公开(公告)号：US10415079B2

公开(公告)日：2019-09-17

申请号：US15192225

申请日：2016-06-24

Applicant: LIFE TECHNOLOGIES CORPORATION

Inventor： Jonathan M. Rothberg ,  Wolfgang Hinz

IPC: C12Q1/68 ,  C12Q1/6825 ,  H01L29/78 ,  G01N27/26 ,  G01N33/68 ,  G01N27/414 ,  C12Q1/6874 ,  G01N33/543 ,  H01L29/788 ,  C12Q1/6869

Abstract: Methods and apparatuses relating to large scale FET arrays for analyte detection and measurement are provided. ChemFET (e.g., ISFET) arrays may be fabricated using conventional CMOS processing techniques based on improved FET pixel and array designs that increase measurement sensitivity and accuracy, and at the same time facilitate significantly small pixel sizes and dense arrays. Improved array control techniques provide for rapid data acquisition from large and dense arrays. Such arrays may be employed to detect a presence and/or concentration changes of various analyte types in a wide variety of chemical and/or biological processes.

公开(公告)号：US20160274056A1

公开(公告)日：2016-09-22

申请号：US15049638

申请日：2016-02-22

Applicant: Life Technologies Corporation

Inventor： Jonathan M. ROTHBERG ,  Wolfgang Hinz ,  Kim L. Johnson ,  James Bustillo

IPC: G01N27/414 ,  C12Q1/68 ,  G01N33/543

CPC classification number: G01N27/4148 ,  C12Q1/6818 ,  C12Q1/6874 ,  G01N27/4145 ,  G01N33/54373 ,  G01N33/5438 ,  H01L27/088 ,  H01L29/42324 ,  H01L29/78 ,  H01L2924/01006 ,  H01L2924/01013 ,  H01L2924/01015 ,  H01L2924/01073 ,  H01L2924/14 ,  H01L2924/1433 ,  Y10T436/22 ,  C12Q2565/607 ,  C12Q2565/301 ,  C12Q2533/101

Abstract: Methods and apparatus relating to very large scale FET arrays for analyte measurements. ChemFET (e.g., ISFET) arrays may be fabricated using conventional CMOS processing techniques based on improved FET pixel and array designs that increase measurement sensitivity and accuracy, and at the same time facilitate significantly small pixel sizes and dense arrays. Improved array control techniques provide for rapid data acquisition from large and dense arrays. Such arrays may be employed to detect a presence and/or concentration changes of various analyte types in a wide variety of chemical and/or biological processes. In one example, chemFET arrays facilitate DNA sequencing techniques based on monitoring changes in hydrogen ion concentration (pH), changes in other analyte concentration, and/or binding events associated with chemical processes relating to DNA synthesis.

公开(公告)号：US09267914B2

公开(公告)日：2016-02-23

申请号：US14244849

申请日：2014-04-03

Applicant: LIFE TECHNOLOGIES CORPORATION

Inventor： Kristopher Barbee ,  John F. Davidson ,  Wolfgang Hinz ,  Shifeng Li ,  James Bustillo

IPC: G01N27/414 ,  B01J19/00

CPC classification number: G01N27/4473 ,  B01J19/0046 ,  B01J2219/00286 ,  B01J2219/00317 ,  B01J2219/00459 ,  B01J2219/00466 ,  B01J2219/00468 ,  B01J2219/005 ,  B01J2219/00596 ,  B01J2219/00648 ,  B01J2219/00653 ,  B01J2219/00704 ,  B01J2219/00722 ,  C12Q1/6874 ,  G01N27/4145 ,  G01N27/4148 ,  G01N27/44743

Abstract: An apparatus includes a device substrate including an array of sensors. Each sensor of the array of sensors can include a electrode structure disposed at a surface of the device substrate. The apparatus further includes a wall structure overlying the surface of the device substrate and defining an array of wells at least partially corresponding with the array of sensors. The well structure including an electrode layer and an insulative layer.

