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1. 发明授权

US06534293B1 Accelerating identification of single nucleotide polymorphisms and alignment of clones in genomic sequencing 有权
标题翻译：加速单核苷酸多态性的鉴定和基因组测序中克隆的比对
公开(公告)号：US06534293B1
公开(公告)日：2003-03-18
申请号：US09478189
申请日：2000-01-05
申请人： Francis Barany , Jianzhao Liu , Brian W. Kirk , Monib Zirvi , Norman P. Gerry , Philip B. Paty
发明人： Francis Barany , Jianzhao Liu , Brian W. Kirk , Monib Zirvi , Norman P. Gerry , Philip B. Paty
IPC分类号： C12P1934
CPC分类号： C12Q1/6827 , C12Q1/6837 , C12Q1/6841 , C12Q1/6855 , C12Q1/6874 , Y10T436/143333 , C12Q2525/155 , C12Q2521/301 , C12Q2539/107 , C12Q2535/113 , C12Q2525/191 , C12Q2565/501 , C12Q2561/125 , C12Q2565/514
摘要： The present invention is directed to a method of assembling genomic maps of an organism's DNA or portions thereof. A library of an organism's DNA is provided where the individual genomic segments or sequences are found on more than one clone in the library. Representations of the genome are created, and nucleic acid sequence information is generated from the representations. The sequence information is analyzed to determine clone overlap from a representation. The clone overlap and sequence information from different representations is combined to assemble a genomic map of the organism. Once the genomic map is obtained, genomic sequence information from multiple individuals can be applied to the map and compared with one another to identify single nucleotide polymorphisms. These single nucleotide polymorphisms can be detected, and alleles quantified, by conducting (1) a global PCR amplification which creates a genome representation, and (2) a ligation detection reaction process whose ligation products are captured by hybridization to a support.
摘要翻译：本发明涉及一种组装生物体DNA或其部分的基因组图谱的方法。提供了生物体DNA的文库，其中在文库中的多于一个克隆上发现各个基因组片段或序列。创建基因组的表示，并从表示生成核酸序列信息。分析序列信息以从表示确定克隆重叠。来自不同表示的克隆重叠和序列信息被组合以组装生物体的基因组图。一旦得到基因组图谱，可以将多个个体的基因组序列信息应用于该图并相互比较以鉴定单核苷酸多态性。通过进行（1）产生基因组表达的全局PCR扩增，以及（2）通过与载体杂交捕获其连接产物的连接检测反应过程，可以检测这些单核苷酸多态性和等位基因进行定量。

2. 发明授权

US08367322B2 Accelerating identification of single nucleotide polymorphisms and alignment of clones in genomic sequencing 有权
公开(公告)号：US08367322B2
公开(公告)日：2013-02-05
申请号：US10198235
申请日：2002-07-17
申请人： Francis Barany , Jianzhao Kiu , Brian W. Kirk , Monib Zirvi , Norman P. Gerry , Philip B. Paty
发明人： Francis Barany , Jianzhao Kiu , Brian W. Kirk , Monib Zirvi , Norman P. Gerry , Philip B. Paty
IPC分类号： C12Q1/68 , C12P19/34 , C07H21/02 , C07H21/04 , C07H21/00
CPC分类号： C12Q1/6874 , C12Q1/6827 , C12Q1/6855 , G06F19/22 , C12Q2565/501 , C12Q2561/125 , C12Q2525/191 , C12Q2539/107 , C12Q2565/514
摘要： The present invention is directed to a method of assembling genomic maps of an organism's DNA or portions thereof. A library of an organism's DNA is provided where the individual genomic segments or sequences are found on more than one clone in the library. Representations of the genome are created, and nucleic acid sequence information is generated from the representations. The sequence information is analyzed to determine clone overlap from a representation. The clone overlap and sequence information from different representations is combined to assemble a genomic map of the organism. Once the genomic map is obtained, genomic sequence information from multiple individuals can be applied to the map and compared with one another to identify single nucleotide polymorphisms. These single nucleotide polymorphisms can be detected, and alleles quantified, by conducting (1) a global PCR amplification which creates a genome representation, and (2) a ligation detection reaction process whose ligation products are captured by hybridization to a support.

