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1. 发明授权

US10403000B2 Methods and systems for analyzing biological reaction systems 有权
公开(公告)号：US10403000B2
公开(公告)日：2019-09-03
申请号：US15899308
申请日：2018-02-19
申请人： LIFE TECHNOLOGIES CORPORATION
发明人： Yong Chu , Jeffrey Marks
IPC分类号： G06K9/00 , G06T5/00 , G06T7/00 , G06T7/11 , G06T7/73 , C12Q1/686 , G06T7/136 , G06T7/194
摘要： 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.

2. 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.

3. 发明授权

US09898820B2 Methods and systems for analyzing biological reaction systems 有权
公开(公告)号：US09898820B2
公开(公告)日：2018-02-20
申请号：US14778415
申请日：2014-03-18
申请人： LIFE TECHNOLOGIES CORPORATION
发明人： Yong Chu , Jeffrey Marks
IPC分类号： G06K9/00 , G06T7/00 , G06T5/00 , C12Q1/68 , G06T7/73 , G06T7/11 , G06T7/194 , G06T7/136
CPC分类号： 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
摘要： 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.

4. 发明申请

US20160237474A1 METHODS AND SYSTEMS FOR PURE DYE INSTRUMENT NOMALIZATION 有权
标题翻译：纯粹的仪器仪表化方法和系统
公开(公告)号：US20160237474A1
公开(公告)日：2016-08-18
申请号：US15016713
申请日：2016-02-05
申请人： LIFE TECHNOLOGIES CORPORATION
发明人： Jeffrey Marks
IPC分类号： C12Q1/68 , G01N21/64
CPC分类号： C12Q1/686 , G01N21/274 , G01N21/6428 , G01N21/6452 , G01N2021/6421 , G01N2201/04 , G01N2201/068 , G01N2201/12746
摘要： The present teachings relate to a method and system for normalizing spectra across multiple instruments. In an embodiment of the present invention, the method comprises at least one reference instrument and a test instrument. Each instrument comprises at least one excitation filter and at least one emission filter arranged in pairs. Each instrument further comprises a pure dye plate comprising a plurality of wells. Each well contains a plurality of dyes where each dye comprises a fluorescent component. Fluorescent spectra are obtained from each instrument for each dye across multiple filter combinations to contribute to a pure dye matrix Mref for the reference instrument and pure dye matrix M for the test instrument. The pure dye spectra can then be multiplied by correction factors for each filter pair to result in corrected pure dye spectra, then normalized and the multicomponenting data can be extracted.
摘要翻译：本教导涉及用于在多个仪器上归一化光谱的方法和系统。在本发明的一个实施例中，该方法包括至少一个参考仪器和测试仪器。每个仪器包括至少一个激励滤波器和成对布置的至少一个发射滤波器。每个仪器还包括包含多个孔的纯染料板。每个孔含有多种染料，其中每种染料包含荧光组分。从每个仪器获得的荧光光谱可以通过多种滤光片组合为每种染料获得，从而有助于参考仪器的纯染料矩阵Mref和测试仪器的纯染料矩阵M. 然后可以将纯染料光谱乘以每个过滤器对的校正因子，以产生校正的纯染料光谱，然后进行归一化，并且可以提取多组分数据。

5. 发明申请

US20160230209A1 System and Methods for Calibrating Binding Dyes 审中-公开
标题翻译：校准结合染料的系统和方法
公开(公告)号：US20160230209A1
公开(公告)日：2016-08-11
申请号：US15017034
申请日：2016-02-05
申请人： LIFE TECHNOLOGIES CORPORATION
发明人： Yong Chu , Jacob Freudenthal , Jeffrey Marks
IPC分类号： C12Q1/68 , G01N21/64
CPC分类号： C12Q1/686 , G01N21/274 , G01N21/6428 , G01N21/6452 , G01N21/6456 , G01N2021/6421 , G01N2021/6441 , G01N2201/127
摘要： Some embodiments describe a computer-implemented method for calibrating a fluorescent dye. The method can comprise imaging a sample holder, loaded into an instrument, at more than one channel. The sample holder can comprise a plurality of reaction sites and more than one dye type, with each dye occupying more than one reaction site. The method can further comprise identifying a peak channel for each dye on the sample holder, normalizing each channel to the peak channel for each dye, and producing a dye matrix that can comprise a set of dye reference values.
摘要翻译：一些实施例描述了用于校准荧光染料的计算机实现的方法。该方法可以包括在多个通道上成像加载到仪器中的样品架。样品架可以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。该方法还可以包括鉴定样品架上每种染料的峰通道，将每个通道标准化为每种染料的峰通道，以及产生可包含一组染料参考值的染料基质。

6. 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.

7. 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.

8. 发明申请

US20160231246A1 METHODS AND SYSTEMS FOR BIOLOGICAL INSTRUMENT CALIBRATION 有权
标题翻译：生物仪器校准的方法和系统
公开(公告)号：US20160231246A1
公开(公告)日：2016-08-11
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： G01N21/64 , C12Q1/68
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

US20180230511A1 METHODS AND SYSTEMS FOR PURE DYE INSTRUMENT NORMALIZATION 审中-公开
公开(公告)号：US20180230511A1
公开(公告)日：2018-08-16
申请号：US15715063
申请日：2017-09-25
申请人： Life Technologies Corporation
发明人： Jeffrey Marks
IPC分类号： C12Q1/686 , G01N21/64 , G01N21/27
CPC分类号： C12Q1/686 , G01N21/274 , G01N21/6428 , G01N21/6452 , G01N2021/6421 , G01N2201/04 , G01N2201/068 , G01N2201/12746
摘要： The present teachings relate to a method and system for normalizing spectra across multiple instruments. In an embodiment of the present invention, the method comprises at least one reference instrument and a test instrument. Each instrument comprises at least one excitation filter and at least one emission filter arranged in pairs. Each instrument further comprises a pure dye plate comprising a plurality of wells. Each well contains a plurality of dyes where each dye comprises a fluorescent component. Fluorescent spectra are obtained from each instrument for each dye across multiple filter combinations to contribute to a pure dye matrix Mref for the reference instrument and pure dye matrix M for the test instrument. The pure dye spectra can then be multiplied by correction factors for each filter pair to result in corrected pure dye spectra, then normalized and the multicomponenting data can be extracted.

10. 发明申请

US20170161429A1 Methods and Systems for Streamlining Optical Calibration 审中-公开
公开(公告)号：US20170161429A1
公开(公告)日：2017-06-08
申请号：US15350444
申请日：2016-11-14
申请人： LIFE TECHNOLOGIES CORPORATION
发明人： Jacob Freudenthal , Jeffrey Marks , Francis Cheng , Thomas Wessel
IPC分类号： G06K9/00
CPC分类号： G06T7/0012 , G06T5/008 , G06T5/50 , G06T2207/10024 , G06T2207/10064 , G06T2207/10144 , G06T2207/20021 , G06T2207/20216 , G06T2207/30072
摘要： A method for calibrating a biological instrument is provided. The method comprises the steps of acquiring an image of at least one biological sample array, determining a first region of interest within the image, wherein the first region of interest comprises a first plurality of locations on the at least one biological array; and identifying within the first region of interest, a plurality of image elements associated with each of the first plurality of locations on the at least one biological array.

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