Flow Cytometer Sheath Fluid Mixing System

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Solution Overview

Problem

The existing methods for mixing deionized water and concentrated sheath fluid in flow cytometry often introduce turbulence and micro-bubbles when the fluids are combined at a high rate, leading to operational issues and requiring manual mixing several hours in advance, which is impractical and labor-intensive.

Innovation Solution

A system using a three-way valve and a continuous pump to slowly mix deionized water and concentrated sheath fluid at a controlled rate, ensuring no bubbles form, with a controller adjusting the flow to maintain a uniform concentration of sheath fluid, matching the outflow rate to prevent turbulence and automate the process.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If deionized water and concentrated sheath fluid are mixed at a high rate, then mixing time is reduced and productivity is improved, but turbulence and micro-bubbles are introduced into the mixture

Engineering Contradiction:
Improvemixing speedVSAvoidbubbles and turbulence
Core Design Contradiction:
ProductivityVSObject-generated harmful factors

Solution Approach 1:

A three-way valve is introduced as an intermediary device between the fluid sources and the mixing reservoir. This valve enables controlled, sequential delivery of deionized water and concentrated sheath fluid at low flow rates, preventing turbulence and bubble formation while maintaining efficient mixing through automated control sequences.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The system performs preliminary actions by pre-positioning the three-way valve to deliver deionized water first to establish a bubble-free base layer in the reservoir, then sequentially introducing concentrated sheath fluid. This staged approach prevents premature turbulence and ensures smooth mixing from the outset.

Inventive Principle:
Principle #10Preliminary action

2Quantity of substance

If concentrated sheath fluid is used to reduce storage costs, then the volume of fluid to be stored is reduced, but the mixing process becomes more critical to avoid bubbles

Engineering Contradiction:
Improvestorage volumeVSAvoidmixing quality
Core Design Contradiction:
Quantity of substanceVSReliability

Solution Approach 1:

The controller monitors the mixing process and automatically adjusts the three-way valve positions and pump operations based on pre-programmed sequences. This feedback control ensures that deionized water and concentrated sheath fluid are delivered in precise proportions and at controlled rates, maintaining high mixing quality and reliability while using concentrated fluid formulations.

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The system dynamically adjusts flow rates and valve positions during the mixing process. The three-way valve switches between positions to control which fluid is delivered, and the pump operates at variable speeds to maintain optimal flow conditions that prevent bubble formation while ensuring thorough mixing of the concentrated sheath fluid.

Inventive Principle:
Principle #15Dynamics

3Object-generated harmful factors

If manual mixing is performed several hours in advance to avoid bubbles, then bubble-free mixing is achieved, but labor intensity and operational complexity increase

Engineering Contradiction:
Improvebubble formationVSAvoidoperational simplicity
Core Design Contradiction:
Object-generated harmful factorsVSEase of operation

Solution Approach 1:

The system performs self-service mixing by automatically controlling the three-way valve and pump through an integrated controller. The automated sequence eliminates the need for manual intervention, achieving bubble-free mixing without requiring operators to perform time-consuming manual mixing procedures hours in advance. The system manages the entire mixing process autonomously.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The mixing process is made continuous and on-demand through automated control. Instead of requiring advance preparation, the three-way valve and pump system can mix sheath fluid continuously or on-demand at the precise moment it is needed, maintaining bubble-free conditions throughout the continuous operation without interruption or manual intervention.

Inventive Principle:
Principle #20Continuity of useful 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

This solution allows for the efficient and automated creation of sheath fluid with the correct concentration, eliminating bubbles and turbulence, thereby improving the usability and reliability of flow cytometers while reducing labor and storage costs through the use of concentrated sheath fluid.

Implementation Method 1

a pump that is interposed between the valve and the pressurized reservoir and that, when operating and depending on the position of the valve, delivers the deionized water or the concentrated sheath fluid into the pressurized reservoir at a rate that is sufficiently slow that no bubbles form in the pressurized reservoir

Methodology Applied
Scientific EffectPressure gradient: Pressure Gradient

Implementation Method 2

a valve that has: a first input that is coupled to the first container, a second input that is coupled to the second container, and an output, wherein the valve supplies the deionized water through the output to the pressurized reservoir when the valve is in a first position, and supplies the concentrated sheath fluid through the output to the pressurized reservoir when the valve is in a second position

Methodology Applied
Scientific EffectValve flow control: Valve

Data Source

PatentEP2864849B1Fluid mixing and rinsing system for a flow cytometer
Publication Date: 2020.09.02 BIO RAD LABORATORIES INC
  • EP2864849B1 patent drawingFigure 1
  • EP2864849B1 patent drawingFigure 2
  • EP2864849B1 patent drawingFigure 3

AI summary

Disclosed is a system (100) that can mix deionized water (144) and concentrated sheath fluid (146) to provide sheath fluid (148) in a flow cytometer system having a desired concentration. Flow rates are low, which substantially match the flow rate of sheath fluid through the nozzle (142), so that turbulence and air bubbles are not formed in the sheath fluid. The available deionized water is then used for back flushing and removal of sample cells and deposited salts from the sheath fluid.