FLIM-SLM Microscopy Synchronization for Motion-Distortion Correction
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Solution Overview
Problem
Combining off-the-shelf fluorescence lifetime imaging microscopy (FLIM) and scanning light microscopy (SLM) systems faces challenges such as slow sample rates, limited resolutions, non-matched clock sampling frequencies, and image distortion due to sample movement, particularly in applications like retinal imaging and scanning brain or cancerous tissue.
Innovation Solution
A microscopy imaging system and method that integrates a FLIM system with a SLM system, utilizing synchronized fast and slow scanning mirrors, data processing, and real-time data alignment to optimize photon flux and image contrast, correcting for sample movement and transverse chromatic aberration, and compensating for scan image distortion.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If off-the-shelf FLIM and SLM systems are combined, then imaging functionality is enhanced, but sample rate decreases and resolution is limited
Solution Approach 1:
The patent merges FLIM and SLM systems into a single integrated platform with shared optical paths and synchronized data acquisition, enabling simultaneous multi-modal imaging while maintaining high sample rates through unified hardware control
Solution Approach 2:
The integrated system provides multi-functionality by enabling both FLIM and SLM imaging modes through a single platform, allowing users to switch between or combine imaging techniques without requiring separate dedicated systems
2Adaptability or versatility
If off-the-shelf FLIM and SLM systems are combined, then imaging functionality is enhanced, but manufacturing precision and image quality deteriorate due to non-matched clock sampling frequencies and image distortion
Solution Approach 1:
The patent implements dynamic parameter synchronization that adjusts clock sampling frequencies and timing parameters in real-time to match between FLIM and SLM subsystems, eliminating image distortion caused by frequency mismatches and ensuring precise spatial alignment
Solution Approach 2:
The system employs feedback mechanisms that continuously monitor and adjust timing synchronization between subsystems, using real-time data from clock sampling frequency measurements to correct timing offsets and maintain precise image registration
3Adaptability or versatility
If off-the-shelf FLIM and SLM systems are combined, then imaging functionality is enhanced, but measurement precision decreases due to image distortion from sample movement
Solution Approach 1:
The patent implements preliminary spatial calibration and registration procedures that establish reference transformations between FLIM and SLM coordinate systems before imaging, pre-compensating for expected sample movements and maintaining measurement precision throughout the imaging session
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
Achieves high-resolution, synchronized imaging with improved sample rates and reduced distortion, enabling cellular-level resolution and enhanced imaging of biological samples, particularly retinal structures.
Implementation Method 1
Fluorescence is the emission of light by some substances that have absorbed electromagnetic radiation. Many important biologic molecules fluoresce.
Implementation Method 2
A photo detector such as a photomultiplier tube (PMT), a photon-counting PMT, a hybrid PMT, an avalanched photodiode (APD) a photon-counting APD, a silicon photomultiplier (SiPM), or similar detector, is used to detect the emitted fluorescent photons
Data Source
AI summary
A microscopy imaging system comprises a fluorescence lifetime imaging microscopy (FLIM) system comprising a pulsed light source configured to direct a plurality of excitation light pulses onto a sample, a photo detector configured to detect emitted fluorescent photons created by the plurality of excitation pulses interacting with the sample, and a FLIM data acquisition system configured to measure the time interval between the excitation light pulses and the detected emitted fluorescent photons, a scanning light microscopy (SLM) system comprising a SLM data acquisition system, a fast scanning mirror and a slow scanning mirror, wherein the mirrors are configured to scan the light pulses across the sample; and a data processing system communicatively connected to the FLIM and SLM systems. Microscopy imaging methods are also disclosed.


