公开(公告)号：US08262900B2

公开(公告)日：2012-09-11

申请号：US12002781

申请日：2007-12-17

Applicant: Jonathan M. Rothberg ,  Wolfgang Hinz

Inventor： Jonathan M. Rothberg ,  Wolfgang Hinz

IPC: C12Q1/25 ,  G01N27/414

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.

公开(公告)号：US20120129703A1

公开(公告)日：2012-05-24

申请号：US13019354

申请日：2011-02-02

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

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

IPC: C40B20/00

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：US20120071363A1

公开(公告)日：2012-03-22

申请号：US13149262

申请日：2011-05-31

Applicant: Jonathan M. ROTHBERG ,  Wolfgang HINZ

Inventor： Jonathan M. ROTHBERG ,  Wolfgang HINZ

IPC: C40B60/12 ,  G01N27/414

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：US20120061256A1

公开(公告)日：2012-03-15

申请号：US13229439

申请日：2011-09-09

Applicant: Jonathan M. Rothberg ,  Wolfgang Hinz

Inventor： Jonathan M. Rothberg ,  Wolfgang Hinz

IPC: G01N27/414 ,  G01N33/50

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.

公开(公告)号：US20120055813A1

公开(公告)日：2012-03-08

申请号：US13033062

申请日：2011-02-23

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

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

IPC: G01N27/414

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：US20120013392A1

公开(公告)日：2012-01-19

申请号：US13149279

申请日：2011-05-31

Applicant: Jonathan M. ROTHBERG ,  James M. BUSTILLO ,  Mark J. MILGREW ,  Jonathan C. SCHULTZ ,  David MARRAN ,  Todd M. REARICK ,  Kim L. JOHNSON

Inventor： Jonathan M. ROTHBERG ,  James M. BUSTILLO ,  Mark J. MILGREW ,  Jonathan C. SCHULTZ ,  David MARRAN ,  Todd M. REARICK ,  Kim L. JOHNSON

IPC: G01N27/26 ,  H05K13/00 ,  G01N30/00

CPC classification number: G01N27/4145 ,  C12Q1/6869 ,  C12Q1/6874 ,  G01N27/27 ,  G01N27/414 ,  Y10T29/49002

Abstract: Methods and apparatus relating to FET arrays including large FET arrays for monitoring chemical and/or biological reactions such as nucleic acid sequencing-by-synthesis reactions. Some methods provided herein relate to improving signal (and also signal to noise ratio) from released hydrogen ions during nucleic acid sequencing reactions.

Abstract translation: 涉及FET阵列的方法和装置，包括用于监测化学和/或生物反应的大型FET阵列，例如核酸序列合成反应。 本文提供的一些方法涉及在核酸测序反应期间从释放的氢离子改进信号（以及信噪比）。

公开(公告)号：US20110301041A1

公开(公告)日：2011-12-08

申请号：US13036526

申请日：2011-02-28

Applicant: John DAVIDSON ,  Wolfgang Hinz ,  Jonathan M. Rothberg ,  Richard Whitaker

Inventor： John DAVIDSON ,  Wolfgang Hinz ,  Jonathan M. Rothberg ,  Richard Whitaker

IPC: C40B20/00 ,  C12Q1/68

CPC classification number: C12Q1/6869 ,  C12N9/1252 ,  C12Q2563/113 ,  C12Q2563/116

Abstract: Methods, compositions, systems, apparatuses and kits comprising modified proteins, particularly modified nucleic acid-binding proteins with altered buffering properties are provided. For example, in some embodiments, methods of forming modified proteins including one or more amino acid modifications to achieve desired pKa values are described. Furthermore, the invention provides methods for using such modified proteins in ion-producing reactions, such as ion-based nucleic acid sequencing reactions.

公开(公告)号：US20110281741A1

公开(公告)日：2011-11-17

申请号：US13027420

申请日：2011-02-15

Applicant: Jonathan M. ROTHBERG ,  Wolfgang HINZ ,  John F. DAVIDSON ,  Antoine M. van OIJEN ,  John H. LEAMON ,  Martin HUBER

Inventor： Jonathan M. ROTHBERG ,  Wolfgang HINZ ,  John F. DAVIDSON ,  Antoine M. van OIJEN ,  John H. LEAMON ,  Martin HUBER

IPC: C40B30/00 ,  C12Q1/68

CPC classification number: G01N27/4145 ,  C12Q1/6869 ,  C12Q1/6874 ,  G01N27/4148 ,  H01L21/82 ,  C12Q2565/607

Abstract: Methods and apparatus relating to FET arrays including large FET arrays for monitoring chemical and/or biological reactions such as nucleic acid sequencing-by-synthesis reactions. Some methods provided herein relate to improving signal (and also signal to noise ratio) from released hydrogen ions during nucleic acid sequencing reactions.

