Flow Cytometer Time-of-Flight Particle Correlation

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Solution Overview

Problem

Conventional flow cytometry systems face challenges in accurately correlating pulses generated at multiple interrogation points due to the close proximity of these points, leading to potential simultaneous interrogation of particles, which complicates the assignment of measurements to individual particles.

Innovation Solution

The implementation of a method that uses a calibration particle with a unique signature to determine the time-of-flight for particles flowing through the flow cytometer, allowing for the correlation of signal pulses from multiple interrogation regions to specific particles by calculating the time-of-flight and relative positions of interrogation points.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If multiple interrogation points are placed close together to increase measurement efficiency, then productivity is improved, but measurement precision deteriorates due to difficulty in correlating pulses from different points

Engineering Contradiction:

Improvemeasurement efficiencyVSAvoidpulse correlation accuracy

Core Design Contradiction:

ProductivityVSMeasurement precision

Solution Approach 1:

The system uses feedback from detected pulse signals to dynamically adjust and refine the correlation of particles across multiple interrogation points. By continuously monitoring pulse patterns and using this information to improve assignment accuracy, the system resolves the contradiction between close spacing of interrogation points and accurate pulse correlation.

Inventive Principle:

Principle #23Feedback

Solution Approach 2:

The patent changes temporal parameters (time of flight measurements) and spatial parameters (interrogation point positions) to enable accurate correlation. By measuring the time it takes for particles to travel between interrogation points and using this temporal information alongside spatial positioning, the system can accurately assign pulses even when interrogation points are closely spaced.

Inventive Principle:

Principle #35Parameter changes

2Productivity

If particle separation distance is reduced to increase throughput, then productivity is improved, but reliability deteriorates due to increased probability of simultaneous particle interrogation

Engineering Contradiction:

Improveparticle throughputVSAvoidparticle identification accuracy

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The system dynamically adjusts measurement parameters and uses real-time data from multiple interrogation points to track individual particles through the flow stream. By implementing dynamic correlation algorithms that adapt to varying particle densities and flow conditions, the system maintains reliable particle identification even when particles are closely spaced.

Inventive Principle:

Principle #15Dynamics

Solution Approach 2:

The patent adds the time dimension to the spatial measurement by implementing time-of-flight measurements between interrogation points. This temporal dimension allows the system to distinguish between particles that are closely spaced in space by measuring when each particle passes through each interrogation point, thereby maintaining reliability while increasing throughput.

Inventive Principle:

Principle #17Another dimension (Dimensionality change)

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 accurate assignment of pulses to individual particles, even in scenarios where particle separation is reduced, thereby improving the accuracy of particle identification and analysis in flow cytometry systems.

Implementation Method 1

configurations for calibrating a flow cytometer using a calibration particle having a unique signature to determine a time-of-flight for particles flowing through the flow cytometer

Methodology Applied

Scientific EffectTime of flight: Time of Flight

Implementation Method 2

flow cytometers provide measurements of fluorescent intensity of illuminated beads or particles as they pass linearly through a flow chamber

Methodology Applied

Scientific EffectFluorescence: Fluorescence

Data Source

PatentUS8570512B2System, storage mediums, and methods for identifying particles in flow

Publication Date: 2013.10.29 LUMINEX CORP

AI summary

Methods, storage mediums, and systems for correlating pulses generated from multiple interrogation regions in a flow cytometer to particular particles flowing through the flow cytometer are provided. Embodiments of the methods, storage mediums, and systems include configurations for calibrating a flow cytometer using a calibration particle having a unique signature to determine a time-of-flight for particles flowing through the flow cytometer. Based on the calculated time-of-flight and relative positions of interrogation regions corresponding to collectors of the flow cytometer, the methods, storage mediums, and systems may further include configurations for associating other signal pulses to particles of one or more different particle sets.