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

VSEngineering 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

Engineering Contradiction:
Improveimaging functionalityVSAvoidsample rate
Core Design Contradiction:
Adaptability or versatilityVSProductivity

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

Inventive Principle:
Principle #5Merging (Combining)

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

Inventive Principle:
Principle #6Universality (Multi-functionality)

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

Engineering Contradiction:
Improveimaging functionalityVSAvoidimage quality
Core Design Contradiction:
Adaptability or versatilityVSManufacturing precision

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

Inventive Principle:
Principle #35Parameter changes

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

Inventive Principle:
Principle #23Feedback

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

Engineering Contradiction:
Improveimaging functionalityVSAvoidspatial accuracy
Core Design Contradiction:
Adaptability or versatilityVSMeasurement precision

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

Inventive Principle:
Principle #10Preliminary action

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.

Methodology Applied
Scientific EffectFluorescence: Fluorescence

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

Methodology Applied
Scientific EffectPhotoelectric Effect: Photoelectric Effect

Data Source

PatentUS12484785B2Microscopy imaging system and methods
Publication Date: 2025.12.02 UNIVERSITY OF ROCHESTER
  • US12484785B2 patent drawing
  • US12484785B2 patent drawing
  • US12484785B2 patent drawing

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.