3. 发明申请

US20110257034A1 METHODS FOR IDENTIFYING GENES WHICH PREDICT DISEASE OUTCOME FOR PATIENTS WITH COLON CANCER 审中-公开
标题翻译：识别患有结肠癌患者预防疾病的基因的方法
公开(公告)号：US20110257034A1
公开(公告)日：2011-10-20
申请号：US13123689
申请日：2009-10-13
申请人： Francis Barany , Owen Parker , Manny D. Bacolod , Sarah F. Giardina , Yu-wei Cheng , Daniel A. Notterman , Gunter S. Schemmann , Philip B. Paty , Monib Zirvi
发明人： Francis Barany , Owen Parker , Manny D. Bacolod , Sarah F. Giardina , Yu-wei Cheng , Daniel A. Notterman , Gunter S. Schemmann , Philip B. Paty , Monib Zirvi
IPC分类号： C40B30/04 , C40B40/06 , G01N33/53 , C40B40/08 , C12Q1/68 , G01N33/566
CPC分类号： G01N33/57419
摘要： Closures for containers and methods for using same are provided. In a general embodiment/the present disclosure provides a closure having a top portion (12), a bottom portion (14) and a side portion (16), an aperture (18) extending though the closure, a projection (20) extending from the closure and at least two rib members (36) on an interior of the projection. The projection may also include a cover (22). In another embodiment, a method for using a closure includes inserting a. spike member into a projection, piercing a membrane that hermetically seals a medical container, pushing rib members within the projection to center the spike member inserted into the projection, and tearing the membrane to create a vent hole in the membrane.
摘要翻译：提供容器的封闭件和使用容器的方法。在一般实施例中，本公开提供了一种具有顶部部分（12），底部部分（14）和侧部部分（16）的封闭件，通过封闭件延伸的孔口（18）所述封闭件和所述突起的内部上的至少两个肋构件（36）。突起还可以包括盖（22）。在另一个实施例中，一种使用闭合件的方法包括：突出部件突入，刺穿密封医疗容器的膜，推动突起内的肋构件以使插入突起中的钉构件居中，并撕裂膜以在隔膜中形成通气孔。

4. 发明授权

US08492085B2 Method of designing addressable array suitable for detection of nucleic acid sequence differences using ligase detection reaction 有权
标题翻译：使用连接酶检测反应设计适用于检测核酸序列差异的可寻址阵列的方法
公开(公告)号：US08492085B2
公开(公告)日：2013-07-23
申请号：US12252169
申请日：2008-10-15
申请人： Francis Barany , Monib Zirvi , Norman P. Gerry , Reyna Favis , Richard Kliman
发明人： Francis Barany , Monib Zirvi , Norman P. Gerry , Reyna Favis , Richard Kliman
IPC分类号： C12Q1/68 , C12M1/00 , C12M1/34 , C12M3/00
CPC分类号： C12Q1/6837 , C12Q1/6827 , C12Q1/6874 , C12Q1/6886 , C12Q2527/107 , C12Q2521/501 , C12Q2521/319 , C12Q2565/501
摘要： The present invention is directed to a method of designing a plurality of capture oligonucleotide probes for use on a support to which complementary oligonucleotide probes will hybridize with little mismatch, where the plural capture oligonucleotide probes have melting temperatures within a narrow range. The first step of the method involves providing a first set of a plurality of tetramers of four nucleotides linked together, where (1) each tetramer within the first set differs from all other tetramers in the first set by at least two nucleotide bases, (2) no two tetramers within the first set are complementary to one another, (3) no tetramers within the first set are palindromic or dinucleotide repeats, and (4) no tetramer within the first set has one or less or three or more G or C nucleotides. Groups of 2 to 4 of the tetramers from the first set are linked together to form a collection of multimer units. From the collection of multimer units, all multimer units formed from the same tetramer and all multimer units having a melting temperature in .degree. C. of less than 4 times the number of tetramers forming a multimer unit are removed to form a modified collection of multimer units. The modified collection of multimer units is arranged in a list in order of melting temperature. The order of the modified collection of multimer units is randomized in 2.degree. C. increments of melting temperature.
摘要翻译：本发明涉及一种设计多个捕获寡核苷酸探针的方法，所述多个捕获寡核苷酸探针用于互补寡核苷酸探针与少量错配杂交的载体上，其中多个捕获寡核苷酸探针具有在窄范围内的熔融温度。该方法的第一步涉及提供连接在一起的四个核苷酸的多个四聚体的第一组，其中（1）第一组中的每个四聚体与第一组中的所有其它四聚体相差至少两个核苷酸碱基（2 ）第一组中没有两个四聚体彼此互补，（3）第一组中没有四聚体是回文或二核苷酸重复，和（4）第一组中没有四聚体具有一个或更少或三个或更多个G或C 核苷酸。来自第一组的4至4个四聚体的组连接在一起以形成多聚体单元的集合。从多聚体单元的收集中，由相同四聚体形成的所有多聚体单元和具有等温熔融温度的所有多聚体单元。去除形成多聚体单元的四聚体数目的小于4倍的C.形成多聚体单元的修改的集合。修改的多聚体单元的集合按照熔融温度的顺序排列在列表中。修饰的多聚体单位收集的顺序是随机分为2度。 C.熔化温度升高。

