Microtissue Phase Imaging Without Staining or Reference Beams
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Solution Overview
Problem
Current imaging techniques for biological tissues, particularly fluorescence microscopy, histology, capacitance measurement, and standard transmission imaging, are invasive, destructive, or limited in their ability to characterize living tissues, especially microtissues, and lack the capability for rapid, non-invasive, quantitative measurement of phase.
Innovation Solution
A phase measurement technique without a reference beam is used to characterize biological microtissues, reducing speckle contrast and managing beam coherence to enable quantitative characterization of microtissues greater than 20µm, allowing for the measurement of phase, density, and local absorption without destruction.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional imaging techniques are used to image small biological tissue samples, then the imaging process is simple, but the images lack sufficient detail and require staining procedures
Solution Approach 1:
A reference grid pattern is introduced as an intermediary element during the imaging process. This grid serves as a mediator that enables phase extraction and transformation of the imaging data, allowing conventional imaging systems to achieve quantitative phase imaging capabilities without requiring complex modifications to the core imaging hardware
Solution Approach 2:
The patent replaces traditional staining-based contrast mechanisms with phase-based contrast extraction. By using computational methods to extract phase information from interferometric patterns, the system achieves high-contrast imaging of transparent biological samples without mechanical or chemical staining procedures
2Measurement precision
If staining procedures are used to enhance image contrast, then image detail improves, but the tissue samples may be damaged or altered
Solution Approach 1:
The patent substitutes chemical staining mechanisms with optical phase-based contrast mechanisms. By measuring the phase shift of light passing through the sample and using computational algorithms to extract quantitative phase information, the system achieves high-contrast imaging without introducing any chemical substances that could damage or alter the biological tissue
Solution Approach 2:
The reference grid acts as an intermediary that enables phase information extraction without direct interaction with the sample. The grid creates an interferometric pattern that encodes sample information, allowing contrast enhancement through computational processing rather than chemical treatment
3Measurement precision
If multiple imaging techniques are combined to characterize tissue, then measurement accuracy improves, but the process time and complexity increase
Solution Approach 1:
The quantitative phase imaging system achieves multi-functionality by extracting multiple tissue characteristics from a single imaging modality. The phase information contains rich data about cell density, biomass, and structural properties, allowing the system to perform multiple types of tissue characterization simultaneously without requiring separate imaging techniques
Solution Approach 2:
The patent combines the reference grid pattern with the sample imaging in a single integrated process. By superimposing the grid pattern during image acquisition and using computational algorithms to extract phase information, the system merges multiple functions (phase measurement, contrast enhancement, and tissue characterization) into one unified imaging approach
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 high-throughput, non-invasive characterization of living microtissues, measuring biomass, cell viability, differentiation, and phenotype, and monitoring tissue organization, without altering the samples, suitable for applications in research and therapy.
Implementation Method 1
The method comprises obtaining a quantitative phase image of the biological micro tissue. The quantitative phase image provides information about the optical path length differences through the tissue sample, enabling visualization of transparent structures without staining.
Implementation Method 2
The method comprises obtaining an absorption image of the biological micro tissue. The absorption image reveals the distribution of light-absorbing components within the tissue, providing information about tissue composition and density variations.
Data Source
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AI summary
The invention relates to a method for in vitro imaging characterisation of a eucaryotic biological micro tissue using a technique for measuring the phase without a reference beam, and the use of said method in particular for: - assessing the quality of micro tissue, - measuring the increase in the biomass of a micro tissue during its growth and/or its amplification, - monitoring the differentiation and/or the organisation of a micro tissue during its maturation, - determining the phenotype of micro tissue cells, and/or - confirming the absence of non-differentiated cells in the micro tissue.