High-Throughput Screening Fluidic Assembly with Flow Cell Damage Switching
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Solution Overview
Problem
Existing high-throughput screening systems for molecular interactions face issues such as test surface damage, irreversible compound binding, ligand bioactivity loss, and difficulty in comparing results due to varying test surface characteristics, necessitating manual intervention and repeated screening.
Innovation Solution
A fluidic assembly with multiple flow cell groups, each individually addressable, and a method to check for flow cell damage, allowing automatic switching to a functional group for screening, combined with parallel or series flow cell configurations and selective ligand immobilization for high-throughput biochemical sensing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If a single flow cell is used for high-throughput screening, then the device complexity is low, but the productivity decreases due to manual intervention when test surface damage occurs
Solution Approach 1:
The flow cell assembly is divided into multiple flow cell groups (first flow cell group, second flow cell group, etc.), each containing multiple flow cells with test surfaces. This segmentation allows the system to switch between different groups when damage occurs, enabling continuous high-throughput screening without manual intervention.
Solution Approach 2:
The system monitors parameters such as ligand activity levels and test surface integrity in real-time. When parameters indicate damage or degradation, the system automatically switches to a different flow cell group, changing the operational state to maintain productivity.
2Reliability
If multiple flow cell groups are added to enable automatic switching, then the reliability improves, but the device complexity increases
Solution Approach 1:
The flow cell assembly is divided into multiple flow cell groups (first flow cell group, second flow cell group, etc.), each containing multiple flow cells with test surfaces. This segmentation allows the system to switch between different groups when damage occurs, enabling continuous high-throughput screening without manual intervention.
Solution Approach 2:
The system includes monitoring that detects test surface damage and ligand activity levels. When damage is detected, the system automatically switches to a different flow cell group, creating a feedback loop that maintains reliability without requiring complex manual intervention systems.
3Loss of time
If manual checking and switching of flow cells is performed, then the device complexity is low, but the loss of time increases due to repeated screening
Solution Approach 1:
The system proactively monitors test surface integrity and ligand activity levels before complete failure occurs. By detecting early signs of damage, the system can switch to a backup flow cell group before the current one becomes completely unusable, minimizing screening interruptions.
Solution Approach 2:
The system includes monitoring that detects test surface damage and ligand activity levels. When damage is detected, the system automatically switches to a different flow cell group, creating a feedback loop that maintains reliability without requiring complex manual intervention systems.
4Measurement precision
If test surfaces are reused without checking for damage, then the ease of operation is high, but the measurement precision decreases due to varying test surface characteristics
Solution Approach 1:
The system includes monitoring that detects test surface damage and ligand activity levels. When damage is detected, the system automatically switches to a different flow cell group, creating a feedback loop that maintains reliability without requiring complex manual intervention systems.
Solution Approach 2:
The system monitors parameters such as ligand activity levels and test surface integrity in real-time. When parameters indicate damage or degradation, the system automatically switches to a different flow cell group, changing the operational state to maintain productivity.
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 efficient, automated high-throughput screening with reduced manual intervention, ensuring consistent results by addressing damaged test surfaces and varying ligand immobilization, thereby improving screening efficiency and data comparability.
Implementation Method 1
optical sensors, which probe the local refractive index near a sensor surface. This refractive index is changed by the presence of analyte molecules, typically when binding to a target molecule
Data Source
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AI summary
According to the present invention there is provided various methods for screening a plurality of sample fluids for molecules which can bind to predefined ligands, using the assembly comprising, a sample delivery unit which can receive sample fluids to be screened, and a plurality of groups of flow cells, each group having at least two flow cells, and a means for selectively fluidly connecting the sample delivery unit to any one of saidgroups of flow cells, the method comprising the steps of, selecting one of said plurality of flow cell groups by fluidly connecting said flow cell group to the need unit; carrying out an injection step which comprises injecting a sample fluid to be screened from the sample delivery unit into the flow cells in the selected flow cell group; for each flow cell in the flow cell group, recording a signal using a sensor which represent the binding of molecules of the sample fluid to ligands on the test surface of that flow cell and/or the dissociation of molecules from ligands on the test surface of that flow cell; carrying out a damage assessment step, using said recorded signals, to determine if the test surface of a flow cell in the selected flow cell group is damaged; if it is determined from the damage assessment step that the test surface of a flow cell in the selected flow cell group is damaged, then selecting another one of said plurality of flow cell groups by fluidly connecting said other flow cell group to the need unit; injecting the next sample fluid to be screened from the sample delivery unit into the flow cells in said other flow cell unit. There is further provided assemblies which can be used to implement the afore-mentioned methods.