5. 发明授权

US07455965B2 Method of designing addressable array for detection of nucleic acid sequence differences using ligase detection reaction 有权
标题翻译：使用连接酶检测反应设计用于检测核酸序列差异的可寻址阵列的方法
公开(公告)号：US07455965B2
公开(公告)日：2008-11-25
申请号：US10257158
申请日：2001-04-04
申请人： Francis Barany , Monib Zirvi , Norman P. Gerry , Reyna Favis , Richard Kliman
发明人： Francis Barany , Monib Zirvi , Norman P. Gerry , Reyna Favis , Richard Kliman
IPC分类号： C12Q1/68 , C12P19/34
CPC分类号： C12Q1/6837 , C12Q1/6827 , C12Q1/6874 , C12Q1/6886 , C12Q2527/107 , C12Q2521/501 , C12Q2521/319 , C12Q2565/501
摘要： The present invention is directed to a method of designing a plurality of capture oligonucleotide probes for use on a support to which complementary oligonucleotide probes will hybridize with little mismatch, where the plural capture oligonucleotide probes have melting temperatures within a narrow range. The first step of the method involves providing a first set of a plurality of tetramers of four nucleotides linked together, where (1) each tetramer within the first set differs from all other tetramers in the first set by at least two nucleotide bases, (2) no two tetramers within the first set are complementary to one another, (3) no tetramers within the first set are palindromic or dinucleotide repeats, and (4) no tetramer within the first set has one or less or three or more G or C nucleotides. Groups of 2 to 4 of the tetramers from the first set are linked together to form a collection of multimer units. From the collection of multimer units, all multimer units formed from the same tetramer and all multimer units having a melting temperature in ° C. of less than 4 times the number of tetramers forming a multimer unit are removed to form a modified collection of multimer units. The modified collection of multimer units is arranged in a list in order of melting temperature. The order of the modified collection of multimer units is randomized in 2° C. increments of melting temperature.
摘要翻译：本发明涉及一种设计多个捕获寡核苷酸探针的方法，所述多个捕获寡核苷酸探针用于互补寡核苷酸探针与少量错配杂交的载体上，其中多个捕获寡核苷酸探针具有在窄范围内的熔融温度。该方法的第一步涉及提供连接在一起的四个核苷酸的多个四聚体的第一组，其中（1）第一组中的每个四聚体与第一组中的所有其它四聚体相差至少两个核苷酸碱基（2 ）第一组中没有两个四聚体彼此互补，（3）第一组中没有四聚体是回文或二核苷酸重复，和（4）第一组中没有四聚体具有一个或更少或三个或更多个G或C 核苷酸。来自第一组的4至4个四聚体的组连接在一起以形成多聚体单元的集合。从多聚体单元的收集中，除去由相同的四聚体形成的所有多聚体单元和具有小于形成多聚体单元的四聚体数目的4倍的熔点在℃℃的所有多聚体单元以形成多聚体单元的修饰的聚集体。修改的多聚体单元的集合按照熔融温度的顺序排列在列表中。修改的多聚体单元收集的顺序在2℃的熔融温度增量下随机化。

