Biased Sample Injection Flow Cell for High-Resolution Cytometry
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Solution Overview
Problem
Conventional flow cytometers face challenges in maintaining measurement resolution at higher sample stream rates due to increased spatial variation of particles in the transverse direction, often resulting in reduced reproducibility and potential system clogging or complexity.
Innovation Solution
A flow cell design with an inlet chamber featuring a profiled surface that guides the sample stream to flow in biased proximity to a specific profile, allowing for asymmetric positioning of the sample injector to ensure the sample stream travels obliquely through the aperture, thereby maintaining spatial consistency and reducing clogging risks.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If hydrodynamic focusing is used to align particles, then measurement resolution is maintained, but sample stream rate is limited to 10-30 μL/min
Solution Approach 1:
The sample injector is positioned asymmetrically (off-center) within the inlet chamber, creating a biased flow path that directs the sample stream toward one wall. This asymmetric positioning allows the sample stream to be confined by wall effects rather than relying solely on hydrodynamic focusing, enabling higher sample stream rates while maintaining spatial consistency and measurement resolution
Solution Approach 2:
The invention utilizes the local flow conditions near the inlet chamber wall where the sample stream is directed. By positioning the sample injector to bias the stream toward a wall, the local flow characteristics (velocity profile, confinement) are optimized for maintaining particle alignment at higher flow rates, creating a region of improved flow quality without affecting the entire chamber
2Measurement precision
If sample injector diameter is reduced to narrow the sample stream core, then spatial consistency is improved, but system clogging increases
Solution Approach 1:
Instead of symmetrically reducing the injector diameter, the invention uses asymmetric positioning of the injector within the inlet chamber. This allows the sample stream to be directed toward a wall where flow confinement is achieved through the biased positioning rather than through extreme diameter reduction, thereby maintaining spatial consistency while reducing clogging risk
Solution Approach 2:
The invention transitions from controlling stream width primarily through injector diameter (one-dimensional control) to utilizing the spatial positioning of the injector within the inlet chamber (adding positional dimensions). By controlling the lateral position of the injector, the sample stream path is biased toward a wall, achieving stream confinement through positional geometry rather than solely through diameter reduction
3Measurement precision
If ultrasonic waves are used to focus the sample stream, then particle alignment is improved, but system complexity increases
Solution Approach 1:
The invention extracts the focusing function from complex external systems (ultrasonic devices) and replaces it with a simple geometric feature - the asymmetric positioning of the sample injector within the inlet chamber. The biased flow path created by off-center positioning naturally focuses the sample stream without requiring additional ultrasonic focusing components
Solution Approach 2:
The asymmetrically positioned sample injector creates a self-focusing effect through its own geometric positioning within the inlet chamber. The biased flow path directs the sample stream toward a wall, and the stream naturally confines itself through this geometric constraint without requiring external ultrasonic focusing assistance
4Productivity
If higher sample stream rates are used, then productivity is improved, but spatial variation in transverse direction increases
Solution Approach 1:
The asymmetric positioning of the sample injector creates a biased flow path that maintains spatial reproducibility at higher flow rates. By directing the sample stream toward a wall where flow confinement is enhanced, the transverse spatial variation is reduced even at higher sample stream rates, allowing improved productivity without sacrificing measurement precision
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 design enables higher sample stream rates while maintaining low coefficient of variation, enhancing measurement resolution and avoiding system complexity or clogging issues.
Implementation Method 1
In hydrodynamic focusing, a suspension of particles is injected into the center of a laminar sheath fluid flow. The forces of the sheath fluid confine the sample stream to a narrow core, thereby aligning the particles entrained therein.
Implementation Method 2
the sample injector positioned such that the sample stream travels in biased proximity to the profile
Data Source
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AI summary
Apparatuses, components, methods, and systems for interrogating samples are provided. An example system includes a flow cell (110). An example flow cell includes an aperture (116), an inlet chamber (112), and a sample injector (114) positioned within the inlet chamber. An example sample injector is configured to generate a sample steam that flows in biased proximity to a profile (154) included in the inlet chamber. An example method includes the steps of causing sheath fluid to flow into an inlet chamber and through an aperture, injecting sample into an inlet chamber with a sample injector to form a sample stream that is entrained in the sheath fluid, and interrogating the sample stream as the sample stream passes through an interrogation region (140) within the aperture. An example sample injector includes an outlet (146) that is disposed in an off-center position within the inlet chamber.