Dual-Excitation Flow Analysis for Single-Particle Velocity Correlation
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Solution Overview
Problem
Flow-based analysis of small particles, such as extracellular vesicles, is challenging due to their high diffusivity and varying velocities within channels, making it difficult to differentiate and characterize them effectively.
Innovation Solution
A method involving a microfluidic chip with a high-NA air objective and dual excitation light sources, coupled with emission fiber bundles and photodetectors, allows for precise interrogation and characterization of particles and molecules by correlating emission signals to determine velocity and colocalize target molecules.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If flow-based analysis is used for small particles, then particle analysis capability is improved, but measurement precision deteriorates due to high diffusivity and velocity variation
Solution Approach 1:
The patent segments the flow analysis into discrete interrogation zones along the channel, with multiple detection points that sample particles at different positions. This segmentation allows reconstruction of particle properties by combining measurements from multiple zones, overcoming the limitation of single-point measurement precision
Solution Approach 2:
The patent transitions from single-point measurement to multi-dimensional spatial sampling along the channel length. By measuring particles at multiple longitudinal positions and combining these measurements, the system achieves improved precision through dimensional expansion of the measurement space
2Measurement precision
If multiple detection points are used along the channel, then velocity measurement accuracy is improved, but device complexity increases
Solution Approach 1:
The patent implements a universal detection platform where identical detector modules are replicated at multiple positions along the channel. Each module performs the same measurement function, allowing standardized design and simplified manufacturing while achieving multi-point velocity measurements through temporal correlation of signals from different positions
Solution Approach 2:
The patent uses identical detector module copies at multiple channel positions rather than complex unique detectors at each location. This copying approach maintains measurement precision through replicated functionality while reducing device complexity through standardization and modular design
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
Enhances the detection and characterization of small particles and molecules by correcting for diffusion-based challenges, enabling accurate measurement and identification of sub-populations and concentrations.
Implementation Method 1
collecting emission light emitted from the channel with a light collection system comprising a high-NA air objective having a numerical aperture in a range of 0.91 to less than 0.99
Implementation Method 2
outputting first excitation light through an interrogation window onto a first portion of the channel; outputting second excitation light through the interrogation window onto a second portion of the channel distinct from the first portion; generating a first emission signal with a first photodetector based on first emission light received
Data Source
Figure 1A
Figure 1B~2
Figure 3A~3B
AI summary
Systems and methods for analyzing particles flowing in a channel are described. In an embodiment, the channel is configured to flow a particle through a lumen of the channel, the channel defining an interrogation window configured to allow light to pass into and out of the lumen; a light engine comprising: a first light source positioned to output first excitation light onto a first portion of the channel in the interrogation window; and a second light source positioned to output second excitation light onto a second portion of the channel in the interrogation window separate from the first portion. In an embodiment, the systems include an emission fiber bundle comprising a first emission optical fiber and a second emission optical fiber, wherein a proximal end of first emission optical fiber and second emission optical fiber are arranged in an emission fiber bundle head.