High-Throughput Screening System with Rapid Fluorescence Detection
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Solution Overview
Problem
Current high-throughput screening methods are limited by low time resolution, particularly in instruments using 384- or 1536-well plate formats, which restricts the determination of rapid binding kinetics and enzyme reactions, necessitating a method that combines high throughput with high time resolution for the identification and development of new drugs.
Innovation Solution
A system comprising a dosing device with pressure chambers and capillary tubes for precise and fast liquid dispensing, combined with an illumination and detection system using LED light modules for rapid fluorescence measurements, enabling simultaneous excitation and detection across multiple wells with high temporal resolution.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If plate formats with 384 or 1536 test wells are used for high-throughput screening, then sample throughput is improved, but temporal resolution deteriorates
Solution Approach 1:
The system segments the detection process by using multiple independent single-channel detectors, each capable of rapid sequential measurement across different wells. This segmentation allows the system to maintain high temporal resolution for each measurement while achieving high overall throughput through parallel processing architectures and optimized measurement sequences.
2Loss of time
If multidispenser systems are used to improve temporal resolution, then time range is improved to seconds, but throughput is limited
Solution Approach 1:
The system achieves multi-functionality by combining the capabilities of multi-well plate handling with rapid single-channel detection. The detector system can rapidly switch between wells while maintaining stopped-flow temporal resolution, effectively making a single detection channel serve multiple wells sequentially, thus achieving both high temporal resolution and high throughput without requiring complex multidispenser mechanisms.
3Loss of time
If continuous-flow or stopped-flow devices are used for fast mixing, then temporal resolution is improved, but material consumption increases
Solution Approach 1:
The system employs dynamic measurement sequences where the detector rapidly switches between different wells based on optimized measurement patterns. This dynamic approach allows complete kinetic curves to be obtained for multiple concentrations and conditions using minimal amounts of sample and reagent, as the system intelligently sequences measurements to maximize information gain while minimizing material usage.
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 approach allows for efficient and precise kinetic measurements in high-throughput screening, achieving time resolutions comparable to stopped-flow instruments while maintaining high sample throughput, enabling the elucidation of rapid biological processes such as ligand binding and enzyme kinetics.
Implementation Method 1
illumination and detection system using LED light modules for rapid fluorescence measurements
Implementation Method 2
fluorescence light is emitted from each sample. To excite the fluorescence, the samples in the wells of the microtiter plate are illuminated through the transparent base of the plate with a light source
Data Source
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AI summary
The invention relates to a method and a system for a quick kinetic fluorescence measurement in a high-throughput screening with a high time resolution using a microtiter plate with a transparent base with a plurality of test depressions, a metering system which is arranged above the microtiter plate for simultaneously adding liquid into multiple test depressions, a lighting system below the microtiter plate, said lighting system being suitable for simultaneously lighting the multiple test depressions through the transparent base, and a detection system which is suitable for simultaneously detecting electromagnetic radiation from multiple or all of the test depressions, wherein per test depression 0.5 - 300 µl of liquid from the metering system is added into the multiple test depressions simultaneously within 5 - 200 ms at a pressure ranging from 0.5 bar to 2 bar, the multiple test depressions are lit simultaneously through the transparent base by the lighting system before or at the moment the addition begins, and the electromagnetic radiation from multiple or all of the test depressions is detected simultaneously with a delay of 1 - 1000 ms between the individual measurement points.