Microfluidic Flow Cell With External Gasket Ports
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Solution Overview
Problem
Current methods for multiplexed in situ biomarker analysis are time-consuming and prone to errors due to manual staining and data collection processes, and existing microfluidic flow cells require fluidic connections through substrates, which limits material choices and introduces structural weaknesses.
Innovation Solution
A microfluidic subassembly with a stacked planar assembly comprising an adherent layer, a transparent substrate layer, and a gasket layer, where fluidic connections are made outside the substrate, allowing for flexible thin film fluidic connectors and eliminating the need for through-holes in the substrate, enabling automation and optimal reagent delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If fluidic connections are made through the substrate, then the flow cell can be assembled, but the substrate material choices are limited and structural weaknesses are introduced
Solution Approach 1:
The patent moves the fluidic connection interface from the substrate dimension to the gasket layer dimension. The gasket layer extends beyond the substrate edges to form inlet/outlet ports, allowing fluidic connections to be made at the gasket layer rather than through the substrate. This dimensional shift enables use of thin, optically clear substrates without compromising their structural integrity.
Solution Approach 2:
The patent separates the functions of the substrate and gasket layer. The substrate is dedicated solely to providing optical clarity and structural support, while the gasket layer handles sealing and fluidic connections. This functional segmentation allows each component to be optimized independently, enabling substrate material choices that would be impossible if fluidic connections required through-holes.
2Productivity
If manual staining and data collection methods are used, then the process can be performed with simple equipment, but the analysis is time-consuming and prone to errors
Solution Approach 1:
The microfluidic flow cell system enables automated reagent delivery and staining processes. The system self-regulates fluid flow through the extended gasket layer channels, eliminating the need for manual intervention in reagent application and reducing human error in the staining process.
Solution Approach 2:
The patent replaces manual mechanical operations (hand-placing coverslips, manual reagent application) with an automated microfluidic system. The extended gasket layer integrates with automated fluid handling equipment, allowing precise, error-free reagent delivery and staining without manual manipulation of the sample.
3Ease of operation
If coverslip is placed and removed for each staining round, then the sample can be accessed for staining, but sample loss or movement occurs confounding downstream analysis
Solution Approach 1:
The extended gasket layer creates permanent access ports and fluidic channels before staining begins. Reagent inlet/outlet ports are pre-formed by extending the gasket layer beyond the substrate, eliminating the need to remove the coverslip during staining. The sample remains permanently secured while reagents are delivered through the pre-configured fluidic pathways.
Solution Approach 2:
The extended gasket layer acts as an intermediary structure that provides both sealing and fluidic access functions. Instead of removing the coverslip to access the sample, reagents are delivered through the gasket layer's extended channels that reach the sample area without requiring coverslip removal, thus maintaining sample stability while enabling staining.
4Ease of manufacture
If drilling holes in glass coverslip is performed, then fluidic connections can be made, but the process is time-consuming and costly due to risk of cracks
Solution Approach 1:
The patent extracts the fluidic connection function from the substrate and relocates it to the gasket layer. Instead of drilling holes in the glass coverslip substrate, the gasket layer is designed with extended regions that form inlet/outlet ports. This extraction eliminates the time-consuming and risky drilling process while maintaining functional fluidic connections.
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 solution automates the biomarker analysis workflow, ensures uniform reagent distribution, and maintains sample integrity by avoiding the need for substrate drilling, thus enhancing analysis precision and reducing sample loss or movement.
Implementation Method 1
at least one flexible thin film fluidic connector comprising at least one microfluidic channel in fluid connection with the stacked planar assembly
Implementation Method 2
an adherent layer, a substrate layer wherein the substrate layer comprises material having optical transparency, and a gasket layer where each layer is adhered to one another
Data Source
Figure 1A~1C
Figure 2A~2C
Figure 3
AI summary
A microfluidic flow cell subassembly, which may be assembled into a flow cell having fluidic connections outside of the main substrate, is described for encapsulating a sample to allow for subsequent controlled delivery of reagents to the sample, such as multiplexed in situ biomarker staining and analysis. The fluidic connectors are thin film fluidic connectors capable of connecting to a fluid delivery system. The subassembly may be sealed against a solid support to form a flow cell. Methods of use are also disclosed.