Super-resolution microscopy for podocyte foot process effacement diagnosis
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Solution Overview
Problem
Current methods for diagnosing podocyte foot process effacement in kidney diseases, such as minimal change disease and focal segmental glomerulosclerosis, are time-consuming and inefficient, relying on transmission electron microscopy, which is not suitable for routine diagnostics.
Innovation Solution
A method using structured illumination microscopy to determine the length and density of the slit diaphragm formed by podocyte foot processes in renal tissue samples, comparing these measurements to healthy controls to diagnose or pre-diagnose diseases associated with podocyte foot process effacement.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If transmission electron microscopy is used to diagnose podocyte foot process effacement, then measurement precision is improved, but loss of time increases
Solution Approach 1:
The patent replaces the mechanical electron microscopy system with an optical super-resolution microscopy system. This substitution maintains the ability to visualize ultrastructural details of podocyte foot processes while eliminating the time-consuming sample preparation and imaging procedures required by electron microscopy, thereby resolving the contradiction between measurement precision and time loss
Solution Approach 2:
The patent employs preliminary staining of the renal tissue sample with fluorescent markers that specifically label podocyte foot processes and slit diaphragms. This preliminary action allows the tissue to be prepared in advance using standard histological techniques, enabling rapid super-resolution imaging without the time-intensive preparation required by electron microscopy, thus reducing loss of time while maintaining measurement precision
2Measurement precision
If transmission electron microscopy is used for routine diagnostics, then measurement precision is improved, but device complexity increases
Solution Approach 1:
The patent substitutes the complex electron microscopy apparatus with a more accessible super-resolution optical microscopy system. This replacement maintains the capability to measure podocyte foot process effacement with high precision while using equipment and techniques that are more suitable for routine diagnostic laboratories, thereby reducing device complexity
Solution Approach 2:
The patent changes the imaging modality from electron microscopy to optical microscopy with super-resolution capabilities. This parameter change allows the use of standard fluorescent staining protocols and optical microscopes with specialized objectives or illumination systems, making the diagnostic process less complex while preserving the ability to achieve the necessary measurement precision for diagnosing podocyte foot process effacement
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 approach allows for faster and more efficient diagnosis of podocyte foot process effacement, reducing the time and cost of kidney biopsy analysis while providing a reliable indicator of disease presence or risk, with results correlating linearly with conventional measurements.
Implementation Method 1
SIM works by sequential illumination of a sample through a defined grate. In the different illumination steps, the grate is shifted and rotated, so that the illumination pattern of the grate interferes with the original pattern of the sample creating so called Moiré patterns.
Implementation Method 2
structured illumination microscopy (SIM) has been successfully developed to overcome this resolution limit
Data Source
AI summary
The present invention relates to a method for diagnosing or pre-diagnosing a disease associated with podocyte foot process effacement in a subject or for determining the risk of a subject to develop a disease associated with podocyte foot process effacement, said method comprising the steps of a) determining the length of the slit diaphragm (ISD) formed by podocyte foot processes in a specific area A in a renal tissue sample of said subject by super resolution light microscopy; b) comparing the length of the slit diaphragm (ISD) formed by podocyte foot processes in a specific area A as determined in step (a) with the length of the slit diaphragm (ISD) formed by podocyte foot processes in a comparable specific area A in a renal tissue sample of a subject who at the time of the sampling showed no clinical symptoms of a disease associated with podocyte foot process effacement, wherein a deviation indicates a disease associated with podocyte foot process effacement.