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1. 发明申请

WO2016127032A1 METHODS AND SYSTEMS FOR INSTRUMENT VALIDATION 审中-公开
标题翻译：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
申请人： LIFE TECHNOLOGIES CORPORATION
发明人： WESSEL, Thomas , CHU, Yong , FREUDENTHAL, Jacob , WOO, David
IPC分类号： G01N21/27 , G01N21/64 , C12Q1/68 , G06F19/26
CPC分类号： G01N21/6428 , G01N21/274 , G01N21/6452 , G01N21/6456 , G01N2021/6439 , G06F19/24
摘要： 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).
摘要翻译：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。

2. 发明申请

WO2018151843A2 AUTOMATED QUALITY CONTROL AND SPECTRAL ERROR CORRECTION FOR SAMPLE ANALYSIS INSTRUMENTS 审中-公开
公开(公告)号：WO2018151843A2
公开(公告)日：2018-08-23
申请号：PCT/US2018/000058
申请日：2018-02-16
申请人： LIFE TECHNOLOGIES CORPORATION
发明人： MAJUMDAR, Nivedita , GEORGE, Wallace , MARKS, Jeffrey , JIANG, Ming , CHANG, Sylvia , WOO, David
IPC分类号： G01N27/447
摘要： Embodiments implementing selected automated quality control operations in sample processing instruments and systems are disclosed. Embodiments for implementing automated correction of spectral error in such instruments and systems are also disclosed. These and other embodiments are further disclosed herein.

3. 发明申请

WO2016168713A1 METHODS AND SYSTEMS FOR DETECTING VARIATIONS IN NUCLEIC ACID SEQUENCES 审中-公开
标题翻译：用于检测核酸序列变异的方法和系统
公开(公告)号：WO2016168713A1
公开(公告)日：2016-10-20
申请号：PCT/US2016/027908
申请日：2016-04-15
申请人： LIFE TECHNOLOGIES CORPORATION
发明人： DENNY, David , WOO, David , ALIMINATI, Manjula , SAMSANI, Siva Kumar , SCHNEIDER, Stephanie , LIM, Yoke Peng , CHANG, Sylvia
IPC分类号： G06F19/22
CPC分类号： G01N27/44717 , G06F19/22
摘要： In one exemplary embodiment, a method for detecting variants in electropherogram data is provided. The method includes receiving electropherogram data from an instrument and analyzing the electropherogram data to identify mixed bases in the electropherogram data. The method further includes identifying features within the electropherogram data indicative of errors and validating the identified mixed bases. Then the method includes determining variants in the electropherogram data based on the validated mixed bases.
摘要翻译：在一个示例性实施例中，提供了一种用于检测电泳图数据中的变体的方法。该方法包括从仪器接收电泳图数据，并分析电泳图数据以识别电泳图数据中的混合碱基。该方法还包括识别电泳图中指示错误并验证所识别的混合碱基的特征。然后该方法包括基于经验证的混合碱基来确定电泳图数据中的变体。

4. 发明申请

WO2021252798A1 BASECALLER WITH DILATED CONVOLUTIONAL NEURAL NETWORK 审中-公开
公开(公告)号：WO2021252798A1
公开(公告)日：2021-12-16
申请号：PCT/US2021/036872
申请日：2021-06-10
申请人： LIFE TECHNOLOGIES CORPORATION
发明人： CHU, Yong , SCHNEIDER, Stephanie, Jo , SCHAEFFER, Rylan , WOO, David
IPC分类号： G16B40/10 , G16B30/00 , G06N3/02 , C12Q1/6869 , G06K9/6201 , G06K9/623 , G06K9/6256 , G06K9/6277 , G06N3/0445 , G06N3/0454 , G06N3/0472 , G06N3/0481 , G06N3/082 , G06N3/084 , G06N3/088 , G06N5/046 , G16B25/00 , G16B40/00
摘要： A method of automatically sequencing or basecalling one or more DNA (deoxyribonucleic acid) molecules of a biological sample is described. The method comprises using a capillary electrophoresis genetic analyzer to measure the biological sample to obtain at least one input trace comprising digital data corresponding to fluorescence values for a plurality of scans. Scan labelling probabilities for the plurality of scans are generated using a trained artificial neural network comprising a plurality of layers including convolutional layers. A basecall sequence comprising a plurality of basecalls for the one or more DNA molecules based on the scan labelling probabilities for the plurality of scans is determined.

5. 发明申请

WO2020123552A1 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
申请人： LIFE TECHNOLOGIES CORPORATION
发明人： CHU, Yong , SCHNEIDER, Stephanie , SCHAEFFER, Rylan , WOO, David
IPC分类号： G16B30/20 , G16B40/20
摘要： 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.

