Flow Cytometer Positional Velocity Sensing for Laser Timing Control
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Solution Overview
Problem
Flow cytometers face issues with laser crosstalk and baseline noise due to temperature fluctuations affecting fluid viscosity, limiting accurate electronic measurements to when a cell interacts with a laser, and requiring second-hand indicators for transit time determination.
Innovation Solution
The method involves irradiating particles in a flow stream with multiple lasers in different interrogation regions, using photodetectors to calculate positional velocity based on light detection, minimizing laser crosstalk and baseline noise by adjusting laser delays and drop delays based on positional velocity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If multiple lasers are used to irradiate particles in different interrogation regions, then measurement capability is improved, but laser crosstalk and baseline noise increase due to temperature fluctuations affecting fluid viscosity
Solution Approach 1:
The system performs preliminary velocity measurement using acoustic signal processing before particle sorting. By measuring the velocity of particles in the flow stream using sound waves and calculating their position, the system can pre-adjust laser timing and drop timing to account for velocity variations, thereby reducing laser crosstalk and baseline noise while maintaining multiple lasers for enhanced measurement capability
Solution Approach 2:
The system implements feedback control by continuously measuring particle velocity using acoustic signals and using this information to dynamically adjust laser timing and drop timing. This feedback loop ensures that particles are accurately illuminated and detected despite temperature-induced viscosity changes, reducing laser crosstalk while maintaining high measurement precision
2Measurement precision
If laser timing is adjusted based on temperature measurements, then transit time prediction is improved, but measurement accuracy deteriorates because temperature is only a second-hand indicator
Solution Approach 1:
The system replaces temperature-based indirect measurement with acoustic-based direct measurement. By using sound waves to measure particle velocity directly in the flow stream, the system obtains reliable real-time velocity data without relying on temperature as a second-hand indicator, thereby improving both transit time prediction and measurement accuracy
Solution Approach 2:
The system introduces acoustic waves as an intermediary to measure particle velocity. Sound waves interact with particles in the flow stream to provide direct velocity information, serving as a more reliable mediator than temperature measurements for predicting transit time and maintaining measurement accuracy
3Object-generated harmful factors
If electronic measurements are taken only when cells interact with lasers, then laser crosstalk is minimized, but measurement opportunities are limited
Solution Approach 1:
The system performs preliminary velocity measurement using acoustic signals before particles reach the laser interrogation regions. This preliminary measurement allows for pre-adjustment of laser timing, enabling measurements to be taken at optimal moments when particles are in the correct position, thereby increasing measurement opportunities while maintaining minimal laser crosstalk
Solution Approach 2:
The system dynamically adjusts laser timing based on real-time velocity measurements of individual particles. By making the laser timing adaptive rather than fixed, the system can capture measurement opportunities for particles with varying velocities while keeping laser exposure brief to minimize crosstalk, thus increasing overall productivity
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 reduces laser interference and noise, enabling precise positional velocity measurement and dynamic adjustment of laser timing for improved particle sorting accuracy and yield, with increased sorting purity and efficiency.
Implementation Method 1
The flow stream is irradiated with light. Variations in the materials in the flow stream, such as morphologies or the presence of fluorescent labels, may cause variations in the observed light
Implementation Method 2
The flow stream is irradiated with light. Variations in the materials in the flow stream, such as morphologies or the presence of fluorescent labels, may cause variations in the observed light
Implementation Method 3
detecting light from the irradiated particle by a first photodetector channel in the first interrogation region and by a second photodetector channel in the second interrogation region
Data Source
AI summary
Aspects of the present disclosure include methods for determining positional velocity of a particle in a flow stream of a particle analyzer. Methods according to certain embodiments include irradiating a sample having a particle in a flow stream of a particle analyzer with a first laser in a first interrogation region and a second laser in a second interrogation region, detecting light from the irradiated particle by a first photodetector channel in the first interrogation region and by a second photodetector channel in the second interrogation region, calculating a velocity of the particle in the flow stream based on the light detected by the first photodetector and by the second photodetector, determining a parameter of the particle in the flow stream and calculating a positional velocity of the particle in the flow stream based on the calculated velocity and the parameter of the particle. Systems and non-transitory computer-readable storage media configured to carry out the subject methods are also provided.