Flow Cytometer Setup Using Imaging-Based Stream Alignment

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Existing flow cytometers require substantial user input for setup and alignment, leading to inefficiencies in sorting cells due to manual adjustment of fluidics parameters and collection vessel alignment.

Innovation Solution

An automated system using imaging sensors and processors to capture images of the flow stream, determine key parameters, and adjust settings such as nozzle diameter, hydrostatic pressure, and droplet charging, reducing the need for manual intervention.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Extent of automation

If manual alignment and adjustment of fluidics parameters is used, then the flow cytometer can be set up, but substantial user input and time are required

Engineering Contradiction:
Improvesetup automationVSAvoidsetup time
Core Design Contradiction:
Extent of automationVSLoss of time

Solution Approach 1:

The system uses imaging sensors to automatically detect flow stream position and characteristics, and the controller autonomously adjusts fluidics parameters and collection vessel alignment without requiring user intervention. The system serves itself by using its own sensors and actuators to perform setup tasks that traditionally required manual operation.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

Manual mechanical alignment and adjustment operations are replaced by an automated control system that uses imaging sensors for detection and electronic actuators for adjustment. The mechanical system of manual alignment is substituted with an automated optoelectronic control system that images the flow stream and electronically adjusts parameters.

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

2Measurement precision

If manual alignment of collection vessels is used, then proper collection can be achieved, but positioning accuracy is limited by manual adjustment precision

Engineering Contradiction:
Improvestream position detection accuracyVSAvoidalignment system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

An imaging sensor acts as an intermediary between the flow stream and the control system. Instead of direct manual alignment, the imaging sensor captures images of the flow stream position and transmits this information to the controller, which then makes precise adjustments. The imaging sensor mediates the measurement process, enabling accurate detection without direct human intervention.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The alignment problem is solved by introducing the imaging dimension. Instead of relying solely on mechanical positioning senses, the system uses visual imaging to detect flow stream position in two-dimensional space, providing more precise positional information than manual mechanical alignment alone could achieve.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

3Manufacturing precision

If fluidics parameters are manually matched with nozzle diameter, then sorting can proceed, but parameter optimization is time-consuming and imprecise

Engineering Contradiction:
Improveparameter matching precisionVSAvoidsorting throughput
Core Design Contradiction:
Manufacturing precisionVSProductivity

Solution Approach 1:

The imaging sensor provides continuous feedback on flow stream position and characteristics to the controller. The controller uses this feedback information to automatically optimize fluidics parameters in real-time, ensuring precise matching with nozzle diameter. This closed-loop feedback system replaces manual trial-and-error parameter matching, achieving both high precision and efficiency.

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

Enhances the accuracy and efficiency of cell sorting by automatically aligning collection vessels and optimizing fluidics parameters, improving particle collection and sorting precision.

Implementation Method 1

an imaging sensor configured to capture one or more images of a flow stream of the flow cytometer

Methodology Applied
Scientific EffectLight detection: Photoelectric Effect

Implementation Method 2

the flow cell is rapidly vibrated by an acoustic device, such as a piezoelectric element

Methodology Applied
Scientific EffectPiezoelectric effect: Piezoelectric Effect

Implementation Method 3

The laser light also excites components in the cell stream that have fluorescent properties

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Data Source

PatentEP2984468B1Automated set-up for cell sorting
Publication Date: 2021.11.17 BECTON DICKINSON & CO
  • EP2984468B1 patent drawingFigure 1
  • EP2984468B1 patent drawingFigure 2
  • EP2984468B1 patent drawingFigure 3

AI summary

Apparatus and methods are described for automatically performing set-up steps for flow cytometry operations. The invention provides for the spatial determination of a flow stream and the subsequent automatic alignment of analysis devices and/or collection vessels. The automatic determination of flow stream properties provides for the automatic configuration flow cytometer parameters.