3D Refractive Index Imaging for Label-Free Molecular Image Generation
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Solution Overview
Problem
Conventional molecular microscopy methods require labeling processes that are time-consuming, costly, and can deform cells, limiting their application in monitoring and measuring cellular structures, and making it difficult to track samples over time due to fluorescence molecule staining difficulties.
Innovation Solution
A method and apparatus using 3-D refractive index imaging and deep learning to generate molecular images without labeling, by measuring 3-D refractive index images of cells and applying convolutional neural networks to predict molecular images, allowing for the extraction of morphologic and physical-chemical characteristics.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If labeling process is used to monitor and measure molecules in cells, then molecular images can be obtained, but time and costs are required for dyeing process and cell deformation occurs
Solution Approach 1:
The patent replaces the chemical labeling process with optical measurement. Specifically, it uses 3-D refractive index imaging to directly visualize molecular distributions without requiring any dyeing or labeling steps. The refractive index measurement system captures optical properties of cells to generate molecular images, eliminating the time-consuming chemical labeling process while maintaining measurement capability.
Solution Approach 2:
The patent changes the measurement parameter from fluorescence intensity (requiring labels) to refractive index (label-free). By measuring the refractive index distribution of cells in 3-D space, the system can infer molecular compositions and structures without introducing external labels, thus avoiding both time loss and cell deformation associated with labeling.
2Measurement precision
If labeling process is used to monitor and measure molecules in cells, then molecular images can be obtained, but costs are required for dyeing process and cell deformation occurs
Solution Approach 1:
The patent substitutes the harmful chemical labeling process with a non-invasive optical measurement system. The refractive index imaging technique uses light to probe cellular structures without introducing any foreign substances, thereby eliminating cell deformation caused by dyeing processes while still achieving molecular-level imaging capability.
Solution Approach 2:
The patent utilizes the inherent optical properties of cellular components (their natural refractive indices) to generate images. Instead of requiring external labels to make molecules visible, the system exploits the self-characteristic optical signatures of different cellular structures, allowing label-free visualization that avoids all harmful effects of labeling.
3Measurement precision
If fluorescence molecule staining is performed on samples, then molecular images can be obtained, but it is difficult to track and monitor samples for a long time
Solution Approach 1:
The patent replaces fluorescence staining with refractive index imaging, enabling long-term monitoring. Since no chemical labels are introduced, the measurement process does not alter or degrade the sample over time, allowing repeated measurements and continuous tracking of cellular dynamics for extended periods without the limitations of fluorescence probe stability.
4Loss of information
If labeling process is used to obtain molecular images, then molecular information can be obtained, but quality of corresponding image is not constant
Solution Approach 1:
The patent changes from measuring fluorescence intensity (label-dependent) to measuring refractive index (intrinsic property). The refractive index is a fundamental physical property of materials that does not depend on external labels, ensuring consistent and reliable measurements across different samples and conditions without the variability introduced by labeling efficiency differences.
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 rapid and accurate generation of molecular images without affecting the cell, providing consistent and stable analysis by avoiding the limitations of labeling processes, and allowing for the monitoring of cellular structures without deformation.
Implementation Method 1
3-D refractive index image measurement unit configured to measure a 3-D refractive index image of a cell
Data Source
AI summary
Disclosed are a method and apparatus for generating a three-dimensional (3-D) molecular image based on a label-free method using a 3-D refractive index image and deep learning. The apparatus for generating a 3-D molecular image based on a label-free method using a 3-D refractive index image and deep learning may include a 3-D refractive index cell image measurement unit configured to measure a 3-D refractive index image of a cell to be monitored and a 3-D refractive index and fluorescence molecule staining image conversion unit configured to input a measured value of the 3-D refractive index image to a deep learning algorithm and to output a 3-D fluorescence molecule staining cell image of the cell.