Neuron Aggregate Imaging for Survival State Classification

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Solution Overview

Problem

Existing methods for analyzing neurons using fluorescent proteins lack the capability to accurately detect protein aggregates and classify neurons based on their survival state, which is crucial for understanding neuronal health and disease progression.

Innovation Solution

A method and device for analyzing neurons using time-series imaging to identify neurite and cell body regions, detect protein aggregates, and classify neurons into groups based on aggregate presence and survival state, utilizing fluorescent proteins tagged with specific proteins like GFP or RFP, and analyzing survival or death states through luminance thresholds.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If fluorescent protein is introduced into neurons to track aggregates and determine survival states, then the ability to analyze neuronal health and dynamics is improved, but the complexity of the imaging and analysis system increases

Engineering Contradiction:
Improveaccuracy of neuron survival state analysisVSAvoidcomplexity of imaging and analysis system
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent segments the neuron into distinct regions of interest (cell body and neurite processes) and analyzes aggregate presence separately in each region. This segmentation allows precise differentiation between neuronal compartments, enabling accurate survival state classification while maintaining manageable analysis complexity through structured processing

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent applies different luminance thresholds and detection parameters to different regions (cell body versus neurite). By customizing detection criteria for each region based on their specific characteristics, the system achieves high measurement precision without requiring a completely complex unified system

Inventive Principle:
Principle #3Local quality

2Duration of action of moving object

If time-series imaging is performed to track aggregate dynamics, then the ability to analyze survival states is improved, but the amount of data processing and analysis time increases

Engineering Contradiction:
Improvesurvival period tracking capabilityVSAvoiddata processing time
Core Design Contradiction:
Duration of action of moving objectVSLoss of time

Solution Approach 1:

The patent performs preliminary identification of cell body and neurite regions using phase difference images and luminance thresholding before conducting detailed aggregate detection. This preliminary segmentation establishes a framework that guides subsequent time-series analysis, reducing the time required for comprehensive data processing while maintaining full tracking capability

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent extracts and focuses analysis on specific regions of interest (cell body and neurite) rather than processing the entire neuron uniformly. By concentrating computational resources on biologically relevant regions where aggregates form, the system reduces overall data processing time while preserving survival state analysis accuracy

Inventive Principle:
Principle #2Taking out (Extraction)

3Measurement precision

If multiple luminance thresholds are used to distinguish cell body and neurite regions, then the precision of region identification is improved, but the complexity of threshold determination increases

Engineering Contradiction:
Improveprecision of cell region identificationVSAvoidcomplexity of threshold determination
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent uses phase difference images as an intermediary to guide luminance threshold determination. The phase difference data provides structural information about cell body and neurite boundaries, which serves as a mediator to select appropriate luminance thresholds for each region. This approach achieves precise region identification without requiring complex threshold calculation methods

Inventive Principle:
Principle #24Intermediary (Mediator)

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 precise classification of neurons into groups based on aggregate presence and survival state, providing insights into neuronal health and disease progression by tracking luminance and survival periods.

Implementation Method 1

introducing a gene encoding fluorescent protein into a living cell. As the fluorescent protein, green fluorescent protein (GFP), red fluorescent protein (RFP), and the like are used. These types of fluorescent protein are used as markers indicating localization of genes in cells and protein in cells.

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 2

detecting aggregates by detecting, on the basis of the time-series images obtained by imaging, in time series, first fluorescent protein tagged to specific protein expressed in the neuron, presence or absence of aggregates of the specific protein aggregated in the region of the neurite or the region of the cell body identified in the identifying the cell region by using, as a basis, luminance of the first fluorescent protein included in the time-series images

Methodology Applied
Scientific EffectLight detection:

Data Source

PatentUS12618829B2Method of analyzing neurons, device for analyzing neurons, and computer program
Publication Date: 2026.05.05 NIKON CORP
  • US12618829B2 patent drawing
  • US12618829B2 patent drawing
  • US12618829B2 patent drawing

AI summary

A method of analyzing neurons includes: identifying a cell region by identifying a region of a neurite or a region of a cell body of a neuron on the basis of time-series images obtained by imaging the neuron in time series; detecting aggregates by imaging, in time series, first fluorescent protein tagged to specific protein expressed in the neuron and detecting presence or absence of aggregates of the specific protein aggregated in the region of the neurite or the region of the cell body identified in the identifying the cell region on the basis of luminance of the first fluorescent protein included in the time-series images; and performing an analysis by classifying the neuron into a plurality of groups on the basis of a detection result of the detecting the aggregates and analyzing a survival state of the neuron for each of the groups.