Microlens Array Super Resolution Microscopy for Live Cell Tracking
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Solution Overview
Problem
Current microscopy technologies face limitations in achieving super resolution imaging in all three dimensions and in live cell tracking over extended periods without bleaching, particularly in capturing sub-diffraction resolution and temporal resolution of biological processes.
Innovation Solution
A super resolution microscopy system is developed, incorporating a sample stage, a coherent light source, a microlens array, and an image detector, with the microlens array positioned in both the excitation and emission beam paths to enhance resolution and reduce photo-toxicity, utilizing a rotating microlens and pinhole array configuration for efficient imaging.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional particle-tracking fluorescence microscopy is used to achieve sub-diffraction spatial localization accuracy, then spatial resolution is improved, but temporal resolution deteriorates due to longer acquisition times required to accumulate sufficient signal
Solution Approach 1:
The patent divides the excitation light path into multiple parallel paths using a microlens array, creating multiple focal spots that simultaneously illuminate different regions of the sample. This segmentation allows parallel acquisition of signal from multiple locations, improving temporal resolution while maintaining spatial localization accuracy through the use of multiple detectors or camera channels.
Solution Approach 2:
The patent introduces a third dimension by using a microlens array to create multiple focal planes or depths of field. This allows simultaneous imaging at multiple depths or focal positions, enabling temporal resolution improvement by capturing dynamic processes across different spatial dimensions without requiring sequential scanning.
2Measurement precision
If high intensity light is used to improve signal accumulation and spatial resolution, then measurement precision is improved, but photo-toxicity and photobleaching increase, limiting extended live cell tracking
Solution Approach 1:
The microlens array segments the total light intensity into multiple lower-intensity focal spots distributed across the sample. Each spot delivers sufficient intensity for high-resolution imaging, but the distributed nature reduces peak intensity and overall photo-toxicity compared to a single high-intensity illumination path, enabling extended live cell tracking.
Solution Approach 2:
The microlens array acts as an intermediary optical element that redistributes excitation light more efficiently. It creates multiple intermediate focal points that collectively illuminate the sample with reduced peak intensity while maintaining total signal accumulation, thereby reducing photodamage and photobleaching during extended imaging sessions.
3Measurement precision
If traditional diffraction-limited microscopy is used, then device complexity is low, but spatial resolution is limited to 200-280 nanometers, concealing sub-cellular structures
Solution Approach 1:
The patent uses a microlens array to segment the optical path into multiple parallel imaging channels. This segmentation approach achieves super-resolution by simultaneously capturing information from multiple focal spots, breaking the diffraction limit without requiring complex scanning mechanisms or post-processing algorithms, thus maintaining relatively simple device architecture.
Solution Approach 2:
The microlens array introduces an additional optical dimension by creating multiple focal planes or depth layers. This dimensional approach enables super-resolution imaging by encoding spatial information across multiple depths, achieving enhanced resolution without adding mechanical complexity or requiring sophisticated computational reconstruction methods.
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 high-speed, high-resolution imaging with low photo-toxicity, achieving improved spatial and temporal resolution, allowing for extended live cell tracking and detailed sub-diffraction imaging.
Implementation Method 1
The microlens array is positioned in a beam path of the coherent light from the at least one light source. The beam path of the coherent light extends between the at least one light source and the sample stage.
Implementation Method 2
at least one light source configured to produce a coherent excitation light and cause luminescence of probe molecules in the sample
Implementation Method 3
cause luminescence of probe molecules in the sample
Implementation Method 4
The microlens array is also positioned in a beam path of the luminescence from the probe molecules. The beam path of the luminescence extends between the sample stage and the image detector.
Implementation Method 5
The microlens array is arranged on a microlens disk which is adapted to connect to a motor and is configured to rotate.
Data Source
AI summary
A super resolution microscope system is disclosed and described. The system can include a sample stage (180) adapted to receive a sample (185) including probe molecules. At least one light source (105) is provided to produce a coherent excitation light to excite the probe molecules and cause luminescence of the probe molecules. An image detector (100) can detect the luminescence from the probe molecules. A microlens array (125) can be positioned in a beam path (110) of the coherent light from the at least one light source (105). The beam path (110) of the coherent light extends between the light source (105) and the sample stage (180). The microlens array (125) can also be positioned in a beam path (112) of the luminescence from the probe molecules. The beam path (112) of the luminescence extends between the sample stage (180) and the image detector (100).