Nanopore Polymer Sequencing With Partial-Read Similarity Screening
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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, as they require complete translocation and post-translocation analysis, leading to inefficiencies and wasted data acquisition.
Innovation Solution
A method for controlling nanopore-based systems that analyzes partial translocation measurements using reference data to determine similarity or fit to a model, allowing on-the-fly rejection of non-relevant polymers, thereby accelerating the analysis process.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If complete translocation and post-translocation analysis is performed, then measurement precision is improved, but productivity deteriorates
Solution Approach 1:
The patent applies preliminary action by performing analysis on partial translocation data before complete translocation occurs. The system analyzes measurements taken during partial translocation to determine sequence information, allowing rejection or acceptance decisions to be made before the polymer fully translocates through the nanopore, thereby reducing total analysis time while maintaining measurement precision.
2Measurement precision
If measurements are taken from all translocating polymers, then measurement precision is improved, but loss of time increases
Solution Approach 1:
The patent extracts only the necessary measurements needed for sequence determination from the translocating polymer. By analyzing partial translocation data, the system takes out only the relevant sequence information required, avoiding unnecessary measurement of the entire polymer length, thus reducing time loss while maintaining measurement precision for the extracted sequence data.
Solution Approach 2:
The patent applies discarding and recovering by rejecting polymers that do not meet selection criteria after analyzing only their partial translocation data. The system discards non-relevant polymers early in the translocation process, recovering time that would otherwise be wasted on complete measurement of unwanted polymers, while maintaining measurement precision for polymers that are retained for full analysis.
3Reliability
If complete translocation is performed for all polymers, then reliability is improved, but productivity deteriorates
Solution Approach 1:
The patent applies preliminary action by performing reliability assessment on partial translocation data before complete translocation. The system determines sequence reliability from incomplete measurements, allowing confident rejection or acceptance decisions to be made early, thereby maintaining sequence determination reliability for retained polymers while improving overall sequencing throughput through early filtering.
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 reduces analysis time by identifying and 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.