In Vivo Bioluminescence Kit with Tracking-Dye Normalization

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Solution Overview

Problem

Existing methods for detecting and quantifying bioluminescence in living animals lack the necessary accuracy and validation to ensure reliable and statistically valid measurements.

Innovation Solution

A method involving the administration of a bioluminescent substrate, such as luciferin, combined with a tracking dye, like a fluorescent dye, to normalize the bioluminescent signal by measuring and comparing it to the tracking dye's signal, ensuring proper distribution and statistical validity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If a bioluminescent substrate is administered to an animal for signal detection, then bioluminescent signal can be generated, but the distribution and injection accuracy cannot be validated

Engineering Contradiction:
Improvemeasurement reliabilityVSAvoiddistribution validation information
Core Design Contradiction:
ReliabilityVSLoss of information

Solution Approach 1:

A fluorescent tracking dye is introduced as an intermediary substance that co-distributes with the bioluminescent substrate. The tracking dye serves as a mediator to provide visual confirmation of substrate distribution and injection accuracy through fluorescence imaging, thereby validating the reliability of subsequent bioluminescence measurements without interfering with the bioluminescent signal generation

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If bioluminescence measurement is performed without normalization, then measurement process is simple, but measurement precision is insufficient

Engineering Contradiction:
Improvebioluminescence signal precisionVSAvoidmeasurement process complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The fluorescent signal from the tracking dye provides feedback information about substrate distribution. This feedback is used to normalize the bioluminescent signal by calculating a normalization factor based on the ratio of bioluminescence to fluorescence signals. The feedback mechanism enables precise quantification of bioluminescence while accounting for variations in substrate distribution and injection efficiency

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The method transforms the measurement approach by introducing a secondary parameter (fluorescence signal intensity) that correlates with substrate distribution. By measuring and comparing both fluorescence and bioluminescence parameters, the system achieves precise normalization of bioluminescence signals, converting a single-parameter measurement into a dual-parameter comparative analysis

Inventive Principle:
Principle #35Parameter changes

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 method allows for the normalization and validation of bioluminescent signals, providing greater accuracy and reliability in bioluminescence measurements by correcting for deviations in substrate distribution and ensuring proper injection.

Implementation Method 1

luciferase (e.g., encoded by eukaryotic luc gene), catalyses the oxidation of D-luciferin (D-(-)-2-(6'-hydroxy-2'benzothioazolyl)thiazoline-4-carboxylic acid) in the presence of ATP to generate light signals

Methodology Applied
Scientific EffectBioluminescence: Bioluminescence

Implementation Method 2

measuring the signal of the tracking dye (e.g., fluorescence)

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentEP4151746B1Kit with a composition for in vivo evaluation of bioluminescence
Publication Date: 2025.11.05 CALIPER LIFE SCIENCES INC
  • EP4151746B1 patent drawingFigure 1~2B
  • EP4151746B1 patent drawingFigure 3
  • EP4151746B1 patent drawingFigure 4

AI summary

Compositions and methods are described for normalizing a bioluminescent signal in a live animal.