Dynamic Charging Timing for Flow Cytometer Droplet Sorting
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Solution Overview
Problem
Conventional flow cytometer systems face errors in droplet sorting due to varying particle trajectories and velocities, leading to inconsistent timing of droplet break-off and charging, resulting in reduced purity and increased dilution of sorted samples.
Innovation Solution
A method and system that monitor particle presence within a fluid transport chamber, generating an output pulse representing the particle's trajectory, and calculating a composite time delay based on geometry parameters and acceleration functions to control the droplet charging timing, ensuring accurate sorting and increased sample purity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If a fixed time delay is used between particle sensing and droplet charging, then the system operation is simple, but the sorting accuracy deteriorates due to varying particle trajectories and velocities
Solution Approach 1:
The patent applies the dynamics principle by transitioning from a fixed time delay system to a dynamic variable time delay system. The time delay is now calculated individually for each particle based on its measured velocity and trajectory, allowing the charging timing to adapt to each particle's specific path through the fluid stream. This resolves the contradiction by maintaining operational simplicity through automated calculation while achieving high sorting accuracy through particle-specific timing adjustment.
Solution Approach 2:
The patent implements parameter changes by varying the time delay parameter based on measured particle characteristics. Instead of using a constant time delay, the system calculates a specific delay for each particle using its velocity, position, and geometric parameters of the fluid stream. This allows the system to maintain simple operation while achieving accurate sorting by adjusting the timing parameter to match each particle's actual trajectory.
2Device complexity
If particle trajectories are not compensated for, then the device complexity is low, but the sample purity deteriorates due to inconsistent droplet charging timing
Solution Approach 1:
The patent applies feedback by using the measured particle velocity and position information to adjust the charging timing. The system senses particle characteristics, calculates the appropriate time delay based on these measurements and geometric parameters, and then applies the charge at the optimally timed moment. This feedback loop maintains relatively simple device architecture while significantly improving sample purity through accurate, particle-specific charging timing.
Solution Approach 2:
The patent implements preliminary action by calculating the time delay before the actual charging event occurs. The system measures particle properties, computes the required delay using geometric parameters and velocity data, and then executes the charging at the precisely calculated moment. This preliminary calculation step enables accurate sorting without requiring complex real-time adjustment mechanisms during the charging process itself.
3Speed
If a fixed time delay is used, then the processing speed is high, but the productivity deteriorates due to increased dilution and reduced sorting efficiency
Solution Approach 1:
The patent applies dynamics by making the time delay variable rather than fixed, allowing each particle to receive charging at its optimal moment based on its specific trajectory. This dynamic adjustment improves sorting efficiency and reduces dilution by ensuring that each droplet is charged at the precise moment when the target particle is in the correct position, thereby maintaining high processing speed while enhancing overall productivity.
Solution Approach 2:
The patent implements parameter changes by adjusting the time delay parameter for each particle based on its velocity and position measurements. This allows the system to process particles efficiently without the dilution problems associated with fixed timing, as each particle's charging time is optimized individually. The result is improved productivity through reduced sample dilution while maintaining high processing speeds.
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
The dynamic charging mechanism adapts to varying particle trajectories, enhancing the purity of sorted samples and reducing dilution by accurately timing droplet charging, thereby improving the efficiency of the sorting process.
Implementation Method 1
Located optically in the path of the laser output beam 31 after its being intercepted by the carrier fluid stream are one or more sensors of a photodetector subsystem 32. The photodetecting subsystem is positioned to receive light modulated by the contents of (particles/cells within) the carrier fluid stream
Implementation Method 2
downstream of the fluid flow chamber is positioned an electrostatic charging collar 208, which charges a droplet 205 containing the particle of interest as the droplet breaks off of the fluid stream
Implementation Method 3
a stream of charged droplets pass through a pair of oppositely charged, high voltage deflection plates 209, 210, which deflect the charged droplets along a sorted droplet path 213
Data Source
Figure 1~2
Figure 3
AI summary
A flow cytometer subsystem monitors a particle sensing zone within a fluid transport chamber for the presence of a particle (e.g., blood cell) traveling therethrough, and produces an output pulse, whose width is representative of the trajectory and thereby the length of time that the particle is within the particle sensing zone as it travels through the fluid transport chamber. This output pulse is then processed in accordance with geometry parameters of successive time delay zones of the particle fluid transport chamber through which the particle passes, in order to derive a composite time delay between the sensing of the particle to the time at which a fluid droplet containing the particle will break off from the carrier fluid. The composite time delay is employed to accurately establish the time at which the particle is controllably charged as the particle breaks off from the carrier fluid.