Microfluidic Chamber for Automated Multiplex Tissue Imaging
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Solution Overview
Problem
Current multiplex immunohistochemistry (IHC) techniques require repeated sample handling, such as coverslip attachment and removal, which are time-consuming and prone to sample damage, and lack automation capabilities when using standard microscope slide formats.
Innovation Solution
A modular sample enclosure system on a microscope slide with a microfluidic chamber allows for automated multiplex IHC by integrating a windowed chamber with ports for reagent introduction and removal, enabling laminar flow and efficient, sequential staining and imaging cycles without manual handling.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If repeated manual handling (coverslip attachment and removal) is performed for multiplex IHC, then multiple imaging cycles can be completed, but the process becomes time-consuming and prone to sample damage
Solution Approach 1:
The patent merges multiple handling operations into a single integrated chamber system. The chamber remains attached to the slide throughout all imaging cycles, combining what would otherwise be separate attachment/detachment operations into one persistent structure that enables continuous automated processing without repeated manual intervention.
Solution Approach 2:
The chamber system is designed to remain self-attached to the slide throughout the entire multiplex IHC process. Once attached, the chamber serves itself by providing continuous access for reagent delivery and waste removal without requiring manual reattachment or repositioning, thereby eliminating repetitive handling steps and enabling automated operation.
2Ease of manufacture
If standard microscope slide formats are used for multiplex IHC, then sample preparation is simplified, but automation capabilities are limited due to repeated manual handling requirements
Solution Approach 1:
The chamber acts as an intermediary device between the standard microscope slide and the automated imaging system. It attaches to the slide once and remains in place, providing a stable interface that allows automated reagent delivery and waste removal systems to operate without requiring manual sample handling, thereby enabling automation while maintaining compatibility with standard slide formats.
3Quantity of substance
If larger chamber volumes are used for IHC staining, then reagent availability is improved, but laminar flow control becomes difficult and uneven staining occurs due to vortices and gradients
Solution Approach 1:
The patent changes the key parameter of chamber volume to a small scale (5 microliters or less). This parameter change enables laminar flow conditions to be maintained throughout the chamber, preventing vortices and concentration gradients that would cause uneven staining. The small volume is sufficient for reagent availability while ensuring uniform flow and consistent staining across the sample.
4Loss of substance
If small chamber volumes (5 microliters or less) are used, then laminar flow is achieved and reagent waste is reduced, but the chamber design becomes more complex with precise volume requirements
Solution Approach 1:
The chamber is designed as a segmented, modular structure with defined geometric features that naturally constrain the internal volume to 5 microliters or less. By segmenting the chamber into specific dimensional proportions, the design achieves precise volume control through geometric definition rather than complex active control mechanisms, making the precision requirement inherent to the structure rather than an added layer of complexity.
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 high-throughput, automated multiplex IHC with reduced reagent consumption and sample preservation, allowing for efficient processing and analysis of multiple samples with minimal sample damage and rapid turnaround times.
Implementation Method 1
the relatively small chamber volumes allow compositions of probes and capture agents to flow in laminar fashion across the biological sample, ensuring that uneven staining (e.g., due to vortices, gradients, and other non-laminar flow phenomena) are controlled or even eliminated
Implementation Method 2
forming an enclosed chamber around a sample on a substrate such as a microscope slide
Data Source
AI summary
An apparatus attaches to a microscope slide to form an enclosed fluidic chamber with input and output ports, where a tissue or cell sample on the slide can be processed using techniques such as immunohistochemical staining. Flow of reagents within the chamber can be laminar and highly uniform across the sample surface to achieve staining that is free of gradients. The sample can be imaged prior to, during, or after any given processing step. Methods for staining and imaging a sample can be implemented through one or more rounds of labeling, label removal or erasure and imaging. Samples can be imaged many times to achieve very high multiplexing levels. Samples can be placed on an imaging apparatus at various times and removed from the imaging apparatus for certain steps.