6. 发明申请

WO2020047455A1 METHODS AND APPARATUS FOR EXTENDED DYNAMIC RANGE FROM SINGLE EXPOSURES IN CAPILLARY ELECTROPHORESIS 审中-公开
公开(公告)号：WO2020047455A1
公开(公告)日：2020-03-05
申请号：PCT/US2019/049132
申请日：2019-08-30
申请人： LIFE TECHNOLOGIES CORPORATION
发明人： MARKS, Jeffrey , WOO, David , GEORGE, Wallace
IPC分类号： G01N27/44
摘要： A biological analysis system and an associated method are provided. The method is used for recovering off scale data in an image produced by a camera in a capillary electrophoresis instrument. The method comprises the steps of identifying bins of the image where electron counts exceed a maximum number of counts; setting an off-scale flag for the identified bins; and processing the image to obtain a recovered dye signal, based on the flag set for each bin, and using a dye matrix.

7. 发明申请

WO2018151843A3 AUTOMATED QUALITY CONTROL AND SPECTRAL ERROR CORRECTION FOR SAMPLE ANALYSIS INSTRUMENTS 审中-公开
公开(公告)号：WO2018151843A3
公开(公告)日：2018-08-23
申请号：PCT/US2018/000058
申请日：2018-02-16
申请人： LIFE TECHNOLOGIES CORPORATION
发明人： MAJUMDAR, Nivedita , GEORGE, Wallace , MARKS, Jeffrey , JIANG, Ming , CHANG, Sylvia , WOO, David
IPC分类号： G01N27/447
摘要： Embodiments implementing selected automated quality control operations in sample processing instruments that analyze dye-labeled samples are disclosed. In some embodiments, temperature and/or pressure parameters are measured and compared to thresholds to determine whether warning should be provided and/or actions taken. Embodiments for implementing automated correction of spectral error during the instrument's normal runtime operation without requiring the user to conduct a special, separate calibration run are also disclosed.

8. 发明申请

WO2016127124A2 METHODS AND SYSTEMS FOR BIOLOGICAL INSTRUMENT CALIBRATION 审中-公开
标题翻译：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
申请人： LIFE TECHNOLOGIES CORPORATION
发明人： CHU, Yong , MARKS, Jeffrey , FREUDENTHAL, Jacob , WESSEL, Thomas , WOO, David
IPC分类号： G01N21/27 , G01N21/64
CPC分类号： G01N21/6428 , C12Q1/6851 , C12Q1/686 , G01N21/274 , G01N21/278 , G01N21/6452 , G01N21/6456 , G01N2021/6439 , G01N2021/6471 , G01N2201/127 , G01N2201/13 , G01N2333/922
摘要： 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.
摘要翻译：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。

9. 发明申请

WO2016127107A2 SYSTEMS AND METHODS FOR BIOLOGICAL ANALYSIS 审中-公开
标题翻译：生物分析系统与方法
公开(公告)号：WO2016127107A2
公开(公告)日：2016-08-11
申请号：PCT/US2016/016856
申请日：2016-02-05
申请人： LIFE TECHNOLOGIES CORPORATION
发明人： CHU, Yong , MARKS, Jeffrey , FREUDENTHAL, Jacob , CHEN, Mingsong , TOH, Tiong Han , AGUANNO, Mauro , LAU, Lik Seng , LOH, Lian Seng , TEO, Kok Siong , CHU, Zeng Wei , MATHERS, Xin , UY, Michael , YEO, Huei Steven , BOO, Kuan Moon , LEE, Way Xuang , KOO, Chin Yong , TEO, Wei Fuh , LAU, Soo Yong , SHIN, Hon Siu , TAN, Zeqi , WESSEL, Thomas , WOO, David
IPC分类号： B01L7/00 , G01N21/64 , G01N35/02 , G01N35/00
CPC分类号： B01L7/52 , B01L2200/145 , B01L2300/18 , B01L2300/1822 , C12Q1/6806 , G01N21/274 , G01N21/6452 , G01N21/6486 , G01N35/026 , G01N2021/6439 , G01N2035/00316 , G01N2035/00366 , G01N2201/061 , G01N2201/12
摘要： A biological analysis system is provided. The system comprises a sample block assembly. The sample block assembly comprises a sample block configured to accommodate a sample holder, the sample holder configured to receive a plurality of samples. The system also comprises a control system configured to cycle the plurality of samples through a series of temperatures. The system further comprises an automated tray comprising a slide assembly, the tray configured to reversibly slide the sample block assembly from a closed to an open position to allow user access to the plurality of sample holders.
摘要翻译：提供生物分析系统。该系统包括样品块组件。样品块组件包括被配置为容纳样品架的样品块，样品保持器被配置为接收多个样品。该系统还包括配置成使多个样品循环通过一系列温度的控制系统。所述系统还包括自动盘，其包括滑动组件，所述托盘被配置为可将所述样品块组件从关闭位置可逆地滑动到打开位置，以允许使用者接近所述多个样品保持器。

10. 发明公开

EP3895171A1 DEEP BASECALLER FOR SANGER SEQUENCING 审中-实审
公开(公告)号：EP3895171A1
公开(公告)日：2021-10-20
申请号：EP19832518.5
申请日：2019-12-10
申请人： Life Technologies Corporation
发明人： CHU, Yong , SCHNEIDER, Stephanie , SCHAEFFER, Rylan , WOO, David
IPC分类号： G16B30/20 , G16B40/20

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