Fluidic Channel System for Single Particle Isolation and Flow Control
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Solution Overview
Problem
Current methods for single-cell analysis face challenges in yield, quality, throughput, and cost, particularly in isolating and analyzing genetically heterogeneous cell populations in cancer biology, where traditional bulk tumor measurements are insufficient.
Innovation Solution
The development of systems and methods for flowing and isolating particles, such as biological entities, in fluidic channels, allowing for the separation and collection of individual particles at controlled frequencies and spacings, using intersecting fluidic channels and pressure management to maintain flow rates and prevent particle dilution or shear forces.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If traditional bulk tumor measurements are used, then analysis is simplified, but genetic heterogeneity cannot be resolved and measurement precision is insufficient
Solution Approach 1:
The system segments the particle analysis process into distinct functional modules: particle introduction channel, isolation chamber with detection zone, and collection channel. This segmentation allows each module to be optimized independently for its specific function while maintaining overall system precision for single-cell analysis.
Solution Approach 2:
The patent introduces an intermediary isolation chamber with detection zone that mediates between particle introduction and collection. This intermediary structure enables precise detection and isolation of single particles without requiring complex direct manipulation systems, thus improving measurement precision while managing device complexity.
2Measurement precision
If particles are isolated individually, then genetic heterogeneity analysis is improved, but throughput decreases due to sequential processing
Solution Approach 1:
The system employs periodic action by cycling through different flow rates in the introduction channel versus the collection channel. The introduction channel operates at higher flow rates to deliver particles efficiently, while the collection channel uses lower flow rates to prevent dilution. This periodic flow rate modulation enables both high throughput and precise single-particle analysis.
Solution Approach 2:
The patent implements dynamic flow rate adjustment where the fluid flow rate in the introduction channel is modulated independently from the collection channel. This dynamic control allows the system to adapt flow conditions optimally for each stage of particle processing, maximizing throughput while maintaining detection accuracy.
3Productivity
If flow rate is increased to improve throughput, then particle delivery is faster, but particle dilution and shear forces increase
Solution Approach 1:
The system segments the flow path into an introduction channel and a collection channel with independent flow rate control. This segmentation allows the introduction channel to operate at high flow rates for rapid particle delivery, while the collection channel maintains lower flow rates to preserve particle integrity and prevent dilution, thus resolving the contradiction between throughput and reliability.
Solution Approach 2:
Different flow rate conditions are applied locally to different sections of the system. The introduction channel receives high flow rates locally to maximize delivery speed, while the collection channel maintains optimized lower flow rates locally to protect particle integrity. This local quality differentiation enables simultaneous high throughput and high reliability.
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
Enables the measurement and observation of single particles over extended periods, allowing for the monitoring of growth and physical property changes, and the efficient collection of individual cells without significant dilution or shear, improving the analysis of biological entities like cells and bacteria.
Implementation Method 1
introducing a single particle into a second fluidic channel from a first fluidic channel containing a plurality of particles
Implementation Method 2
detecting, with a detector, the presence of the single particle in the second fluidic channel
Data Source
AI summary
Systems and methods for flowing particles, such as biological entities, in a fluidic channel(s) are generally provided. In some cases, the systems described herein are designed such that a single particle may be isolated from a plurality of particles and flowed into a fluidic channel (e.g., a microfluidic channel) and/or collected e.g., on fluidically isolated surfaces. For example, the single particle may be present in a plurality of particles of relatively high density and the single particle is flowed into a fluidic channel, such that it is separated from the plurality of particles. The particles may be spaced within a fluidic channel so that individual particles may be measured/observed over time. In certain embodiments, the particle may be a biological entity. Such article and methods may be useful, for example, for isolating single cells into individual wells of multi-well cell culture dishes (e.g., for single-cell analysis).