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1. 发明申请

WO2022081741A1 ELECTROPHORETIC DEVICES AND METHODS FOR NEXT-GENERATION SEQUENCING LIBRARY PREPARATION 审中-公开
公开(公告)号：WO2022081741A1
公开(公告)日：2022-04-21
申请号：PCT/US2021/054826
申请日：2021-10-13
申请人： ROCHE SEQUENCING SOLUTIONS, INC. , KAPA BIOSYSTEMS, INC. , ROCHE DIAGNOSTICS GMBH , F. HOFFMANN-LA ROCHE AG
发明人： ASTIER, Yann , FIRFIREY, Taariq , YANG, Jaeyoung
IPC分类号： B01D57/02 , C12Q1/68 , C12Q1/6806
摘要： The present disclosure is directed to automated systems including an electrophoretic device including one or more separation conduits. In some embodiments, the automated systems are suitable for use in sample cleanup and/or target enrichment processes, such as sample cleanup and/or target enrichment processes conducted prior to sequencing, e.g., next generation sequencing.

2. 发明申请

WO2018024670A1 TUNNEL JUNCTIONS IN MICROFLUIDIC ARRAYS FOR MOLECULAR RECOGNITION 审中-公开
标题翻译：微流控阵列中的隧道连接用于分子识别
公开(公告)号：WO2018024670A1
公开(公告)日：2018-02-08
申请号：PCT/EP2017/069307
申请日：2017-07-31
申请人： F. HOFFMANN-LA ROCHE AG , ROCHE DIAGNOSTICS GMBH , ROCHE SEQUENCING SOLUTIONS, INC.
发明人： ASTIER, Yann , TOPOLANCIK, Juraj
IPC分类号： G01N33/487 , G01N27/327
摘要： A system (500) for analyzing a molecule includes a device (502) that comprises a first conductive element (504), a second conductive element (506) and an insulating layer (508) disposed between said conductive elements (504, 506). The insulating layer (508) is tapered in a direction to reach a minimum thickness at a first end (512) of the device (502). The device (502) includes a voltage source and an electrical meter in electrical communication with said conductive elements (504, 506).
摘要翻译：一种用于分析分子的系统（500）包括设备（502），所述设备包括第一导电元件（504），第二导电元件（506）和设置在所述第一导电元件导电元件（504,506）。绝缘层（508）沿着在装置（502）的第一端（512）处达到最小厚度的方向逐渐变细。装置（502）包括电压源和与所述导电元件（504,506）电连通的电表。

3. 发明申请

WO2019243421A1 TUNNELING JUNCTIONS FOR SEQUENCING 审中-公开
公开(公告)号：WO2019243421A1
公开(公告)日：2019-12-26
申请号：PCT/EP2019/066203
申请日：2019-06-19
申请人： F. HOFFMANN-LA ROCHE AG , ROCHE DIAGNOSTICS GMBH , ROCHE SEQUENCING SOLUTIONS, INC.
发明人： ASTIER, Yann , BERGMANN, Frank , HEINDL, Dieter , KUCHELMEISTER, Hannes , STENGELE, Nikolaus, Klaus-Peter , TOPOLANCIK, Juraj
IPC分类号： C12Q1/6869
摘要： Molecules may be analyzed (e.g., sequencing of nucleic acid molecules) by tunneling recognition at a tunneling junction. Embodiments of the present invention may allow detecting individual nucleotides and the sequencing of a nucleic acid molecule using a tunneling junction. By labeling a specific nucleotide with a moiety, tunneling junctions may generate a signal with a suitable signal-to-noise ratio. The tunneling recognition uses a tunneling current that is mostly through the moiety rather than mostly through the nucleotide or a portion of the molecule of interest. Because a single nucleotide can be detected with a signal with a suitable signal-to-noise ratio resulting from the tunneling current passing through the moiety, embodiments of the present invention may allow for fast detection of nucleotides using a tunneling current.

4. 发明申请

WO2022011067A1 SINGLE-MOLECULE. REAL-TIME. LABEL-FREE DYNAMIC BIOSENSING WITH NANOSCALE MAGNETIC FIELD SENSORS 审中-公开
公开(公告)号：WO2022011067A1
公开(公告)日：2022-01-13
申请号：PCT/US2021/040767
申请日：2021-07-08
申请人： ROCHE SEQUENCING SOLUTIONS, INC. , WESTERN DIGITAL TECHNOLOGIES, INC. , ROCHE DIAGNOSTICS GMBH , F. HOFFMANN-LA ROCHE AG
发明人： TOPOLANCIK, Juraj , BRAGANCA, Patrick , ASTIER, Yann , SHIN, Seong-Ho , MAJZIK, Zsolt
IPC分类号： G01N27/74 , G01N15/10 , G01N33/543 , G01R33/12 , H01L43/14
摘要： Disclosed herein are devices, systems, and methods for monitoring single-molecule biological processes using magnetic sensors and magnetic particles (MNP). A MNP is attached to a biopolymer (e.g., a nucleic acid, protein, etc.), and motion of the MNP is detected and/or monitored using a magnetic sensor. Because the MNP is small (e.g., its size is comparable to the size of the molecule being monitored) and is tethered to a biopolymer, changes in the volume of Brownian motion of the MNP in a solution can be monitored to monitor the movement of the MNP and, by inference, the tethered biopolymer. The magnetic sensor is small (e.g., nanoscale or having a size on the order of the sizes of the MNP and the biopolymer) and can be used to detect even small changes in the position of the MNP within the sensing region of the magnetic sensor.

