Microfluidic Fluid Network for Parallel Biological Sample Analysis
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Solution Overview
Problem
Existing sequencing-by-synthesis technologies face challenges in miniaturization due to the need for multiple washing and rinsing steps, which require large volumes of fluid and are inefficient.
Innovation Solution
A microfluidic fluid network with a flow array containing multiple reaction rooms connected via supply channels and a circulation line, allowing for the reduction of reagent volumes and efficient incorporation of test reagents into reaction rooms using a displacement medium.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If traditional sequencing-by-synthesis methods are used with multiple washing and rinsing steps, then complete reagent replacement and reaction control are achieved, but large volumes of fluid (up to 100 mL) are required per sequencing run
Solution Approach 1:
The system segments the fluid handling into individual reaction chambers (microwells) arranged in a flow array, where each chamber can be independently filled and processed. This segmentation allows parallel processing of multiple samples simultaneously, reducing the total time required while using minimal volumes of reagents in each chamber.
Solution Approach 2:
The invention transitions from traditional bulk liquid handling to a microfluidic two-phase system where aqueous reagent plugs are transported through an immiscible carrier fluid (oil phase). This dimensional change in fluid organization enables precise delivery of small reagent volumes through the circulation line to multiple reaction chambers in parallel.
2Volume of moving object
If microfluidic devices are miniaturized, then reagent volumes are reduced, but multiple washing and rinsing steps become inefficient and require complex fluid management
Solution Approach 1:
The circulation line serves multiple functions: it delivers reagents to reaction chambers, removes spent reagents, and enables washing steps all through a single integrated fluid path. The two-phase system (aqueous plugs in oil carrier) universally handles all fluid management tasks, simplifying the overall device architecture despite miniaturization.
Solution Approach 2:
The immiscible carrier fluid (oil phase) acts as an intermediary that enables efficient microfluidic operation. It allows aqueous reagent plugs to be transported, positioned, and exchanged in a controlled manner through the circulation line, facilitating complete reagent replacement in miniaturized chambers without complex valve systems.
3Productivity
If parallel examinations are performed in a flow array, then sequencing throughput is increased, but the complexity of reagent distribution and washing increases
Solution Approach 1:
The system merges the delivery and removal functions into a single circulation line that serves all reaction chambers. The same fluid path used to deliver reagents is also used to remove spent reagents and perform washing, eliminating the need for separate inlet and outlet systems for each chamber and reducing overall system complexity despite parallel processing.
Solution Approach 2:
The circulation line operates in periodic cycles, delivering reagent plugs to all reaction chambers in sequence, allowing incubation, then removing spent reagents, and performing washing steps. This periodic operation enables coordinated control of multiple parallel reactions through a single fluid management system.
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
The described device reduces the volume of reagents required for sequencing, minimizes the amount of washing solution needed, and enables efficient optical detection and sequencing, thereby improving the cost-effectiveness and efficiency of DNA sequencing processes.
Implementation Method 1
at least one component which is connected to the circulation line and into which test reagents can be introduced with which the test reagents can be introduced into the reaction spaces of the flow array
Implementation Method 2
Optical detection of fluorescence events and identification of where the nucleotides have been incorporated
Data Source
Figure 1
Figure 2
Figure 3~4
AI summary
A fluidic network (1) for carrying out, in parallel, a plurality of analyses of biological samples, the network having a flow cell array (2) with a plurality of reaction chambers (14), the reaction chambers (14) each having a first channel connection (20) and a second channel connection (21), wherein: the first channel connections (20) are connected to a first supply channel (16) and the second channel connections (21) are connected to a second supply channel (19); the first supply channel (16) and the second channel connection (19) are interconnected by a circulation line (6); and at least one component (3, 4, 5, 7) is connected to the circulation line, by means of which component test reagents can be introduced into the reaction chambers (14) of the flow cell array (2).