Flow Cell Manifold for Biological Sample Analysis
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Solution Overview
Problem
Conventional flow cell systems for biological and biochemical analyses, such as genomic sequencing, face challenges in efficiency, throughput, reagent management, and substrate mounting, particularly in maintaining vertical orientation during initial loading, which can lead to contamination and reagent loss.
Innovation Solution
The development of a device with multiple independently positionable flow cells, including a manifold for fluid distribution and electrowetting for reagent movement, integrated funnels for reagent addition, and laminated substrates for improved sealing and thermal control, allowing for horizontal to vertical orientation transitions and efficient reagent recycling.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If multiple flow cells are used to increase throughput, then productivity is improved, but device complexity increases
Solution Approach 1:
The system is divided into multiple independent flow cells (first flow cell, second flow cell, etc.), each capable of independent operation. This segmentation allows parallel processing of multiple samples, increasing throughput while maintaining manageable complexity through modular design.
Solution Approach 2:
The manifold is designed to serve multiple flow cells simultaneously, providing universal fluid distribution to all cells. This multi-functional component reduces the need for separate fluid management systems for each flow cell, thereby increasing productivity without proportionally increasing device complexity.
2Area of stationary object
If substrates are mounted vertically during initial loading, then space utilization is improved, but contamination and reagent loss increase
Solution Approach 1:
The flow cell incorporates a movable substrate holder that can transition between horizontal and vertical orientations. During initial loading, the substrate is mounted horizontally to prevent reagent loss and contamination. After loading, the holder rotates to position the substrate vertically for the reaction phase, dynamically adapting to different operational requirements.
Solution Approach 2:
The substrate is initially mounted in a horizontal orientation during the loading phase to prevent reagent loss and contamination. This preliminary horizontal positioning ensures that reagents are properly distributed before the substrate is rotated to vertical for the reaction phase, preventing harmful effects during the critical loading period.
3Productivity
If reagents are continuously flowed through flow cells, then reaction efficiency is improved, but reagent consumption increases
Solution Approach 1:
The system implements reagent recycling where spent reagents from the flow cells are collected and reused in subsequent reactions. The manifold is designed with recirculation pathways that allow reagents to be recovered and重新introduced into the flow cells, reducing overall reagent consumption while maintaining continuous flow for reaction efficiency.
Solution Approach 2:
The manifold enables continuous reagent flow through multiple flow cells simultaneously, ensuring that reactions proceed efficiently without interruption. This continuous action maintains high productivity while the recirculation design ensures that reagents are reused rather than discarded, reducing consumption.
4Reliability
If sealing members are added to seal the reaction chamber, then reliability is improved, but device complexity increases
Solution Approach 1:
The sealing mechanism utilizes flexible O-rings and gaskets that conform to the flow cell geometry. These thin, flexible sealing members provide reliable seals between the substrate holder and flow cell body, as well as around the substrate perimeter, without requiring complex rigid sealing structures. The flexibility of these components allows them to adapt to slight variations in positioning while maintaining seal integrity.
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
Enhances the efficiency of biological sample reactions by improving throughput, reducing reagent usage, and facilitating precise optical detection and thermal management, while minimizing contamination and reagent loss through advanced fluid handling and substrate handling mechanisms.
Implementation Method 1
electrowetting for reagent movement
Data Source
AI summary
A device for performing biological sample reactions comprising a plurality of flow cells each with at least one port for receiving reaction fluids delivered to a chamber of each flow cell and a manifold configured to receive the plurality of flow cells, wherein the manifold is configured to receive at least one reaction fluid, and wherein each flow cell is configured with a sample holder wherein the sample holder contains biological sample.