Laser Rastering Flow Cytometer for Rare Cell Detection
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Solution Overview
Problem
Current flow cytometry systems face challenges in efficiently detecting and analyzing rare cellular events due to complex sample preparation processes, high resource consumption, and low sensitivity, which results in inefficient identification and counting of rare cells like Circulating Tumor Cells and fetal cells in maternal blood.
Innovation Solution
A high-throughput, low-cost flow cytometry system utilizing a laser rastering flow cytometer with increased flow rates and fluorescence detection, combined with monoclonal antibodies to distinguish rare cells from normal cells, allowing for rapid scanning and sorting of rare cellular events.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If complex multi-part sample preparation processes are used, then detection sensitivity is improved, but analysis time and resource consumption increase significantly
Solution Approach 1:
The patent extracts and removes red blood cells from the sample through lysis before analysis. By taking out the abundant red blood cells that interfere with rare cell detection, the system achieves high sensitivity without requiring complex multi-step preparation processes, thereby reducing analysis time while maintaining detection capability
Solution Approach 2:
The patent performs preliminary lysis of red blood cells and enrichment of rare cellular events before the main detection process. This preliminary action simplifies subsequent detection steps and reduces the time required for analysis while improving detection sensitivity by pre-concentrating the target cells
2Productivity
If flow rate is increased to improve throughput, then analysis speed is improved, but detection accuracy may be compromised
Solution Approach 1:
The patent employs dynamic laser rastering that scans across the flow stream at high speed, adapting the detection process to match the increased flow rate. The laser scanning speed and pattern are dynamically adjusted to ensure accurate detection of fluorescent signals even at throughput rates exceeding 300,000 cells per second, thereby maintaining detection accuracy while achieving high productivity
Solution Approach 2:
The patent replaces traditional mechanical sorting and analysis methods with optical detection using fluorescence-activated cell sorting (FACS). This substitution allows for non-contact, high-speed detection and sorting of rare cells based on fluorescent markers, enabling high throughput without compromising accuracy since the optical detection can resolve individual cells even at very high flow rates
3Measurement precision
If rare cells are enriched through complex preparation, then detection sensitivity is improved, but device complexity and cost increase
Solution Approach 1:
The patent employs antibody-conjugated magnetic beads that automatically bind to and enrich rare cellular events with specific surface markers as the sample flows through the system. This self-service enrichment mechanism occurs passively during normal sample processing without requiring additional complex preparation steps or specialized equipment, thereby maintaining high detection sensitivity while minimizing device complexity
Solution Approach 2:
The patent changes the physical and chemical parameters of the sample by introducing fluorescently-labeled antibodies that specifically bind to surface markers on rare cells. This parameter change (adding fluorescent labels) enables direct detection of rare cells through fluorescence activation, simplifying the overall detection system while improving sensitivity without requiring complex mechanical or manual preparation procedures
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 system achieves reliable, high-yield detection and analysis of rare cellular events with increased throughput, reducing analysis time and cost, while sacrificing some accuracy for the ability to identify and sort clinically important cells effectively.
Implementation Method 1
one or more processors configured to detect rare cellular events based on fluorescence emission from cell-binding surface markers
Implementation Method 2
a laser positioned to emit a laser beam directed to the flow cell; one or more deflector components disposed between the laser and the flow cell, wherein the deflector component is configured to affect a position of the laser beam relative to the sample flow
Data Source
AI summary
Systems and methods for the detection, analysis, and collection of rare cellular events, wherein rare cellular events are defined by events comprising less than 5% of a total number of cells in a sample. The systems and methods generally include: (1) a flow cell dimensioned so as to permit a flow of a sample through the flow cell at a flow rate greater than 300,000 cells per second; (2) a laser positioned to emit a laser beam directed to the flow cell; (3) one or more deflector components disposed between the laser and the flow cell, wherein the deflector component is configured to affect a position of the laser beam relative to the sample flow; (4) one or more fluorescence emission detectors; and (5) one or more processor configured to detect rare cellular events based on fluorescence emission from cell-binding surface markers introduced into the sample prior to the sample being flowed through the flow cell.