Off-Axis Detector Cell Analysis Reducing Orientation Waste
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Solution Overview
Problem
Conventional flow cytometers and microfluidic devices face challenges in reliably analyzing aspherical cells due to difficulties in fully orienting them, resulting in 25-40% of analyzed cells producing unreliable results, particularly for valuable sperm cells, leading to waste and inefficiency.
Innovation Solution
The introduction of an off-axis detector technology that includes a cell analysis apparatus with multiple fluorescence detectors configured to detect fluorescence from cells at various angles, ensuring accurate alignment and illumination, even for cells not fully radially oriented, thereby enhancing the reliability of cell analysis and reducing waste.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional flow cytometers use radial orientation channels to orient cells, then cell orientation is improved, but 25-40% of cells still produce unreliable analysis results
Solution Approach 1:
The patent divides the single fluorescence detection function into multiple detection channels with different collection angles. Instead of relying on a single detector that requires perfect radial orientation, the system segments the detection task across multiple detectors (e.g., 0°, 45°, 90°, 135° detectors) that can collectively analyze cells regardless of their specific orientation angle, thereby resolving the contradiction between orientation reliability and usable cell proportion.
Solution Approach 2:
The patent extends the detection system from a single-dimensional radial detection approach to a multi-dimensional detection space by introducing detectors at various angles around the flow axis. This dimensional expansion allows the system to capture fluorescence signals from cells oriented at different angles, converting the limitation of radial orientation into a multi-angle detection advantage and increasing the proportion of usable cells.
2Measurement precision
If flow cytometers require full radial orientation for reliable fluorescence readings, then measurement precision is improved, but device complexity increases
Solution Approach 1:
The patent creates a universal detection system where multiple fluorescence detectors serve both as orientation verification tools and as primary measurement devices. Each detector can independently provide reliable measurements for cells within its detection angle range, making the system multi-functional and reducing the need for complex single-purpose orientation mechanisms.
Solution Approach 2:
The patent uses multiple copies of the fluorescence detection capability at different angular positions rather than relying on a single complex radial orientation system. By duplicating the detection function across multiple detectors, the system achieves measurement precision without requiring the complexity of perfect radial orientation control.
3Measurement precision
If conventional systems discard 25-40% of cells with unreliable results, then analysis accuracy is maintained, but loss of substance increases
Solution Approach 1:
The patent recovers previously discarded cells by capturing their fluorescence signals through multiple detection angles. Cells that would have been discarded due to improper radial orientation are now detected by detectors positioned at angles matching their orientation, converting waste into usable data and reducing substance loss while maintaining accuracy.
Solution Approach 2:
The patent converts the previously harmful effect of cell misorientation (which caused unreliable readings and cell waste) into a benefit by using multiple detectors at different angles. Cells oriented at various angles, which were previously problematic, now provide useful signals to the appropriate detectors, turning the orientation variability from a harm into a beneficial diversification of detectable signals.
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 approach increases the percentage of analyzed cells with reliable results, allowing for the efficient analysis and sorting of previously unanalyzable cells, particularly valuable sperm cells, by ensuring accurate fluorescence readings regardless of cell orientation, thus reducing sample waste and improving processing efficiency.
Implementation Method 1
fluorescence emitted as a result of the cell illumination
Implementation Method 2
projection of electromagnetic radiation (EMR) on a lateral side
Data Source
Figure 1A~1B
Figure 2
Figure 3
AI summary
Particular embodiments of the inventive technology relate to 'off-axis detector' technology that employs a third detector 23 exhibiting a flow orthogonal axis 43 as defined by its EMR collection angle, where such axis is from 30 degrees to 60 degrees from an intended, flow orthogonal, cell cross section long axis alignment line 13, in addition to employing a fourth detector 24 exhibiting a flow orthogonal axis 44 as defined by its collection angle, where such axis is orthogonal to the flow orthogonal, third detector axis 43. Particular embodiments of the inventive technology relate to 'axially spaced illumination' technology featuring more than one cell illumination site, where, other than the most upflow illumination site (e.g., 121), all illumination site(s) are downflow of at least one other illumination site. Particular embodiments of the inventive technology may feature aspects of both technologies.