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1. 发明授权

US08846378B2 Fluidics system for sequential delivery of reagents 有权
标题翻译：用于顺序递送试剂的流体系统
公开(公告)号：US08846378B2
公开(公告)日：2014-09-30
申请号：US13245649
申请日：2011-09-26
申请人： Jonathan Schultz , David Marran
发明人： Jonathan Schultz , David Marran
IPC分类号： C12M1/00 , C12M3/00 , C12M1/34 , B01L3/00 , G01N27/447 , C12Q1/68 , G01N35/10
CPC分类号： B01L3/502715 , B01J2219/00389 , B01J2219/00394 , B01L3/502 , B01L3/50273 , B01L3/502738 , B01L3/502746 , B01L3/502769 , B01L3/502776 , B01L3/52 , B01L2200/16 , B01L2300/0636 , B01L2300/0645 , B01L2300/0861 , B01L2300/0864 , B01L2300/0867 , B01L2300/0874 , B01L2300/0877 , B01L2400/0487 , C12Q1/6869 , G01N27/447 , G01N35/1002 , G01N35/1097 , Y10T137/0318 , Y10T137/0424 , Y10T137/85938 , C12Q2565/629 , C12Q2527/119
摘要： Fluidic circuits and methods of using same are provided herein. In some embodiments, the circuit can direct different fluids to a common volume, such as a reaction chamber or flow cell, without intermixing or cross contamination. The direction and rate of flow through junctions, nodes and passages of the fluidics circuit can be controlled, for example, by the states of upstream valves, differential fluid pressures at circuit inlets or upstream reservoirs, or flow path resistances. Free diffusion or leakage of fluids from unselected inlets into the common outlet or other inlets at junctions or nodes can be prevented by the flow of the selected inlet fluid, a portion of which can sweep by the inlets of unselected fluids and exit the fluidics circuit by waste ports.
摘要翻译：本文提供了流体电路及其使用方法。在一些实施例中，电路可以将不同的流体引导到公共体积，例如反应室或流动池，而不会混合或交叉污染。可通过例如上游阀的状态，电路入口或上游储存器处的差分流体压力或流动阻力来控制流过流体回路的结，节点和通道的流动方向和速率。可以通过所选择的入口流体的流动来防止流体从未选择的入口到共同出口或其他入口处的自由扩散或泄漏，其一部分可以被未选择的流体的入口扫过并且通过废物港口。

2. 发明授权

US08746984B2 Mechanism for mounting and dismounting bearing 有权
标题翻译：安装和拆卸轴承的机构
公开(公告)号：US08746984B2
公开(公告)日：2014-06-10
申请号：US13253476
申请日：2011-10-05
申请人： Daniel Putt , Jonathan Schultz
发明人： Daniel Putt , Jonathan Schultz
IPC分类号： F16C43/00
CPC分类号： F16D1/096 , F16C19/38 , F16C23/086 , F16C35/073 , Y10T29/49 , Y10T29/49636 , Y10T29/49696 , Y10T29/49698 , Y10T29/49947 , Y10T29/53104 , Y10T403/5793 , Y10T403/7069
摘要： A mechanism and method for locking a bearing to a shaft includes a split sleeve and a receptive flange adapted to be fixed to the bearing. A positioning flange is coupled to the split sleeve. A screw extends through the positioning flange and threadingly engages the receptive flange. Rotation of the screw in a first direction axially drives the sleeve into engagement with the bearing to collapse the split sleeve into engagement with the shaft.
摘要翻译：用于将轴承锁定到轴的机构和方法包括分开套筒和适于固定到轴承的容纳凸缘。定位凸缘与分开的套筒相连。螺钉延伸穿过定位凸缘并与接收凸缘螺纹接合。螺杆在第一方向的旋转轴向地驱动套筒与轴承接合，以使分开的套筒与轴接合。

3. 发明授权

US08592153B1 Methods for manufacturing high capacitance microwell structures of chemically-sensitive sensors 有权
标题翻译：用于制造化学敏感传感器的高电容微孔结构的方法
公开(公告)号：US08592153B1
公开(公告)日：2013-11-26
申请号：US13603631
申请日：2012-09-05
申请人： James Bustillo , Jonathan Schultz , Todd Rearick , Mark Milgrew
发明人： James Bustillo , Jonathan Schultz , Todd Rearick , Mark Milgrew
IPC分类号： C12Q1/68 , C12M1/34 , C12M3/00 , G01N27/403
CPC分类号： G01N27/4145 , C12Q1/6869 , C12Q1/6874 , G01N27/27 , G01N27/414 , Y10T29/49002
摘要： Methods and apparatus relating to 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.
摘要翻译：与用于监测化学和/或生物反应的FET阵列相关的方法和装置，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）。

4. 发明授权

US08524057B2 Methods and apparatus for measuring analytes using large scale FET arrays 有权
公开(公告)号：US08524057B2
公开(公告)日：2013-09-03
申请号：US13193128
申请日：2011-07-28
申请人： Jonathan M. Rothberg , Wolfgang Hinz , Kim L. Johnson , James M. Bustillo , John H. Leamon , Jonathan Schultz
发明人： Jonathan M. Rothberg , Wolfgang Hinz , Kim L. Johnson , James M. Bustillo , John H. Leamon , Jonathan Schultz
IPC分类号： G01N27/414
CPC分类号： C12Q1/6874 , B01L3/502761 , B01L2300/046 , B01L2300/0663 , B01L2300/0851 , B01L2400/086 , C12Q1/6869 , G01N27/4145 , G01N27/4148 , C12Q2565/607 , C12Q2565/301 , C12Q2565/629
摘要： 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 the concentration of inorganic pyrophosphate (PPi), hydrogen ions, and nucleotide triphosphates.

