公开(公告)号：US12216079B2

公开(公告)日：2025-02-04

申请号：US17651766

申请日：2022-02-18

Applicant: Roche Sequencing Solutions, Inc.

Inventor： Kevin Deierling ,  Roger J. A. Chen ,  David J. Fullagar

IPC: G01N27/447 ,  C12Q1/6869 ,  C12Q1/6874 ,  G01N33/487

Abstract: A device for controlling, detecting, and measuring a molecular complex is disclosed. The device comprises a common electrode. The device further comprises a plurality of measurement cells. Each measurement cell includes a cell electrode and an integrator electronically coupled to the cell electrode. The integrator measures the current flowing between the common electrode and the cell electrode. The device further comprises a plurality of analog-to-digital converters, wherein an integrator from the plurality of measurement cells is electrically coupled to one analog-to-digital converter of the plurality of analog-to-digital converters.

公开(公告)号：US10976302B2

公开(公告)日：2021-04-13

申请号：US16868457

申请日：2020-05-06

Applicant: Roche Sequencing Solutions, Inc.

Inventor： Roger J. A. Chen ,  Jennifer Hovis ,  Hui Tian

IPC: G01N33/487

Abstract: A nanopore sequencing device is disclosed. The nanopore sequencing device includes a working electrode. It further includes a dielectric layer, wherein a portion of the dielectric layer is disposed horizontally adjacent to the working electrode and a portion of the dielectric layer is disposed above and covering a portion of the working electrode, and wherein the dielectric layer forms a well having an opening above an uncovered portion of the working electrode. A base surface area of the working electrode is greater than a base surface area of the opening above the uncovered portion of the working electrode.

公开(公告)号：US10920271B2

公开(公告)日：2021-02-16

申请号：US16386888

申请日：2019-04-17

Applicant: Roche Sequencing Solutions, Inc.

Inventor： Randall W. Davis ,  Roger J. A. Chen

IPC: C12Q1/68 ,  C12Q1/6869 ,  C12Q1/6816 ,  B82Y15/00 ,  G01N33/487 ,  G01N27/447 ,  C12Q1/6825 ,  B82Y10/00

Abstract: The present invention relates to a method of using nanopores to obtain sequence information of sample DNAs in ss test DNAs. The method comprises using speed bumps to stall the ss test DNAs in the nanopores at random positions of the ss test DNAs to obtain sequence information of each and every nucleotides of the sample DNAs, and to construct the whole sequences of the sample DNAs. The present invention also relates to identification and/or isolation of test DNAs having desired sequence(s) using nanopore detectors facilitated by speed bump.

公开(公告)号：US10465240B2

公开(公告)日：2019-11-05

申请号：US15085713

申请日：2016-03-30

Applicant: Roche Sequencing Solutions, Inc.

Inventor： Ashraf Wahba ,  William Nielsen ,  J. William Maney, Jr. ,  Kevin Aliado ,  Kyle Umeda ,  Roger J. A. Chen ,  Jing Luo

IPC: C12Q1/68 ,  C12Q1/6869 ,  G01N33/487

Abstract: A method of forming a plurality of lipid bilayers over an array of cells in a nanopore based sequencing chip is disclosed. Each of the cells comprises a well. A salt buffer solution is flowed over the array of cells in the nanopore based sequencing chip to substantially fill the wells in the cells with the salt buffer solution. A lipid and solvent mixture is flowed over the array of cells to deposit the lipid and solvent mixture over at least some of the wells in the cells. A first portion of the cells, each having a lipid bilayer over its well, is detected. A second portion of the cells, each having a lipid membrane but not a lipid bilayer over its well, is detected. An electrical lipid-thinning stimulus is selectively applied to the second portion of the cells but not to the first portion of the cells.

公开(公告)号：US11667966B2

公开(公告)日：2023-06-06

申请号：US17146138

申请日：2021-01-11

Applicant: Roche Sequencing Solutions, Inc.

Inventor： Randall W. Davis ,  Roger J. A. Chen

IPC: C12Q1/6869 ,  C12Q1/6816 ,  B82Y15/00 ,  G01N33/487 ,  G01N27/447 ,  C12Q1/6825 ,  B82Y10/00

CPC classification number: C12Q1/6869 ,  B82Y15/00 ,  C12Q1/6816 ,  C12Q1/6825 ,  G01N27/447 ,  G01N33/48721 ,  B82Y10/00 ,  Y10S977/924 ,  C12Q1/6816 ,  C12Q2525/119 ,  C12Q2525/121 ,  C12Q2525/204 ,  C12Q2527/101 ,  C12Q2563/149 ,  C12Q2565/631 ,  C12Q1/6869 ,  C12Q2525/119 ,  C12Q2525/121 ,  C12Q2525/204 ,  C12Q2527/101 ,  C12Q2563/149 ,  C12Q2565/631

Abstract: The present invention relates to a method of using nanopores to obtain sequence information of sample DNAs in ss test DNAs. The method comprises using speed bumps to stall the ss test DNAs in the nanopores at random positions of the ss test DNAs to obtain sequence information of each and every nucleotides of the sample DNAs, and to construct the whole sequences of the sample DNAs. The present invention also relates to identification and/or isolation of test DNAs having desired sequence(s) using nanopore detectors facilitated by speed bump.

