Mesoscopic Quantitative Phase Imaging for Wide-Field Cell Dynamics
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Solution Overview
Problem
Existing mesoscopic imaging systems face limitations in achieving high spatiotemporal resolution and large field of view simultaneously, often requiring costly and complex designs that hinder the visualization of subcellular details across a large cell population, and rely on fluorescent markers that perturb the natural state of cells.
Innovation Solution
The Omni-Mesoscope integrates quantitative phase microscopy for label-free live-cell imaging with highly multiplex fluorescence microscopy, using a cost-effective design with a numerical aperture of 0.2 to 0.6, a large-format image sensor with small pixel size, and a tube lens for optical magnification, achieving sub-micrometer spatial resolution across a wide field of view.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If existing mesoscopic imaging systems use high numerical aperture objectives to achieve high spatial resolution, then subcellular details can be visualized, but the field of view becomes limited and the system becomes more complex and expensive
Solution Approach 1:
The patent uses a large-format image sensor (40 megapixels or more) to expand the detection area in the imaging plane, allowing a wider field of view to be captured simultaneously while maintaining adequate spatial resolution through the optical system design with NA 0.2 to 0.6
2Loss of information
If existing mesoscopic imaging systems use fluorescent markers to achieve molecular characterization, then molecular information can be obtained, but the natural state of cells is perturbed
Solution Approach 1:
The patent extracts and eliminates the need for fluorescent markers by implementing label-free quantitative phase imaging, which directly captures optical phase information from cells to infer molecular and functional characteristics without introducing external fluorescent substances that perturb cellular natural state
Solution Approach 2:
The patent uses quantitative phase imaging as an intermediary method that measures optical phase shifts caused by cellular properties (refractive index, thickness, density) to indirectly obtain molecular information without direct fluorescent labeling, thus avoiding cellular perturbation
3Measurement precision
If existing mesoscopic imaging systems are designed with high cost and complex components to achieve high spatiotemporal resolution, then imaging quality is improved, but the system becomes less accessible and more difficult to maintain
Solution Approach 1:
The patent replaces expensive, complex specialized mesoscopic imaging components with more affordable, commercially available optical components including standard objectives (NA 0.2 to 0.6), tube lenses, and large-format consumer-grade image sensors (40 megapixels or more), achieving high spatiotemporal resolution through intelligent system integration rather than costly hardware
Solution Approach 2:
The patent designs a multiplex imaging platform that integrates multiple imaging modalities (quantitative phase imaging, fluorescence imaging) into a single system, allowing the same optical train and image sensor to perform different imaging functions, thereby reducing overall system complexity and cost while maintaining high performance
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 system enables continuous monitoring of live-cell dynamics and detailed molecular analysis over a large cell population, identifying rare events and providing comprehensive insights into cellular processes without sacrificing functional information, and supports 3D volumetric super-resolution imaging through expansion microscopy.
Implementation Method 1
an objective lens having a numerical aperture (NA) of 0.2 to 0.6, the objective lens being configured to receive a response light emitted by the sample
Implementation Method 2
a filter wheel comprising a plurality of emission filters configured to filter the response light to generate a filtered light
Implementation Method 3
a tube lens configured to provide an optical magnification to the filtered light
Implementation Method 4
an image sensor having 40 megapixels or more and a pixel size of less than or equal to 4 μm, the image sensor being configured to receive the filtered light and generate image data based on the received filtered light
Data Source
AI summary
Mesoscopic imaging systems and methods comprise or utilize a light source configured to generate an illumination light; an optical system configured to direct the illumination light toward a sample; an objective lens having a numerical aperture (NA) of 0.2 to 0.6, the objective lens being configured to receive a response light emitted by the sample in response to the illumination light; a filter wheel comprising a plurality of emission filters configured to filter the response light to generate a filtered light; a tube lens configured to provide an optical magnification to the filtered light; and an image sensor having 40 megapixels or more and a pixel size of less than or equal to 4 μm, the image sensor being configured to receive the filtered light and generate image data based on the received filtered light.