公开(公告)号：WO1997026539A1

公开(公告)日：1997-07-24

申请号：PCT/US1997000274

申请日：1997-01-08

Applicant: BECKMAN INSTRUMENTS, INC.

Inventor： BECKMAN INSTRUMENTS, INC. ,  COASSIN, Peter, J. ,  MC NEAL, Jack, D. ,  HELPHREY, David, B.

IPC: G01N35/00

CPC classification number: G01N35/0099 ,  B01J19/0046 ,  B01J2219/00292 ,  B01J2219/00315 ,  B01J2219/00378 ,  B01J2219/0043 ,  B01J2219/00432 ,  B01J2219/00513 ,  B01J2219/00527 ,  B01J2219/00585 ,  B01J2219/0059 ,  B01J2219/00596 ,  B01J2219/00605 ,  B01J2219/0061 ,  B01J2219/00612 ,  B01J2219/00626 ,  B01J2219/0063 ,  B01J2219/00657 ,  B01J2219/00659 ,  B01J2219/00691 ,  B01J2219/00711 ,  B01J2219/00722 ,  B01L3/0275 ,  B01L3/508 ,  B01L3/5085 ,  B01L2300/0636 ,  B82Y30/00 ,  C40B40/06 ,  C40B60/14 ,  G01N21/6452 ,  G01N35/00029 ,  G01N2035/00118 ,  G01N2035/00158 ,  G01N2035/1055 ,  G01N2035/1062 ,  Y10T436/11 ,  Y10T436/112499 ,  Y10T436/25

Abstract: An analytical biochemistry system featuring a substrate with reactants immobilized thereon at fixed, known locations, a holder supporting the substrate and a manipulator for transporting the holder to a fixed sample and to an inspection station. The reactants are binding agents for a target biomolecule in a sample which forms a bound substance having a detectable characteristic. The holder may be a standard pipettor, optionally carried by a robot arm or hand as the manipulator to contact the sample for detection of the presence of target biomolecules within the sample. In one embodiment, the holder is a pipette tip within which the substrate is housed, or it may be a pipette adapter which bears the substrate and fits within the sample wells of a standard microtiter plate. After appropriate incubation, the substrate and holder may be moved from contact with the sample, and the substrate may be exposed to any necessary development steps before being moved by the manipulator to a location for probing, such as by a beam. Probing of the substrate is performed to identify binding or complexing of target biomolecules of the sample with the reactants immobilized on the substrate, and may be accomplished via fluorescence detection, light scattering, autoradiography, or some other detection method.

Abstract translation: 一种分析生物化学系统，其特征在于在固定的已知位置处固定有反应物的基底，支撑基底的保持器和用于将保持器运送到固定样品的操纵器和检查站。 反应物是样品中靶生物分子的结合剂，其形成具有可检测特征的结合物质。 保持器可以是标准移液器，可选地由机器人手臂或手携带作为操纵器以接触样品以检测样品内目标生物分子的存在。 在一个实施例中，保持器是其中容纳基底的移液管尖端，或者其可以是承载基底并且配合在标准微量滴定板的样品孔内的移液管适配器。 在适当的温育之后，衬底和保持器可以与样品接触移动，并且衬底可以在被操纵器移动到用于探测的位置（例如通过光束）之前暴露于任何必要的显影步骤。 进行底物的检测以鉴定样品的目标生物分子与固定在底物上的反应物的结合或络合，并且可以通过荧光检测，光散射，放射自显影或其它检测方法来实现。

公开(公告)号：WO1997002095A1

公开(公告)日：1997-01-23

申请号：PCT/US1996010635

申请日：1996-06-24

Applicant: BECKMAN INSTRUMENTS, INC.

Inventor： BECKMAN INSTRUMENTS, INC. ,  FURST, Allen

IPC: B04B13/00

CPC classification number: B04B13/00

Abstract: A system and method of operating a centrifuge is disclosed. The operational parameters of the centrifuge are determined on the basis of the experimental protocol selected by the user. Parameters relevant to the particular experimental protocol are supplied by the user, while the run-time operating parameters of the centrifuge are automatically computed by the system. The centrifugal protocols contemplated in the present invention include pelleting, rate-zonal and isopycnic experiments. Depending upon the specific experimental protocol, the user must provide certain minimum information such as sedimentation rate and gradient concentrations used in the experiment. The user also must identify the rotor to be used, unless the centrifuge device is capable of auto-identification of rotors. For unusual situations, the user may set the specific operating parameters of a centrifugal run in order to provide for customized experiments.

