公开(公告)号：US11130128B2

公开(公告)日：2021-09-28

申请号：US16667811

申请日：2019-10-29

Applicant: Bio-Rad Laboratories, Inc.

Inventor： Kevin D. Ness ,  Donald A. Masquelier ,  Billy W. Colston, Jr. ,  Benjamin J. Hindson

IPC: B01L3/00 ,  B01F3/08 ,  C12Q1/686 ,  B01F5/00 ,  G01N35/08 ,  B01F5/02 ,  B01F13/00 ,  B01F13/10 ,  B01L9/00

Abstract: Method of detecting a target nucleic acid. In an exemplary method, at least two thermal zones of different temperature may be created using a heating assembly. A first emulsion and a second emulsion may be formed. The first and second emulsions may be thermally cycled by passing them through tubing in a spaced relation to one another, with the tubing being wound around a central axis of the heating assembly and extending through each thermal zone multiple times. Thermally cycling may promote amplification of the target nucleic acid in droplets of each emulsion. Droplets of each emulsion may be passed through a detection channel located downstream of the tubing. Fluorescence may be detected from the droplets being passed through the detection channel.

公开(公告)号：US10677693B2

公开(公告)日：2020-06-09

申请号：US16236116

申请日：2018-12-28

Applicant: Bio-Rad Laboratories, Inc.

Inventor： Benjamin J. Hindson ,  Billy W. Colston, Jr. ,  Kevin D. Ness ,  Donald A. Masquelier

IPC: G01N1/30 ,  B01J19/00 ,  C12Q1/6876 ,  G01N21/75 ,  C12Q1/6844 ,  G01N33/50 ,  B01F13/00 ,  B01L3/00 ,  G01N35/08 ,  B01L7/00 ,  G01N1/44 ,  C40B50/08 ,  C40B60/14

Abstract: System, including methods, apparatus, compositions, and kits, for the mixing of small volumes of fluid by coalescence of multiple emulsions.

公开(公告)号：US10279350B2

公开(公告)日：2019-05-07

申请号：US15365894

申请日：2016-11-30

Applicant: Bio-Rad Laboratories, Inc.

Inventor： Benjamin J. Hindson ,  Kevin D. Ness ,  Billy W. Colston, Jr. ,  Fred P. Milanovich ,  Donald A. Masquelier

IPC: B01L3/00 ,  B01F13/00 ,  B01F15/00 ,  B01L3/02 ,  B01L7/00 ,  B29C45/00 ,  C12Q1/686 ,  G01N21/3563 ,  G01N21/49 ,  G01N21/64 ,  B01F3/08 ,  B29L31/00

CPC classification number: B01L3/502784 ,  B01F3/0807 ,  B01F13/0062 ,  B01F15/00922 ,  B01F2003/0834 ,  B01F2003/0842 ,  B01F2215/0037 ,  B01L3/0241 ,  B01L3/502715 ,  B01L7/52 ,  B01L7/525 ,  B01L2200/0673 ,  B01L2200/0689 ,  B01L2200/10 ,  B01L2200/12 ,  B01L2300/041 ,  B01L2300/0654 ,  B01L2300/0816 ,  B01L2300/0819 ,  B01L2300/0858 ,  B01L2300/0867 ,  B01L2300/1822 ,  B01L2400/0478 ,  B01L2400/0487 ,  B01L2400/049 ,  B01L2400/0622 ,  B29C45/0053 ,  B29C45/006 ,  B29C2045/0079 ,  B29L2031/752 ,  C12Q1/686 ,  G01N21/3563 ,  G01N21/49 ,  G01N21/6428 ,  G01N21/6486 ,  G01N2021/6439 ,  Y02A90/26

Abstract: Methods of generating droplets. In an exemplary method, a device including a sample well, a carrier well, a droplet well, and a plurality of microfluidic channels is selected. The microfluidic channels include a first channel, a second channel, and a third channel. A discrete volume of sample-containing fluid is placed into the sample well, and a discrete volume of carrier fluid is placed into the carrier well. A pressure differential is created after placing the discrete volumes, to cause fluid flow. Sample-containing fluid flows from the sample well to a droplet-generation region of the device via the first channel. Carrier fluid flows from the carrier well to the droplet-generation region via the second channel. Sample-containing droplets and carrier fluid flow from the droplet-generation region to the droplet well via the third channel.

公开(公告)号：US10258989B2

公开(公告)日：2019-04-16

申请号：US15365888

申请日：2016-11-30

Applicant: Bio-Rad Laboratories, Inc.

