Nanopore Polymer Analysis With Early Sequence Rejection
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Solution Overview
Problem
Existing biochemical analysis systems using nanopores for polymer sequencing are limited by slow analysis speeds, particularly in determining the sequence of long polymers like polynucleotides, due to the need for complete measurement before identifying non-relevant sequences.
Innovation Solution
A method for controlling nanopore-based biochemical analysis systems that involves analyzing partial translocation measurements using reference data to determine similarity or fit to a model, allowing for on-the-fly rejection of non-relevant polymers and focusing measurements on relevant ones.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If complete measurement of polymer translocation is performed before rejection, then measurement precision is improved, but productivity deteriorates
Solution Approach 1:
The system performs preliminary analysis of measurements during partial translocation to determine if the polymer is relevant before completing full measurement. This preliminary action allows rejection of non-relevant polymers early, improving productivity while maintaining measurement precision for polymers that require full analysis.
Solution Approach 2:
The system continuously monitors measurements during translocation and uses feedback from reference data comparison to dynamically determine whether to continue or reject the polymer. This feedback mechanism enables real-time decision-making that balances measurement precision with productivity.
2Reliability
If complete translocation measurement is performed for all polymers, then reliability is improved, but loss of time increases
Solution Approach 1:
The system performs preliminary comparison of partial measurements with reference data to identify non-relevant polymers before complete translocation. This preliminary action reduces time loss by avoiding full measurement of polymers that will ultimately be rejected, while maintaining reliability through continued measurement of relevant polymers.
Solution Approach 2:
The system performs partial measurement and analysis during translocation rather than waiting for complete translocation. This partial action allows early identification and rejection of non-relevant polymers, reducing time loss while maintaining sufficient reliability for decision-making.
3Productivity
If reference data analysis is performed during partial translocation, then productivity is improved, but device complexity increases
Solution Approach 1:
The system uses a universal reference data structure and analysis algorithm that can compare measurements against multiple reference sequences. This multi-functional approach enables productivity improvement through early rejection while managing complexity by reusing the same reference data framework across different polymer types and applications.
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 significantly speeds up the analysis process by rejecting non-relevant polymers during partial translocation, enabling faster and more efficient sequencing of polymers, particularly polynucleotides, with potential for higher accuracy and resource optimization.
Implementation Method 1
The data gathered in this way comprises measurements, such as measurements of ion current, where each translocation of the sequence through the sensitive part of the nanopore results in a slight change in the measured property.
Data Source
AI summary
A biochemical analysis system analyses polymers by taking measurements of a polymer from a sensor element comprising a nanopore during translocation of the polymer through the nanopore. When a polymer has partially translocated, the series of measurements is analysed using reference data derived from a reference sequence to provide a measure of similarity. Responsive to the measure of similarity, the sensor element may be selectively operated to eject the polymer and thereby make the nanopore available to receive a further polymer. Where the biochemical analysis system comprises an array of sensor elements and is takes measurements from sensor elements selected in a multiplexed manner, responsive to the measure of similarity, the biochemical analysis system ceases taking measurements from the currently selected sensor element and to starts taking measurements from a newly selected sensor element.