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    Solid phase sequencing of biopolymers
    1.
    发明授权
    Solid phase sequencing of biopolymers 有权
    生物聚合物的固相测序

    公开(公告)号：US07803529B1

    公开(公告)日：2010-09-28

    申请号：US09395409

    申请日：1999-09-14

    Applicant: Charles Cantor ,  Hubert Köster

    Inventor： Charles Cantor ,  Hubert Köster

    IPC: C12Q1/68

    CPC classification number: C12Q1/6872 ,  C12Q1/6874 ,  C12Q2565/501 ,  C12Q2531/113 ,  C12Q2521/525 ,  C12Q2565/627 ,  C12Q2531/119 ,  C12Q2523/301 ,  C12Q2531/137 ,  C12Q2521/301 ,  C12Q2531/149

    Abstract: This invention relates to methods for detecting and sequencing target nucleic acid sequences, to mass modified nucleic acid probes and arrays of probes useful in these methods, and to kits and systems which contain these probes. Useful methods involve hybridizing the nucleic acids or nucleic acids which represent complementary or homologous sequences of the target to an array of nucleic acid probes. These probes comprise a single-stranded portion, an optional double-stranded portion and a variable sequence within the single-stranded portion. The molecular weights of the hybridized nucleic acids of the set can be determined by mass spectroscopy, and the sequence of the target determined from the molecular weights of the fragments. Nucleic acids whose sequences can be determined include DNA or RNA in biological samples such as patient biopsies and environmental samples. Probes may be fixed to a solid support such as a hybridization chip to facilitate automated molecular weight analysis and identification of the target sequence.

    Abstract translation: 本发明涉及用于检测和测序靶核酸序列，批量修饰的核酸探针和可用于这些方法的探针阵列的方法，以及含有这些探针的试剂盒和系统。 有用的方法包括将代表靶的互补或同源序列的核酸或核酸与核酸探针阵列进行杂交。 这些探针包括在单链部分内的单链部分，任选的双链部分和可变序列。 该组的杂交核酸的分子量可以通过质谱法测定，并且靶标的序列由片段的分子量确定。 可以确定其序列的核酸包括生物样品中的DNA或RNA，例如患者活组织检查和环境样品。 探针可以固定在固体支持物例如杂交芯片上以促进自动化分子量分析和靶序列的鉴定。

    SOLID PHASE SEQUENCING OF BIOPOLYMERS
    4.
    发明申请
    SOLID PHASE SEQUENCING OF BIOPOLYMERS 失效
    生物聚合物的固相序列

    公开(公告)号：US20110172111A1

    公开(公告)日：2011-07-14

    申请号：US12852336

    申请日：2010-08-06

    Applicant: Charles Cantor ,  Hubert Köster

    Inventor： Charles Cantor ,  Hubert Köster

    IPC: C40B30/04

    CPC classification number: C12Q1/6872 ,  C12Q1/6874 ,  C12Q2565/501 ,  C12Q2531/113 ,  C12Q2521/525 ,  C12Q2565/627 ,  C12Q2531/119 ,  C12Q2523/301 ,  C12Q2531/137 ,  C12Q2521/301 ,  C12Q2531/149

    Abstract: This invention relates to methods for detecting and sequencing target nucleic acid sequences, to mass modified nucleic acid probes and arrays of probes useful in these methods, and to kits and systems which contain these probes. Useful methods involve hybridizing the nucleic acids or nucleic acids which represent complementary or homologous sequences of the target to an array of nucleic acid probes. These probes comprise a single-stranded portion, an optional double-stranded portion and a variable sequence within the single-stranded portion. The molecular weights of the hybridized nucleic acids of the set can be determined by mass spectroscopy, and the sequence of the target determined from the molecular weights of the fragments. Nucleic acids whose sequences can be determined include DNA or RNA in biological samples such as patient biopsies and environmental samples. Probes may be fixed to a solid support such as a hybridization chip to facilitate automated molecular weight analysis and identification of the target sequence.