Abstract translation: 涉及FET阵列的方法和装置，包括用于监测化学和/或生物反应的大型FET阵列，例如核酸序列合成反应。 本文提供的一些方法涉及在核酸测序反应期间从释放的氢离子改进信号（以及信噪比）。

公开(公告)号：US20110263463A1

公开(公告)日：2011-10-27

申请号：US13125133

申请日：2009-10-22

Applicant: Jonathan M. Rothberg ,  James Bustillo ,  Mark Milgrew ,  Jonathan Schultz ,  David Marran ,  Todd Rearick ,  Kim Johnson

Inventor： Jonathan M. Rothberg ,  James Bustillo ,  Mark Milgrew ,  Jonathan Schultz ,  David Marran ,  Todd Rearick ,  Kim Johnson

IPC: C40B60/12 ,  B82Y15/00

CPC classification number: G01N27/4145 ,  C12Q1/6869 ,  C12Q1/6874 ,  G01N27/4148 ,  H01L21/82 ,  C12Q2565/607

Abstract: The invention is directed to apparatus and chips comprising a large scale chemical field effect transistor arrays that include an array of sample-retaining regions capable of retaining a chemical or biological sample from a sample fluid for analysis. In one aspect such transistor arrays have a pitch of 10 μm or less and each sample-retaining region is positioned on at least one chemical field effect transistor which is configured to generate at least one output signal related to a characteristic of a chemical or biological sample in such sample-retaining region. In one embodiment, the characteristic of said chemical or biological sample is a concentration of a charged species and wherein each of said chemical field effect transistors is an ion-sensitive field effect transistor having a floating gate with a dielectric layer on a surface thereof, the dielectric layer contacting said sample fluid and being capable of accumulating charge in proportion to a concentration of the charged species in said sample fluid. In one embodiment such charged species is a hydrogen ion such that the sensors measure changes in pH of the sample fluid in or adjacent to the sample-retaining region thereof. Apparatus and chips of the invention may be adapted for large scale pH-based DNA sequencing and other bioscience and biomedical applications.

Abstract translation: 本发明涉及包括大规模化学场效应晶体管阵列的装置和芯片，其包括能够保留来自样品流体的化学或生物样品用于分析的样品保持区阵列。 在一个方面，这种晶体管阵列具有10μm或更小的间距，并且每个采样保持区域位于至少一个化学场效应晶体管上，该晶体管被配置为产生与化学或生物样品的特性相关的至少一个输出信号 在这样的样品保留区域中。 在一个实施方案中，所述化学或生物样品的特征是带电物质的浓度，并且其中每个所述化学场效应晶体管是离子敏感场效应晶体管，其具有在其表面上具有介电层的浮置栅极， 电介质层与所述样品流体接触并且能够与所述样品流体中的带电物质的浓度成比例地积累电荷。 在一个实施方案中，这种带电物质是氢离子，使得传感器测量样品流体在其样品保持区域中或其附近的pH值的变化。 本发明的装置和芯片可适用于大规模的基于pH的DNA测序和其他生物科学和生物医学应用。

公开(公告)号：US20110262903A1

公开(公告)日：2011-10-27

申请号：US13035081

申请日：2011-02-25

Applicant: John DAVIDSON ,  Wolfgang Hinz ,  Jonathan M. Rothberg

Inventor： John DAVIDSON ,  Wolfgang Hinz ,  Jonathan M. Rothberg

IPC: C12Q1/68

CPC classification number: C12N9/1252

Abstract: Methods, compositions, systems, apparatuses and kits comprising modified proteins, particularly modified nucleic acid-binding proteins with altered buffering properties are provided. For example, in some embodiments, methods of forming modified proteins including one or more amino acid modifications to achieve desired pKa values are described. Furthermore, the invention provides methods for using such modified proteins in ion-producing reactions, such as ion-based nucleic acid sequencing reactions.