Inventor： Kevin D. Ness ,  Benjamin J. Hindson ,  Billy W. Colston, Jr. ,  Donald A. Masquelier

IPC: B01L3/00 ,  B01F3/08 ,  B01F13/00 ,  B01L3/02 ,  B01L7/00 ,  G01N21/3563 ,  C12Q1/686 ,  G01N21/64 ,  B01F15/00 ,  B29C45/00 ,  G01N21/49 ,  B29L31/00

Abstract: Methods of making a droplet-generating device. In an exemplary method, an upper member is injection molded. The upper member includes a bottom surface and also includes a first microfluidic channel, a second microfluidic channel, and a third microfluidic channel each formed in the bottom surface. The upper member has a plurality of openings each extending completely through the upper member from the bottom surface and creating a side wall region of a sample well, a carrier well, and a droplet well. A cover layer is attached to the bottom surface of the upper member, such that the cover layer seals a bottom side of each microfluidic channel. The microfluidic channels meet one another to create a droplet-generation region. The sample well, the carrier well, and the droplet well are connected to the droplet-generation region via the first, second, and third microfluidic channels, respectively.

公开(公告)号：US12168231B2

公开(公告)日：2024-12-17

申请号：US17486804

申请日：2021-09-27

Applicant: Bio-Rad Laboratories, Inc.

Inventor： Billy W. Colston, Jr. ,  Benjamin J. Hindson ,  Kevin D. Ness ,  Donald A. Masquelier

IPC: B01L3/00 ,  B01F23/41 ,  B01F33/3011 ,  B01F35/10 ,  B01L3/02 ,  B01L7/00 ,  B29C45/00 ,  C12Q1/686 ,  G01N21/3563 ,  G01N21/49 ,  G01N21/64 ,  B01F101/23 ,  B29L31/00

Abstract: Method of analysis. In the method, a microfluidic device defining a flow path extending from an inlet to an outlet may be selected. A sample-containing fluid may be introduced into the flow path via the inlet. Volumes of the sample-containing fluid may be isolated from one another on the flow path. A two-dimensional monolayer of the volumes may be imaged. The two-dimensional monolayer may be formed along the flow path between the inlet and the outlet.

公开(公告)号：US12097495B2

公开(公告)日：2024-09-24

申请号：US17750195

申请日：2022-05-20

Applicant: Bio-Rad Laboratories, Inc.

Inventor： Benjamin J. Hindson ,  Serge Saxonov ,  Phillip Belgrader ,  Kevin D. Ness ,  Michael Y. Lucero ,  Billy W. Colston, Jr. ,  Shawn Paul Hodges ,  Nicholas J. Heredia ,  Jeffrey Clark Mellen ,  Camille Bodley Troup ,  Paul Wyatt

IPC: B01L3/00 ,  B01F23/41 ,  B01F33/3011 ,  B01F33/81 ,  B01L9/00 ,  C12Q1/686 ,  B01F25/00 ,  B01F25/23 ,  B01F33/302 ,  G01N35/08

CPC classification number: B01L3/50273 ,  B01F23/41 ,  B01F33/3011 ,  B01F33/813 ,  B01L3/502 ,  B01L3/502784 ,  B01L3/52 ,  B01L9/527 ,  C12Q1/686 ,  B01F25/14 ,  B01F25/23 ,  B01F33/3021 ,  B01L3/502761 ,  B01L2200/025 ,  B01L2200/0636 ,  B01L2200/0647 ,  B01L2200/0673 ,  B01L2200/14 ,  B01L2200/16 ,  B01L2300/0609 ,  B01L2300/0681 ,  B01L2300/0816 ,  B01L2300/0829 ,  B01L2300/0861 ,  B01L2400/049 ,  G01N35/08

Abstract: The present disclosure provides methods and compositions for detecting polynucleotides in a sample and for quantifying polynucleotide load in a sample. The polynucleotides can be associated with a disease, disorder, or condition. In some applications, methylated DNA is quantified, e.g., in order to determine the load of polynucleotides in a sample. The present disclosure also provides methods and compositions for determining the load of fetal polynucleotides in a biological sample, e.g., the load of fetal polynucleotides (e.g., DNA, RNA) in maternal plasma. The present disclosure provides methods and compositions for detecting cellular processes such as cellular viability, growth rates, and infection rates. This disclosure also provides compositions and methods for detecting differences in copy number of a target polynucleotide. In some embodiments, the methods and compositions provided herein are useful for diagnosis of fetal genetic abnormalities, when the starting sample is maternal tissue (e.g., blood, plasma). The methods and materials described apply techniques for allowing detection of small, but statistically significant, differences in polynucleotide copy number.