    Abstract translation: 本发明涉及用于检测和测序靶核酸序列，批量修饰的核酸探针和可用于这些方法的探针阵列的方法，以及含有这些探针的试剂盒和系统。 有用的方法包括将代表靶的互补或同源序列的核酸或核酸与核酸探针阵列进行杂交。 这些探针包括在单链部分内的单链部分，任选的双链部分和可变序列。 该组的杂交核酸的分子量可以通过质谱法测定，并且靶标的序列由片段的分子量确定。 可以确定其序列的核酸包括生物样品中的DNA或RNA，例如患者活组织检查和环境样品。 探针可以固定在固体支持物例如杂交芯片上以促进自动化分子量分析和靶序列的鉴定。

    Systems and methods for performing reactions in an unsealed environment
    5.
    发明授权
    Systems and methods for performing reactions in an unsealed environment 有权
    在非密封环境中进行反应的系统和方法

    公开(公告)号：US06225061B1

    公开(公告)日：2001-05-01

    申请号：US09266409

    申请日：1999-03-10

    Applicant: Thomas Becker ,  Hubert Köster ,  Charles Cantor

    Inventor： Thomas Becker ,  Hubert Köster ,  Charles Cantor

    IPC: C12Q168

    CPC classification number: B01J19/16 ,  B01J2219/00317 ,  B01J2219/00367 ,  B01J2219/00378 ,  B01J2219/00495 ,  B01J2219/00603 ,  B01J2219/0068 ,  C40B60/14 ,  G01N2035/00287 ,  Y10T436/11 ,  Y10T436/25375

    Abstract: An open system is provided for performing a submicroliter reaction. An open system can contain a solid support having a target site for performing the reaction; a liquid dispensing system such as a nanoliter dispensing pipette for dispensing a submicroliter amount of a liquid to the target site; a temperature controlling device for regulating the temperature of the support; and means for controlling the amount of liquid dispensed, which corresponds to the amount of liquid that evaporates from the target site. Also provided is an open system, including a solid support having a target site; a liquid dispensing system, which can dispense a liquid to the target site; a temperature controlling system, which regulates the temperature of the solid support; and an interface, which regulates an amount of liquid dispensed from the liquid dispensing system. Also provided is a method for performing a reaction in a submicroliter volume in an unsealed environment by dispensing a submicroliter volume of liquid onto the surface of a support; monitoring the temperature of the support; monitoring an amount or rate of evaporation of the liquid; and dispensing to the surface of the support a further amount of the liquid, which corresponds to the amount lost from the support due to evaporation, thereby maintaining the reaction volume at a predetermined volume throughout the course of the reaction. A method also is provided for maintaining a volume of a reaction mixture, which can be one of a plurality of reaction mixtures, on a solid support in an unsealed environment by monitoring the rate of evaporation of a liquid from the reaction mixture; and dispensing into the reaction mixture an amount of liquid that corresponds to the amount that evaporates.

    Abstract translation: 提供了用于进行亚微米级反应的开放系统。 开放系统可以含有具有用于进行反应的靶位点的固体支持物; 液体分配系统，例如用于将目标部位的微量剂量的液体分配的纳升分配移液管; 用于调节支撑件的温度的温度控制装置; 以及用于控制分配的液体量的装置，其对应于从目标部位蒸发的液体的量。 还提供了一种开放系统，包括具有目标地点的固体支撑物; 液体分配系统，其可以将液体分配到目标部位; 温度控制系统，其调节固体支持物的温度; 以及界面，其调节从液体分配系统分配的液体的量。 还提供了一种在非密封环境中通过将亚微米级体积的液体分配到载体的表面上来进行亚微米体积的反应的方法; 监测支架的温度; 监测液体的蒸发量或速率; 并且向支撑体的表面分配更多量的液体，其对应于由于蒸发而从支撑物损失的量，从而在反应过程中将反应体积保持在预定体积。 还提供了一种方法，用于通过监测来自反应混合物的液体的蒸发速率来保持反应混合物的体积，反应混合物可以是多个反应混合物中的一种，在固体支持物上在未密封环境中; 并向反应混合物中分配一定量的与蒸发量对应的液体。

