公开(公告)号：US09605308B2

公开(公告)日：2017-03-28

申请号：US13689252

申请日：2012-11-29

Applicant: LIFE TECHNOLOGIES CORPORATION

Inventor： Jonathan Schultz ,  John Davidson

IPC: C12Q1/68 ,  B01L3/00

CPC classification number: C12Q1/6869 ,  B01L3/5027 ,  C12Q1/6874 ,  C12Q2537/155 ,  C12Q2563/149 ,  C12Q2565/301 ,  C12Q2565/629

Abstract: A method for sequencing a polynucleotide strand by using sequencing-by-synthesis techniques. To address the problem of incomplete extension (IE) and/or carry forward (CF) errors that can occur in sequencing-by-synthesis reactions, an alternative flow ordering of dNTPs is used. In contrast to conventional flow orderings, the dNTPs are flowed in an ordering that is not a continuous repeat of an ordering of the four different dNTPs. This alternate flow ordering may reduce the loss of phasic synchrony in the population of template polynucleotide strands that result from IE and/or CF errors.

公开(公告)号：US09550183B2

公开(公告)日：2017-01-24

申请号：US14291372

申请日：2014-05-30

Applicant: LIFE TECHNOLOGIES CORPORATION

Inventor： Jonathan Schultz ,  David Marran

IPC: C12M1/00 ,  C12M3/00 ,  C12M1/34 ,  B01L3/00 ,  C12Q1/68 ,  G01N27/447 ,  G01N35/10

CPC classification number: 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

Abstract: 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. The invention is particularly advantageous in apparatus for performing sensitive multistep reactions, such as pH-based DNA sequencing reactions.

Abstract translation: 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。 本发明在用于进行灵敏多步反应（例如基于pH的DNA测序反应）的装置中特别有利。

公开(公告)号：US09375716B2

公开(公告)日：2016-06-28

申请号：US14740573

申请日：2015-06-16

Applicant: LIFE TECHNOLOGIES CORPORATION

Inventor： Jonathan Schultz

IPC: B01L3/00 ,  C12Q1/68 ,  F16K7/07 ,  G05D16/06 ,  G05D16/18

CPC classification number: F16K7/07 ,  B01L3/567 ,  B01L2200/06 ,  C12Q1/6869 ,  F16K7/04 ,  G05D16/0638 ,  G05D16/185

Abstract: A valve for regulating fluid flow includes a housing base defining a lower cavity and comprising a pinch structure within the lower cavity, a gas inlet providing external access to the lower cavity, a base fluid inlet, and a base fluid outlet. A housing cover defines an upper cavity and comprises a cover fluid inlet and a cover fluid outlet. The cover fluid inlet is in fluidic communication with the base fluid outlet between the upper cavity and the lower cavity, and the cover fluid outlet provides external access from the upper cavity. A diaphragm is disposed between the housing base and the housing cover. A pinch plate is disposed in the lower cavity and comprises a pinch point disposed opposite the pinch structure. A pinch tube is in fluidic communication between the base fluid inlet and the base fluid outlet in the lower cavity.

Abstract translation: 用于调节流体流动的阀包括限定下腔的壳体底座，并且在下腔体内包括夹紧结构，提供对下腔室的外部通路的气体入口，基础流体入口和基础流体出口。 壳体盖限定上腔，并且包括盖流体入口和盖流体出口。 覆盖流体入口与上腔和下腔之间的基础流体出口流体连通，并且盖流体出口提供从上腔体的外部通路。 隔膜设置在壳体基座和壳体盖之间。 压板设置在下腔体中，并且包括与夹紧结构相对设置的夹点。 夹管在底部流体入口和下腔体中的基础流体出口之间流体连通。

公开(公告)号：US20160168634A1

公开(公告)日：2016-06-16

申请号：US15043296

申请日：2016-02-12

Applicant: LIFE TECHNOLOGIES CORPORATION

Inventor： Todd REARICK ,  Mark James Milgrew ,  Jonathan Schultz ,  Chris Papalias ,  Kim L. Johnson

IPC: C12Q1/68

CPC classification number: C12Q1/6874 ,  G06F19/22

Abstract: In one implementation, a method is described. The method includes determining an operational characteristic of sensors of a sensor array. The method further includes selecting a group of sensors in the array based on the operational characteristic of sensors in the group. The method further includes enabling readout of the sensors in the selected group. The method further includes receiving output signals from the enabled sensors, the output signals indicating chemical reactions occurring proximate to the sensors of the sensor array.

Abstract translation: 在一个实现中，描述了一种方法。 该方法包括确定传感器阵列的传感器的操作特性。 该方法还包括基于组中的传感器的操作特性来选择阵列中的一组传感器。 该方法还包括使得能够读出所选择的组中的传感器。 所述方法还包括接收来自所述使能的传感器的输出信号，所述输出信号指示在所述传感器阵列的传感器附近发生的化学反应。

公开(公告)号：US09194000B2

公开(公告)日：2015-11-24

申请号：US14520558

申请日：2014-10-22

Applicant: LIFE TECHNOLOGIES CORPORATION

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

IPC: C12Q1/68 ,  G01N27/414

CPC classification number: C12Q1/6874 ,  B01L3/502761 ,  B01L2300/046 ,  B01L2300/0663 ,  B01L2300/0851 ,  B01L2400/086 ,  C12Q1/6869 ,  G01N27/4145 ,  G01N27/4148 ,  C12Q2565/607 ,  C12Q2565/301 ,  C12Q2565/629

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 the concentration of inorganic pyrophosphate (PPi), hydrogen ions, and nucleotide triphosphates.

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。 在一个示例中，chemFET阵列基于监测无机焦磷酸盐（PPi），氢离子和核苷酸三磷酸盐的浓度变化来促进DNA测序技术。