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1. 发明授权

US12105310B2 Illumination of optical analytical devices 有权
公开(公告)号：US12105310B2
公开(公告)日：2024-10-01
申请号：US18310315
申请日：2023-05-01
申请人： Pacific Biosciences of California, Inc.
发明人： Annette Grot , Shang Wang , Hans Callebaut , Paul Lundquist , Stephen Turner
IPC分类号： F21V8/00 , G01N21/64 , G01N21/77 , G02B6/024 , G02B6/10 , G02B6/12 , G02B6/122 , G02F1/365 , B82Y15/00 , B82Y20/00 , G02B23/24
CPC分类号： G02B6/0016 , G01N21/648 , G01N21/7703 , G02B6/024 , G02B6/10 , G02B6/12004 , G02B6/122 , G02F1/365 , B82Y15/00 , B82Y20/00 , G01N21/6452 , G01N21/6486 , G02B23/2461
摘要： Optical analytical devices and their methods of use are provided. The devices are useful in the analysis of highly multiplexed optical reactions in large numbers at high densities, including biochemical reactions, such as nucleic acid sequencing reactions. The devices include optical waveguides for illumination of the optical reactions. The devices further provide for the efficient coupling of optical excitation energy from the waveguides to the optical reactions. Optical signals emitted from the reactions can thus be measured with high sensitivity and discrimination using features such as spectra, amplitude, and time resolution, or combinations thereof. The devices of the invention are well suited for miniaturization and high throughput.

2. 发明公开

US20240320826A1 DENSLEY-PACKED ANALYTE LAYERS AND DETECTION METHODS 审中-公开
公开(公告)号：US20240320826A1
公开(公告)日：2024-09-26
申请号：US18613562
申请日：2024-03-22
申请人： Pacific Biosciences of California, Inc.
发明人： Dennis BALLINGER , Norman BURNS , Manohar FURTADO , Niandong LIU , Windsor OWENS , Bryan STAKER
IPC分类号： G06T7/00 , C12Q1/6816 , G06T7/174 , G06T7/70
CPC分类号： G06T7/0012 , C12Q1/6816 , G06T7/174 , G06T7/70 , G06T2207/30072
摘要： Disclosed herein are methods and systems for detection and discrimination of optical signals from a densely packed substrate. These have broad applications for biomolecule detection near or below the diffraction limit of optical systems, including in improving the efficiency and accuracy of polynucleotide sequencing applications.

3. 发明公开

US20240318247A1 COMPOSITIONS AND METHODS FOR DENSLEY-PACKED ANALYTE ANALYSIS 审中-公开
公开(公告)号：US20240318247A1
公开(公告)日：2024-09-26
申请号：US18587683
申请日：2024-02-26
申请人： Pacific Biosciences of California, Inc.
发明人： Bojan BERGHUIS , Bryan STAKER
IPC分类号： C12Q1/6874 , C12Q1/689
CPC分类号： C12Q1/6874 , C12Q1/689
摘要： Disclosed herein are methods and systems for detection and discrimination of optical signals from a densely packed substrate. These have broad applications for biomolecule detection near or below the diffraction limit of optical systems, including in improving the efficiency and accuracy of polynucleotide sequencing applications.

4. 发明公开

US20240294977A1 FRET-LABELED COMPOUNDS AND USES THEREFOR 审中-公开
公开(公告)号：US20240294977A1
公开(公告)日：2024-09-05
申请号：US18375440
申请日：2023-09-29
申请人： Pacific Biosciences of California, Inc.
发明人： Xiangxu Kong , Gene Shen
IPC分类号： C12Q1/6869 , C07H19/207 , C12Q1/6818 , G01N21/64 , G01N33/542 , G01N33/58
CPC分类号： C12Q1/6869 , C07H19/207 , C12Q1/6818 , G01N21/6428 , G01N33/542 , G01N33/582 , G01N2021/6441 , Y10T436/143333
摘要： Reaction mixtures are provided having at least a first reactant and a second reactant that produce signals in response to excitation illumination. The signals produced by the reactants have peaks at the same wavelengths, but have distinct signal intensities. In some embodiments, the reactants are FRET-labeled.

