Analysis of a polymer

Patent metadata

Field	Value
Publication number	US-11401549-B2
Application number	US-202015930198-A
Country	US
Kind code	B2
Filing date	May 12, 2020
Priority date	Oct 16, 2014
Publication date	Aug 2, 2022
Grant date	Aug 2, 2022

Abstract

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.

First claim

The invention claimed is:

1. A method of controlling a biochemical analysis system, the method comprising:
analyzing a series of measurements obtained from a portion of a first polymer that is partially translocated through a nanopore of the biochemical analysis system, and reference data derived from at least one reference sequence of polymer units, wherein the first polymer is a polynucleotide, and the series of measurements is obtained from around 30 nucleotides to about 250 nucleotides of the first polymer;
providing a measure of similarity during translocation between the analyzed series of measurements and the reference data; and
operating the biochemical analysis system to eject the first polymer from the nanopore responsive to the measure of similarity; wherein
(i) at least one sensor element is operable to eject a polymer that is translocating through the nanopore, and the step of operating the biochemical analysis system to eject the first polymer from the nanopore comprises operating the sensor element to eject the first polymer from the nanopore and accept a further polymer in the nanopore and taking measurements from the further polymer, wherein the further polymer is a polynucleotide; or
(ii) the biochemical analysis system comprises an array of sensor elements and is operable to take successive measurements of a polymer from sensor elements selected in an electrically multiplexed manner, and the step of operating the biochemical analysis system to eject the first polymer from the nanopore comprises operating the biochemical analysis system to cease taking measurements from a currently selected sensor element and to start taking measurements of a further polymer from a newly selected sensor element, wherein the further polymer is a polynucleotide.

2. The method according to claim 1 , further comprising obtaining the series of measurements from the first polymer during the partial translocation.

3. The method according to claim 1 , wherein the series of measurements is obtained by taking successive measurements of the polymer as it translocates through the nanopore.

4. The method according to claim 3 , wherein the successive measurements comprise one or more groups of plural measurements that are dependent on a single k-mer without a priori knowledge of the number of measurements in each group.

5. The method according to claim 1 , wherein analyzing the series of measurements and the reference data to provide the measure of similarity comprises using a distance function to provide, as the measure of similarity, a measure of the distance between the series of measurements and the reference data.

6. The method according to claim 1 , wherein the nanopore is a biological pore.

7. A computer-implemented method of controlling a biochemical analysis system, the method comprising the method according to claim 1 .

8. The method of claim 1 , wherein the series of measurements is a series of electrical measurements.

9. The method according to claim 1 , wherein the measurements are raw measurements, wherein the raw measurements are electrical measurements or optical measurements or a combination thereof.

Assignees

• Oxford Nanopore Tech Plc

Inventors

• Reid Stuart William
• Harper Gavin
• Brown Clive Gavin
• Turner Daniel John
• Heron Andrew John
• Wright Christopher James

Classifications

• G01N33/48721

  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

• C12Q1/6869 Primary

  Methods for sequencing · CPC title

• G16B30/10

  Sequence alignment; Homology search · CPC title

• G16B30/00

  ICT specially adapted for sequence analysis involving nucleotides or amino acids · CPC title

• C12Q2565/631

  being a biochannel or pore · CPC title