公开(公告)号：US09249461B2

公开(公告)日：2016-02-02

申请号：US14044712

申请日：2013-10-02

Applicant: LIFE TECHNOLOGIES CORPORATION

Inventor： Wolfgang Hinz ,  John Leamon ,  David Light ,  Jonathan M. Rothberg

IPC: C12Q1/68 ,  G01N27/414 ,  B01J19/00 ,  C12N15/10 ,  C40B40/08 ,  C40B50/06

CPC classification number: B01J19/0046 ,  B01J2219/00466 ,  B01J2219/005 ,  B01J2219/00596 ,  B01J2219/00722 ,  C12N15/1093 ,  C12Q1/6874 ,  C40B40/08 ,  C40B50/06 ,  Y10T428/2982

Abstract: The invention provides particle compositions having applications in nucleic acid analysis. Nucleic acid polymer particles of the invention allow polynucleotides to be attached throughout their volumes for higher loading capacities than those achievable solely with surface attachment. In one aspect, nucleic acid polymer particles of the invention comprise polyacrylamide particles with uniform size distributions having low coefficients of variations, which result in reduced particle-to-particle variation in analytical assays. Such particle compositions are used in various amplification reactions to make amplicon libraries from nucleic acid fragment libraries.

公开(公告)号：US20160011146A1

公开(公告)日：2016-01-14

申请号：US14863173

申请日：2015-09-23

Applicant: LIFE TECHNOLOGIES CORPORATION

Inventor： Shifeng LI ,  James Bustillo ,  Wolfgang Hinz

IPC: G01N27/414 ,  H01L21/302 ,  H01L21/31

CPC classification number: G01N27/4148 ,  B01L3/5027 ,  B01L2200/0668 ,  B01L2200/12 ,  B01L2300/0636 ,  B01L2300/0645 ,  B01L2300/0819 ,  B01L2300/0877 ,  B01L2300/0893 ,  G01N27/26 ,  G01N27/27 ,  G01N27/4145 ,  H01L21/302 ,  H01L21/31 ,  Y10T436/14 ,  Y10T436/142222 ,  Y10T436/143333

Abstract: A system includes a sensor including a sensor pad and includes a well wall structure defining a well operatively connected to the sensor pad. The sensor pad is associated with a lower surface of the well. The well wall structure defines an upper surface and a wall surface extending between the upper surface and the lower surface. The upper surface is defined by an upper buffer material having an intrinsic buffer capacity of at least 2×1017 groups/m2. The wall surface is defined by a wall material having an intrinsic buffer capacity of not greater than 1.7×1017 groups/m2.

公开(公告)号：US20150329904A1

公开(公告)日：2015-11-19

申请号：US14703565

申请日：2015-05-04

Applicant: LIFE TECHNOLOGIES CORPORATION

Inventor： Jonathan M. ROTHBERG ,  Wolfgang Hinz ,  Kim L. Johnson ,  James Bustillo

IPC: C12Q1/68

CPC classification number: C12Q1/6869 ,  C12Q1/6874 ,  G01N27/414 ,  G01N27/4145 ,  G01N27/4148 ,  H01L21/306 ,  H01L24/18 ,  H01L24/20 ,  H01L24/82 ,  H01L27/088 ,  H01L29/78 ,  H01L2224/04105 ,  H01L2224/16 ,  H01L2224/76155 ,  H01L2224/82102 ,  H01L2924/01005 ,  H01L2924/01006 ,  H01L2924/01011 ,  H01L2924/01012 ,  H01L2924/01013 ,  H01L2924/01015 ,  H01L2924/01019 ,  H01L2924/0102 ,  H01L2924/01023 ,  H01L2924/01024 ,  H01L2924/01027 ,  H01L2924/01029 ,  H01L2924/0103 ,  H01L2924/01033 ,  H01L2924/01046 ,  H01L2924/01047 ,  H01L2924/01052 ,  H01L2924/01056 ,  H01L2924/01059 ,  H01L2924/01073 ,  H01L2924/01074 ,  H01L2924/01075 ,  H01L2924/01082 ,  H01L2924/1306 ,  H01L2924/13091 ,  H01L2924/14 ,  H01L2924/1433 ,  H01L2924/19041 ,  H01L2924/19042 ,  H01L2924/19043 ,  H01L2924/30105 ,  H01L2924/3011 ,  H01L2924/3025 ,  C12Q2565/607 ,  C12Q2565/301 ,  C12Q2533/101 ,  H01L2924/00

Abstract: Methods and apparatus relating to very large scale FET arrays for analyte measurements. ChemFET (e.g., ISFET) arrays may be fabricated using conventional CMOS processing techniques based on improved FET pixel and array designs that increase measurement sensitivity and accuracy, and at the same time facilitate significantly small pixel sizes and dense arrays. Improved array control techniques provide for rapid data acquisition from large and dense arrays. Such arrays may be employed to detect a presence and/or concentration changes of various analyte types in a wide variety of chemical and/or biological processes. In one example, chemFET arrays facilitate DNA sequencing techniques based on monitoring changes in hydrogen ion concentration (pH), changes in other analyte concentration, and/or binding events associated with chemical processes relating to DNA synthesis.