6. 发明授权

US07914981B2 Detection of nucleic acid sequence differences using the ligase detection reaction with addressable arrays 有权
公开(公告)号：US07914981B2
公开(公告)日：2011-03-29
申请号：US10854678
申请日：2004-05-25
申请人： Francis Barany , George Barany , Robert P. Hammer , Maria Kempe , Herman Blok , Monib Zirvi
发明人： Francis Barany , George Barany , Robert P. Hammer , Maria Kempe , Herman Blok , Monib Zirvi
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6827 , B01J19/0046 , B01J2219/00432 , B01J2219/00527 , B01J2219/00529 , B01J2219/00536 , B01J2219/00585 , B01J2219/0059 , B01J2219/00596 , B01J2219/00605 , B01J2219/00608 , B01J2219/0061 , B01J2219/00612 , B01J2219/00621 , B01J2219/00626 , B01J2219/00637 , B01J2219/00659 , B01J2219/00711 , B01J2219/00722 , B01J2219/00729 , B82Y30/00 , C12Q1/6816 , C12Q1/6837 , C12Q1/6876 , C12Q2600/156 , C40B40/06 , C40B60/14 , Y02A50/58 , C12Q2565/501 , C12Q2561/125 , C12Q2537/143 , C12Q2565/514
摘要： The present invention describes a method for identifying one or more of a plurality of sequences differing by one or more single base changes, insertions, deletions, or translocations in a plurality of target nucleotide sequences. The method includes a ligation phase, a capture phase, and a detection phase. The ligation phase utilizes a ligation detection reaction between one oligonucleotide probe, which has a target sequence-specific portion and an addressable array-specific portion, and a second oligonucleotide probe, having a target sequence-specific portion and a detectable label. After the ligation phase, the capture phase is carried out by hybridizing the ligated oligonucleotide probes to a solid support with an array of immobilized capture oligonucleotides at least some of which are complementary to the addressable array-specific portion. Following completion of the capture phase, a detection phase is carried out to detect the labels of ligated oligonucleotide probes hybridized to the solid support.

7. 发明申请

US20050233320A1 DETECTION OF NUCLEIC ACID SEQUENCE DIFFERENCES USING THE LIGASE DETECTION REACTION WITH ADDRESSABLE ARRAYS 失效
标题翻译：使用可寻址阵列检测反应的核酸序列差异的检测
公开(公告)号：US20050233320A1
公开(公告)日：2005-10-20
申请号：US09963920
申请日：2001-09-26
申请人： Francis Barany , George Barany , Robert Hammer , Maria Kempe , Herman Blok , Monib Zirvi
发明人： Francis Barany , George Barany , Robert Hammer , Maria Kempe , Herman Blok , Monib Zirvi
IPC分类号： B01J19/00 , C12Q1/68 , C40B40/06 , C40B60/14 , C12M1/34
CPC分类号： C12Q1/6827 , B01J19/0046 , B01J2219/00432 , B01J2219/00527 , B01J2219/00529 , B01J2219/00536 , B01J2219/00585 , B01J2219/0059 , B01J2219/00596 , B01J2219/00605 , B01J2219/00608 , B01J2219/0061 , B01J2219/00612 , B01J2219/00621 , B01J2219/00626 , B01J2219/00637 , B01J2219/00659 , B01J2219/00711 , B01J2219/00722 , B01J2219/00729 , B82Y30/00 , C12Q1/6816 , C12Q1/6837 , C12Q1/6876 , C12Q2600/156 , C40B40/06 , C40B60/14 , Y02A50/58 , C12Q2565/501 , C12Q2561/125 , C12Q2537/143 , C12Q2565/514
摘要： The present invention describes a method for identifying one or more of a plurality of sequences differing by one or more single base changes, insertions, deletions, or translocations in a plurality of target nucleotide sequences. The method includes a ligation phase, a capture phase, and a detection phase. The ligation phase utilizes a ligation detection reaction between one oligonucleotide probe, which has a target sequence-specific portion and an addressable array-specific portion, and a second oligonucleotide probe, having a target sequence-specific portion and a detectable label. After the ligation phase, the capture phase is carried out by hybridizing the ligated oligonucleotide probes to a solid support with an array of immobilized capture oligonucleotides at least some of which are complementary to the addressable array-specific portion. Following completion of the capture phase, a detection phase is carried out to detect the labels of ligated oligonucleotide probes hybridized to the solid support. The ligation phase can be preceded by an amplification process. The present invention also relates to a kit for practicing this method, a method of forming arrays on solid supports, and the supports themselves.
摘要翻译：本发明描述了用于鉴定多个靶核苷酸序列中一个或多个单碱基变化，插入，缺失或易位不同的多个序列中的一个或多个的方法。该方法包括连接阶段，捕获阶段和检测阶段。连接阶段利用具有目标序列特异性部分的一个寡核苷酸探针与可寻址阵列特异性部分之间的连接检测反应和具有靶序列特异性部分和可检测标记的第二寡核苷酸探针。在连接阶段之后，捕获阶段通过将连接的寡核苷酸探针与具有固定化捕获寡核苷酸阵列的固体支持物杂交进行，其中至少一些与可寻址阵列特异性部分互补。捕获阶段完成后，进行检测阶段以检测与固体支持物杂交的连接的寡核苷酸探针的标记。连接阶段之前可以进行扩增过程。本发明还涉及一种用于实施该方法的试剂盒，在固体支持物上形成阵列的方法，以及载体本身。