5. 发明申请

US20120172241A1 MODELS FOR ANALYZING DATA FROM SEQUENCING-BY-SYNTHESIS OPERATIONS 审中-公开
标题翻译：用于分析合成数据的模型
公开(公告)号：US20120172241A1
公开(公告)日：2012-07-05
申请号：US13339846
申请日：2011-12-29
申请人： Todd REARICK , Jonathan SCHULTZ
发明人： Todd REARICK , Jonathan SCHULTZ
IPC分类号： C40B30/00 , G06F17/10
CPC分类号： G06F19/24 , C12Q1/6869 , C12Q2527/119 , C12Q2563/159 , C12Q2565/607
摘要： Mathematical models for the analysis of signal data generated by sequencing of a polynucleotide strand using a pH-based method of detecting nucleotide incorporation(s). In an embodiment, the measured output signal from the reaction confinement region of a reactor array is mathematically modeled. The output signal may be modeled as a linear combination of one or more signal components, including a background signal component. This model is solved to determine the nucleotide incorporation signal. In another embodiment, the incorporation signal from the reaction confinement region of a reactor array is mathematically modeled.
摘要翻译：用于通过使用基于pH的检测核苷酸掺入的方法测序多核苷酸链产生的信号数据分析的数学模型。在一个实施例中，来自反应堆阵列的反应限制区域的测量的输出信号在数学上被建模。输出信号可以被建模为包括背景信号分量的一个或多个信号分量的线性组合。该模型被解决以确定核苷酸掺入信号。在另一个实施方案中，来自反应器阵列的反应限制区域的掺入信号在数学上被建模。

6. 发明申请

US20120074165A1 FLUIDICS SYSTEM FOR SEQUENTIAL DELIVERY OF REAGENTS 审中-公开
标题翻译：用于顺序递送试剂的流体系统
公开(公告)号：US20120074165A1
公开(公告)日：2012-03-29
申请号：US13245684
申请日：2011-09-26
申请人： Jonathan SCHULTZ , David Marran
发明人： Jonathan SCHULTZ , David Marran
IPC分类号： B01L3/02
CPC分类号： B01L3/502715 , B01J2219/00389 , B01J2219/00394 , B01L3/502 , B01L3/50273 , B01L3/502738 , B01L3/502746 , B01L3/502769 , B01L3/502776 , B01L3/52 , B01L2200/16 , B01L2300/0636 , B01L2300/0645 , B01L2300/0861 , B01L2300/0864 , B01L2300/0867 , B01L2300/0874 , B01L2300/0877 , B01L2400/0487 , C12Q1/6869 , G01N27/447 , G01N35/1002 , G01N35/1097 , Y10T137/0318 , Y10T137/0424 , Y10T137/85938 , C12Q2565/629 , C12Q2527/119
摘要： The invention provides a passive fluidics circuit for directing different fluids to a common volume, such as a reaction chamber or flow cell, without intermixing or cross contamination. The direction and rate of flow through junctions, nodes and passages of the fluidics circuit are controlled by the states of upstream valves (e.g. opened or closed), differential fluid pressures at circuit inlets or upstream reservoirs, flow path resistances, and the like. Free diffusion or leakage of fluids from unselected inlets into the common outlet or other inlets at junctions or nodes is prevented by the flow of the selected inlet fluid, a portion of which sweeps by the inlets of unselected fluids and exits the fluidics circuit by waste ports, thereby creating a barrier against undesired intermixing with the outlet flow through leakage or diffusion.
摘要翻译：本发明提供了一种用于将不同流体引导到公共体积（例如反应室或流动池）的无源流体回路，而不会混合或交叉污染。通过流体回路的连接点，节点和通道的流动方向和流速由上游阀（例如打开或关闭）的状态，电路入口或上游储存器处的差分流体压力，流动阻力等来控制。通过所选择的入口流体的流动防止流体从未选择的入口到共同的出口或其他入口处的自由扩散或泄漏，其一部分由未选择的流体的入口扫过并且通过废物端口离开流体回路，从而产生阻止与出口流通过泄漏或扩散的不期望的混合的屏障。

