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1. 发明申请

US20090048436A1 Methods of synthesizing chemically cleavable phosphoramidite linkers 审中-公开
标题翻译：化学可裂解亚磷酰胺接头的合成方法
公开(公告)号：US20090048436A1
公开(公告)日：2009-02-19
申请号：US11893614
申请日：2007-08-15
申请人： Keith Anderson , Michael Jensen , Ronald W. Davis , Charles K. Brush , Kaizhang He
发明人： Keith Anderson , Michael Jensen , Ronald W. Davis , Charles K. Brush , Kaizhang He
IPC分类号： C07H21/00
CPC分类号： C07H21/00
摘要： The present invention provides a method of synthesizing phosphoramidite linkers that are useful for the production of synthesizing two or more oligonucleotides in tandem. The inventive linker has the following desirable properties: (i) enhanced stability to alkali conditions versus the linkers previously published, (ii) cleaves to produce 5′ and 3′ ends that are fully biologically compatible, (iii) cleaves completely under conditions that are already used in cleavage/deprotection processes so it is fully compatible with conditions that are common in laboratories and does not require additives that necessitate further purification after cleavage, (iv) integrates easily onto commercially available synthesizers because it is compatible with standard coupling chemistry, and (v) is compatible with DNA, RNA, forward, reverse, and LNA, synthesis chemistries. In addition, the inventive linkers may be coupled to a solid support. Thus, the inventive linkers provide a significant advancement in the state of the art.
摘要翻译：本发明提供了一种合成亚磷酰胺接头的方法，其可用于串联合成两种或多种寡核苷酸。本发明的接头具有以下所需的性质：（i）与先前公开的接头相比，提高了对碱性条件的稳定性，（ii）切割产生完全生物相容的5'和3'末端，（iii）在条件下完全切割已经用于裂解/去保护过程，因此它与实验室常见的条件完全相容，并且不需要在裂解后需要进一步纯化的添加剂，（iv）容易地与市售合成仪整合，因为它与标准偶联化学相容，并且（v）与DNA，RNA，正向，反向和LNA的合成化学物质相容。此外，本发明的接头可以连接到固体支持物。因此，本发明的接头提供了现有技术的显着进步。

2. 发明申请

US20090047712A1 Chemically cleavable phosphoramidite linkers 审中-公开
标题翻译：化学上可裂解的亚磷酰胺接头
公开(公告)号：US20090047712A1
公开(公告)日：2009-02-19
申请号：US11893596
申请日：2007-08-15
申请人： Keith Anderson , Michael Jensen , Ronald W. Davis
发明人： Keith Anderson , Michael Jensen , Ronald W. Davis
IPC分类号： C07H21/00 , C07H21/02 , C07H21/04 , C07H19/00 , C12P19/34
CPC分类号： C07H21/00 , C07H19/00 , C07H21/02 , C07H21/04 , C12P19/34
摘要： The present invention provides phosphoramidite linkers that are useful for the production of synthesizing two or more oligonucleotides in tandem. The inventive linkers have the following desirable properties: (i) enhanced stability to alkali conditions versus the linkers previously published, (ii) cleave to produce 5′ and 3′ ends that are fully biologically compatible, (iii) cleave completely under conditions that are already used in cleavage/deprotection processes so they are fully compatible with conditions that are common in laboratories and do not require additives that necessitate further purification after cleavage, (iv) integrate easily onto commercially available synthesizers because they are compatible with standard coupling chemistry, and (v) are compatible with DNA, RNA, forward, reverse, and synthesis chemistries. In addition, the inventive linkers may be coupled to a solid support. Thus, the inventive linkers provide a significant advancement in the state of the art.
摘要翻译：本发明提供了可用于串联合成两种或多种寡核苷酸的亚磷酰胺接头。本发明的接头具有以下所需的性质：（i）与先前公布的接头相比，提高了对碱性条件的稳定性，（ii）切割产生完全生物相容的5'和3'末端，（iii）在条件下完全切割已经用于裂解/去保护过程，因此它们与实验室常见的条件完全相容，并且不需要在裂解后需要进一步纯化的添加剂，（iv）容易地与市售的合成仪结合，因为它们与标准偶联化学相容，（v）与DNA，RNA，正向，反向和合成化学物质相容。此外，本发明的接头可以连接到固体支持物。因此，本发明的接头提供了现有技术的显着进步。

3. 发明授权

US08580504B2 Methods and compositions for use in analyte detection using proximity probes 有权
公开(公告)号：US08580504B2
公开(公告)日：2013-11-12
申请号：US13012715
申请日：2011-01-24
申请人： Simon Fredriksson , Ronald W. Davis
发明人： Simon Fredriksson , Ronald W. Davis
IPC分类号： C12Q1/68 , C07H21/04
CPC分类号： C12Q1/6876 , C12Q1/6804 , G01N33/542 , C12Q2563/179 , C12Q2522/101 , C12Q2561/125 , C12Q2537/162 , C12Q2537/125
摘要： Methods and compositions for detecting an analyte in a sample are provided. In practicing the subject methods, a sample is combined with at least a pair of proximity probes that each include an analyte binding domain and a nucleic acid domain. The resultant mixture is then contacted with a pair of asymmetric nucleic acid connectors. Proximity dependent connector mediated interaction between the nucleic acid domains of the proximity probes is then detected to determine the presence of the analyte in the sample. Also provided are kits and systems for practicing the subject methods.