5. 发明申请

WO2021216627A1 HIGH-THROUGHPUT NUCLEIC ACID SEQUENCING WITH SINGLE-MOLECULE SENSOR ARRAYS 审中-公开
公开(公告)号：WO2021216627A1
公开(公告)日：2021-10-28
申请号：PCT/US2021/028263
申请日：2021-04-21
申请人： ROCHE SEQUENCING SOLUTIONS, INC. , ROCHE DIAGNOSTICS GMBH , F. HOFFMANN-LA ROCHE AG , WESTERN DIGITAL TECHNOLOGIES, INC.
发明人： TOPOLANCIK, Juraj , BRAGANCA, Patrick , ASTIER, Yann , PALADUGU, Sri
IPC分类号： B01L3/00 , C12Q1/6869 , C12Q1/6837
摘要： Disclosed herein are embodiments of single-molecule array sequencing (SMAS) devices and systems. Each sensor of an array of sensors of the SMAS device is capable of detecting labels attached to nucleotides incorporated into a single nucleic acid strand bound to a respective binding site. Each sensor can detect a single label (e.g., fluorescent, magnetic, organometallic, charged molecule, etc.) attached to the incorporated nucleotide. Also disclosed are methods of using SMAS devices and systems for highly- scalable nucleic acid (e.g., DNA) sequencing based on sequencing by synthesis (SBS) of multiple instances of clonally amplified DNA immobilized on such SMAS devices. Also disclosed are error correction methods that mitigate errors (e.g., errant label detections or non-detections) made in sequencing individual nucleic acid strands.

6. 发明申请

WO2021123074A1 METHODS OF SEQUENCING BY SYNTHESIS USING A CONSECUTIVE LABELING SCHEME 审中-公开
公开(公告)号：WO2021123074A1
公开(公告)日：2021-06-24
申请号：PCT/EP2020/086902
申请日：2020-12-17
申请人： F. HOFFMANN-LA ROCHE AG , ROCHE DIAGNOSTICS GMBH , ROCHE SEQUENCING SOLUTIONS, INC.
发明人： ASTIER, Yann , BERGMANN, Frank , HEINDL, Dieter
IPC分类号： C07H19/00 , C12Q1/6837 , C12Q1/6874 , C07H19/04 , C07H19/10
摘要： The present disclosure provides a method for sequencing target polynucleotide molecules. In some embodiments, the present disclosure provides a method of sequencing by synthesis where different subsets of nucleotide-conjugate complexes are sequentially formed and detected during each iterative extension of a plurality of nascent nucleic acid copy strands, where each nascent nucleic acid copy strand is complementary to one of a plurality of target polynucleotide molecules. In some embodiments, the plurality of target polynucleotide molecules are arrayed on a solid support.

7. 发明申请

WO2020078595A1 ELECTRIC FIELD-ASSISTED JUNCTIONS FOR SEQUENCING 审中-公开
公开(公告)号：WO2020078595A1
公开(公告)日：2020-04-23
申请号：PCT/EP2019/066199
申请日：2019-06-19
申请人： F. HOFFMANN-LA ROCHE AG , ROCHE DIAGNOSTICS GMBH , ROCHE SEQUENCING SOLUTIONS, INC.
发明人： ASTIER, Yann , MAJZIK, Zsolt , MITCHELL, Flint , TOPOLANCIK, Juraj
IPC分类号： C12Q1/6869
摘要： Molecules may be analyzed (e.g., sequencing of nucleic acid molecules) by tunneling recognition at a tunneling junction. Embodiments of the present invention may allow detecting individual nucleotides and the sequencing of a nucleic acid molecule using a tunneling junction. By labeling a specific 5 nucleotide with a moiety, tunneling junctions may generate a signal with a suitable signal-to-noise ratio. An electric field may be applied to move the nucleic acid molecule and the moiety close to the tunneling junction so that a current may travel through the moiety. Because a single nucleotide can be detected with a signal with a suitable signal-to-noise ratio resulting from the tunneling current passing through 10 the moiety, embodiments of the present invention may allow for fast detection of nucleotides using a tunneling current.

