Fourier Ptychographic Microscopy for High-Resolution Large Field Imaging
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Solution Overview
Problem
Current microscopic imaging technologies face limitations such as restricted field of view, diminished light availability at high magnifications, and sample damage from high-intensity waves, making it challenging to achieve high-resolution imaging of large sample areas.
Innovation Solution
The development of an automated system for microscopic imaging using Fourier ptychography, which combines multiple low-resolution images captured under different illumination conditions to produce high-resolution, large-field-of-view images without the need for sample staining or extensive preparation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If high magnification is used to achieve high-resolution imaging, then imaging resolution is improved, but field of view decreases exponentially
Solution Approach 1:
The patent segments the imaging process into multiple low-resolution images captured at different illumination angles, which are then computationally synthesized to produce a high-resolution image with extended field of view. This segmentation allows the system to overcome the exponential field of view limitation while achieving high-resolution imaging.
Solution Approach 2:
The patent introduces angular illumination as an additional dimension to capture multiple images. By varying the illumination angle and synthesizing images from different angular perspectives, the system achieves high-resolution imaging across a large field of view without being constrained by traditional magnification limitations.
2Illumination intensity
If high-intensity electromagnetic waves are used to increase light availability at high magnification, then imaging capability is improved, but sample damage increases
Solution Approach 1:
The patent uses multiple low-intensity illuminations from different angles rather than a single high-intensity illumination. Each individual illumination is of low intensity and causes minimal sample damage, but the cumulative effect of synthesizing multiple such images produces the desired high-resolution result without excessive sample damage.
Solution Approach 2:
The patent employs continuous low-intensity illumination from varying angles to capture multiple images, maintaining a steady supply of useful light information without the need for high-intensity pulses that would damage the sample. The synthesis process continuously integrates information from all illumination angles.
3Measurement precision
If traditional staining techniques are used to visualize sample characteristics, then molecular detail is improved, but sample fixation is required which alters the sample
Solution Approach 1:
The patent replaces the chemical staining mechanism with a computational imaging approach. Instead of using chemical stains to highlight molecular characteristics, the system uses angular illumination and computational synthesis to extract and enhance molecular detail from the optical images, thereby preserving sample integrity while achieving comparable or superior visualization.
4Stability of the object's composition
If phase contrast microscopy is used to view translucent samples without staining, then sample integrity is preserved, but molecular detail and field of view are limited
Solution Approach 1:
The patent merges multiple phase contrast images captured at different illumination angles through computational synthesis. This combination preserves the sample integrity advantage of phase contrast microscopy while overcoming its limitations by integrating information from multiple angular perspectives to enhance molecular detail and extend the effective field of view.
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 the acquisition of high-resolution images with a wide field of view, reducing the need for sample preparation and minimizing sample damage, while also improving the accuracy of microscopic analysis.
Implementation Method 1
an illumination source configured to emit light that passes through a biological sample
Implementation Method 2
a sensor configured to capture a plurality of images based on one or more diffraction patterns generated from an optical transmission function of the biological sample
Implementation Method 3
one or more diffraction patterns generated from an optical transmission function of the biological sample
Implementation Method 4
a lens configured to project the one or more diffraction patterns onto the sensor
Data Source
AI summary
Described herein are systems and methods for assessing a biological sample. The methods include: characterizing a speckled pattern to be applied by a diffuser; positioning a biological sample relative to at least one coherent light source such that at least one coherent light source illuminates the biological sample; diffusing light produced by the at least one coherent light source; capturing a plurality of illuminated images with the embedded speckle pattern of the biological sample based on the diffused light; iteratively reconstructing the plurality of speckled illuminated images of the biological sample to recover an image stack of reconstructed images; stitching together each image in the image stack to create a whole slide image, wherein each image of the image stack at least partially overlaps with a neighboring image; and identifying one or more features of the biological sample. The methods may be performed by a near-field Fourier Ptychographic system.