公开(公告)号：US07914981B2

公开(公告)日：2011-03-29

申请号：US10854678

申请日：2004-05-25

Applicant: Francis Barany ,  George Barany ,  Robert P. Hammer ,  Maria Kempe ,  Herman Blok ,  Monib Zirvi

Inventor： Francis Barany ,  George Barany ,  Robert P. Hammer ,  Maria Kempe ,  Herman Blok ,  Monib Zirvi

IPC: C12Q1/68

CPC classification number: 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

Abstract: 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.

公开(公告)号：US20050233320A1

公开(公告)日：2005-10-20

申请号：US09963920

申请日：2001-09-26

Applicant: Francis Barany ,  George Barany ,  Robert Hammer ,  Maria Kempe ,  Herman Blok ,  Monib Zirvi

Inventor： Francis Barany ,  George Barany ,  Robert Hammer ,  Maria Kempe ,  Herman Blok ,  Monib Zirvi

IPC: B01J19/00 ,  C12Q1/68 ,  C40B40/06 ,  C40B60/14 ,  C12M1/34

CPC classification number: 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

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US08288521B2

公开(公告)日：2012-10-16

申请号：US13072442

申请日：2011-03-25

Applicant: Francis Barany ,  George Barany ,  Robert P. Hammer ,  Maria Kempe ,  Herman Blok ,  Monib Zirvi

Inventor： Francis Barany ,  George Barany ,  Robert P. Hammer ,  Maria Kempe ,  Herman Blok ,  Monib Zirvi

IPC: C07H21/04 ,  C12N15/11

CPC classification number: 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

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US20120071364A1

公开(公告)日：2012-03-22

申请号：US13229198

申请日：2011-09-09

Applicant: Francis BARANY ,  George BARANY ,  Robert P. HAMMER ,  Maria KEMPE ,  Herman BLOK ,  Monib ZIRVI

Inventor： Francis BARANY ,  George BARANY ,  Robert P. HAMMER ,  Maria KEMPE ,  Herman BLOK ,  Monib ZIRVI

IPC: C40B60/12

CPC classification number: 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

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US20110257034A1

公开(公告)日：2011-10-20

申请号：US13123689

申请日：2009-10-13

Applicant: Francis Barany ,  Owen Parker ,  Manny D. Bacolod ,  Sarah F. Giardina ,  Yu-wei Cheng ,  Daniel A. Notterman ,  Gunter S. Schemmann ,  Philip B. Paty ,  Monib Zirvi

Inventor： 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: C40B30/04 ,  C40B40/06 ,  G01N33/53 ,  C40B40/08 ,  C12Q1/68 ,  G01N33/566

CPC classification number: G01N33/57419

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US07893233B2

公开(公告)日：2011-02-22

申请号：US12725230

申请日：2010-03-16

Applicant: Francis Barany ,  George Barany ,  Robert P. Hammer ,  Maria Kempe ,  Herman Blok ,  Monib Zirvi

Inventor： Francis Barany ,  George Barany ,  Robert P. Hammer ,  Maria Kempe ,  Herman Blok ,  Monib Zirvi

IPC: C07H21/04 ,  C12N15/11

CPC classification number: 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

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US07888009B2

公开(公告)日：2011-02-15

申请号：US10854482

申请日：2004-05-25

Applicant: Francis Barany ,  George Barany ,  Robert P. Hammer ,  Maria Kempe ,  Herman Blok ,  Monib Zirvi

Inventor： Francis Barany ,  George Barany ,  Robert P. Hammer ,  Maria Kempe ,  Herman Blok ,  Monib Zirvi

IPC: C12Q1/68 ,  C12P19/34

CPC classification number: 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

Abstract: 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.

公开(公告)号：US20100173802A1

公开(公告)日：2010-07-08

申请号：US12725230

申请日：2010-03-16

Applicant: Francis BARANY ,  George BARANY ,  Robert P. HAMMER ,  Maria KEMPE ,  Herman BLOK ,  Monib ZIRVI

Inventor： Francis BARANY ,  George BARANY ,  Robert P. HAMMER ,  Maria KEMPE ,  Herman BLOK ,  Monib ZIRVI

IPC: C40B40/06 ,  C40B60/12

CPC classification number: 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

Abstract: 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.

公开(公告)号：US07083917B2

公开(公告)日：2006-08-01

申请号：US09963920

申请日：2001-09-26

Applicant: Francis Barany ,  George Barany ,  Robert P. Hammer ,  Maria Kempe ,  Herman Blok ,  Monib Zirvi

Inventor： Francis Barany ,  George Barany ,  Robert P. Hammer ,  Maria Kempe ,  Herman Blok ,  Monib Zirvi

IPC: C12Q1/68 ,  C07H21/02 ,  G01N33/543

CPC classification number: 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

Abstract: 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.

公开(公告)号：US20050142543A1

公开(公告)日：2005-06-30

申请号：US10257158

申请日：2001-04-04

Applicant: Francis Barany ,  Monib Zirvi ,  Norman Gerry ,  Reyna Favis ,  Richard Kliman

Inventor： Francis Barany ,  Monib Zirvi ,  Norman Gerry ,  Reyna Favis ,  Richard Kliman

IPC: G01N33/53 ,  C12M1/00 ,  C12N15/09 ,  C12Q1/25 ,  G01N33/569 ,  G01N37/00 ,  C12Q1/68 ,  C12P19/34

CPC classification number: C12Q1/6837 ,  C12Q1/6827 ,  C12Q1/6874 ,  C12Q1/6886 ,  C12Q2527/107 ,  C12Q2521/501 ,  C12Q2521/319 ,  C12Q2565/501

Abstract: 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.

Abstract translation: 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。