US 11,921,103 B2
Method of operating a measurement system to analyze a polymer
Stuart William Reid, Oxford (GB); Gavin Harper, Oxford (GB); Clive Gavin Brown, Oxford (GB); James Anthony Clarke, Oxford (GB); and Andrew John Heron, Oxford (GB)
Assigned to Oxford Nanopore Technologies PLC, Oxford (GB)
Filed by Oxford Nanopore Technologies PLC, Oxford (GB)
Filed on Jun. 21, 2019, as Appl. No. 16/449,272.
Application 16/449,272 is a continuation of application No. 15/487,329, filed on Apr. 13, 2017.
Application 15/487,329 is a continuation of application No. 14/346,549, abandoned, previously published as PCT/GB2012/052343, filed on Sep. 21, 2012.
Claims priority of provisional application 61/617,880, filed on Mar. 30, 2012.
Claims priority of provisional application 61/538,721, filed on Sep. 23, 2011.
Prior Publication US 2019/0310242 A1, Oct. 10, 2019
Int. Cl. G01N 33/487 (2006.01); B82Y 15/00 (2011.01); C12Q 1/6869 (2018.01); G01N 27/447 (2006.01); G01N 33/483 (2006.01); G06F 17/18 (2006.01); G06N 7/01 (2023.01); G16B 30/00 (2019.01); G16B 30/10 (2019.01)
CPC G01N 33/48721 (2013.01) [C12Q 1/6869 (2013.01); G01N 27/44791 (2013.01); G01N 33/483 (2013.01); G06F 17/18 (2013.01); G06N 7/01 (2023.01); G16B 30/00 (2019.02); G16B 30/10 (2019.02); B82Y 15/00 (2013.01)] 13 Claims
 
1. A method of operating a measurement system comprising a nanopore to make measurements of a polymer comprising polymer units, the method comprising:
performing a translocation of said polymer in a single direction through the nanopore of the measurement system using a molecular brake that controls a rate at which the polymer moves through the nanopore during said translocation, resulting in the measurement system being in a sequence of states during said translocation, wherein each state of the sequence of states is dependent on a respective k-mer of the polymer being in the nanopore, wherein each k-mer is k polymer units of the polymer, where k is a positive integer;
during said translocation of the polymer through the nanopore, repeatedly applying a continuously varying voltage cycle across the nanopore a plurality of times, wherein applying the voltage cycle comprises applying a plurality of different voltage levels across the nanopore, including a first voltage level and a second voltage level, different from the first voltage level, and wherein the voltage cycle has a cycle period shorter than a duration of a state of the sequence of states; and
measuring, by the measurement system during said translocation of the polymer through the nanopore, ion current flow through the nanopore one or more times at each of the first and second voltage level of each voltage cycle applied across the nanopore, the ion current flow being dependent on an identity of the k-mer in the nanopore at each state of the sequence of states, thereby producing an input signal comprising a plurality of ion current flow measurements each made at one of the first or second voltage levels of the voltage cycle.