Acridinium-Fluorophore Conjugates for Multiplexed Chemiluminescent Detection

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Solution Overview

Problem

Current in vitro diagnostic methods face challenges in multiplexing, where detecting multiple analytes from a single sample efficiently is hindered by the inability to effectively differentiate and measure signals, particularly due to limitations in chemiluminescence wavelength shifting technologies.

Innovation Solution

Development of compounds with an acridinium moiety linked to a fluorophore via a rigid diamine linker, which upon chemiluminescent triggering, shifts light output to the emission wavelength of the fluorophore, enabling the detection of two or more analytes in a single test by exploiting chemiluminescent energy or electron transfer processes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If chemiluminescence is used for signal detection, then detection sensitivity is improved, but the ability to differentiate multiple signals (multiplexing) deteriorates due to limited wavelength shifting capability

Engineering Contradiction:

Improvedetection sensitivityVSAvoidmultiplexing capability

Core Design Contradiction:

Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent changes the emission wavelength parameter of chemiluminescent compounds by introducing fluorophore acceptors with different energy levels. The acridinium ester donor transfers energy to fluorophores (fluorescein, rhodamine, cyanine) with varying emission wavelengths, enabling spectral differentiation for multiplexing while preserving detection sensitivity

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent introduces fluorophore molecules as intermediary energy transfer acceptors between the chemiluminescent reaction and the detection system. These fluorophores receive energy from the acridinium ester donor and re-emit at distinct wavelengths, serving as mediators that enable signal differentiation without compromising the underlying chemiluminescent detection sensitivity

Inventive Principle:

Principle #24Intermediary (Mediator)

2Measurement precision

If multiple separate tests are performed to detect different analytes, then measurement accuracy is improved, but productivity deteriorates due to reduced throughput and increased time per result

Engineering Contradiction:

Improvemeasurement accuracyVSAvoidthroughput

Core Design Contradiction:

Measurement precisionVSProductivity

Solution Approach 1:

The patent merges multiple detection capabilities into a single assay by using combinations of acridinium ester-d fluorophore acceptor conjugates, each targeting different analytes. Multiple analytes are detected simultaneously in one sample processing run, maintaining measurement accuracy through specific binding members while dramatically improving throughput by eliminating sequential testing

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The patent creates a universal detection platform where the acridinium ester donor can work with multiple different fluorophore acceptors (fluorescein, rhodamine, cyanine families) across various excitation and emission wavelengths. This multi-functional system allows a single chemiluminescent platform to perform multiple analyte detections with the same fundamental mechanism

Inventive Principle:

Principle #6Universality (Multi-functionality)

3Device complexity

If conventional chemiluminescent compounds are used, then device complexity is minimized, but the ability to achieve wavelength shift deteriorates, limiting multiplexing potential

Engineering Contradiction:

Improvesystem complexityVSAvoidwavelength shifting capability

Core Design Contradiction:

Device complexityVSAdaptability or versatility

Solution Approach 1:

The patent creates composite chemiluminescent systems by combining acridinium ester donors with fluorophore acceptors in defined molecular conjugates. These composite structures integrate the high-energy chemiluminescent reaction of acridinium with the wavelength-tunable emission properties of various fluorophores, achieving wavelength shifting without adding complex external instrumentation

Inventive Principle:

Principle #40Composite materials

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 allows for 100% shifted emission, effectively differentiating and measuring multiple analytes in a single test, enhancing diagnostic throughput and reducing costs by enabling the use of multiple conjugates with different fluorophores in a single assay.

Implementation Method 1

upon chemiluminescent triggering, shifts light output to the emission wavelength of the fluorophore, enabling the detection of two or more analytes in a single test by exploiting chemiluminescent energy or electron transfer processes

Methodology Applied

Scientific EffectChemiluminescence: Chemiluminescence

Implementation Method 2

exploiting chemiluminescent energy or electron transfer processes

Methodology Applied

Scientific EffectEnergy transfer:

Implementation Method 3

exploiting chemiluminescent energy or electron transfer processes

Methodology Applied

Scientific EffectElectron transfer:

Data Source

PatentUS20220291223A1Chemiluminescent compounds for multiplexing

Publication Date: 2022.09.15 ABBOTT LAB INC

AI summary

Disclosed herein are compounds, conjugates, and methods that may be used to detect the presence of an analyte in a sample, such as a biological sample.