Flow Cytometer Entrainment Factor for Clumping Assessment

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Flow cytometry faces challenges in efficiently sorting cells due to clumping or aggregation, leading to reduced sorting yield and poor recovery, especially in samples with adherent cells or increased cell-to-cell interaction, where current methods struggle to assess sample behavior in real-time effectively.

Innovation Solution

The method calculates an 'entrainment factor' by comparing observed signal frequencies to expected frequencies based on a Poisson distribution, allowing for corrective actions such as halting or adjusting the flow to address clumping, and using a flow system to compare experimental signal frequencies to predetermined frequencies for purging or resuming signal collection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If flow cytometry is used to sort cells, then cell characterization and sorting capability are improved, but clumping or aggregation reduces sorting yield and recovery

Engineering Contradiction:
Improvesorting yieldVSAvoidsample behavior stability
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The system performs preliminary assessment of sample behavior by calculating the entrainment factor before sorting begins. This allows identification of clumping issues in advance, enabling corrective actions such as adjusting sample preparation or instrument parameters to prevent yield loss during sorting

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The system continuously monitors sample behavior during sorting by comparing observed signal frequencies to expected Poisson distribution frequencies. This real-time feedback enables dynamic adjustment of sorting parameters to maintain optimal yield despite variations in sample behavior

Inventive Principle:
Principle #23Feedback

2Measurement precision

If current methods are used to assess sample behavior, then basic monitoring is possible, but real-time effective assessment of clumping is insufficient

Engineering Contradiction:
Improvesample behavior assessment accuracyVSAvoidresponse time to clumping
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The system replaces manual or post-sorting assessment methods with automated real-time monitoring using computational analysis. By comparing observed signal frequencies to Poisson distribution expectations, the system provides precise, objective measurement of clumping behavior instantaneously during sorting

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The system autonomously monitors and assesses sample behavior without requiring external intervention. The automated calculation of entrainment factors and real-time comparison to theoretical distributions enables the system to self-diagnose clumping issues and trigger corrective actions independently

Inventive Principle:
Principle #25Self-service

Data Source

PatentEP2951557B1Methods and systems for assessing sample behavior in a flow cytometer
Publication Date: 2022.10.05 BECTON DICKINSON & CO
  • EP2951557B1 patent drawingFigure 1
  • EP2951557B1 patent drawingFigure 2
  • EP2951557B1 patent drawingFigure 3

AI summary

Methods and systems are disclosed for generating an entrainment factor in a flow cytometry sample. The methods comprise flowing a sample with a series of particles through the flow cytometer, detecting events and calculating an expected frequency of those events based on a distribution, such as a Poisson distribution, and measuring an observed frequency of particle events. An entrainment factor may be generated from a ratio of observed event frequency to expected event frequency. Further adjustment to the flow cytometer maybe performed based on the indicated entrainment factor such as adjusted sorting bias.