5. 发明公开

US20240271203A1 RECOMBINANT POLYMERASES FOR INCORPORATION OF PROTEIN SHIELD NUCLEOTIDE ANALOGS 审中-公开
公开(公告)号：US20240271203A1
公开(公告)日：2024-08-15
申请号：US18544190
申请日：2023-12-18
申请人： Pacific Biosciences of California, Inc.
发明人： Satwik Kamtekar , Erik Miller
IPC分类号： C12Q1/6869 , C12N9/12 , C12Q1/686
CPC分类号： C12Q1/6869 , C12N9/1252 , C12Q1/686 , C12Y207/07007
摘要： Provided are compositions comprising recombinant DNA polymerases that include amino acid substitutions, insertions, deletions, and/or exogenous features that confer modified properties upon the polymerase for enhanced single molecule sequencing or nucleic acid amplification. Such properties include enhanced performance with large nucleotide analogs, increased stability, increased readlength, and improved detection of modified bases, and can also include resistance to photodamage, enhanced metal ion coordination, reduced exonuclease activity, reduced reaction rates at one or more steps of the polymerase kinetic cycle, decreased branching fraction, altered cofactor selectivity, increased yield, increased accuracy, altered speed, increased cosolvent resistance, and the like. Also provided are nucleic acids which encode the polymerases with the aforementioned phenotypes, as well as methods of using such polymerases to make a DNA or to sequence a DNA template.

6. 发明授权

US12060608B2 Sequencing and high resolution imaging 有权
公开(公告)号：US12060608B2
公开(公告)日：2024-08-13
申请号：US18181440
申请日：2023-03-09
申请人： Pacific Biosciences of California, Inc.
发明人： Bryan P. Staker , Niandong Liu , Manohar R. Furtado , Rixun Fang , Norman Burns , Windsor Owens
IPC分类号： G06T7/73 , C12Q1/6874 , G06V20/69 , G16B25/30 , G16B30/00 , G16B30/10
CPC分类号： C12Q1/6874 , G06T7/73 , G06V20/69 , G16B25/30 , G16B30/00 , G16B30/10 , G06F2218/18 , G06T2207/20056 , G06T2207/30072 , G06V20/695
摘要： Disclosed herein are methods and systems for detection and discrimination of optical signals from a densely packed substrate. There have broad applications for biomolecule detection near or below the diffraction limit of optical systems, including in improving the efficiency and accuracy or polynucleotide sequencing applications.

7. 发明授权

US11983790B2 Multiprocessor pipeline architecture 有权
公开(公告)号：US11983790B2
公开(公告)日：2024-05-14
申请号：US15147835
申请日：2016-05-05
申请人： Pacific Biosciences of California, Inc.
发明人： Scott E. Helgesen , Marco Milletti , Mark T. Lakata , James N. LaBrenz
IPC分类号： G06T1/20 , C12Q1/6869 , G16B30/00 , G16B50/30
CPC分类号： G06T1/20 , C12Q1/6869 , G16B30/00 , G16B50/30 , G06T2200/28
摘要： Exemplary embodiments for a multiprocessor pipeline architecture that converts signals from sequencing sample acquisition into sequence data, comprising: a custom coprocessor card configured to directly receive a stream of serialized sensor data generated by an image sensor, wherein the sensor data represents frame-by-frame intensity values for pixels comprising the image sensor, wherein the image sensor captures images of light emitted from a plurality of reaction cells of a removable integrated sequencing chip; a first coprocessor that continually receives the stream of serialized sensor data and transposes the frame-by-frame intensity values into reaction cell chunks, each of the reaction cell chunks representing movie data of the pixel intensity values of a corresponding reaction cell across the frames over a predetermined time window; a buffer that repeatedly receives the reaction cell chunks and stores in contiguous memory locations the reaction cell chunks for each respective reaction cell over a larger predetermined time window to create larger reaction cell chunks; and a plurality of second coprocessors that retrieve the larger reaction cell chunks from the buffer and convert, in parallel, the pixel intensity values into base-by-base sequence data even as additional reaction cell chunks are received by the buffer, such that the second coprocessors begin raw base calling before all the sensor data for the sequencing sample acquisition is obtained. Aspects of the invention include methods for base calling using single instruction multiple data vector processing units.

