Multi-Z Imaging for Cell Detection in Multi-Well Devices
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Solution Overview
Problem
Current methods for analyzing complex diseases like cancer and neurological disorders face challenges in distinguishing rare cell types from normal cells due to the masking effect of sequencing bulk cell populations, which accumulate somatic mutations over time, leading to polyclonal cell populations.
Innovation Solution
The development of a system that allows for multi-Z imaging and processing of cell-containing wells in a multi-well device, enabling the capture and imaging of cells at multiple z-planes to generate composite images with all cells in focus, thereby accurately detecting and counting individual cells without the need for centrifugation or complex equipment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If single-plane imaging is used to image cells in multi-well devices, then the imaging process is simple and fast, but cells at different depths cannot be simultaneously captured in focus
Solution Approach 1:
The patent applies multi-Z-plane imaging that extends the imaging capability from a single focal plane to multiple Z-planes (depth planes). By capturing images at multiple focal depths and combining them, the system achieves comprehensive cell detection throughout the well depth without requiring complex mechanical manipulation of the sample.
2Manufacturing precision
If multiple processing steps including centrifugation are used to prepare cell samples, then cell distribution in wells is improved, but the handling and processing time increases
Solution Approach 1:
The patent eliminates the centrifugation step from the traditional sample preparation workflow. By using direct imaging of cells as they naturally distribute in the wells, the method removes the time-consuming centrifugation process while still achieving accurate cell detection and counting through multi-Z-plane imaging capability.
3Measurement precision
If complex equipment and multiple processing steps are used for single-cell analysis, then cell analysis accuracy is improved, but the ease of operation decreases
Solution Approach 1:
The patent combines the imaging and cell analysis functions into an integrated workflow that eliminates separate preparation steps. The multi-Z-plane imaging system directly captures and analyzes cells in the wells without requiring external centrifugation equipment or complex sample manipulation, thereby simplifying the overall operation while maintaining analytical accuracy.
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 simplifies single-cell analysis by reducing the need for handling and processing steps, improving the accuracy of cell detection and counting, and allowing for the identification of candidate wells containing a desired number of cells, thereby uncovering underlying disease mechanisms.
Implementation Method 1
an image acquisition component capable of focusing and generating images at different z-planes above a multi-well device
Data Source
Figure 1A~1B
Figure 2
Figure 3A~3B
AI summary
Provided are methods, devices, assemblies, and systems for dispensing into the wells of a multi-well device and imaging such wells from multiple Z-planes. Multi-Z imaging of the present methods and systems may allow for the detection of wells of a multi-well device that contain a desired number of cells. Also provided are methods, devices, assemblies, and systems for processing cell-containing wells of a multi-well device identified through the use of multi-Z imaging.