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1. 发明授权

US10648912B2 Methods and systems for instrument validation 有权
公开(公告)号：US10648912B2
公开(公告)日：2020-05-12
申请号：US15016485
申请日：2016-02-05
申请人： LIFE TECHNOLOGIES CORPORATION
发明人： Thomas Wessel , Yong Chu , Jacob Freudenthal , David Woo
IPC分类号： G01N21/64 , G01N21/27 , G16B40/00
摘要： In one exemplary embodiment, 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. 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 and determining, for each fluorescence threshold of the set, a first set of cycle threshold (Ct) values of amplification curves generated from the samples of the first quantity and a second set of Ct values of amplification curves generated from the samples of the second quantity. The method includes calculating if the first and second quantities are sufficiently distinguishable based on Ct values at each of the plurality of fluorescence thresholds.

2. 发明授权

US10557821B2 Methods and systems for variant detection 有权
公开(公告)号：US10557821B2
公开(公告)日：2020-02-11
申请号：US16265806
申请日：2019-02-01
申请人： Life Technologies Corporation
发明人： David Denny , David Woo , Manjula Aliminati , Siva Kumar Samsani , Stephanie Schneider , Yoke Peng Lim , Sylvia Chang
IPC分类号： G01N27/447 , G16B30/00
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 validating the identified mixed bases. Then the method includes determining variants in the electropherogram data based on the validated mixed bases.

3. 发明申请

US20180292320A1 METHODS AND SYSTEMS FOR BIOLOGICAL INSTRUMENT CALIBRATION 审中-公开
公开(公告)号：US20180292320A1
公开(公告)日：2018-10-11
申请号：US16010359
申请日：2018-06-15
申请人： Life Technologies Corporation
发明人： Yong Chu , Jeffrey Marks , Jacob Freudenthal , Thomas Wessel , David Woo
IPC分类号： G01N21/64 , C12Q1/686 , G01N21/27 , C12Q1/6851
摘要： In one exemplary embodiment, a method for calibrating an instrument is provided. The instrument includes an optical system capable of imaging fluorescence 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.

4. 发明申请

US20210398615A1 BASECALLER WITH DILATED CONVOLUTIONAL NEURAL NETWORK 有权
公开(公告)号：US20210398615A1
公开(公告)日：2021-12-23
申请号：US16899545
申请日：2020-06-11
申请人： Life Technologies Corporation
发明人： Yong Chu , Stephanie Jo Schneider , Rylan Schaeffer , David Woo
IPC分类号： G16B30/00 , G16B25/00 , G16B40/00 , G06N3/08 , G06N5/04 , G06K9/62 , C12Q1/6869
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

US20200003728A1 AUTOMATED QUALITY CONTROL AND SPECTRAL ERROR CORRECTION FOR SAMPLE ANALYSIS INSTRUMENTS 审中-公开
公开(公告)号：US20200003728A1
公开(公告)日：2020-01-02
申请号：US16486137
申请日：2018-02-16
申请人： Life Technologies Corporation
发明人： Nivedita Majumdar , Wallace George , Jeffrey Marks , Ming Jiang , Sylvia Chang , David Woo
IPC分类号： G01N27/416 , 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.

6. 发明授权

US10197529B2 Methods and systems for variant detection 有权
公开(公告)号：US10197529B2
公开(公告)日：2019-02-05
申请号：US15130532
申请日：2016-04-15
申请人： LIFE TECHNOLOGIES CORPORATION
发明人： David A. Denny , David Woo , Manjula Aliminati , Siva Kumar Samsani , Stephanie J. Schneider , Yoke Peng Lim , Sylvia Chang
IPC分类号： G01N27/447 , 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.

