Flow Cytometer Droplet Charging Timing Adjustment

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Solution Overview

Problem

Flow cytometers face challenges in accurately charging droplets during the separation process, leading to inconsistent droplet charging due to timing and phase issues, which affects the efficiency and accuracy of particle sorting and analysis.

Innovation Solution

A system that adjusts the timing and phase of the charge pulse applied to the fluid stream using a controller, in conjunction with a piezoelectric voltage generator and charge pulse generator, ensures proper charging of droplets by synchronizing the charge pulse with droplet separation, utilizing a conductive mesh to accumulate and measure charge for optimization.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If the charge pulse timing is not precisely synchronized with droplet separation, then droplet charging consistency deteriorates, but increasing timing adjustment complexity increases device complexity

Engineering Contradiction:
Improvedroplet charging consistencyVSAvoidtiming adjustment complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The system employs a feedback mechanism where the actual droplet separation timing is detected and used to automatically adjust the charge pulse timing. The controller monitors the separation event and dynamically synchronizes the charge pulse delivery, ensuring consistent charging without requiring manual timing calibration or complex preset adjustments.

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The system performs self-calibration by automatically detecting droplet separation timing and adjusting its own charge pulse synchronization without external intervention. The controller autonomously determines the optimal timing based on detected separation events and configures the charge pulse generator accordingly, eliminating the need for operator intervention in timing adjustment.

Inventive Principle:
Principle #25Self-service

2Measurement precision

If automated timing adjustment is implemented, then charging accuracy improves, but system complexity increases

Engineering Contradiction:
Improvecharging accuracyVSAvoidsystem complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The controller serves multiple functions: it detects droplet separation events, determines optimal charge timing, generates control signals for the charge pulse generator, and monitors charging effectiveness. By consolidating these functions into a single controller, the system achieves automated precise charging without proportionally increasing overall system complexity.

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The system replaces manual mechanical timing adjustment mechanisms with an automated electronic control system. The controller uses electronic detection and signal processing to synchronize charge pulse timing, eliminating the need for manual mechanical calibration devices and reducing the complexity of physical adjustment mechanisms.

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

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 ensures consistent and optimal charging of droplets, improving the accuracy and efficiency of particle sorting and analysis by maintaining precise control over the charge applied to each droplet, thereby enhancing the overall performance of the flow cytometer.

Implementation Method 1

The nozzle includes a piezoelectric actuator 112, which generates vibrations in the fluid stream 114 to cause the fluid stream 114 to break into droplets at the droplet separation point 116

Methodology Applied
Scientific EffectPiezoelectric effect: Piezoelectric Effect

Implementation Method 2

The droplets become charged by applying a charge pulse from charge pulse generator 150 to the stream 114 during, but not after, prior to the time that droplets become separated from the fluid stream 114

Methodology Applied
Scientific EffectElectrical charge transfer: Conduction (electrical)

Implementation Method 3

The droplets are then deflected by deflection plates 124, 126 that are charged with positive and negative voltages

Methodology Applied
Scientific EffectElectric field deflection: Electric Field

Data Source

PatentEP3017288B1Timing and/or phase adjustment of the charging of drops from a fluid stream in a flow cytometer
Publication Date: 2020.10.07 BIO RAD LABORATORIES INC
  • EP3017288B1 patent drawingFigure 1
  • EP3017288B1 patent drawingFigure 2~3B
  • EP3017288B1 patent drawingFigure 4

AI summary

Disclosed is a system for setting the timing or phase of the separation of droplets from a fluid stream in a flow cytometer, or the timing or phase of a charge pulse generator, based upon the collected charge of charged droplets. In one embodiment, a conductive mesh can be used to collect the charged droplets that are either deflected or not deflected by the deflection plates. In another embodiment, the charge can be collected from metal plates in the waste collection device. In addition, a defanning device is disclosed that allows substantially uniform deflection of charged cells.