Abstract translation: 与用于分析物测量的非常大规模的FET阵列相关的方法和装置。 可以使用基于提高测量灵敏度和精度的改进的FET像素和阵列设计的传统CMOS处理技术来制造ChemFET（例如，ISFET）阵列，并且同时促进显着小的像素尺寸和致密阵列。 改进的阵列控制技术提供了从大型和密集阵列的快速数据采集。 可以使用这样的阵列来检测各种化学和/或生物过程中各种分析物类型的存在和/或浓度变化。 在一个实例中，chemFET阵列基于监测氢离子浓度（pH），其他分析物浓度变化和/或与DNA合成相关的化学过程相关联的结合事件的变化来促进DNA测序技术。

公开(公告)号：US09139666B2

公开(公告)日：2015-09-22

申请号：US14082368

申请日：2013-11-18

Applicant: LIFE TECHNOLOGIES CORPORATION ,  LIFE TECHNOLOGIES AS

Inventor： Geir Fonnum ,  Grete I. Modahl ,  Nini H. Kjus ,  Astrid E. Molteberg ,  Diem Tran ,  Jo Aaserud ,  Talha M. Gokmen ,  Steven M. Menchen ,  Carl Fuller ,  Luisa Andruzzi ,  Wolfgang Hinz

IPC: C12Q1/68 ,  C08F8/34 ,  C07F7/18 ,  C08F6/24 ,  C08F130/08 ,  C08F2/20 ,  C08F2/26 ,  C08F220/58 ,  C08F230/08 ,  C08F222/38 ,  C08F8/32

CPC classification number: C08F130/08 ,  C07F7/1804 ,  C07F7/188 ,  C08F2/20 ,  C08F2/26 ,  C08F6/24 ,  C08F8/12 ,  C08F8/32 ,  C08F8/34 ,  C08F220/58 ,  C08F222/385 ,  C08F230/08 ,  C08F2800/20 ,  C08J9/20 ,  C08J2343/04 ,  C12P19/34 ,  C12Q1/686 ,  C12Q1/6874 ,  G01N27/4145 ,  Y10T428/2982 ,  C08F257/02 ,  C08F2222/1013 ,  C08F212/36 ,  C08F220/60 ,  C12Q2563/149 ,  C12Q2563/159 ,  C12Q2565/543

Abstract: A method of forming a particle includes, in a disperse phase within an aqueous suspension, polymerizing a plurality of mer units of a hydrophilic monomer having a hydrophobic protection group, thereby forming a polymeric particle including a plurality of the hydrophobic protection groups. The method further includes converting the polymeric particle to a hydrophilic particle.

Abstract translation: 形成颗粒的方法包括在水性悬浮液中的分散相中聚合具有疏水保护基团的亲水性单体的多个聚合单元，从而形成包含多个疏水保护基团的聚合物颗粒。 该方法还包括将聚合物颗粒转化为亲水性颗粒。

公开(公告)号：US09080968B2

公开(公告)日：2015-07-14

申请号：US13734696

申请日：2013-01-04

Applicant: LIFE TECHNOLOGIES CORPORATION

Inventor： Christina Inman ,  Alexander Mastroianni ,  Wolfgang Hinz ,  Shifeng Li ,  Scott Benson

IPC: H01L27/14 ,  G01N27/414

CPC classification number: H01L21/31105 ,  G01N27/4145 ,  H01L21/31144

Abstract: A method of manufacturing a sensor, the method including forming an array of chemically-sensitive field effect transistors (chemFETs), depositing a dielectric layer over the chemFETs in the array, depositing a protective layer over the dielectric layer, etching the dielectric layer and the protective layer to form cavities corresponding to sensing surfaces of the chemFETs, and removing the protective layer. The method further includes, etching the dielectric layer and the protective layer together to form cavities corresponding to sensing surfaces of the chemFETs. The protective layer is at least one of a polymer, photoresist material, noble metal, copper oxide, and zinc oxide. The protective layer is removed using at least one of sodium hydroxide, organic solvent, aqua regia, ammonium carbonate, hydrochloric acid, acetic acid, and phosphoric acid.