8. 发明申请

WO2021183403A2 MAGNETIC SENSOR ARRAYS FOR NUCLEIC ACID SEQUENCING AND METHODS OF MAKING AND USING THEM 审中-公开
公开(公告)号：WO2021183403A2
公开(公告)日：2021-09-16
申请号：PCT/US2021/021274
申请日：2021-03-07
申请人： WESTERN DIGITAL TECHNOLOGIES, INC. , F. HOFFMANN-LA ROCHE AG , ROCHE DIAGNOSTICS GMBH , ROCHE SEQUENCING SOLUTIONS, INC.
发明人： BRAGANCA, Patrick , SMITH, Neil , TOPOLANCIK, Juraj , ASTIER, Yann
IPC分类号： B01L3/00 , C12Q1/6869 , B01L2200/12 , B01L2300/0663 , B01L2300/0877
摘要： Disclosed herein are apparatuses for nucleic acid sequencing using magnetic labels (e.g., magnetic particles) and magnetic sensors. Also disclosed are methods of making and using such apparatuses. An apparatus for nucleic acid sequencing comprises a plurality of magnetic sensors, a plurality of binding areas disposed above the plurality of magnetic sensors, each of the binding areas for holding fluid, and at least one line for detecting a characteristic of at least a first magnetic sensor of the plurality of magnetic sensors, the characteristic indicating presence or absence of one or more magnetic nanoparticles coupled to a first binding area associated with the first magnetic sensor.

9. 发明申请

WO2021148488A2 MICROFLUIDIC BEAD TRAPPING DEVICES AND METHODS FOR NEXT GENERATION SEQUENCING LIBRARY PREPARATION 审中-公开
公开(公告)号：WO2021148488A2
公开(公告)日：2021-07-29
申请号：PCT/EP2021/051232
申请日：2021-01-21
申请人： F. HOFFMANN-LA ROCHE AG , ROCHE DIAGNOSTICS GMBH , ROCHE SEQUENCING SOLUTIONS, INC.
发明人： ASTIER, Yann , BURGESS, Daniel , SCHLECHT, Ulrich , YANG, Jaeyoung
IPC分类号： B01L3/00 , C07K16/00 , B01L2200/0642 , B01L2200/0668 , B01L2300/0848 , B01L2300/0867 , B01L2300/0877 , B01L2300/0883 , B01L3/502761 , C12Q1/68
摘要： The present disclosure is directed to automated systems including a microfluidic chip having one or more independently operable processing conduits. In some embodiments, the automated systems are suitable for use in sample cleanup and/or target enrichment processes, such as sample cleanup and/or target enrichment processes conducted prior to sequencing.

10. 发明申请

WO2017207613A1 METHODS AND SYSTEMS FOR NUCLEIC ACID SEQUENCING BY TUNNELING RECOGNITION 审中-公开
标题翻译：通过隧道识别进行核酸测序的方法和系统
公开(公告)号：WO2017207613A1
公开(公告)日：2017-12-07
申请号：PCT/EP2017/063125
申请日：2017-05-31
申请人： F. HOFFMANN-LA ROCHE AG , ROCHE DIAGNOSTICS GMBH , ROCHE SEQUENCING SOLUTIONS, INC.
发明人： ASTIER, Yann
IPC分类号： C12Q1/68 , G01N27/327 , G01N33/487
摘要： Embodiments may include a method of analyzing a nucleic acid molecule. The method may include attaching the nucleic acid molecule to a protein. The protein may be attached to a particle with a first diameter. The method may also include applying an electric field to move a first portion of the nucleic acid molecule into an aperture. The aperture may be defined by a first electrode, an insulator, and a second electrode. The aperture may have a second diameter less than the first diameter. The method may further include contacting the first portion of the nucleic acid molecule to both the first electrode and the second electrode. The method may include applying a voltage across the first electrode and the second electrode. The current through the electrodes and the portion of the nucleic acid molecule may be measured, and a nucleotide of the nucleic acid molecule may be identified.
摘要翻译：实施方式可以包括分析核酸分子的方法。该方法可以包括将核酸分子附着到蛋白质上。蛋白质可以附着到具有第一直径的颗粒上。该方法还可以包括施加电场以将核酸分子的第一部分移动到孔中。该孔可以由第一电极，绝缘体和第二电极限定。该孔可以具有小于第一直径的第二直径。该方法可以进一步包括将核酸分子的第一部分接触第一电极和第二电极。该方法可以包括在第一电极和第二电极上施加电压。可以测量通过电极和核酸分子部分的电流，并且可以鉴定核酸分子的核苷酸。

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