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    METHODS AND SYSTEMS FOR INSTRUMENT VALIDATION
    1.
    发明申请
    METHODS AND SYSTEMS FOR INSTRUMENT VALIDATION 审中-公开
    仪器验证的方法和系统

    公开(公告)号：WO2016127032A1

    公开(公告)日：2016-08-11

    申请号：PCT/US2016/016730

    申请日：2016-02-05

    Applicant: LIFE TECHNOLOGIES CORPORATION

    Inventor： WESSEL, Thomas ,  CHU, Yong ,  FREUDENTHAL, Jacob ,  WOO, David

    IPC: G01N21/27 ,  G01N21/64 ,  C12Q1/68 ,  G06F19/26

    CPC classification number: G01N21/6428 ,  G01N21/274 ,  G01N21/6452 ,  G01N21/6456 ,  G01N2021/6439 ,  G06F19/24

    Abstract: A method for validating an instrument is provided. The method includes receiving amplification data from a validation plate to generate a plurality of amplification curves (102, 202). The validation plate includes a sample of a first quantity and a second quantity, and each amplification curve includes an exponential region. The method further includes determining a set of fluorescence thresholds based on the exponential regions of the plurality of amplification curves (104, 204) and determining, for each fluorescence threshold of the set, a first set of cycle threshold (C t ) values of amplification curves generated from the samples of the first quantity and a second set of C t values of amplification curves generated from the samples of the second quantity (106, 206). The method includes calculating if the first and second quantities are sufficiently distinguishable based on C t values at each of the plurality of fluorescence thresholds (108, 208-218).

    Abstract translation: 提供了一种验证仪器的方法。 该方法包括从验证板接收放大数据以产生多个放大曲线（102,202）。 验证板包括第一数量和第二数量的样本，并且每个扩增曲线包括指数区域。 该方法还包括基于多个扩增曲线（104,204）的指数区域来确定一组荧光阈值，并且针对该组的每个荧光阈值确定放大曲线的第一组周期阈值（Ct）值 从第一数量的样本和从第二数量（106,206）的样本生成的第二组扩增曲线的Ctval值产生。 该方法包括基于多个荧光阈值（108,208-218）中的每一个的Ct值来计算第一和第二量是否足够可区分。

    METHODS AND SYSTEMS FOR DETERMINING OPTICAL REGIONS OF INTEREST
    2.
    发明申请
    METHODS AND SYSTEMS FOR DETERMINING OPTICAL REGIONS OF INTEREST 审中-公开
    用于确定光学区域的方法和系统

    公开(公告)号：WO2016127082A1

    公开(公告)日：2016-08-11

    申请号：PCT/US2016/016821

    申请日：2016-02-05

    Applicant: LIFE TECHNOLOGIES CORPORATION

    Inventor： CHU, Yong

    IPC: G01N21/27 ,  G01N21/64 ,  G06F19/18

    CPC classification number: G01N21/763 ,  G01N21/274 ,  G01N21/6428 ,  G01N21/6452 ,  G01N21/6456 ,  G01N21/77 ,  G01N2021/7786 ,  G01N2201/127 ,  G06K9/00134 ,  G06K9/0014 ,  G06K9/3233

    Abstract: The present teachings relate to a method (300) and system for determining Regions of Interest (ROI) for one or more biological samples in a laboratory instrument. The method can include an optical system (200) capable of imaging florescence emission from a plurality of sample wells (210). An initial ROI, its center location (310) and size (320) can be estimated from the fluorescence detected from each well. From this information the average size of the ROIs (330) can be determined and global gridding models (340) can be derived to better locate each of the ROIs. The global gridding models can then be applied to the ROIs to improve the precision of the ROI center locations (350). Sample wells not originally providing fluorescence ROIs can be recovered (360) through the use of mapping functions. The radius of each ROI can then be adjusted (370) to improve the signal-to-noise ratio of the optical system.

