Quantitative Phase-Contrast Microscopy for Tissue Sample Analysis
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Solution Overview
Problem
Current digital holographic microscopes are not suitable for analyzing larger tissue samples, such as biopsy samples, which are crucial for diagnosing diseases like pancreatic cancer, as they require slow and costly cytopathologic and histopathologic techniques that often yield ambiguous results.
Innovation Solution
A method using a quantitative phase-contrast microscope and microfluidic system to dissolve tissue samples into single cells or cell aggregates in a carrier fluid, allowing for fast and reliable analysis by generating a flow to a measurement volume for imaging, eliminating the need for additional sample preparation steps.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Volume of moving object
If digital holographic microscopy is used for cell analysis, then labeling-free high-throughput analysis is achieved, but it is not suitable for studying larger tissue samples such as biopsy samples
Solution Approach 1:
The tissue sample is segmented into smaller units by dissolving it into single cells and cell aggregates using enzymatic digestion and mechanical disruption in the microfluidic system. This segmentation enables the quantitative phase-contrast microscope to analyze individual cells from larger tissue samples, resolving the contradiction between sample size and microscope applicability
Solution Approach 2:
A microfluidic system serves as an intermediary between the tissue sample and the quantitative phase-contrat microscope. The microfluidic device processes the tissue sample through dissolution and filtration, transforming it into a form suitable for microscopic analysis while preserving the ability to handle larger original sample volumes
2Reliability
If cytopathologic and histopathologic techniques are used for tissue sample analysis, then diagnosis is obtained, but the process is slow and costly with ambiguous results in some cases
Solution Approach 1:
The patent replaces complex mechanical and chemical processing steps of traditional cytopathologic and histopathologic techniques with a streamlined microfluidic dissolution process combined with quantitative phase-contrat imaging. This substitution eliminates time-consuming staining and preparation steps while maintaining diagnostic reliability through label-free cellular characterization
Solution Approach 2:
The invention changes the analysis parameters by using quantitative phase-contrat microscopy to measure optical path length differences and cellular morphological parameters directly, rather than relying on staining intensity or DNA sequencing. This parameter change enables faster analysis with comparable or improved diagnostic accuracy
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 fast and reliable determination of cell types and morphology within tissue samples, providing more accurate disease diagnosis without the need for staining or DNA sequencing, and facilitating automated high-throughput analysis.
Implementation Method 1
Digital holographic microscopy uses interference between an imaging beam and a reference beam to obtain phase as well as amplitude information of light transmitted by a sample
Implementation Method 2
The tissue sample is dissolved into single cells and/or cell aggregates in a carrier fluid in the sample volume
Data Source
AI summary
Disclosed herein is a method of analyzing a tissue sample using a quantitative phase-contrast microscope as well as a corresponding microfluidic system and a corresponding device. The method comprises providing the tissue sample in a sample volume of a microfluidic system, wherein the tissue sample comprises a plurality of biological cells forming a continuous tissue material. At least a part of the tissue sample is dissolved into single cells and/or cell aggregates in a carrier fluid in the sample volume. A flow of the carrier fluid is generated from the sample volume to a measurement volume of the microfluidic system and a first phase shift image of the single cells and/or cell aggregates in the measurement volume is taken with the quantitative phase-contrast microscope.