Microfluidic Flow Cell With External Thin Film Connectors
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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 substrate layer, and a gasket layer, where fluidic connections are made outside the substrate, allowing for a wide range of substrate materials and eliminating the need for through-holes, using thin film fluidic connectors with integrated microfluidic channels and valves for controlled reagent delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If fluidic connections are made through substrate layers in conventional microfluidic flow cells, then fluid delivery is enabled, but substrate material choices are limited and structural robustness is compromised due to required through-holes
Solution Approach 1:
The patent moves fluidic connections from a through-substrate approach (one dimension) to an external connection approach where channels are formed in sealing layers and connect to inlet/outlet ports on the exterior surfaces of substrate layers (adding spatial dimensionality). This eliminates the need for through-holes in substrates while maintaining fluid delivery capability, thereby preserving substrate structural integrity and expanding material choices.
Solution Approach 2:
The patent segments the fluidic connection function into separate components: sealing layers contain the fluidic channels, while substrate layers provide structural support. The sealing layers are positioned between substrate layers and connect to inlet/outlet ports that extend beyond substrate boundaries, allowing fluid delivery without compromising substrate robustness.
2Productivity
If manual staining and data collection methods are used, then flexibility in procedure is maintained, but time consumption increases and error susceptibility rises
Solution Approach 1:
The microfluidic flow cell system enables automated reagent delivery and staining processes. The system self-regulates fluid flow through controlled inlet and outlet ports, eliminating the need for manual intervention in reagent application and data collection, thereby increasing both productivity and reliability.
Solution Approach 2:
The patent replaces manual mechanical operations (hand-staining, cover slipping) with an automated microfluidic system that uses controlled fluid flow through channels to deliver reagents and perform staining, reducing human error and increasing consistency.
3Stability of the object's composition
If coverslips are used to maintain sample moisture during imaging, then sample preservation is improved, but sample loss or movement occurs during repeated cover slipping and de-cover slipping
Solution Approach 1:
The patent merges the sample containment function with the flow cell structure itself. The sealing layers and substrate layers together form an enclosed chamber that holds the sample and maintains moisture, eliminating the need for separate coverslips that would need to be repeatedly applied and removed.
Solution Approach 2:
The flow cell is assembled and sealed before the staining and imaging process begins. This preliminary sealing action maintains sample moisture throughout the entire workflow without requiring repeated cover slipping, thereby preventing sample loss or movement.
4Quantity of substance
If reagent volumes are reduced for precise control, then reagent consumption decreases, but uniform reagent delivery and mixing become more difficult to achieve
Solution Approach 1:
The patent uses microfluidic channels and controlled fluid flow (hydraulics) to deliver reagents precisely through the flow cell. The channel geometry and flow control mechanisms ensure uniform distribution of small reagent volumes across the sample, achieving both low reagent consumption and staining uniformity.
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, ensuring uniform reagent delivery and minimizing sample loss or movement, while allowing for the use of various substrate materials without compromising structural integrity, thereby enhancing the accuracy and efficiency of multiplexed biomarker analysis.
Implementation Method 1
at least one thin film fluidic connector comprising at least one microfluidic channel in fluid connection with the stacked planar assembly
Implementation Method 2
The stacked planar assembly comprises an adherent layer, a substrate layer, and a gasket layer where each layer is adhered to one another
Data Source
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.