8. 发明授权

US11976319B2 Methods and compositions for generating asymmetrically-tagged nucleic acid fragments 有权
公开(公告)号：US11976319B2
公开(公告)日：2024-05-07
申请号：US17359247
申请日：2021-06-25
申请人： Pacific Biosciences of California, Inc.
发明人： Joan Wilson
IPC分类号： C12Q1/6855 , C12Q1/68 , C12Q1/6806 , C12Q1/6809 , C12Q1/6858 , C12Q1/686
CPC分类号： C12Q1/6809 , C12Q1/6806 , C12Q1/6855 , C12Q1/6858 , C12Q1/686 , C12Q1/68 , C12Q2525/155 , C12Q2525/191 , C12Q2531/107 , C12Q1/6806 , C12Q2521/101 , C12Q2521/501 , C12Q2525/191 , C12Q2525/301
摘要： The present disclosure provides improved methods for generating asymmetrically-tagged nucleic acid constructs, compositions comprising such constructs, and kits and systems for generating such constructs.

9. 发明授权

US11891659B2 Recombinant polymerases for incorporation of protein shield nucleotide analogs 有权
公开(公告)号：US11891659B2
公开(公告)日：2024-02-06
申请号：US17523670
申请日：2021-11-10
申请人： Pacific Biosciences of California, Inc.
发明人： Satwik Kamtekar , Erik Miller
IPC分类号： C12N9/12 , C12Q1/6869 , C12Q1/686
CPC分类号： C12Q1/6869 , C12N9/1252 , C12Q1/686 , C12Y207/07007
摘要： Provided are compositions comprising recombinant DNA polymerases that include amino acid substitutions, insertions, deletions, and/or exogenous features that confer modified properties upon the polymerase for enhanced single molecule sequencing or nucleic acid amplification. Such properties include enhanced performance with large nucleotide analogs, increased stability, increased readlength, and improved detection of modified bases, and can also include resistance to photodamage, enhanced metal ion coordination, reduced exonuclease activity, reduced reaction rates at one or more steps of the polymerase kinetic cycle, decreased branching fraction, altered cofactor selectivity, increased yield, increased accuracy, altered speed, increased cosolvent resistance, and the like. Also provided are nucleic acids which encode the polymerases with the aforementioned phenotypes, as well as methods of using such polymerases to make a DNA or to sequence a DNA template.

10. 发明公开

US20240035082A1 NUCLEIC ACID SEQUENCING METHODS AND SYSTEMS 审中-公开
公开(公告)号：US20240035082A1
公开(公告)日：2024-02-01
申请号：US18045687
申请日：2022-10-11
申请人： Pacific Biosciences of California, Inc.
发明人： Kandaswamy VIJAYAN , Eugene TU , Mark A. BERNARD
IPC分类号： C12Q1/6869
CPC分类号： C12Q1/6869
摘要： The present disclosure provides compositions, methods and systems for sequencing a template nucleic acid using a polymerase based, nucleic acid binding reaction involving examination of the interaction between a polymerase and template nucleic acid in the presence of one or more unlabeled nucleotides. The methods rely, in part, on identifying a base of a template nucleic acid during nucleic acid synthesis by controlling the sequencing reaction conditions. Template nucleic acid bases may be identified during an examination step followed by an optional incorporation step.

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