Radiofrequency-Multiplexed Fluorescence for Phase-Corrected Particle Imaging

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Solution Overview

Problem

Existing flow cytometry techniques face challenges in accurately characterizing and sorting particles in a flow stream due to variations in light interactions with particles, such as morphologies or fluorescent labels, leading to poor resolution and noise in imaging and sorting processes.

Innovation Solution

The method involves generating frequency-encoded fluorescence data from particles in a flow stream and applying a phase correction component through transforms like Fourier transforms or digital lock-in amplifiers to calculate phase-corrected spatial data, enhancing imaging resolution and enabling precise sorting.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If traditional flow cytometry techniques are used to detect light interactions with particles, then the sorting function can be performed, but the resolution and image clarity are poor due to noise and variations in light interactions

Engineering Contradiction:

Improveparticle characterization accuracyVSAvoidnoise and resolution degradation

Core Design Contradiction:

Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The patent introduces frequency encoding as an intermediary representation layer between light detection and particle characterization. By converting spatial information into frequency-domain signals through heterodyne detection, the system mediates the transformation of optical interactions into robust spectral signatures that resist noise and enable precise particle differentiation

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces traditional spatial/image-based particle characterization with frequency-domain signal processing. Instead of analyzing spatial distributions of light interactions, the system uses frequency-encoded spectral signatures to represent particle properties, substituting mechanical/optical image analysis with spectral signal analysis that is more resistant to noise

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Measurement precision

If frequency-encoded fluorescence data is generated and phase correction is applied, then the resolution and accuracy of particle characterization improve, but the device complexity and computational requirements increase

Engineering Contradiction:

Improvespatial data accuracyVSAvoidsignal processing complexity

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent applies phase correction as a preliminary processing step before final particle characterization. By pre-correcting phase distortions in the frequency-encoded signals using reference measurements and computational algorithms, the system prepares cleaner spectral data for subsequent analysis, reducing the complexity of later processing stages

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent implements feedback mechanisms through reference beam measurements and iterative phase correction algorithms. The system continuously monitors and adjusts for phase distortions by comparing detected signals against reference standards, enabling real-time compensation that simplifies the overall processing chain through adaptive correction

Inventive Principle:

Principle #23Feedback

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 improves the resolution and accuracy of particle characterization and sorting by reducing noise and enhancing the clarity of images, allowing for better differentiation and separation of particles based on their spatial dimensions and properties.

Implementation Method 1

a light beam generator component configured to generate a plurality of frequency-shifted laser beams

Methodology Applied

Scientific EffectFrequency shifting:

Implementation Method 2

Each spatial location across the particle in the flow stream is characterized by a different beat frequency which corresponds to the difference between the frequency of the local oscillator beam and the frequency of the radiofrequency-shifted beam at that location

Methodology Applied

Scientific EffectHeterodyne detection: Heterodyne

Implementation Method 3

The particle having one or more fluorophores is irradiated with a plurality of frequency shifted beams of light from a light beam generator to generate frequency-encoded fluorescence

Methodology Applied

Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS12366519B2Phase-correction of radiofrequency-multiplexed signals

Publication Date: 2025.07.22 BECTON DICKINSON & CO

AI summary

Aspects of the present disclosure include methods for characterizing particles of a sample in a flow stream. Methods according to certain embodiments include generating frequency-encoded fluorescence data from a particle of a sample in a flow stream; and calculating phase-corrected spatial data of the particle by performing a transform of the frequency-encoded fluorescence data with a phase correction component. In certain embodiments, methods include generating an image of the particle in the flow stream based on the phase-corrected spatial data. Systems having a processor with memory operably coupled to the processor having instructions stored thereon, which when executed by the processor, cause the processor to calculate phase-corrected spatial data from frequency-encoded fluorescence data of a particle a flow stream are also described. Integrated circuit devices (e.g., field programmable gate arrays) having programming for practicing the subject methods are also provided.