Abstract translation: 一种制造传感器的方法，所述方法包括形成化学敏感场效应晶体管阵列（chemFET），在阵列中的chemFET上沉积介电层，在电介质层上沉积保护层，蚀刻电介质层和 保护层以形成对应于chemFET的感测表面的空腔，以及去除保护层。 该方法还包括：将电介质层和保护层一起蚀刻以形成对应于chemFET的感测表面的空腔。 保护层是聚合物，光致抗蚀剂材料，贵金属，氧化铜和氧化锌中的至少一种。 使用氢氧化钠，有机溶剂，王水，碳酸铵，盐酸，乙酸和磷酸中的至少一种除去保护层。

公开(公告)号：US09039888B2

公开(公告)日：2015-05-26

申请号：US14033934

申请日：2013-09-23

Applicant: LIFE TECHNOLOGIES CORPORATION

Inventor： Jonathan Rothberg ,  Wolfgang Hinz

IPC: G01N27/414 ,  G01N33/50 ,  G01N33/543 ,  C12Q1/68 ,  H01L29/78 ,  G01N27/26 ,  G01N33/68

CPC classification number: C12Q1/6825 ,  C12Q1/6869 ,  C12Q1/6874 ,  G01N27/26 ,  G01N27/4145 ,  G01N27/4148 ,  G01N33/54373 ,  G01N33/6818 ,  H01L29/78 ,  H01L29/788 ,  H01L2924/01006

Abstract: Methods and apparatuses relating to large scale FET arrays for analyte detection and measurement are provided. ChemFET (e.g., ISFET) arrays may be fabricated using conventional CMOS processing techniques based on improved FET pixel and array designs that increase measurement sensitivity and accuracy, and at the same time facilitate significantly small pixel sizes and dense arrays. Improved array control techniques provide for rapid data acquisition from large and dense arrays. Such arrays may be employed to detect a presence and/or concentration changes of various analyte types in a wide variety of chemical and/or biological processes.

Abstract translation: 提供了与用于分析物检测和测量的大规模FET阵列相关的方法和装置。 可以使用基于提高测量灵敏度和精度的改进的FET像素和阵列设计的传统CMOS处理技术来制造ChemFET（例如，ISFET）阵列，并且同时促进显着小的像素尺寸和致密阵列。 改进的阵列控制技术提供了从大型和密集阵列的快速数据采集。 可以使用这样的阵列来检测各种化学和/或生物过程中各种分析物类型的存在和/或浓度变化。

公开(公告)号：US08766328B2

公开(公告)日：2014-07-01

申请号：US13923282

申请日：2013-06-20

Applicant: Life Technologies Corporation

Inventor： Jonathan M. Rothberg ,  Wolfgang Hinz ,  Kim L. Johnson ,  James Bustillo

IPC: G01N27/403

CPC classification number: G01N27/4148 ,  C12Q1/6818 ,  C12Q1/6874 ,  G01N27/4145 ,  G01N33/54373 ,  G01N33/5438 ,  H01L27/088 ,  H01L29/42324 ,  H01L29/78 ,  H01L2924/01006 ,  H01L2924/01013 ,  H01L2924/01015 ,  H01L2924/01073 ,  H01L2924/14 ,  H01L2924/1433 ,  Y10T436/22 ,  C12Q2565/607 ,  C12Q2565/301 ,  C12Q2533/101

Abstract: Methods and apparatus relating to very large scale FET arrays for analyte measurements. ChemFET (e.g., ISFET) arrays may be fabricated using conventional CMOS processing techniques based on improved FET pixel and array designs that increase measurement sensitivity and accuracy, and at the same time facilitate significantly small pixel sizes and dense arrays. Improved array control techniques provide for rapid data acquisition from large and dense arrays. Such arrays may be employed to detect a presence and/or concentration changes of various analyte types in a wide variety of chemical and/or biological processes. In one example, chemFET arrays facilitate DNA sequencing techniques based on monitoring changes in hydrogen ion concentration (pH), changes in other analyte concentration, and/or binding events associated with chemical processes relating to DNA synthesis.

Abstract translation: 与用于分析物测量的非常大规模的FET阵列相关的方法和装置。 可以使用基于提高测量灵敏度和精度的改进的FET像素和阵列设计的传统CMOS处理技术来制造ChemFET（例如，ISFET）阵列，并且同时促进显着小的像素尺寸和致密阵列。 改进的阵列控制技术提供了从大型和密集阵列的快速数据采集。 可以使用这样的阵列来检测各种化学和/或生物过程中各种分析物类型的存在和/或浓度变化。 在一个实例中，chemFET阵列基于监测氢离子浓度（pH），其他分析物浓度变化和/或与DNA合成相关的化学过程相关联的结合事件的变化来促进DNA测序技术。