Serial Flow Cytometer With Waveguides for Lower Uncertainty
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Solution Overview
Problem
Conventional flow cytometers face limitations in quantifying uncertainty in individual measurements, making it difficult to characterize biomarker distributions, discriminate cell populations, and detect rare events, with uncertainties undefined in single measurements, limiting object classification and discrimination of rare events.
Innovation Solution
A microfluidic flow cytometer with integrated waveguides for optical signals and multiple measurement regions, allowing repeated measurements of particles in a microchannel, focusing the sample fluid into a single aligned stream using hydrodynamic and inertial forces to achieve lower uncertainties and discriminate complex samples.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional flow cytometers perform single measurements, then the measurement process is simple and fast, but the uncertainty in individual measurements is undefined and measurement precision is poor
Solution Approach 1:
The flow cytometer is divided into multiple independent measurement regions (first measurement region, second measurement region, etc.) along the microchannel. Each region can independently measure particles, enabling multiple measurements of the same particle population. This segmentation allows the system to accumulate statistical data for uncertainty quantification while maintaining modular simplicity
Solution Approach 2:
The system continuously measures particles as they flow through the microchannel across multiple measurement regions. Instead of discrete single measurements, the flow cytometer performs continuous repeated measurements on the same particle population, enabling real-time uncertainty assessment and improved measurement precision without interrupting the flow
2Reliability
If multiple measurement regions are added to achieve repeated measurements, then measurement reliability improves, but device complexity increases
Solution Approach 1:
Multiple measurement regions are integrated into a single continuous microchannel structure. The first measurement region, second measurement region, and other components are merged along the flow path, sharing common fluidic pathways and control systems. This merging approach enables repeated measurements while avoiding the complexity of completely separate measurement systems
Solution Approach 2:
Each measurement region is designed with universal functionality to measure the same particle properties using the same optical and detection principles. This multi-functional design allows any measurement region to independently perform complete particle characterization, improving reliability through redundancy while maintaining design simplicity and reducing the need for region-specific components
3Measurement precision
If sample fluid is focused into a single aligned stream, then measurement precision improves, but fluid flow control complexity increases
Solution Approach 1:
Hydrodynamic focusing is implemented using a focusing fluid delivered through dedicated focusing microchannels. The focusing fluid creates a hydraulic pressure field that confines the sample fluid into a narrow single-file stream within the microchannel. This hydraulic approach achieves precise particle alignment and measurement precision using fluid pressure control rather than complex mechanical positioning systems
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 device achieves robust and repeatable measurements with well-defined uncertainty, enabling accurate characterization of samples like fluorescently labeled cancer cells, improving discrimination of complex samples and accounting for particle shape, deformability, and stability.
Implementation Method 1
a plurality of fluid focusing microchannels intersecting the second microchannel, wherein each of the plurality of fluid focusing microchannels conveys a focusing fluid to the second microchannel such that the plurality of particles in the sample fluid is focused to form a substantially axially aligned particle stream
Implementation Method 2
an excitation light interacts with the at least one of the plurality of particles received in the interrogation region to produce an output light
Implementation Method 3
the first output light further includes emitted light, scattered light, transmitted light, or a combination including at least one of the foregoing types of light
Implementation Method 4
a first light collection path to propagate the output light from the interrogation region to a first optical detector
Data Source
AI summary
Embodiments of the present invention described herein provide a device that can measure a single particle in flow several times along a microchannel with integrated waveguides that carry optical signals (e.g. excitation, emission, transmission, and scattered light) to and from measurement regions. Embodiments of the present invention used to perform multiple measurements of particles, such as microspheres or cells, traveling in a sample fluid through a microfluidic channel achieve lower uncertainties, discriminate complex samples, and account for sources of uncertainty that might be related to the shape, deformability, stability, or activity of objects in a liquid sample.