Cytologic Sample Preparation for Digital Pathology Imaging
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Solution Overview
Problem
Fine needle aspiration (FNA) and fine needle biopsy (FNB) samples often contain blood clots that render them inadequate for downstream diagnosis, and existing methods for digital pathology imaging are limited by slow imaging speed and variability in sample preparation, requiring a novel approach to concentrate specimens, reduce nondiagnostic tissue impact, and maintain molecular analysis capabilities in real-time with minimal operator training.
Innovation Solution
The method involves dispersing cytologic samples in a preparation solution, filtering through a filter to generate a layer of analytes adhered to the filter, and imaging using digital microscopy techniques such as stimulated Raman scattering (SRS) or fluorescent microscopy, allowing for real-time, on-site analysis with minimal sample loss and no need for fixation or air-drying.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional FNA/FNB samples are used for digital pathology imaging, then sample preparation variability and slow imaging speed occur, but diagnostic accuracy and imaging quality deteriorate
Solution Approach 1:
The system performs preliminary sample preparation actions automatically before imaging. The sample is dispersed in preparation solution, filtered to concentrate analytes, and mounted on a carrier slide through automated mechanisms, eliminating manual preparation variability and preparing the sample in advance for rapid imaging
Solution Approach 2:
Manual mechanical sample preparation operations are replaced with automated mechanical systems. The filter assembly, carrier mounting mechanism, and slide positioning system are automated, ensuring consistent sample preparation and enabling faster imaging by eliminating manual intervention steps
2Quantity of substance
If blood clots are present in FNA/FNB samples, then sample adequacy is improved, but diagnostic quality deteriorates due to inadequate samples for downstream analysis
Solution Approach 1:
The system extracts and removes blood clots and non-diagnostic portions from the sample through filtration. The filter assembly separates cellular analytes from blood clots and other debris, concentrating the diagnostic cells in the filtered sample while discarding harmful components that would compromise sample adequacy
Solution Approach 2:
The filter assembly acts as an intermediary between the raw aspirate and the final diagnostic sample. It mediates the separation process, allowing cellular analytes to pass through while blocking blood clots and debris, thereby transforming an inadequate sample into an adequate diagnostic sample
3Reliability
If rapid on-site evaluation (ROSE) is performed manually, then sample adequacy can be assessed, but operator training requirements and time consumption increase
Solution Approach 1:
The system performs self-service sample preparation and imaging without requiring skilled operators. The automated filter assembly, carrier mounting mechanism, and imaging system execute the entire workflow autonomously, eliminating the need for operator training while maintaining reliable sample adequacy assessment
Solution Approach 2:
Manual ROSE operations are replaced with automated mechanical and optical systems. The filter assembly automatically concentrates and mounts samples, and the imaging system automatically captures and processes images, substituting human skill with automated mechanisms that require minimal training
4Reliability
If conventional sample preparation methods are used, then fixation and staining can be performed, but molecular analysis capabilities are compromised and additional needle passes are required
Solution Approach 1:
The system performs preliminary filtering and concentration actions that preserve molecular integrity before any fixation or staining. By concentrating the sample analytes on the filter carrier in their native state, the system prepares the sample for molecular analysis without requiring additional needle passes or complex multi-step processing
Solution Approach 2:
The system discards blood clots and non-diagnostic portions through filtration while recovering and concentrating the diagnostic cellular analytes. This selective separation maintains the integrity of the recovered sample for molecular analysis, eliminating the need for additional procedure steps
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 enables rapid, automated, and accurate analysis of FNA/FNB samples, determining sample adequacy and tumor presence while preserving the specimen for molecular analysis, reducing the need for additional needle passes and improving diagnostic efficiency.
Implementation Method 1
filtering the sample solution by directing the sample solution through a flow channel intersected by a filter, thereby generating a layer of analytes adhered to the filter
Implementation Method 2
dispersing a cytologic sample in a preparation solution to prepare a sample solution
Implementation Method 3
the dispersing the cytologic sample comprises vortexing
Implementation Method 4
the dispersing the cytologic sample comprises ultrasonic actuation
Implementation Method 5
generating a digital microscopic image of the layer of analytes adhered to the filter, thereby imaging the cytologic sample
Implementation Method 6
generating a digital microscopic image of the layer of analytes adhered to the filter, thereby imaging the cytologic sample
Data Source
AI summary
The present disclosure provides methods and systems for preparing, imaging, analyzing, and reprocessing biopsy or other cytologic samples for digital imaging. Systems and methods provided herein are directed towards digital imaging of a biological sample that allow for greater efficiency in time by imaging samples of biological analytes adhered to filter paper.