8. 发明授权

US07888009B2 Detection of nucleic acid sequence differences using the ligase detection reaction with addressable arrays 有权
公开(公告)号：US07888009B2
公开(公告)日：2011-02-15
申请号：US10854482
申请日：2004-05-25
申请人： Francis Barany , George Barany , Robert P. Hammer , Maria Kempe , Herman Blok , Monib Zirvi
发明人： Francis Barany , George Barany , Robert P. Hammer , Maria Kempe , Herman Blok , Monib Zirvi
IPC分类号： C12Q1/68 , C12P19/34
CPC分类号： C12Q1/6827 , B01J19/0046 , B01J2219/00432 , B01J2219/00527 , B01J2219/00529 , B01J2219/00536 , B01J2219/00585 , B01J2219/0059 , B01J2219/00596 , B01J2219/00605 , B01J2219/00608 , B01J2219/0061 , B01J2219/00612 , B01J2219/00621 , B01J2219/00626 , B01J2219/00637 , B01J2219/00659 , B01J2219/00711 , B01J2219/00722 , B01J2219/00729 , B82Y30/00 , C12Q1/6816 , C12Q1/6837 , C12Q1/6876 , C12Q2600/156 , C40B40/06 , C40B60/14 , Y02A50/58 , C12Q2565/501 , C12Q2561/125 , C12Q2537/143 , C12Q2565/514
摘要： The present invention describes a method for identifying one or more of a plurality of sequences differing by one or more single base changes, insertions, deletions, or translocations in a plurality of target nucleotide sequences. The method includes a ligation phase, a capture phase, and a detection phase. The ligation phase utilizes a ligation detection reaction between one oligonucleotide probe, which has a target sequence-specific portion and an addressable array-specific portion, and a second oligonucleotide probe, having a target sequence-specific portion and a detectable label. After the ligation phase, the capture phase is carried out by hybridizing the ligated oligonucleotide probes to a solid support with an array of immobilized capture oligonucleotides at least some of which are complementary to the addressable array-specific portion. Following completion of the capture phase, a detection phase is carried out to detect the labels of ligated oligonucleotide probes hybridized to the solid support.

9. 发明授权

US07083917B2 Detection of nucleic acid sequence differences using the ligase detection reaction with addressable arrays 失效
公开(公告)号：US07083917B2
公开(公告)日：2006-08-01
申请号：US09963920
申请日：2001-09-26
申请人： Francis Barany , George Barany , Robert P. Hammer , Maria Kempe , Herman Blok , Monib Zirvi
发明人： Francis Barany , George Barany , Robert P. Hammer , Maria Kempe , Herman Blok , Monib Zirvi
IPC分类号： C12Q1/68 , C07H21/02 , G01N33/543
CPC分类号： C12Q1/6827 , B01J19/0046 , B01J2219/00432 , B01J2219/00527 , B01J2219/00529 , B01J2219/00536 , B01J2219/00585 , B01J2219/0059 , B01J2219/00596 , B01J2219/00605 , B01J2219/00608 , B01J2219/0061 , B01J2219/00612 , B01J2219/00621 , B01J2219/00626 , B01J2219/00637 , B01J2219/00659 , B01J2219/00711 , B01J2219/00722 , B01J2219/00729 , B82Y30/00 , C12Q1/6816 , C12Q1/6837 , C12Q1/6876 , C12Q2600/156 , C40B40/06 , C40B60/14 , Y02A50/58 , C12Q2565/501 , C12Q2561/125 , C12Q2537/143 , C12Q2565/514
摘要： The present invention describes a method for identifying one or more of a plurality of sequences differing by one or more single base changes, insertions, deletions, or translocations in a plurality of target nucleotide sequences. The method includes a ligation phase, a capture phase, and a detection phase. The ligation phase utilizes a ligation detection reaction between one oligonucleotide probe, which has a target sequence-specific portion and an addressable array-specific portion, and a second oligonucleotide probe, having a target sequence-specific portion and a detectable label. After the ligation phase, the capture phase is carried out by hybridizing the ligated oligonucleotide probes to a solid support with an array of immobilized capture oligonucleotides at least some of which are complementary to the addressable array-specific portion. Following completion of the capture phase, a detection phase is carried out to detect the labels of ligated oligonucleotide probes hybridized to the solid support. The ligation phase can be preceded by an amplification process. The present invention also relates to a kit for practicing this method, a method of forming arrays on solid supports, and the supports themselves.