4. 发明申请

US20130029851A1 CALORIMETER SENSOR 失效
标题翻译： CALORIMETER传感器
公开(公告)号：US20130029851A1
公开(公告)日：2013-01-31
申请号：US13481363
申请日：2012-05-25
申请人： Hesaam Esfandyarpour , Ronald W. Davis
发明人： Hesaam Esfandyarpour , Ronald W. Davis
IPC分类号： G01N25/48 , C40B60/10 , C40B20/00
CPC分类号： G01N25/4806 , B01L3/5027
摘要： A calorimeter device includes various components located on a common substrate. A first (calorimeter) integrated chip device is located on the substrate. This first device has a first microfluidic channel that has first side and a second side. A first heat sensing circuit is located on the first side of the first channel and a second heat sensing circuit is located on the second side of the channel, opposite the first side and facing the first heat sensing circuit. A second integrated chip device is located on the substrate and proximal to the first device. The second device includes a second microfluidic channel having a fourth side and fifth side. A third heat sensing circuit is located on the third side of the second channel. A fourth heat sensing circuit is located on the fourth side of the channel, opposite the third side and facing the third heat sensing circuit.
摘要翻译：量热器装置包括位于公共基板上的各种部件。第一（量热计）集成芯片器件位于衬底上。该第一装置具有第一微流体通道，其具有第一侧和第二侧。第一热感测电路位于第一通道的第一侧上，并且第二热感测电路位于通道的第二侧上，与第一侧相对并且面向第一热感测电路。第二集成芯片器件位于衬底上并且靠近第一器件。第二装置包括具有第四侧和第五侧的第二微流体通道。第三热感测电路位于第二通道的第三侧。第四热感测电路位于通道的第四侧，与第三侧相对并面对第三热感应电路。

5. 发明授权

US08313907B2 Charge perturbation detection system for DNA and other molecules 有权
标题翻译：用于DNA和其他分子的电荷扰动检测系统
公开(公告)号：US08313907B2
公开(公告)日：2012-11-20
申请号：US13170607
申请日：2011-06-28
申请人： Nader Pourmand , Miloslav Karhanek , Ronald W. Davis
发明人： Nader Pourmand , Miloslav Karhanek , Ronald W. Davis
IPC分类号： C12Q1/68 , C12P19/34 , C07H21/04 , G01C15/06
CPC分类号： C12Q1/6825 , B82Y15/00 , B82Y30/00 , B82Y40/00 , G01N27/3275 , G01N27/3276
摘要： Methods and apparatus for direct detection of chemical reactions are provided. In a preferred embodiment, electric charge perturbations of the local environment during enzyme-catalyzed reactions are sensed by an electrode system with an immobilized target molecule. The target molecule is preferably DNA. The charge perturbation caused by the polymerase reaction can uniquely identify a DNA sequence. The polymerization process generates local perturbations of charge in the solution near the electrode surface and induces a charge in a polarazible gold electrode. This event is detected as a transient current by a voltage clamp amplifier. Detection of single nucleotides in a sequence can be determined by dispensing individual dNTPs to the electrode solution and detecting the charge perturbations. Alternatively, multiple bases can be determined at the same time using a mix of all dNTPs with subsequent analysis of the resulting signal. The initial enzyme attachment to the DNA molecule can be detected prior to polymerization, with electrode capacitance measurement using the same voltage-clamp amplifier. This technique and device may be adapted to other reaction determinations, such as enzymatic reactions, other electrode configurations, and other amplifying circuits.
摘要翻译：提供了用于直接检测化学反应的方法和装置。在优选的实施方案中，酶催化反应期间局部环境的电荷扰动由具有固定化靶分子的电极系统检测。靶分子优选为DNA。由聚合酶反应引起的电荷扰动可以唯一地识别DNA序列。聚合过程在电极表面附近的溶液中产生电荷的局部扰动，并在极化金电极中引起电荷。该事件由电压钳位放大器检测为瞬态电流。可以通过将单个dNTP分配到电极溶液并检测电荷扰动来确定序列中单个核苷酸的检测。或者，可以使用所有dNTP的混合物同时测定多个碱基，随后分析所得信号。可以在聚合前检测到DNA分子的初始酶附着，使用相同的电压钳位放大器进行电极电容测量。该技术和装置可以适用于其他反应测定，例如酶反应，其它电极配置和其它放大电路。