    Abstract translation: 本教导涉及用于确定实验室仪器中的一种或多种生物样品的感兴趣区域（ROI）的方法（300）和系统。 该方法可以包括能够成像来自多个样品阱（210）的荧光发射的光学系统（200）。 可以从从每个孔检测的荧光估计初始ROI，其中心位置（310）和大小（320）。 根据该信息，可以确定ROI的平均大小（330），并且可以导出全局网格化模型（340）以更好地定位每个ROI。 然后可以将全局网格化模型应用于ROI，以提高ROI中心位置的精度（350）。 原始提供荧光ROI的样品孔可以通过使用映射函数来恢复（360）。 然后可以调整每个ROI的半径（370），以提高光学系统的信噪比。

    SYSTEM AND METHODS FOR CALIBRATING BINDING DYES
    3.
    发明申请
    SYSTEM AND METHODS FOR CALIBRATING BINDING DYES 审中-公开
    用于校准结合染色体的系统和方法

    公开(公告)号：WO2016127080A1

    公开(公告)日：2016-08-11

    申请号：PCT/US2016/016817

    申请日：2016-02-05

    Applicant: LIFE TECHNOLOGIES CORPORATION

    Inventor： CHU, Yong ,  FREUDENTHAL, Jacob ,  MARKS, Jeffrey

    IPC: G01N21/27 ,  G01N21/64 ,  C12Q1/68

    CPC classification number: C12Q1/686 ,  G01N21/274 ,  G01N21/6428 ,  G01N21/6452 ,  G01N21/6456 ,  G01N2021/6421 ,  G01N2021/6441 ,  G01N2201/127

    Abstract: A computer-implemented method (500) for calibrating a fluorescent dye is described. The method (500) comprises imaging a sample holder, loaded into an instrument, at more than one channel. The sample holder comprises a plurality of reaction sites and more than one dye type, with each dye occupying more than one reaction site. The method further comprises identifying a peak channel for each dye on the sample holder (508), normalizing each channel to the peak channel for each dye (510), and producing a dye matrix (518) that comprises a set of dye reference values.

    Abstract translation: 描述了用于校准荧光染料的计算机实现的方法（500）。 方法（500）包括在多个通道上成像加载到仪器中的样品保持器。 样品架包括多个反应位点和多于一种染料类型，每种染料占据多于一个反应位点。 该方法还包括鉴定样品保持器（508）上的每种染料的峰值通道，将每个通道标准化为每个染料（510）的峰值通道，以及产生包含一组染料参考值的染料基质（518）。

    IMAGE DRIVEN QUALITY CONTROL FOR ARRAY BASED PCR
    4.
    发明申请
    IMAGE DRIVEN QUALITY CONTROL FOR ARRAY BASED PCR 审中-公开

    公开(公告)号：WO2020047288A1

    公开(公告)日：2020-03-05

    申请号：PCT/US2019/048862

    申请日：2019-08-29

    Applicant: LIFE TECHNOLOGIES CORPORATION

    Inventor： CHU, Yong ,  MAJUMBAR, Nivedita ,  ALIMINATI, Manjula ,  CHEN, Yongzhi ,  PAPENFUSS, Kevin

    IPC: G06N3/04 ,  G06N3/08 ,  G01N35/00 ,  G01N35/02 ,  G06T7/00

    Abstract: A system and methods are provided for image driven quality control for array based PCR. The system comprises a PCR unit, a reaction array plate, a convolutional neural network (CNN) configured to receive a sequence of images of the reaction array plate in the PCR system, and an output of the CNN coupled to a control for the reaction array plate. The method comprises applying a sequence of images from a plurality of subarrays of the reaction array plate to a plurality of CNNs during operation of the PCR system on the reaction plate array, operating the CNNs to generate failure mode predictions for the reaction plate based on the sequence of images, and coupling an output of the CNNs to one or more of a setting for manufacture of the reaction array plate or to control the PCR system.

    METHODS AND SYSTEMS FOR ANALYZING BIOLOGICAL REACTION SYSTEMS
    5.
    发明申请
    METHODS AND SYSTEMS FOR ANALYZING BIOLOGICAL REACTION SYSTEMS 审中-公开
    分析生物反应系统的方法和系统

    公开(公告)号：WO2014153369A1

    公开(公告)日：2014-09-25

    申请号：PCT/US2014/031137

    申请日：2014-03-18

    Applicant: LIFE TECHNOLOGIES CORPORATION

    Inventor： CHU, Yong ,  MARKS, Jeffrey

    IPC: C12Q1/68 ,  G06K9/00 ,  G06T5/00

    CPC classification number: G06T7/74 ,  C12Q1/686 ,  G06K9/00 ,  G06K2209/07 ,  G06T5/002 ,  G06T7/0012 ,  G06T7/11 ,  G06T7/136 ,  G06T7/194 ,  G06T2207/10064 ,  G06T2207/20024 ,  G06T2207/20208 ,  G06T2207/30072

    Abstract: A method for analyzing biological reaction systems is provided. The method includes receiving an image of a substrate including a plurality of reaction sites after a biological reaction has taken place. Next, the method includes removing a noise background from the first image. The method includes determining an initial position of each reaction site based on an intensity threshold to generate a initial position set, then refining the initial position set of each reaction site based on an expected pattern of locations of the plurality of reaction sites to generate a first refined position set. The method further includes determining a presence or absence of a fluorescent emission from each reaction site based on the first refined position set and the first image.

