Single Molecular Decay Detection Using Time-Division Multiplexing

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Solution Overview

Problem

Current flow cytometry technologies face challenges in accurately determining the successive single molecular decay of fluorescent molecules due to short fluorescence lifetimes and interference between different fluorophores, leading to incomplete signal collection and inaccurate quantification of fluorescence signals.

Innovation Solution

A measurement system and method that utilize a vessel with optical sources activated in a repeating pattern to excite molecules, coupled with sensor packages featuring photodetectors to detect emission light and determine successive single molecular decay, allowing for the counting of emission pulses and improved signal collection without interference from multiple lasers.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If multiple lasers are used for excitation, then multiplexed analysis capability is improved, but signal interference between different fluorophores worsens

Engineering Contradiction:

Improvemultiplexed analysis capabilityVSAvoidsignal interference

Core Design Contradiction:

Adaptability or versatilityVSObject-generated harmful factors

Solution Approach 1:

The patent employs time-division multiplexing where a single laser source is modulated at different frequencies to excite different fluorophores sequentially. Each fluorophore is excited during specific time windows, allowing the system to achieve multiplexed analysis capability while avoiding signal interference by ensuring that only one fluorophore type is excited at any given moment.

Inventive Principle:

Principle #19Periodic action

2Ease of operation

If conventional photodetectors are used, then detection simplicity is improved, but measurement precision of single molecular decay worsens

Engineering Contradiction:

Improvedetection simplicityVSAvoidsingle molecular decay detection

Core Design Contradiction:

Ease of operationVSMeasurement precision

Solution Approach 1:

The patent replaces conventional photodetectors with superconducting nanowire single-photon detectors (SNSPDs) that operate at cryogenic temperatures. These detectors provide single-photon sensitivity and precise timing capability necessary for measuring short fluorescence lifetimes, while maintaining relatively simple operation through automated temperature control and signal processing systems.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

3Productivity

If fluorescence lifetime is short, then signal collection speed is improved, but measurement precision of decay determination worsens

Engineering Contradiction:

Improvesignal collection speedVSAvoiddecay determination accuracy

Core Design Contradiction:

ProductivityVSMeasurement precision

Solution Approach 1:

The patent employs superconducting nanowire single-photon detectors with picosecond timing resolution to accurately measure short fluorescence lifetimes. The detectors' ability to precisely timestamp individual photons allows for accurate decay curve reconstruction even when fluorescence lifetimes are very short, maintaining measurement precision while enabling rapid signal collection.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The system uses time-division multiplexing with synchronized detection windows that are optimized for each fluorophore's specific lifetime. This allows the system to collect signals from multiple fluorophores with different lifetimes using a single detector, maintaining high collection speed while achieving precise decay determination through tailored detection timing for each species.

Inventive Principle:

Principle #19Periodic 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

Enables higher multiplexed analyses of particles or cells with simultaneous collection of individual photon effects and total fluorescence signals, enhancing throughput and accuracy in flow cytometry without signal loss from multiple lasers.

Implementation Method 1

molecules of interest emitting emission light in response to being excited by the excitation light

Methodology Applied

Scientific EffectFluorescence: Fluorescence

Implementation Method 2

one or more sensor packages each comprising a plurality of photodetectors configured to receive emission light from the molecules of interest and, in response, provide an output voltage signal corresponding to photoelectron response

Methodology Applied

Scientific EffectPhotoelectric Effect: Photoelectric Effect

Data Source

PatentUS20250020512A1System and method for determining successive single molecular decay

Publication Date: 2025.01.16 MIFTEK CORP

AI summary

A measurement system is disclosed which includes a vessel configured to suspend molecules of interest therein, optical sources configured to excite the molecules of interest by an excitation light activated and deactivated in a repeating fashion, during the activation, the sources activated according to a predetermined pattern, the molecules of interest emitting emission light in response to being excited by the excitation light, one or more sensor packages each comprising a plurality of photodetectors configured to receive emission light from the molecules of interest and, in response, provide an output voltage signal and an output current signal corresponding to photoelectron response of an incident photon on the one or more sensor packages, and a detector configured to determine successive single molecular decay of the molecules of interest, generate an emission pulse associated with each incident photon on the one or more sensor packages, and count the number of emission pulses.