Cytometer Sequence Design for Reduced Side Lobes
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Solution Overview
Problem
Conventional flow cytometers based on spatially modulated fluorescence face challenges in accurately detecting cells due to high side lobes in correlation functions, leading to erroneous detections and reduced sensitivity, especially in noisy conditions and overlapping signal scenarios.
Innovation Solution
The development of sequences with reduced side lobes in autocorrelation and cross-correlation functions, utilizing unipolar sequences and balanced filters, which are optimized to minimize side lobe amplitudes and improve signal detection by reducing noise floor and erroneous detections.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Device complexity
If conventional sequences are used in spatially modulated fluorescence cytometers, then the detection system can operate with simpler optics and support simultaneous flow of multiple cells, but high side lobes in correlation functions cause erroneous detections and reduced sensitivity
Solution Approach 1:
The patent applies parameter changes by optimizing the sequence parameters (autocorrelation and cross-correlation properties) to minimize side lobe amplitudes. Specifically, it uses sequences with reduced side lobes in both autocorrelation and cross-correlation functions, which directly changes the mathematical parameters of the modulation sequence to improve detection accuracy while maintaining the simpler optical setup
Solution Approach 2:
The patent uses temporal scaling copies of the original sequence to create multiple correlation functions that can distinguish between cells moving at different speeds. By creating scaled versions of the sequence and comparing correlation results across multiple scales, the system achieves accurate detection without requiring complex optical narrowing
2Measurement precision
If sequence length is increased to improve detection resolution, then side lobe reduction becomes more effective, but the measurement time and data processing complexity increase
Solution Approach 1:
The patent applies partial action by using temporal scaling with factors greater than 1 (e.g., 2x, 3x scaling) to extend the effective measurement window without proportionally increasing the physical sequence length. This allows the system to achieve the benefits of longer sequences (reduced side lobes) while maintaining reasonable measurement times by selectively applying scaling only where needed
3Measurement precision
If threshold values are lowered to improve detection sensitivity, then more weak signals can be detected, but false positive detections increase due to high side lobes
Solution Approach 1:
The patent converts the harmful effect of side lobes into a beneficial discrimination mechanism. By using sequences with reduced side lobes and applying temporal scaling, the system creates a structured pattern where side lobes from different scaling factors have different characteristics. This allows the system to lower thresholds for sensitivity while using the side lobe patterns themselves as a fingerprint to distinguish true signals from false positives
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 proposed solution enhances the detection accuracy and sensitivity of cells by minimizing side lobes, reducing noise interference, and enabling lower threshold values, thereby improving the overall performance of cytometers in detecting temporally-scaled signals.
Implementation Method 1
These cells emit an optical signal, for example triggered by a light source, like e.g. a laser
Implementation Method 2
The spatial filter provides for the sensor to detect a signal based on the filter for each excited cell
Implementation Method 3
By an analysis of the signal which may be superposed by other cells, the cytometer may determine a number, speed and other characteristics of the cells in the solution
Data Source
AI summary
Embodiments relate to a device (20), a method and a computer program for providing information on at least one sequence, wherein the at least one sequence describes temporally successive signal states, comprising a device (10), a method and a computer program for a cytometer (100) for providing information on one or several cells in a medium in a channel and comprising a cytometer (100). The device (20) comprises an interface (22), which is configured to receive information on a number of the signal states. The device (20) a computational module (24) which is configured to generate a plurality of possible sequences based on the information on the number of the signal states. The computational module (24) is further configured to calculate for at least a subset of the possible sequences correlation functions between a sequence and at least a temporal scaling of the sequence, wherein a correlation function includes a main lobe and one or several side lobes. The computational module (24) is further configured to determine the at least one sequence based on the correlation functions, wherein the order of the signal states within the at least one sequence is selected such that a side lobe in a correlation function of the sequence comprising the at least one temporal scaling of the sequence is reduced as compared to a side lobe which may maximally be acquired in a correlation function by different arrangements of the signal states in the sequence, and to determine the information on the at least one sequence based on the at least one sequence and provide the same via the interface (22).