6. 发明授权

US08137912B2 Methods for the diagnosis of fetal abnormalities 有权
标题翻译：胎儿异常诊断方法
公开(公告)号：US08137912B2
公开(公告)日：2012-03-20
申请号：US11763245
申请日：2007-06-14
申请人： Ravi Kapur , Mehmet Toner , Roland Stoughton , Daniel Shoemaker , Ronald W. Davis
发明人： Ravi Kapur , Mehmet Toner , Roland Stoughton , Daniel Shoemaker , Ronald W. Davis
IPC分类号： C12Q1/68 , C12P19/34 , C07H21/02 , C07H21/04
CPC分类号： C12Q1/6883 , C12Q2600/156 , C12Q2600/158 , C12Q2600/16 , G01N1/30 , G01N33/6893 , G01N2800/385
摘要： The present invention relates to methods for detecting, enriching, and analyzing rare cells that are present in the blood, e.g. fetal cells. The invention further features methods of analyzing rare cell(s) to determine the presence of an abnormality, disease or condition in a subject, e.g. a fetus by analyzing a cellular sample from the subject.
摘要翻译：本发明涉及用于检测，富集和分析存在于血液中的罕见细胞的方法，例如，胎儿细胞。本发明还涉及分析稀有细胞以确定受试者中异常，疾病或病症的存在的方法，例如，通过分析来自受试者的细胞样品的胎儿。

7. 发明申请

US20120065091A1 DIRECT MULTIPLEX CHARACTERIZATION OF GENOMIC DNA 有权
标题翻译：基因DNA的直接多重表征
公开(公告)号：US20120065091A1
公开(公告)日：2012-03-15
申请号：US13206120
申请日：2011-08-09
申请人： Thomas D. Willis , Paul Hardenbol , Maneesh Jain , Viktor Stolc , Mostafa Ronaghi , Ronald W. Davis
发明人： Thomas D. Willis , Paul Hardenbol , Maneesh Jain , Viktor Stolc , Mostafa Ronaghi , Ronald W. Davis
IPC分类号： C40B30/04 , C12Q1/68
CPC分类号： C12Q1/6827 , C12Q1/6858 , C12Q1/686 , C12Q2531/113 , C12Q2525/307 , C12Q2537/143
摘要： The invention is directed to novel methods of multiplexing nucleic acid reactions, including amplification, detection and genotyping. The invention relies on the use of precircle probes that are circularized in the presence of the corresponding target nucleic acids, cleaved, and then amplified.
摘要翻译：本发明涉及复制核酸反应的新方法，包括扩增，检测和基因分型。本发明依赖于在相应靶核酸存在下被环化的前循环探针的使用，被切割，然后扩增。

8. 发明申请

US20120045828A1 Apparatus for Magnetic Separation of Cells 有权
标题翻译：细胞磁分离装置
公开(公告)号：US20120045828A1
公开(公告)日：2012-02-23
申请号：US13284482
申请日：2011-10-28
申请人： Ronald W. Davis , Stefanie S. Jeffrey , Michael N. Mindrinos , R. Fabian Pease , Ashley Ann Powell , AmirAli Hajhossein Talasaz
发明人： Ronald W. Davis , Stefanie S. Jeffrey , Michael N. Mindrinos , R. Fabian Pease , Ashley Ann Powell , AmirAli Hajhossein Talasaz
IPC分类号： C12N5/09 , C12M3/00
CPC分类号： G01N33/54333 , B03C1/01 , B03C1/286 , B03C2201/18 , B03C2201/26
摘要： Described here is an automated robotic device that isolates circulating tumor cells (CTCs) or other biological structures with extremely high purity. The device uses powerful magnetic rods covered in removable plastic sleeves. These rods sweep through blood samples, capturing, e.g., cancer cells labeled with antibodies linked to magnetically responsive particles such as superparamagnetic beads. Upon completion of the capturing protocol, the magnetic rods undergo several rounds of washing, thereby removing all contaminating blood cells. The captured target cells are released into a final capture solution by removing the magnetic rods from the sleeves. Additionally, cells captured by this device show no reduced viability when cultured after capture. Cells are captured in a state suitable for genetic analysis. Also disclosed are methods for single cell analysis. Being robotic allows the device to be operated with high throughput.
摘要翻译：这里描述了一种自动化的机器人装置，其以非常高的纯度分离循环肿瘤细胞（CTC）或其他生物结构。该设备使用强大的磁棒覆盖在可拆卸的塑料袖子。这些棒穿过血液样品，捕获例如用与磁性响应颗粒例如超顺磁珠连接的抗体标记的癌细胞。在完成捕获方案后，磁棒经历几轮洗涤，从而除去所有污染的血细胞。通过从袖子中取出磁棒将捕获的靶细胞释放到最终的捕获溶液中。此外，由该装置俘获的细胞在捕获后培养时显示出不降低的活力。以适合于遗传分析的状态捕获细胞。还公开了用于单细胞分析的方法。机器人允许设备以高吞吐量运行。

