Refractive Index Mapping for Single-Cell Necrosis Region Detection
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Solution Overview
Problem
Existing non-invasive methods struggle to determine the region of cell death, particularly necrosis, with high resolution at the single-cell level, and accurately identify the type of cell death without invasive fluorescent staining or complex treatments.
Innovation Solution
Utilizing refractive index distribution data to determine the region of necrotic cells by analyzing features such as refractive index statistics and nuclear dispersion, potentially with machine learning models, to identify necrotic regions within cell clusters.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If fluorescent staining is used to determine cell death region with high resolution, then measurement precision is improved, but device complexity and ease of operation deteriorate due to labeling requirements and complex treatments
Solution Approach 1:
The patent extracts and utilizes the intrinsic refractive index distribution information that naturally exists in cells, eliminating the need for external fluorescent labels or complex staining procedures. By focusing on the endogenous optical properties of cells, the method achieves high-resolution cell death determination without the complexity of invasive labeling techniques
Solution Approach 2:
The patent replaces the mechanical/chemical process of fluorescent staining with an optical measurement approach based on refractive index distribution. Instead of using chemical labels that require complex application procedures, the method uses light propagation characteristics to directly visualize and determine cell death regions, simplifying the overall observation process
2Measurement precision
If fluorescent staining is used to specify cell death type, then measurement precision is improved, but ease of operation deteriorates due to invasive labeling
Solution Approach 1:
The patent enables cells to serve themselves by utilizing their own refractive index distribution characteristics to reveal their death status. Necrotic cells naturally exhibit different refractive index patterns compared to healthy cells, allowing the method to identify cell death types without requiring external labels or invasive treatments to modify the cells
Solution Approach 2:
The patent substitutes the mechanical/chemical labeling process with an optical detection method that relies on the natural light scattering and refraction properties of cells. This replacement eliminates the need for fluorescent stains while maintaining the ability to distinguish between different cell death types based on optical characteristics
3Ease of operation
If observation of deep parts is attempted without transparentization treatment, then ease of operation is improved, but measurement precision deteriorates due to difficulty in observing deep parts
Solution Approach 1:
The patent develops a measurement method that universally works for both superficial and deep regions within cell clusters without requiring different preparation protocols. The refractive index distribution technique can penetrate and visualize cells at various depths within the cluster simultaneously, eliminating the need for transparentization treatments that would otherwise be required for deep observation
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, high-resolution determination of necrotic regions within cell clusters, improving the evaluation of cell quality and drug efficacy in regenerative medicine.
Implementation Method 1
refractive index distribution data of the observation object
Data Source
AI summary
Disclosed are a method, device, and information processing program for determining a necrosis cell region in an object to be observed, using refractive-index distribution data pertaining to the object to be observed.