Linear Array Detector Brightfield Imaging for Compact Flow Cytometers
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Solution Overview
Problem
Existing flow cytometer and cell sorter systems face challenges in capturing clear images of cells, as the fluorescence of fluorochromes does not provide a clear image of each cell or particle, and existing methods for capturing images are costly and inefficient.
Innovation Solution
An electro-optic imaging system is introduced, which includes a flow cell, a laser for generating broad spectrum light, an optical subsystem for receiving brightfield and forward scattered light, a linear array detector to transduce light into analog signals, and image reconstruction logic to reconstruct brightfield images of cells over time into a single overall image.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If fluorescence detection is used to identify cells, then cell identification capability is improved, but clear imaging of each cell is lost
Solution Approach 1:
The patent divides the detection task into two separate detection paths: one for fluorescence signal detection (cell identification) and another for brightfield image detection (cell imaging). The fluorescence detection path uses photodetectors to identify cells by fluorochrome signals, while the brightfield imaging path uses a linear array detector to capture clear images of each cell. This segmentation allows both functions to operate independently and simultaneously without interfering with each other.
Solution Approach 2:
The flow cytometer system is designed to perform multiple functions simultaneously: it can detect fluorescence signals for cell identification, capture brightfield images for morphological analysis, and sort cells based on either or both signals. The system integrates both detection paths into a single instrument, making it a multi-functional device that eliminates the need for separate imaging systems.
2Measurement precision
If conventional imaging methods are used to capture cell images, then image quality is improved, but system cost and complexity increase
Solution Approach 1:
The patent extracts the imaging function from complex conventional camera systems and implements it using a simplified linear array detector configuration. Instead of using expensive 2D camera systems with complex optics, the invention uses a 1D linear array detector that scans across the cell stream, capturing images with fewer components and lower cost while maintaining adequate image quality for cell analysis.
Solution Approach 2:
The patent employs a cost-effective linear array detector system with simpler optical components compared to conventional imaging systems. The system uses basic optical elements like lenses and mirrors rather than complex camera assemblies, reducing the overall system cost while still providing sufficient image quality for flow cytometry applications.
3Ease of manufacture
If linear array detector is used for imaging, then system cost is reduced, but image reconstruction complexity increases
Solution Approach 1:
The patent incorporates image reconstruction logic that operates in real-time as cells flow through the interrogation region. The system pre-processes the scanned image lines by aligning them based on cell position information from photodetectors, then reconstructs complete cell images before the cells exit the detection region. This preliminary reconstruction approach simplifies downstream data analysis and allows for real-time imaging without requiring complex post-processing.
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 system enables the capture of brightfield images of cells at lower costs compared to prior methods, allowing for further analysis using different imaging modalities and improving the efficiency of cell sorting processes.
Implementation Method 1
a laser to generate a broad spectrum of light coupled into one side of an interrogation region of the flow cell/cuvette to back light each cell
Implementation Method 2
the linear array detector to receive the brightfield image of each cell, the linear array detector to transduce light into analog signals representative of pixels in a plurality of brightfield image lines
Implementation Method 3
an optical subsystem on an opposite side of the interrogation region to receive a brightfield image of each cell formed by the back light and a forward scattered light
Data Source
AI summary
A flow cytometer or cell sorting system includes a linear array detector having a plurality of detectors; a plurality of low noise gain amplifiers respectively coupled to the plurality of detectors in the linear array detector; a plurality of analog to digital converters respectively coupled to the plurality of detectors of the linear array detector; and image reconstruction logic coupled to the plurality of analog to digital converters. The linear array detector receives the brightfield image of each cell of the plurality of biological cells and transduces the light into analog signals representative of pixels in a plurality of brightfield image lines of each cell. The plurality of analog to digital converters transduce the analog signals into digital numeric signals for each pixel. The image reconstruction logic reconstructs the plurality of brightfield image lines of each cell over time periods into a single overall brightfield image of each cell.