公开(公告)号：US20180147573A1

公开(公告)日：2018-05-31

申请号：US15707908

申请日：2017-09-18

Applicant: Bio-Rad Laboratories, Inc.

Inventor： Amy L. Hiddessen ,  Donald A. Masquelier ,  Kevin D. Ness ,  Benjamin J. Hindson ,  Anthony J. Makarewicz, Jr. ,  Erin R. Chia ,  Billy W. Colston, Jr. ,  Serge Saxonov ,  Svilen S. Tzonev ,  Michael Y. Lucero ,  Ryan T. Koehler

IPC: B01L3/00 ,  B01L9/00 ,  B01F13/00 ,  C12Q1/686 ,  B01F13/10 ,  B01F3/08 ,  B01F5/02 ,  B01F5/00 ,  G01N35/08

CPC classification number: B01L3/50273 ,  B01F3/0807 ,  B01F5/0085 ,  B01F5/0256 ,  B01F13/0062 ,  B01F13/0071 ,  B01F13/1022 ,  B01L3/502 ,  B01L3/502761 ,  B01L3/502784 ,  B01L3/52 ,  B01L9/527 ,  B01L2200/025 ,  B01L2200/0636 ,  B01L2200/0647 ,  B01L2200/0673 ,  B01L2200/14 ,  B01L2200/16 ,  B01L2300/0609 ,  B01L2300/0681 ,  B01L2300/0816 ,  B01L2300/0829 ,  B01L2300/0861 ,  B01L2400/049 ,  C12Q1/686 ,  G01N35/08

Abstract: Devices and methods for generating droplets. An exemplary device comprises a substantially planar base portion including a bottom surface having a plurality of microfluidic channels formed therein as recessed regions of the bottom surface. The device also comprises a plurality of protrusions projecting from a top surface of the base portion and each formed integrally with the base portion. The device further comprises a sample well, a carrier well, and a droplet well. Each well has an upper portion created by one of the protrusions. A cover layer is attached to the bottom surface of the base portion and seals a bottom side of each microfluidic channel.

公开(公告)号：US09901927B2

公开(公告)日：2018-02-27

申请号：US15365894

申请日：2016-11-30

Applicant: Bio-Rad Laboratories, Inc.

Inventor： Benjamin J. Hindson ,  Kevin D. Ness ,  Billy W. Colston, Jr. ,  Fred P. Milanovich ,  Donald A. Masquelier

IPC: B01L3/00 ,  B01F3/08 ,  B01F13/00 ,  B01L3/02 ,  B01L7/00 ,  G01N21/3563 ,  C12Q1/68 ,  G01N21/64 ,  B01F15/00 ,  B29C45/00 ,  G01N21/49 ,  B29L31/00

Abstract: Methods of generating droplets. In an exemplary method, a device including a sample well, a carrier well, a droplet well, and a plurality of microfluidic channels is selected. The microfluidic channels include a first channel, a second channel, and a third channel. A discrete volume of sample-containing fluid is placed into the sample well, and a discrete volume of carrier fluid is placed into the carrier well. A pressure differential is created after placing the discrete volumes, to cause fluid flow. Sample-containing fluid flows from the sample well to a droplet-generation region of the device via the first channel. Carrier fluid flows from the carrier well to the droplet-generation region via the second channel. Sample-containing droplets and carrier fluid flow from the droplet-generation region to the droplet well via the third channel.

公开(公告)号：US09417190B2

公开(公告)日：2016-08-16

申请号：US13945661

申请日：2013-07-18

Applicant: Bio-Rad Laboratories, Inc.

Inventor： Benjamin J. Hindson ,  Billy W. Colston, Jr. ,  Kevin D. Ness ,  Donald A. Masquelier

IPC: C12Q1/68 ,  G01N21/64

CPC classification number: G01N21/6486 ,  C12Q1/6848 ,  G01N21/6428 ,  G01N21/6456 ,  G01N2021/6441 ,  G01N2201/1242 ,  C12Q2545/101 ,  C12Q2563/107 ,  C12Q2563/159

Abstract: System, including methods and apparatus, for performing droplet-based assays that are controlled and/or calibrated using signals detected from droplets.

Abstract translation: 用于执行使用从液滴检测的信号来控制和/或校准的基于液滴的测定的系统，包括方法和装置。