Flow Cytometry Imaging with Multi-Velocity Interrogation Zones
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Conventional flow cytometry systems face challenges in achieving high-resolution imaging of cells at high speeds due to short interrogation times, which lead to low photon counts and increased coincidence events, limiting their applicability to niche applications.
Innovation Solution
The system employs multiple velocity zones within the flow channel to adjust particle velocity, combining high-speed data collection with high-resolution imaging by altering the flow channel dimensions, flow characteristics, or applying fields to change particle velocity between interrogation zones, allowing for increased photon collection and reduced blur.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If ultra-short interrogation times are used to reduce coincidence, then coincidence rate is reduced, but photon collection is insufficient for high resolution imaging
Solution Approach 1:
The flow channel is divided into multiple velocity zones with different flow speeds. The first zone has higher velocity for low coincidence, while the second zone has lower velocity for high photon collection. This segmentation allows the system to achieve both low coincidence rates and sufficient photon counts by processing particles through different zones with optimized velocities for each function.
2Quantity of substance
If larger interrogation times are used to increase photon counts, then imaging quality is improved, but event rate is greatly reduced
Solution Approach 1:
The system segments the particle analysis process into two velocity zones. The first zone operates at high velocity for rapid particle transit (maintaining high event rates), while the second zone operates at low velocity for extended photon collection (improving imaging quality). This segmentation allows the system to achieve both high event rates and high photon counts.
Solution Approach 2:
Particles are pre-positioned and initially interrogated at high velocity to quickly establish presence and basic properties. Then, selected particles are transitioned to the low velocity zone for detailed imaging with extended photon collection. This preliminary action at high speed followed by detailed analysis at low speed optimizes both throughput and image quality.
3Quantity of substance
If particle velocity is reduced for better imaging, then photon counts increase, but coincidence detection capability is reduced
Solution Approach 1:
The flow channel is segmented into a first velocity zone optimized for coincidence detection (higher velocity, shorter interrogation time) and a second velocity zone optimized for photon collection (lower velocity, longer interrogation time). By segmenting the zones, the system can maintain high velocity for coincidence detection while achieving low velocity for imaging in a different spatial location.
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 enables high-resolution imaging of cells at rates comparable to conventional flow cytometry while reducing coincidence events, enhancing data quality and throughput.
Implementation Method 1
a first region of the flow channel defines a first cross-sectional area, the second region of the flow channel defines a second cross-sectional area, and the first and second cross-sectional areas differ from one another
Implementation Method 2
the system may further comprise a field module, the field module being configured to increase or reduce a field at a region of the flow channel so as to move at least some particles in a flow in the flow channel and sensitive to the field from a velocity streamline S0
Implementation Method 3
the field module being configured to increase or reduce a field at a region of the flow channel so as to move at least some particles in a flow
Implementation Method 4
where the integrated fluorescence and scattered light are collected by a bank of detectors
Implementation Method 5
where the integrated fluorescence and scattered light are collected by a bank of detectors
Implementation Method 6
photoelectron multiplying detectors (such as photomultiplier tubes (PMTs) and avalanche photodiodes (APDs))
Implementation Method 7
photoelectron multiplying detectors (such as photomultiplier tubes (PMTs) and avalanche photodiodes (APDs))
Data Source
Figure 1
Figure 2
Figure 3A
AI summary
The present disclosure provides apparatuses, systems, and methods for performing particle analysis through flow cytometry at comparatively high event rates and for gathering high resolution images of particles.