7. 发明申请

US20170046308A1 Robust Detection Of Variablility In Multiple Sets Of Data 审中-公开
标题翻译：在多组数据中的可变性的鲁棒检测
公开(公告)号：US20170046308A1
公开(公告)日：2017-02-16
申请号：US15213237
申请日：2016-07-18
申请人： LIFE TECHNOLOGIES CORPORATION
发明人： Chengyong Yang , David Woo
IPC分类号： G06F17/18 , G01N21/64
CPC分类号： G06F17/18 , G01D1/14 , G01N21/6428 , G01N2021/6439
摘要： The present teachings comprise systems and methods for calibrating the background or baseline signal in a PCR or other reaction. The background signal derived from detected emissions of sample wells can be subjected to a normalized statistical metric, and be compared to a threshold or other standard to discard outlier cycles or other extraneous data. According to various embodiments, a relative standard deviation (relativeSTD) for the background component can be generated by dividing the standard deviation by the median of differences across all wells, where the difference is defined as the difference between maximum and minimum pixel values of a well. The relativeSTD as a metric is not sensitive to machine-dependent variations in absolute signal output that can be caused by different gain settings, different LED draw currents, different optical paths, or other instrumental variations. More accurate background characterization can be achieved.
摘要翻译：本教导包括用于在PCR或其他反应中校准背景或基线信号的系统和方法。从检测到的样本井的排放导出的背景信号可以经受归一化的统计度量，并与阈值或其他标准进行比较以丢弃异常周期或其他无关数据。根据各种实施例，可以通过将标准偏差除以所有孔的差异中值来产生背景分量的相对标准偏差（relativeSTD），其中差被定义为井的最大和最小像素值之间的差。作为度量的relativeSTD对于可能由不同的增益设置，不同的LED绘制电流，不同的光路或其他工具变化引起的绝对信号输出的机器相关变化不敏感。可以获得更准确的背景特征。

8. 发明申请

US20160231245A1 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：US20160231245A1
公开(公告)日：2016-08-11
申请号：US15016485
申请日：2016-02-05
申请人： LIFE TECHNOLOGIES CORPORATION
发明人： Thomas Wessel , Yong Chu , Jacob Freudenthal , David Woo
IPC分类号： G01N21/64
CPC分类号： G01N21/6428 , G01N21/274 , G01N21/6452 , G01N21/6456 , G01N2021/6439 , G16B40/00
摘要： In one exemplary embodiment, 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. 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 and determining, for each fluorescence threshold of the set, a first set of cycle threshold (Ct) values of amplification curves generated from the samples of the first quantity and a second set of Ct values of amplification curves generated from the samples of the second quantity. The method includes calculating if the first and second quantities are sufficiently distinguishable based on Ct values at each of the plurality of fluorescence thresholds.
摘要翻译：在一个示例性实施例中，提供了用于验证仪器的方法。该方法包括从验证板接收放大数据以产生多个扩增曲线。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从样品中产生的扩增曲线的第一组循环阈值（Ct）值从第二数量的样本产生的第一数量和第二组扩增曲线的Ct值。该方法包括基于多个荧光阈值中的每个荧光阈值处的Ct值来计算第一和第二量是否足够可区分。

9. 发明授权

US10902593B2 Methods and apparatus for extended dynamic range from single exposures in capillary electrophoresis 有权
公开(公告)号：US10902593B2
公开(公告)日：2021-01-26
申请号：US16557376
申请日：2019-08-30
申请人： LIFE TECHNOLOGIES CORPORATION
发明人： Jeffrey Marks , David Woo , Wallace George
IPC分类号： G06T7/00 , H04N5/372 , H04N5/347 , G01N27/447
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.

10. 发明授权

US10012590B2 Methods and systems for biological instrument calibration 有权
公开(公告)号：US10012590B2
公开(公告)日：2018-07-03
申请号：US15017249
申请日：2016-02-05
申请人： LIFE TECHNOLOGIES CORPORATION
发明人： Yong Chu , Jeffrey Marks , Jacob Freudenthal , Thomas Wessel , David Woo
IPC分类号： H01J40/14 , G01N21/64 , C12Q1/686 , G01N21/27 , C12Q1/6851
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.

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