Microfluidic Tissue Slide Cartridge for Fast Aligned Multiplex Imaging
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Solution Overview
Problem
Conventional tissue sample analysis methods face challenges such as low multiplexity, long turnaround times, sample degradation, and alignment errors due to manual handling, which limit throughput and accuracy in imaging and multiplex processing.
Innovation Solution
A biological sample processing system with a microfluidic cartridge and imaging unit that enables rapid, efficient, and accurate imaging of tissue samples over a large area, using a microfluidic cartridge with a fluid flow network, temperature control, and a displacement mechanism for sample processing units, allowing sequential multiplex processing and simultaneous image capture.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If manual handling and mounting/demounting of imaging coverslips are used in multi-cycle staining, then sample processing can be performed, but alignment errors between images and decreased accuracy of multiplexing occur
Solution Approach 1:
The system divides the sample processing into discrete automated cycles, with each cycle performing specific staining and imaging operations. The automated stage positioning system segments the large area into multiple fields of view that are processed sequentially, eliminating manual intervention and ensuring precise alignment through automated coordinate tracking between cycles.
Solution Approach 2:
The patent replaces manual mechanical handling with an automated stage positioning system that uses computer-controlled mechanisms to position the sample and objectives. This substitution eliminates human error in alignment and ensures consistent, reproducible positioning across multiple staining and imaging cycles.
2Reliability
If conventional multi-cycle staining with long incubation and washing cycles is used, then thorough sample processing is achieved, but extremely long turnaround times and limited throughput occur
Solution Approach 1:
The system performs multiple staining cycles continuously without interrupting the overall process. While one cycle is incubating or washing, the system automatically prepares the next cycle's reagents and positions the sample accordingly. This continuous automated operation maintains staining quality while dramatically reducing total turnaround time compared to manual sequential processing.
Solution Approach 2:
The system pre-positions the sample and pre-warms reagents before each staining cycle begins. The automated stage is pre-programmed with the sequence of operations, and all necessary components are prepared in advance, allowing the actual staining and imaging to proceed rapidly without setup delays between cycles.
3Adaptability or versatility
If repeated mounting/demounting of imaging coverslips is performed, then multi-cycle processing is enabled, but tissue integrity deteriorates
Solution Approach 1:
The system uses a single, reusable coverslip that remains mounted throughout all staining and imaging cycles. The universal design allows the same coverslip to be used for multiple cycles without removal, eliminating the mechanical stress of repeated mounting and demounting while maintaining full multi-cycle processing capability through automated reagent delivery and imaging.
4Area of stationary object
If whole slides are imaged with high magnification objectives using overlaying/stitching software, then large area coverage is achieved, but alignment errors and decreased accuracy occur
Solution Approach 1:
The system dynamically adjusts the imaging approach by automatically dividing the large area into multiple smaller fields of view that are captured sequentially with a high magnification objective. The automated stage positioning system dynamically tracks and records the precise coordinates of each field, enabling perfect alignment when the images are assembled without requiring software stitching algorithms, thus maintaining maximum accuracy across large areas.
Data Source
AI summary
Biological sample processing system comprising an imaging unit comprising a digital image processing system and at least one microscope including at least one lens, a sample processing station comprising a handling platform including a support and a displacement mechanism for moving the support, and a sample processing unit mounted on the handling platform. The sample processing unit comprises a tissue slide holder for mounting thereon a tissue slide with a biological sample fixed thereon and a microfluidic cartridge holder for mounting a microfluidic cartridge thereon. The tissue slide holder is coupled to the microfluidic cartridge holder via a coupling allowing the microfluidic cartridge and the tissue support to be mounted and removed from the sample processing unit in an opened position, and in a closed position for the tissue support to be in sealing contact with the microfluidic cartridge. The sample processing station comprises a plurality of said sample processing units mounted on the handling platform and moveable from a position allowing mounting of the tissue slide, respectively microfluidic cartridge, or removal thereof, to a position in which the viewing window in the microfluidic cartridge holder is positioned in alignment with the lens of said at least one microscope.