Flow-Cell Imaging with Sample Reorientation for Suspension Cultures
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Solution Overview
Problem
Existing imaging systems struggle to efficiently analyze biological samples in suspension cultures without the need for dedicated imaging vessels, particularly in high-throughput applications, especially for cells and cell clusters like spheroids, which are often cultured in microplates but require analysis in stirred tanks or wave bags.
Innovation Solution
An imaging system comprising a main channel with imaging spaces and a reorientation unit to manipulate sample orientation, using fluid flow and various reorientation methods (electrodynamic, hydrodynamic, optical) to enable high-throughput imaging of biological samples in fluid, allowing multiple orientations and repeated imaging.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If biological samples are cultured in suspension in stirred tanks or wave bags, then the culture conditions are improved for biopharmaceutical processes, but imaging analysis becomes difficult without dedicated imaging vessels
Solution Approach 1:
The system segments the continuous flow into discrete imaging events by using a flow cell where samples pass through a defined imaging zone. This allows individual sample analysis while maintaining continuous flow culture conditions, resolving the conflict between suspension culture flexibility and imaging capability.
Solution Approach 2:
A flow cell acts as an intermediary component between the suspension culture vessel and the imaging system. The flow cell provides a transparent, controlled environment where samples can be imaged while maintaining their suspension state, enabling imaging analysis without requiring dedicated imaging vessels.
2Measurement precision
If frequent imaging analysis is performed on single cells or cell clusters, then growth tracking and viability analysis are improved, but system complexity and processing time increase
Solution Approach 1:
Samples are pre-loaded into the flow cell before imaging begins, and the system is pre-configured with the imaging pathway. This preliminary preparation reduces the complexity of performing frequent imaging analyses, as the system is ready to capture images without requiring complex sample handling or system reconfiguration for each imaging event.
Solution Approach 2:
The system uses dynamic flow control to move samples through the imaging zone at controlled rates, enabling frequent imaging of different samples. The flow cell and imaging system work together dynamically to maintain optimal imaging conditions while processing multiple samples, reducing overall system complexity compared to static imaging approaches.
3Productivity
If high-throughput imaging is implemented for suspension cell cultures, then analysis speed is improved, but maintaining sample orientation and image quality becomes challenging
Solution Approach 1:
The system uses periodic flow pulses to move samples through the imaging zone at regular intervals. This periodic action allows the imaging system to capture images at consistent time points, maintaining image quality and orientation control while achieving high throughput by systematically processing multiple samples in sequence.
Solution Approach 2:
The flow cell design incorporates a specific geometric configuration that guides sample orientation as they pass through the imaging zone. By controlling the spatial dimensions and flow path geometry, the system maintains consistent sample orientation relative to the imaging axis, ensuring image quality while processing samples at high speed through the added dimension of controlled fluid flow.
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
Enables efficient, high-quality, and high-throughput imaging of biological samples in suspension cultures, generating detailed three-dimensional representations with improved image resolution and throughput.
Implementation Method 1
The reorientation unit is configured to manipulate or to change the orientation of the samples in the fluid
Implementation Method 2
The reorientation unit is configured to manipulate or to change the orientation of the samples in the fluid
Implementation Method 3
The reorientation unit is configured to manipulate or to change the orientation of the samples in the fluid
Implementation Method 4
at least one imaging unit configured to receive detection light emitted by the biological samples or originating from the biological samples
Data Source
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AI summary
An imaging system (100, 200, 300) for imaging biological samples (102) is provided comprising: at least one main channel (104) having at least one imaging space (114) and configured to transport the biological samples (102) in a fluid; at least one reorientation unit (118) configured to manipulate the orientation of the biological samples (102) in the fluid; at least one imaging unit (115) configured to receive detection light emitted by the biological samples (102) in the imaging space (114). By means of the reorientation unit (118) the biological sample (102) may be rotated around a rotation axis of the biological sample (102). In a further aspect a method for imaging the biological samples with the imaging system is provided.