Thermoreversible Gel Immobilization for Extended Microscopic Imaging
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Solution Overview
Problem
Conventional methods for microscopic imaging of biological specimens are time-consuming, generate biohazardous waste, and require complex machinery, while existing image processing techniques struggle with extended image-capture times and cell mobility, limiting the use of high-throughput and high-resolution imaging.
Innovation Solution
A thermally reversible gel composition is used to immobilize biological specimens, allowing for extended image-capture times by forming a gel matrix at a critical temperature, which inhibits Brownian motion and cell movement, enabling high-resolution image capture.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If automated slide-based imaging is used, then imaging can be performed, but the process is time-consuming and generates large amounts of biohazardous waste
Solution Approach 1:
The patent uses a reusable imaging substrate that can be imaged multiple times instead of creating a new glass slide for each sample. The gel-based specimen containment allows the same substrate to be used repeatedly with different samples, eliminating the need for disposable slides and reducing both time and waste generation.
Solution Approach 2:
The gel composition is discarded after use while the expensive imaging substrate is recovered and reused. This approach eliminates the need to discard entire glass slides with mounted specimens, significantly reducing glass waste and the time required for slide preparation and disposal.
2Measurement precision
If conventional smearing method is used, then specimen can be observed, but cells are ruptured or modified from their native state
Solution Approach 1:
The patent changes the physical state parameter of the specimen containment medium from solid (glass slide) to gel. The gel composition can be liquid at higher temperatures for easy specimen mixing, then transitions to gel state at lower temperatures to immobilize cells without rupture, maintaining cell integrity while simplifying preparation.
Solution Approach 2:
The patent uses a composite system combining gel composition with imaging substrate. The gel provides a gentle, non-rupturing environment for cells while the substrate provides structural support for imaging, achieving both cell integrity and ease of operation.
3Measurement precision
If extended image-capture time is used for high-resolution imaging, then image quality improves, but cell mobility prevents successful imaging
Solution Approach 1:
The patent utilizes the phase transition of the gel composition from liquid to gel state. At liquid state, cells can be easily mixed and positioned. Upon cooling, the gel transitions to gel state, immobilizing cells without rupture. This allows extended image-capture times for high-resolution imaging while maintaining cell stability.
4Productivity
If flow imaging or wet-mount microscopy is used, then imaging can be performed, but extended image-capture times cannot be achieved due to cell mobility
Solution Approach 1:
The patent creates a dynamic system where the gel composition changes state based on temperature. During specimen preparation, the gel is liquid allowing easy mixing. During imaging, the gel is in gel state providing immobilization. This dynamic control allows both fast imaging and high resolution to be achieved.
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
The gel composition provides a stable environment for capturing multiple low-resolution images, which can be post-processed to produce high-resolution images, facilitating high-throughput imaging without cell rupture or modification, and reducing waste generation.
Implementation Method 1
providing a gel composition in a first state, which is a liquid wherein the gel composition is thermally reversible between the first state and a second state at a critical temperature
Implementation Method 2
cooling the aqueous mixture below the critical temperature of the gel composition so that the gel composition is in the second state, which is a gel, to harden the gel composition and to form a gel matrix
Implementation Method 3
forming a gel matrix at a critical temperature, which inhibits Brownian motion and cell movement
Data Source
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AI summary
Embodiments of the present invention generally relate to methods for immobilizing a biological specimen for extended periods of time for image capture. Specific embodiments may be used to support a target specimen in a gel matrix. In some embodiments, the biological specimen may be in liquid form at elevated temperatures, a stain and/or lyse may be added to the biological specimen, and a gelling composition may added. At reduced temperatures, the gelling composition may still the biological specimen to immobilize a biological specimen for extended periods of time for image capture.