measurement is performed, then measurement simplicity is improved, but metabolic status determination accuracy is reduced

Engineering Contradiction:

Improvemeasurement simplicityVSAvoidmetabolic status determination accuracy

Core Design Contradiction:

Device complexityVSMeasurement precision

Solution Approach 1:

The patent performs preliminary measurements at multiple time points before reaching a conclusion about metabolic status. It captures autofluorescence intensity changes in response to metabolic challenges (inhibitor addition, substrate addition) over time, then analyzes the pattern of changes rather than relying on a single time point, improving metabolic status determination accuracy.

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 non-invasive, continuous culture and accurate classification of cell types and metabolic statuses by analyzing changes in autofluorescence luminance, overcoming limitations of previous technologies in discriminating between cells with different metabolic activities.

Implementation Method 1

acquiring information on a cell by using autofluorescence emitted from the cell

Methodology Applied

Scientific EffectAutofluorescence: Fluorescence

Data Source

PatentUS20240319167A1Cell information acquisition method, and program

Publication Date: 2024.09.26 CANON KK

AI summary

A cell information acquisition method of acquiring information on a cell by using autofluorescence emitted from the cell includes a metabolic status changing step of, by changing a metabolic status in the cell, changing at least one of a first autofluorescence luminance indicating a metabolic status of a first metabolic pathway and a second autofluorescence luminance indicating a metabolic status of a second metabolic pathway different from the first metabolic pathway, and an information acquisition step of, after the metabolic status changing step, acquiring information on the cell by using information on the first autofluorescence luminance and information on the second autofluorescence luminance.