    Multiflavor streptavidin
    6.
    发明授权
    Multiflavor streptavidin 失效
    多重链霉抗生物素蛋白

    公开(公告)号：US06368813B1

    公开(公告)日：2002-04-09

    申请号：US09381430

    申请日：2000-03-23

    Applicant: Gabriel O. Reznik ,  Takeshi Sano ,  Sandor Vajda ,  Cassandra Smith ,  Charles Cantor

    Inventor： Gabriel O. Reznik ,  Takeshi Sano ,  Sandor Vajda ,  Cassandra Smith ,  Charles Cantor

    IPC: G01N3353

    CPC classification number: C07K14/36

    Abstract: Compounds and methods are described for producing streptavidin mutants with changed affinities. In particular, modifications to the sequence of the natural streptavidin gene is described to create amino acid substitutions resulting in greater affinity for biotin substitutes than for biotin.

    Abstract translation: 描述了用于生产具有改变的亲和力的链霉抗生物素蛋白突变体的化合物和方法。 特别地，描述了对天然链霉亲和素基因的序列的修饰以产生氨基酸取代，导致对生物素替代物的亲和力高于生物素。

    Method for non-invasive prenatal diagnosis
    7.
    发明申请
    Method for non-invasive prenatal diagnosis 审中-公开
    非侵入性产前诊断方法

    公开(公告)号：US20070207466A1

    公开(公告)日：2007-09-06

    申请号：US11364294

    申请日：2006-02-28

    Applicant: Charles Cantor ,  Chunming Ding ,  Yuk Lo ,  Rossa Chiu

    Inventor： Charles Cantor ,  Chunming Ding ,  Yuk Lo ,  Rossa Chiu

    IPC: C12Q1/68

    CPC classification number: C12Q1/6881 ,  C12Q1/6872 ,  C12Q2600/156 ,  C12Q2600/172 ,  C12Q2535/125

    Abstract: The present invention is directed to methods of detecting nucleic acids in a biological sample. The method is based on a novel combination of a base extension reaction, which provides excellent analytical specificity, and a mass spectrometric analysis, which provides excellent specificity. The method can be used, for example, for diagnostic, prognostic and treatment purposes. The method allows accurate detection of nucleic acids that are present in very small amounts in a biological sample. For example, the method of the present invention is preferably used to detect fetal nucleic acid in a maternal blood sample; circulating tumor-specific nucleic acids in a blood, urine or stool sample; and donor-specific nucleic acids in transplant recipients. In another embodiment, one can detect viral, bacterial, fungal, or other foreign nucleic acids in a biological sample.

    Abstract translation: 本发明涉及检测生物样品中核酸的方法。 该方法基于提供优异分析特异性的碱基延伸反应和提供优异特异性的质谱分析的新型组合。 该方法可用于例如诊断，预后和治疗目的。 该方法允许精确检测在生物样品中以非常少的量存在的核酸。 例如，本发明的方法优选用于检测母体血液样品中的胎儿核酸; 在血液，尿液或粪便样品中循环肿瘤特异性核酸; 和供体特异性核酸。 在另一个实施方案中，可以检测生物样品中的病毒，细菌，真菌或其它外来核酸。

    Fetal genomic analysis from a maternal biological sample
    9.
    发明授权
    Fetal genomic analysis from a maternal biological sample 有权
    母体生物样品的胎儿基因组分析

    公开(公告)号：US08467976B2

    公开(公告)日：2013-06-18

    申请号：US12940993

    申请日：2010-11-05

    Applicant: Yuk Ming Dennis Lo ,  Kwan Chee Chan ,  Wai Kwun Rossa Chiu ,  Charles Cantor

    Inventor： Yuk Ming Dennis Lo ,  Kwan Chee Chan ,  Wai Kwun Rossa Chiu ,  Charles Cantor

    IPC: G06F19/00 ,  C12Q1/68 ,  G11C17/00

    CPC classification number: C12Q1/6876 ,  C12Q1/6827 ,  G06F19/18 ,  G06F19/22 ,  G06F19/24 ,  Y10T436/143333 ,  C12Q2537/165 ,  C12Q2535/101 ,  C12Q2527/125