公开(公告)号：US11499190B2

公开(公告)日：2022-11-15

申请号：US16888434

申请日：2020-05-29

Applicant: Roche Sequencing Solutions, Inc.

Inventor： Randall W. Davis ,  Roger J. A. Chen ,  Arkadiusz Bibillo ,  Daniel Korenblum

IPC: C12Q1/6869 ,  G01N33/487 ,  G01N27/447

Abstract: This disclosure provides chips, systems and methods for sequencing a nucleic acid sample. Tagged nucleotides are provided into a reaction chamber comprising a nanopore in a membrane. An individual tagged nucleotide of the tagged nucleotides can contain a tag coupled to a nucleotide, which tag is detectable with the aid of the nanopore. Next, an individual tagged nucleotide of the tagged nucleotides can be incorporated into a growing strand complementary to a single stranded nucleic acid molecule derived from the nucleic acid sample. With the aid of the nanopore, a tag associated with the individual tagged nucleotide can be detected upon incorporation of the individual tagged nucleotide. The tag can be detected with the aid of the nanopore when the tag is released from the nucleotide.

公开(公告)号：US11150216B2

公开(公告)日：2021-10-19

申请号：US16238451

申请日：2019-01-02

Applicant: Roche Sequencing Solutions, Inc.

Inventor： Roger J. A. Chen ,  Hui Tian ,  J. William Maney, Jr.

IPC: G01N27/447 ,  G01N33/487 ,  B01L3/00 ,  C12Q1/6869

Abstract: A method of analyzing a molecule in a nanopore is disclosed. A voltage is applied across a nanopore that is inserted in a membrane by coupling the nanopore to a voltage source. The nanopore is decoupled from the voltage source. After the decoupling, a rate of decay of the voltage across the nanopore is determined. A molecule in the nanopore is distinguished from other possible molecules based on the determined rate of decay of the voltage across the nanopore.

公开(公告)号：US10429375B2

公开(公告)日：2019-10-01

申请号：US16172633

申请日：2018-10-26

Applicant: Roche Sequencing Solutions, Inc.

Inventor： Roger J. A. Chen ,  Hui Tian ,  Santiago Fernandez-Gomez

IPC: G01N27/447 ,  G01N27/22 ,  G01N33/487 ,  C12Q1/6869 ,  B82Y15/00

Abstract: A method of exporting measurements of a nanopore sensor on a nanopore based sequencing chip is disclosed. An electrical characteristic associated with the nanopore sensor is measured. The electrical characteristic associated with the nanopore sensor is processed. A summary for the electrical characteristic and one or more previous electrical characteristics is determined. The summary for the electrical characteristic and the one or more previous electrical characteristics are exported. Determining the summary includes determining that the electrical characteristic and at least a portion of the one or more previous electrical characteristics correspond to a base call event at the nanopore sensor. The summary represents the electrical characteristic and the at least a portion of the one or more previous electrical characteristics.

公开(公告)号：US12173367B2

公开(公告)日：2024-12-24

申请号：US18482807

申请日：2023-10-06

Applicant: Roche Sequencing Solutions, Inc.

Inventor： Kevin Aliado ,  Roger J. A. Chen ,  Jing Luo ,  J. William Maney, Jr. ,  William Nielsen ,  Kyle Umeda ,  Ashraf Wahba

IPC: G01N33/48 ,  C12Q1/6869 ,  G01N33/487

Abstract: A method of forming a plurality of lipid bilayers over an array of cells in a nanopore based sequencing chip is disclosed. Each of the cells comprises a well. A salt buffer solution is flowed over the array of cells in the nanopore based sequencing chip to substantially fill the wells in the cells with the salt buffer solution. A lipid and solvent mixture is flowed over the array of cells to deposit the lipid and solvent mixture over at least some of the wells in the cells. A first portion of the cells, each having a lipid bilayer over its well, is detected. A second portion of the cells, each having a lipid membrane but not a lipid bilayer over its well, is detected. An electrical lipid-thinning stimulus is selectively applied to the second portion of the cells but not to the first portion of the cells.

公开(公告)号：US11092589B2

公开(公告)日：2021-08-17

申请号：US16516166

申请日：2019-07-18

Applicant: Roche Sequencing Solutions, Inc.

Inventor： Roger J. A. Chen ,  Randall Davis

IPC: B81B1/00 ,  G01N33/483 ,  G01N33/487 ,  G01N15/12 ,  C12Q1/6869 ,  B82Y5/00

Abstract: A method of forming a nanopore in a lipid bilayer is disclosed. A nanopore forming solution is deposited over a lipid bilayer. The nanopore forming solution has a concentration level and a corresponding activity level of pore molecules such that nanopores are substantially not formed un-stimulated in the lipid bilayer. Formation of a nanopore in the lipid bilayer is initiated by applying an agitation stimulus level to the lipid bilayer. In some embodiments, the concentration level and the corresponding activity level of pore molecules are at levels such that less than 30 percent of a plurality of available lipid bilayers have nanopores formed un-stimulated therein.