7. 发明申请

US20110250700A1 Methods for Sequencing Individual Nucleic Acids Under Tension 有权
公开(公告)号：US20110250700A1
公开(公告)日：2011-10-13
申请号：US13044361
申请日：2011-03-09
申请人： Jonathan M. ROTHBERG , John H. LEAMON , John F. DAVIDSON , Antoine M. van OIJEN , Wolfgang HINZ , Melville DAVEY , Bradley Hann , Jonathan SCHULTZ
发明人： Jonathan M. ROTHBERG , John H. LEAMON , John F. DAVIDSON , Antoine M. van OIJEN , Wolfgang HINZ , Melville DAVEY , Bradley Hann , Jonathan SCHULTZ
IPC分类号： G01N33/53 , B03C1/02
CPC分类号： C12Q1/6874 , C12Q2523/303 , C12Q2565/131 , C12Q2525/204 , C12Q2521/101 , C12Q2535/122
摘要： The invention provides apparatuses and methods of use thereof for sequencing nucleic acids subjected to a force, and thus considered under tension. The methods may employ but are not dependent upon incorporation of extrinsically detectably labeled nucleotides.

8. 发明申请

US20110250603A1 Methods for Sequencing Individual Nucleic Acids Under Tension 审中-公开
标题翻译：在张力下测定单个核酸的方法
公开(公告)号：US20110250603A1
公开(公告)日：2011-10-13
申请号：US13044357
申请日：2011-03-09
申请人： Jonathan M. ROTHBERG , John H. LEAMON , John F. DAVIDSON , Antoine M. van OIJEN , Wolfgang HINZ , Melville DAVEY , Bradley HAHN , Jonathan SCHULTZ
发明人： Jonathan M. ROTHBERG , John H. LEAMON , John F. DAVIDSON , Antoine M. van OIJEN , Wolfgang HINZ , Melville DAVEY , Bradley HAHN , Jonathan SCHULTZ
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6874 , C12Q2523/303 , C12Q2565/131 , C12Q2525/204 , C12Q2521/101 , C12Q2535/122
摘要： The invention provides apparatuses and methods of use thereof for sequencing nucleic acids subjected to a force, and thus considered under tension. The methods may employ but are not dependent upon incorporation of extrinsically detectably labeled nucleotides.
摘要翻译：本发明提供了用于测序经受力的核酸的装置及其使用方法，并因此在张力下考虑。所述方法可以采用但不依赖于外源可检测标记的核苷酸的引入。

9. 发明授权

US10146906B2 Models for analyzing data from sequencing-by-synthesis operations 有权
公开(公告)号：US10146906B2
公开(公告)日：2018-12-04
申请号：US13339846
申请日：2011-12-29
申请人： Todd Rearick , Jonathan Schultz
发明人： Todd Rearick , Jonathan Schultz
IPC分类号： G06F19/24 , C12Q1/6869
摘要： Mathematical models for the analysis of signal data generated by sequencing of a polynucleotide strand using a pH-based method of detecting nucleotide incorporation(s). In an embodiment, the measured output signal from the reaction confinement region of a reactor array is mathematically modeled. The output signal may be modeled as a linear combination of one or more signal components, including a background signal component. This model is solved to determine the nucleotide incorporation signal. In another embodiment, the incorporation signal from the reaction confinement region of a reactor array is mathematically modeled.

10. 发明授权

US09428807B2 Phase-protecting reagent flow orderings for use in sequencing-by-synthesis 有权
标题翻译：用于逐段合成的相保护试剂流动顺序
公开(公告)号：US09428807B2
公开(公告)日：2016-08-30
申请号：US13440849
申请日：2012-04-05
申请人： Earl Hubbell , Jonathan Schultz
发明人： Earl Hubbell , Jonathan Schultz
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6869 , C12Q1/6874 , C12Q2533/101 , C12Q2565/301 , C12Q2565/607
摘要： A method for nucleic acid sequencing includes disposing template polynucleotide strands in defined spaces on a sensor array, at least some of the template polynucleotide strands having a sequencing primer and a polymerase operably bound therewith; exposing the template polynucleotide strands to a series of flows of nucleotide species flowed according to a predetermined ordering; and determining, for each of the series of flows of nucleotide species, how many nucleotide incorporations occurred for that particular flow to determine a predicted sequence of nucleotides corresponding to the template polynucleotide strands, wherein the predetermined ordering (a) is not a series of consecutive repetitions of a 4-flow permutation of four different nucleotide species, (b) is not specifically tailored to a particular combination of a particular template polynucleotide strand to be sequenced and a particular sequencing primer to be used, and (c) comprises a phase-protecting flow ordering.
摘要翻译：用于核酸测序的方法包括在传感器阵列上的限定空间中设置模板多核苷酸链，至少一些模板多核苷酸链具有测序引物和与之可操作地结合的聚合酶; 将模板多核苷酸链暴露于根据预定排序流动的一系列核苷酸类型的流; 并且对于核苷酸种类的每一系列流程，确定针对该特定流出现多少个核苷酸掺入以确定对应于模板多核苷酸链的预测的核苷酸序列，其中预定顺序（a）不是一系列连续的重复四种不同核苷酸物种的4流置换，（b）不是特定的针对待测序的特定模板多核苷酸链和特定的待测序列的特定组合而定制的，（c）保护流量顺序。

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