9. 发明申请

US20110281739A1 Charge Perturbation Detection System for DNA and Other Molecules 有权
标题翻译： DNA和其他分子的电荷扰动检测系统
公开(公告)号：US20110281739A1
公开(公告)日：2011-11-17
申请号：US13170607
申请日：2011-06-28
申请人： Nader Pourmand , Miloslav Karhanek , Ronald W. Davis
发明人： Nader Pourmand , Miloslav Karhanek , Ronald W. Davis
IPC分类号： C40B20/00 , C12M1/40 , C40B60/10 , C12Q1/68
CPC分类号： C12Q1/6825 , B82Y15/00 , B82Y30/00 , B82Y40/00 , G01N27/3275 , G01N27/3276
摘要： Methods and apparatus for direct detection of chemical reactions are provided. In a preferred embodiment, electric charge perturbations of the local environment during enzyme-catalyzed reactions are sensed by an electrode system with an immobilized target molecule. The target molecule is preferably DNA. The charge perturbation caused by the polymerase reaction can uniquely identify a DNA sequence. The polymerization process generates local perturbations of charge in the solution near the electrode surface and induces a charge in a polarazible gold electrode. This event is detected as a transient current by a voltage clamp amplifier. Detection of single nucleotides in a sequence can be determined by dispensing individual dNTPs to the electrode solution and detecting the charge perturbations. Alternatively, multiple bases can be determined at the same time using a mix of all dNTPs with subsequent analysis of the resulting signal. The initial enzyme attachment to the DNA molecule can be detected prior to polymerization, with electrode capacitance measurement using the same voltage-clamp amplifier. This technique and device may be adapted to other reaction determinations, such as enzymatic reactions, other electrode configurations, and other amplifying circuits.
摘要翻译：提供了用于直接检测化学反应的方法和装置。在优选的实施方案中，酶催化反应期间局部环境的电荷扰动由具有固定化靶分子的电极系统检测。靶分子优选为DNA。由聚合酶反应引起的电荷扰动可以唯一地识别DNA序列。聚合过程在电极表面附近的溶液中产生电荷的局部扰动，并在极化金电极中引起电荷。该事件由电压钳位放大器检测为瞬态电流。可以通过将单个dNTP分配到电极溶液并检测电荷扰动来确定序列中单个核苷酸的检测。或者，可以使用所有dNTP的混合物同时测定多个碱基，随后分析所得信号。可以在聚合前检测到DNA分子的初始酶附着，使用相同的电压钳位放大器进行电极电容测量。该技术和装置可以适用于其他反应测定，例如酶反应，其它电极配置和其它放大电路。

10. 发明授权

US07875428B2 Multiplexed assay and probes for identification of HPV types 有权
标题翻译：用于鉴定HPV类型的多重测定和探针
公开(公告)号：US07875428B2
公开(公告)日：2011-01-25
申请号：US11707832
申请日：2007-02-13
申请人： Nader Pourmand , Baback Gharizadeh , Ronald W. Davis
发明人： Nader Pourmand , Baback Gharizadeh , Ronald W. Davis
IPC分类号： C12Q1/68 , C12P19/34 , C12M3/00 , C07H21/04
CPC分类号： C12Q1/708
摘要： A DNA microarray, preferably in the form of a chip, contains probes which hybridize to generate primers capable of amplifying approximately 89 HPV types. These target the E1 region of the gene. The design of the chip allows for the detection of any known HPV type, based on a unique probe sequence derived from the HPV E1 region. The present assay utilizes a number of primers that can amplify from about one to six different types of HPV. A large number of primers can be used together. After amplification, the amplicons are contacted with specific probes that are unique for each HPV type. The array further employs a control sequence, which normalizes variability due to sample size.
摘要翻译：优选以芯片形式的DNA微阵列含有杂交以产生能够扩增大约89种HPV类型的引物的探针。这些靶基因的E1区域。基于来自HPV E1区域的唯一探针序列，芯片的设计允许检测任何已知的HPV类型。本测定使用可以扩增大约一至六种不同类型的HPV的许多引物。大量的引物可以一起使用。扩增后，扩增子与特定的探针接触，这些探针对于每种HPV类型是独特的。该阵列进一步采用控制序列，其归一化由于样本大小引起的变异性。

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