Flow Cytometer Fluidics Diagnostics Using Calibration Particles

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Flow cytometers face challenges in detecting and isolating fluidics failures due to the convoluted nature of the fluidic system, which often requires troubleshooting other subsystems before addressing fluidics issues, leading to inefficiencies and potential misdiagnosis.

Innovation Solution

A method and system that utilize calibration particles and multiple light beams to collect and analyze data on light emitted from particles passing through a flow cell, allowing for the determination of fluidics health by analyzing data intensity peak times and comparing them to system specifications, thereby isolating fluidics issues from optical and electronic subsystems.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If traditional troubleshooting methods are used to isolate fluidics failures, then other subsystems (optics, electronics) must be tested before fluidics, but this leads to increased diagnostic time and potential misdiagnosis

Engineering Contradiction:
Improvediagnostic accuracyVSAvoiddiagnostic time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent segments the diagnostic process by introducing a dedicated fluidics diagnostic mode that independently tests fluidics subsystems. This separates fluidics diagnostics from the traditional comprehensive troubleshooting approach, allowing direct measurement of fluidics parameters (pressure, flow rate, particle arrival time) without needing to test optics and electronics first, thereby reducing diagnostic time while maintaining accuracy

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces calibration particles as an intermediary diagnostic tool. These particles serve as a mediator to indirectly measure fluidics system performance by monitoring their arrival times and flow characteristics. The calibration particles provide a measurable proxy for fluidics health, enabling accurate diagnostics without direct intervention in the complex fluidic pathways

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If comprehensive system testing is performed to ensure accurate diagnosis, then all subsystems must be evaluated, but this increases complexity of the diagnostic process

Engineering Contradiction:
Improvediagnostic reliabilityVSAvoiddiagnostic process complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The diagnostic system is segmented into distinct operational modes (acquisition mode, diagnostics mode, calibration mode). The fluidics diagnostic mode is further segmented into specific test types (pressure testing, flow rate testing, particle arrival time analysis). This segmentation allows the system to perform comprehensive fluidics diagnostics independently without requiring simultaneous evaluation of all subsystems, reducing overall diagnostic complexity while maintaining reliability

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The system performs preliminary fluidics diagnostics using calibration particles before full system operation. By pre-characterizing fluidics performance metrics (baseline pressure, flow rate, particle arrival time distribution), the system establishes reference values that simplify subsequent diagnostic comparisons. This preliminary action reduces the complexity of comprehensive testing by having diagnostic criteria already established

Inventive Principle:
Principle #10Preliminary action

3Measurement precision

If traditional fluidics troubleshooting is used without direct measurement capabilities, then extensive experimentation is required, but this leads to loss of time and resources

Engineering Contradiction:
Improvefluidics parameter measurementVSAvoidtroubleshooting time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent replaces manual, mechanical troubleshooting methods with automated electronic measurement and analysis. The system uses electronic sensors to directly measure pressure, flow rate, and particle arrival times, then processes this data computationally to diagnose fluidics issues. This substitution of electronic/mechanical systems eliminates the need for extensive manual experimentation while providing precise measurements of fluidics parameters

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

Solution Approach 2:

The diagnostic system performs self-diagnosis by automatically analyzing its own operational data. The flow cytometer monitors its own fluidics parameters using integrated sensors and calibration particles, comparing real-time measurements against expected ranges. This self-service capability allows the system to identify and report fluidics issues without external intervention or extensive troubleshooting, saving time and resources

Inventive Principle:
Principle #25Self-service

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 the detection of steady-state and dynamic irregularities in fluidic systems, facilitating troubleshooting and adjustment of fluidic systems to meet specifications without the need for extensive experimentation, improving diagnostic efficiency and accuracy.

Implementation Method 1

The high photon flux at this focal spot produces scatter of light by a particle

Methodology Applied
Scientific EffectLight scattering: Scattering

Implementation Method 2

emission of light from the particle or labels attached to the particle

Methodology Applied
Scientific EffectFluorescence emission: Fluorescence

Data Source

PatentEP3114458B1Methods for diagnosing a fluidics system
Publication Date: 2024.08.21 LIFE TECHNOLOGIES CORP
  • EP3114458B1 patent drawingFigure 1
  • EP3114458B1 patent drawingFigure 2
  • EP3114458B1 patent drawingFigure 3

AI summary

The present set of embodiments relates to systems and methods for diagnosing a fluidics system and determining data processing settings for a flow cytometer. Systems and methods for diagnosing a fluidics system require accurate measurement and interpretation of fluctuations within the fluid delivery system. Systems and methods for determining data processing settings require an accurate measurement of peak times among various channels and being able to adjust time delay settings wherein peak time is the measurement of time elapsed from the beginning of the data collection time window to the highest peak in the window.