    Abstract translation: 提供了分析生物反应体系的方法。 该方法包括在发生生物反应之后接收包括多个反应位点的底物的图像。 接下来，该方法包括从第一图像中去除噪声背景。 该方法包括基于强度阈值确定每个反应位点的初始位置以产生初始位置集合，然后基于多个反应位点的预期位置模式来精化每个反应位点的初始位置集合，以产生第一 精致的位置集。 该方法还包括基于第一精制位置集和第一图像来确定来自每个反应位点的荧光发射的存在或不存在。

    DEEP BASECALLER FOR SANGER SEQUENCING
    7.
    发明申请
    DEEP BASECALLER FOR SANGER SEQUENCING 审中-公开

    公开(公告)号：WO2020123552A1

    公开(公告)日：2020-06-18

    申请号：PCT/US2019/065540

    申请日：2019-12-10

    Applicant: LIFE TECHNOLOGIES CORPORATION

    Inventor： CHU, Yong ,  SCHNEIDER, Stephanie ,  SCHAEFFER, Rylan ,  WOO, David

    IPC: G16B30/20 ,  G16B40/20

    Abstract: A deep basecaller system for Sanger sequencing and associated methods are provided. The methods use deep machine learning. A Deep Learning Model is used to determine scan labelling probabilities based on an analyzed trace. A Neural Network is trained to learn the optimal mapping function to minimize a Connectionist Temporal Classification (CTC) Loss function. The CTC function is used to calculate loss by matching a target sequence and predicted scan labelling probabilities. A Decoder generates a sequence with the maximum probability. A Basecall position finder using prefix beam search is used to walk through CTC labelling probabilities to find a scan range and then the scan a position of peak labelling probability within the scan range for each called base. A Quality Value (QV) is determined using a feature vector calculated from CTC labelling probabilities as an index into a QV look-up table to find a quality score.

    METHODS AND SYSTEMS FOR BIOLOGICAL INSTRUMENT CALIBRATION
    8.
    发明申请
    METHODS AND SYSTEMS FOR BIOLOGICAL INSTRUMENT CALIBRATION 审中-公开
    生物仪器校准的方法和系统

    公开(公告)号：WO2016127124A2

    公开(公告)日：2016-08-11

    申请号：PCT/US2016/016882

    申请日：2016-02-05

    Applicant: LIFE TECHNOLOGIES CORPORATION

    Inventor： CHU, Yong ,  MARKS, Jeffrey ,  FREUDENTHAL, Jacob ,  WESSEL, Thomas ,  WOO, David

    IPC: G01N21/27 ,  G01N21/64

    CPC classification number: G01N21/6428 ,  C12Q1/6851 ,  C12Q1/686 ,  G01N21/274 ,  G01N21/278 ,  G01N21/6452 ,  G01N21/6456 ,  G01N2021/6439 ,  G01N2021/6471 ,  G01N2201/127 ,  G01N2201/13 ,  G01N2333/922

    Abstract: In one exemplary embodiment, a method for calibrating an instrument is provided. The instrument includes an optical system capable of imaging florescence emission from a plurality of reaction sites. The method includes performing a region-of-interest (ROI) calibration to determine reaction site positions in an image. The method further includes performing a pure dye calibration to determine the contribution of a fluorescent dye used in each reaction site by comparing a raw spectrum of the fluorescent dye to a pure spectrum calibration data of the fluorescent dye. The method further includes performing an instrument normalization calibration to determine a filter normalization factor. The method includes performing an RNase P validation to validate the instrument is capable of distinguishing between two different quantities of sample.

    Abstract translation: 在一个示例性实施例中，提供了一种用于校准仪器的方法。 该仪器包括能够成像来自多个反应位点的荧光发射的光学系统。 该方法包括执行感兴趣区域（ROI）校准以确定图像中的反应位置位置。 该方法还包括进行纯染料校准，以通过将荧光染料的原始光谱与荧光染料的纯光谱校准数据进行比较来确定每个反应位点中使用的荧光染料的贡献。 该方法还包括执行仪器归一化校准以确定滤波器归一化因子。 该方法包括执行RNase P验证以验证仪器能够区分两种不同数量的样品。

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