Sample Pooling with Bead-Based Target Concentration
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Solution Overview
Problem
Conventional sample pooling methods for diagnostic testing lead to a dilution effect, reducing the sensitivity of target detection and potentially causing false negatives, especially in large-scale testing scenarios like COVID-19 screening, where resources are limited.
Innovation Solution
Processing individual samples to isolate and purify the target molecule before pooling, using techniques like bead-based technology to create a pooled sample without dilution, allowing for high sensitivity detection without the need for multiple individual tests.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If samples are pooled together for testing, then resource usage is reduced and testing efficiency is improved, but the sensitivity of target detection is reduced due to dilution effect
Solution Approach 1:
The patent applies preliminary action by isolating and concentrating the target molecule from each individual sample before pooling. This pre-processing step ensures that when samples are combined, the target molecules are already concentrated and will not be diluted below detectable levels. The method involves adding beads to each sample, incubating to bind target molecules, washing to remove non-specific material, and then combining the bead-bound targets from multiple samples, thereby maintaining detection sensitivity while enabling efficient pool testing.
2Measurement precision
If individual samples are tested separately, then detection sensitivity is maintained, but resource usage increases and testing time is extended
Solution Approach 1:
The patent applies merging by combining multiple individual sample processing steps into a single pooled testing operation. After isolating target molecules from each sample using beads, the method combines the bead-bound targets from multiple samples into one pooled sample for a single detection operation. This merging approach maintains the sensitivity of individual testing while reducing resource consumption and testing time by processing multiple samples simultaneously through pooling.
3Productivity
If large number of samples are pooled together, then resource efficiency is maximized, but the dilution effect becomes more severe and false negatives increase
Solution Approach 1:
The patent applies preliminary action by concentrating target molecules from each individual sample before pooling, ensuring that even when many samples are combined, the target remains above detection thresholds. This pre-concentration step through bead-based isolation and washing prevents the dilution effect that would otherwise cause false negatives in large pools, thereby maintaining reliability while maximizing resource efficiency through extensive pooling.
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 maintains the sensitivity of individual sample testing while reducing resource usage by enabling efficient pooling of multiple samples without dilution, effectively detecting targets in pooled samples with comparable sensitivity to individual testing.
Implementation Method 1
Isolating the target from each individual sample aliquot
Data Source
AI summary
The present disclosure includes, but is not limited to, methods and systems for pooling or combining multiple samples together. Particularly, this disclosure relates to pooling and combining samples in a process and system that combines samples in a way that allows targets in the pooled sample to be analyzed/detected with a similar sensitivity and specificity as for analysis/detection of targets from the individual samples of the pool. Specifically, in some embodiments, methods herein avoid a dilution effect found in commonly used sample pooling methods that can reduce their sensitivity and limit the number of samples that can be pooled. In some embodiments, methods herein include processes to de-convolute the pool down to individual samples. Methods herein may be applicable to creating and testing pooled/combined samples for target molecules and de-convoluting pooled samples to identify an individual sample in a pool containing the target. Systems for performing the methods, including in some embodiments partially or fully automated methods, are also described.