    Abstract: Systems, methods, and apparatus for determining at least a portion of fetal genome are provided. DNA fragments from a maternal sample (maternal and fetal DNA) can be analyzed to identify alleles at certain loci. The amounts of DNA fragments of the respective alleles at these loci can be analyzed together to determine relative amounts of the haplotypes for these loci and determine which haplotypes have been inherited from the parental genomes. Loci where the parents are a specific combination of homozygous and heterozygous can be analyzed to determine regions of the fetal genome. Reference haplotypes common in the population can be used along with the analysis of the DNA fragments of the maternal sample to determine the maternal and paternal genomes. Determination of mutations, a fractional fetal DNA concentration in a maternal sample, and a proportion of coverage of a sequencing of the maternal sample can also be provided.

    Abstract translation: 提供了用于确定胎儿基因组的至少一部分的系统，方法和装置。 可以分析来自母体样品（母体和胎儿DNA）的DNA片段，以鉴定某些位点处的等位基因。 可以一起分析在这些位点处各个等位基因的DNA片段的量，以确定这些基因座的单倍型的相对量，并确定哪些单元型已经从亲代基因组遗传。 可以分析父母是纯合子和杂合子的特异性组合的位点，以确定胎儿基因组的区域。 可以在群体中常见的参考单倍型与母体样品的DNA片段的分析一起使用，以确定母体和父系的基因组。 也可以提供母体样品中突变的确定，胎儿DNA分数的分数以及母体样品测序的覆盖率。

    Fetal Genomic Analysis From A Maternal Biological Sample
    10.
    发明申请
    Fetal Genomic Analysis From A Maternal Biological Sample 有权
    胎儿生物样品的胎儿基因组分析

    公开(公告)号：US20110105353A1

    公开(公告)日：2011-05-05

    申请号：US12940993

    申请日：2010-11-05

    Applicant: Yuk Ming Dennis Lo ,  Kwan Chee Chan ,  Wai Kwun Rossa Chiu ,  Charles Cantor

    Inventor： Yuk Ming Dennis Lo ,  Kwan Chee Chan ,  Wai Kwun Rossa Chiu ,  Charles Cantor

    IPC: G01N33/53 ,  G01N33/48 ,  C12Q1/68

    CPC classification number: C12Q1/6876 ,  C12Q1/6827 ,  G06F19/18 ,  G06F19/22 ,  G06F19/24 ,  Y10T436/143333 ,  C12Q2537/165 ,  C12Q2535/101 ,  C12Q2527/125

    Abstract: Systems, methods, and apparatus for determining at least a portion of fetal genome are provided. DNA fragments from a maternal sample (maternal and fetal DNA) can be analyzed to identify alleles at certain loci. The amounts of DNA fragments of the respective alleles at these loci can be analyzed together to determine relative amounts of the haplotypes for these loci and determine which haplotypes have been inherited from the parental genomes. Loci where the parents are a specific combination of homozygous and heterozygous can be analyzed to determine regions of the fetal genome. Reference haplotypes common in the population can be used along with the analysis of the DNA fragments of the maternal sample to determine the maternal and paternal genomes. Determination of mutations, a fractional fetal DNA concentration in a maternal sample, and a proportion of coverage of a sequencing of the maternal sample can also be provided.

    Abstract translation: 提供了用于确定胎儿基因组的至少一部分的系统，方法和装置。 可以分析来自母体样品（母体和胎儿DNA）的DNA片段，以鉴定某些位点处的等位基因。 可以一起分析在这些位点处各个等位基因的DNA片段的量，以确定这些基因座的单倍型的相对量，并确定哪些单元型已经从亲代基因组遗传。 可以分析父母是纯合子和杂合子的特异性组合的位点，以确定胎儿基因组的区域。 可以在群体中常见的参考单倍型与母体样品的DNA片段的分析一起使用，以确定母体和父系的基因组。 也可以提供母体样品中突变的确定，胎儿DNA分数的分数以及母体样品测序的覆盖率。

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