TRFI System Pulse Shaping for Fluorescence Imaging

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Solution Overview

Problem

Current time-resolved fluorescence imaging (TRFI) methods are limited by the complexity and time-consuming nature of fluorescence lifetime extraction, especially when dealing with multi-exponential decay curves and noisy signals, which can lead to unreliable results when closely spaced lifetimes are involved.

Innovation Solution

A TRFI system that obtains images without the need for lifetime fitting, using a pulse-shaping illumination source circuit with an LED and stub line to generate a linear decay profile, allowing for simple and accurate fluorescence image acquisition through subtraction and division-based methods.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If fluorescence lifetime extraction using nonlinear least squares fitting is used, then fluorescence lifetime can be estimated, but the analysis becomes complicated and time-consuming

Engineering Contradiction:
Improvefluorescence lifetime estimation accuracyVSAvoidalgorithm complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent extracts only the essential information needed for imaging (fluorophore distribution) without performing complete lifetime extraction. By using ratio-based methods, the system obtains imaging data while eliminating the need for complex lifetime fitting algorithms, thus reducing computational complexity while maintaining imaging capability

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

Instead of extracting lifetime from decay curves through complex fitting, the patent inverts the approach by using measured intensity ratios at different time points to directly calculate fluorophore distribution. This reversal eliminates the need for iterative fitting procedures and provides a more straightforward calculation path

Inventive Principle:
Principle #13The other way round (Inversion)

2Adaptability or versatility

If multi-exponential decay curve fitting is performed, then multiple fluorophore lifetimes can be extracted, but the calculation time increases significantly

Engineering Contradiction:
Improveability to handle multiple fluorophoresVSAvoidimage acquisition speed
Core Design Contradiction:
Adaptability or versatilityVSProductivity

Solution Approach 1:

The patent performs partial analysis by measuring intensity ratios at specific time points rather than analyzing the complete decay curve. This partial measurement approach provides sufficient information for imaging multiple fluorophores while avoiding the computational burden of complete multi-exponential fitting, thus maintaining productivity

Inventive Principle:
Principle #16Partial or excessive action

Solution Approach 2:

The patent changes the measurement parameters from continuous decay curve sampling to discrete time-point intensity ratio measurements. By selecting specific time points for measurement, the system can distinguish multiple fluorophores based on their different decay characteristics without requiring full curve fitting, thereby improving acquisition speed

Inventive Principle:
Principle #35Parameter changes

3Reliability

If noise is present in fluorescence signal, then measurement is more realistic, but lifetime extraction becomes even more unreliable

Engineering Contradiction:
Improvelifetime extraction reliabilityVSAvoidsignal noise
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent introduces intensity ratios at different time points as intermediary measurements rather than directly extracting lifetime from noisy decay curves. These ratio measurements serve as mediators that are less sensitive to noise, providing a more reliable pathway to determine fluorophore distribution without the full impact of noise on lifetime extraction

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent performs preliminary measurements of intensity ratios at selected time points before attempting any lifetime extraction. This preliminary data collection provides a noise-resistant foundation for imaging that can be obtained quickly and reliably, even in the presence of significant signal noise

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

This approach enables faster, more reliable time-resolved fluorescence imaging by eliminating the need for complex lifetime calculations, providing clear differentiation of fluorophores and reducing computational power requirements, while maintaining image quality and contrast.

Implementation Method 1

the illumination source comprises an LED and stub line configured for generating a linear decay profile

Methodology Applied
Scientific EffectLight Emitting Diode: Light Emitting Diode

Implementation Method 2

The time-resolved fluorescence signal of a fluorophore is usually a mono-exponential curve

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentEP2820398B1Apparatus for time-resolved fluorescence imaging and pulse shaping
Publication Date: 2018.10.24 RGT UNIV OF CALIFORNIA
  • EP2820398B1 patent drawingFigure 1A~2
  • EP2820398B1 patent drawingFigure 3~4
  • EP2820398B1 patent drawingFigure 5~6

AI summary

A time-resolved fluorescence imaging (TRFI) system that images a target medium without lifetime fitting. Instead of extracting the lifetime precisely, the system images the fluorophore distribution to allow for a simple and accurate method to obtain the fluorescence image without lifetime-extraction for time-resolved fluorescence imaging. An illumination source circuit for TRFI is also disclosed that shapes the excitation pulse. In one embodiment, the illumination source comprises an LED and stub line configured for generating a linear decay profile.