Analysis of a polymer from multi-dimensional measurements
US-2017096703-A1 · Apr 6, 2017 · US
US12545956B2 · US · B2
| Field | Value |
|---|---|
| Publication number | US-12545956-B2 |
| Application number | US-202418991325-A |
| Country | US |
| Kind code | B2 |
| Filing date | Dec 20, 2024 |
| Priority date | Oct 16, 2014 |
| Publication date | Feb 10, 2026 |
| Grant date | Feb 10, 2026 |
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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.
Opening claim text (preview).
The invention claimed is: 1 . A method of controlling a biochemical analysis system for screening of a plurality of polymers, the plurality of polymers comprising a first polymer, the biochemical analysis system comprising a nanopore, the method comprising: (A) during translocation of the first polymer through the nanopore, making a series of measurements corresponding to a portion of the first polymer that has been translocated through the nanopore; determining a measure of similarity between the portion of the first polymer and at least one reference sequence of polymer units by using the series of measurements obtained and reference data derived from the at least one reference sequence of polymer units; and determining, using the measure of similarity, whether to eject the first polymer from the nanopore or continue translocating the first polymer through the nanopore; and (B) based on the determination made using the measure of similarity, either: ejecting the first polymer from the nanopore, or further translocating the first polymer through the nanopore. 2 . The method of claim 1 , wherein: the plurality of polymers comprise a sample extracted from a human; the at least one reference sequence of polymer units comprises human DNA; and the determining, using the measure of similarity, whether to eject the first polymer comprises: determining to eject the first polymer from the nanopore when it is determined, using the measure of similarity to the at least one reference sequence of polymer units comprising human DNA, that the first polymer comprises human DNA; and determining to further translocate the first polymer through the nanopore when it is determined, using the measure of similarity to the at least one reference sequence of polymer units comprising human DNA, that the first polymer does not comprise human DNA. 3 . The method of claim 1 , wherein: the plurality of polymers comprise a sample extracted from a food product; the at least one reference sequence of polymer units comprises nucleic acid of a contaminant; and the determining, using the measure of similarity, whether to eject the first polymer comprises: determining to eject the first polymer from the nanopore when it is determined, using the measure of similarity to the at least one reference sequence of polymer units comprising the nucleic acid of the contaminant, that the first polymer comprises the contaminant; and determining to further translocate the first polymer through the nanopore when it is determined, using the measure of similarity to the at least one reference sequence of polymer units comprising the nucleic acid of the contaminant, that the first polymer does not comprise the nucleic acid of the contaminant. 4 . The method of claim 3 , wherein the contaminant is a non-food product. 5 . The method of claim 3 , wherein the food product comprises a first meat product. 6 . The method of claim 5 , wherein the contaminant is a second meat product that is different from the first meat product. 7 . The method of claim 1 , wherein: the plurality of polymers comprise DNA; the at least one reference sequence of polymer units comprises a target gene; and the determining, using the measure of similarity, whether to eject the first polymer comprises: determining to eject the first polymer from the nanopore when it is determined, using the measure of similarity to the at least one reference sequence of polymer units comprising the target gene, that the first polymer does not comprise the target gene; and determining to further translocate the first polymer through the nanopore when it is determined, using the measure of similarity to the at least one reference sequence of polymer units comprising the target gene, that the first polymer comprises the target gene. 8 . The method of claim 1 , wherein: the plurality of polymers comprise a sample extracted from bacteria; the at least one reference sequence of polymer units comprises an antibiotic resistant gene; and the determining, using the measure of similarity, whether to eject the first polymer comprises: determining to eject the first polymer from the nanopore when it is determined, using the measure of similarity to the at least one reference sequence of polymer units comprising the antibiotic resistant gene, that the first polymer does not comprise the antibiotic resistant gene; and determining to further translocate the first polymer through the nanopore when it is determined, using the measure of similarity to the at least one reference sequence of polymer units comprising the antibiotic resistant gene, that the first polymer comprises the antibiotic resistant gene. 9 . The method of claim 1 , wherein: the plurality of polymers comprise RNA; the at least one reference sequence of polymer units comprises mRNA; and the determining, using the measure of similarity, whether to eject the first polymer comprises: determining to eject the first polymer from the nanopore when it is determined, using the measure of similarity to the at least one reference sequence of polymer units comprising the mRNA, that the first polymer does not comprise mRNA; and determining to further translocate the first polymer through the nanopore when it is determined, using the measure of similarity to the at least one reference sequence of polymer units comprising mRNA, that the first polymer comprises mRNA. 10 . The method of claim 1 , wherein the method further comprises selecting the at least one reference sequence based on the series of measurements. 11 . The method of claim 10 , wherein the plurality of polymers comprise a sample extracted from bacteria, the at least one reference sequence is selected based on a determined strain of the bacteria, and the method is for phenotyping the sample or for detecting a single-nucleotide polymorphism in the sample. 12 . The method of claim 1 , wherein: the plurality of polymers comprise a sample extracted from a patient having cancer; the at least one reference sequence of polymer units comprises at least one gene associated with a class of cancer; and the determining, using the measure of similarity, whether to eject the first polymer comprises: determining to eject the first polymer from the nanopore when it is determined, using the measure of similarity to the at least one reference sequence of polymer units comprising the at least one gene associated with a class of cancer, that the first polymer does not comprise the at least one gene associated with a class of cancer; and determining to further translocate the first polymer through the nanopore when it is determined, using the measure of similarity to the at least one reference sequence of polymer units comprising the at least one gene associated with a class of cancer, that the first polymer comprises the at least one gene associated with a class of cancer. 13 . The method of claim 12 , further comprising: determining a second measure of similarity between the portion of the first polymer and at least one second reference sequence of polymer units by using the series of measurements obtained and second reference data derived from the second at least one second reference sequence, wherein the at least one second reference sequence comprises a sequence of polynucleotides associated with a sub-class of the class cancer; determining to eject the first polymer from the nanopore when it is determined, using the second measure of similarity to the at least one second reference sequence of polymer units comprising the sequence of polynucleotides associated with the sub-class of the cla
Sequence alignment; Homology search · CPC title
Investigating individual macromolecules, e.g. by translocation through nanopores (Coulter counters in general G01N15/12; fabrication methods for nanoscale apertures B81B1/00; sequencing of nucleic acids C12Q1/68) · CPC title
ICT specially adapted for sequence analysis involving nucleotides or amino acids · CPC title
Methods for sequencing · CPC title
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