10. 发明申请

US20050142543A1 Method of designing addressable array for detection of nucleic acid sequence differences using ligase detection reaction 有权
标题翻译：使用连接酶检测反应设计用于检测核酸序列差异的可寻址阵列的方法
公开(公告)号：US20050142543A1
公开(公告)日：2005-06-30
申请号：US10257158
申请日：2001-04-04
申请人： Francis Barany , Monib Zirvi , Norman Gerry , Reyna Favis , Richard Kliman
发明人： Francis Barany , Monib Zirvi , Norman Gerry , Reyna Favis , Richard Kliman
IPC分类号： G01N33/53 , C12M1/00 , C12N15/09 , C12Q1/25 , G01N33/569 , G01N37/00 , C12Q1/68 , C12P19/34
CPC分类号： C12Q1/6837 , C12Q1/6827 , C12Q1/6874 , C12Q1/6886 , C12Q2527/107 , C12Q2521/501 , C12Q2521/319 , C12Q2565/501
摘要： The present invention is directed to a method of designing a plurality of capture oligonucleotide probes for use on a support to which complementary oligonucleotide probes will hybridize with little mismatch, where the plural capture oligonucleotide probes have melting temperatures within a narrow range. The first step of the method involves providing a first set of a plurality of tetramers of four nucleotides linked together, where (1) each tetramer within the set differs from all other tetramers in the set by at least two nucleotide bases, (2) no two tetramers within a set are complementary to one another, (3) no tetramers within a set are palindromic or dinucleotide repeats, and (4) no tetramer within a set has one or less or three or more G or C nucleotides. Groups of 2 to 4 of the tetramers from the first set are linked together to form a collection of multimer units. From the collection of multimer units, all multimer units formed from the same tetramer and all multimer units having a melting temperature in ° C. of less than 4 times the number of tetramers forming a multimer unit are removed to form a modified collection of multimer units. The modified collection of multimer units is arranged in a list in order of melting temperature. The order of the modified collection of multimer units is randomized in 2° C. increments of melting temperature.
摘要翻译：本发明涉及一种设计多个捕获寡核苷酸探针的方法，所述多个捕获寡核苷酸探针用于互补寡核苷酸探针与少量错配杂交的载体上，其中多个捕获寡核苷酸探针具有在窄范围内的熔融温度。该方法的第一步包括提供连接在一起的四个核苷酸的多个四聚体的第一组，其中（1）组中的每个四聚体与组中的所有其他四聚体不同，至少两个核苷酸碱基，（2）否一组内的两个四聚体彼此互补，（3）一组内的四聚体没有回归或二核苷酸重复，以及（4）组内的四聚体没有一个或多个或三个或更多个G或C核苷酸。来自第一组的4至4个四聚体的组连接在一起以形成多聚体单元的集合。从多聚体单元的收集中，除去由相同的四聚体形成的所有多聚体单元和具有小于形成多聚体单元的四聚体数目的4倍的熔点在℃℃的所有多聚体单元以形成多聚体单元的修饰的聚集体。修改的多聚体单元的集合按照熔融温度的顺序排列在列表中。修改的多聚体单元收集的顺序在2℃的熔融温度增量下随机化。

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