Abstract translation: 公开了一种操作离心机的系统和方法。 基于用户选择的实验方案确定离心机的操作参数。 与特定实验协议相关的参数由用户提供，而离心机的运行时间操作参数由系统自动计算。 本发明考虑的离心方案包括造粒，速率区和等压试验。 根据具体的实验方案，用户必须提供一些最低限度的信息，如实验中使用的沉降速率和梯度浓度。 用户还必须识别要使用的转子，除非离心机能够自动识别转子。 对于不寻常的情况，用户可以设置离心运行的具体操作参数，以便提供定制的实验。

公开(公告)号：WO1996030754A1

公开(公告)日：1996-10-03

申请号：PCT/US1996004321

申请日：1996-03-29

Applicant: BECKMAN INSTRUMENTS, INC.

Inventor： BECKMAN INSTRUMENTS, INC. ,  RAMPAL, Sushma ,  RAMPAL, Jang, B. ,  OSBORNE, James, C.

IPC: G01N27/447

CPC classification number: G01N27/44743

Abstract: A sample having both positively and negatively charged components may be separated during the same run by injecting a plug of sample at both ends of the capillary and applying an electric field in the capillary, where there is insufficient electroosmotic flow in the capillary to reverse sample migration direction, such as in the case of a gel-filled column.

Abstract translation: 具有正电荷和负电荷的组分的样品可以在相同的运行期间通过在毛细管的两端注入样品塞并在毛细管中施加电场，其中在毛细管中电渗流不足以反向样品迁移 方向，例如在凝胶填充柱的情况下。

公开(公告)号：WO1995030774A1

公开(公告)日：1995-11-16

申请号：PCT/US1995004899

申请日：1995-04-24

Applicant: BECKMAN INSTRUMENTS, INC. ,  CASKEY, Charles, Thomas

Inventor： BECKMAN INSTRUMENTS, INC. ,  MATSON, Robert, S. ,  COASSIN, Peter, J. ,  RAMPAL, Jang, B.

IPC: C12Q01/68

CPC classification number: C12Q1/6837 ,  C12Q1/6827 ,  C12Q1/6874

Abstract: A solid support based hybridization assay is provided which allows for the systematic and reproducible analysis of repeat and tandem repeat oligonucleotide sequences of DNA and RNA by hybridization to a reverse dot blot array comprising strings of such repeats complementary to those found in particular nucleic acid targets (e.g., analyte PCR product). An addressable library (i.e., an indexed set) of complementary repeats is synthesized on a suitable support. Preferably, the support comprises a low fluorescent background support, thereby facilitating the use of non-radioisotopic modes of detection (such as fluorescence of chemiluminescence); particularly suitable in this regard is an aminated polypropylene support or similar material. Preferred arrays permit screening of DNA and RNA samples for complete sets of particular types of nucleotide repeat sequences (e.g., all nucleotide doublet or triplet repeats).

Abstract translation: 提供了基于固体支持的杂交测定法，其通过与包含与特定核酸靶标中发现的重复序列互补的反向斑点印迹阵列杂交，从而对DNA和RNA的重复和串联重复寡核苷酸序列进行系统和可重复的分析（ 例如分析物PCR产物）。 互补重复序列的可寻址库（即，索引集）在合适的支持上合成。 优选地，载体包含低荧光背景支持，从而有利于使用非放射性同位素检测模式（例如化学发光的荧光）; 在这方面特别合适的是胺化聚丙烯支撑体或类似材料。 优选的阵列允许筛选DNA和RNA样品用于完整的特定类型的核苷酸重复序列（例如，所有核苷酸双重或三重重复）。

公开(公告)号：WO1995030769A1

公开(公告)日：1995-11-16

申请号：PCT/US1995005702

申请日：1995-05-05

Applicant: BECKMAN INSTRUMENTS, INC.

Inventor： BECKMAN INSTRUMENTS, INC. ,  LU, Carrie, J. ,  YEIN, Frederick, S.

IPC: C12Q01/50

CPC classification number: C12Q1/50

Abstract: An aqueous, liquid-stable thiol activator solution is disclosed. The solution can include a thiol activator, such as N-acetyl-L-cysteine and a stabilizing agent, such as mannitol. The thiol is stabilized in the aqueous solution for at least about one year under storage conditions and for at least about 28 days under open-bottle conditions. The solution can be used as a reactivator of creatine kinase catalytic activity.

Abstract translation: 公开了一种水溶性，稳定的硫醇活化剂溶液。 溶液可以包括硫醇活化剂，例如N-乙酰基-L-半胱氨酸和稳定剂，如甘露糖醇。 硫醇在储存条件下在水溶液中稳定至少约一年，在开瓶条件下稳定至少约28天。 该溶液可用作肌酸激酶催化活性的活化剂。

公开(公告)号：WO1995024413A1

公开(公告)日：1995-09-14

申请号：PCT/US1995002831

申请日：1995-03-07

Applicant: BECKMAN INSTRUMENTS, INC.

Inventor： BECKMAN INSTRUMENTS, INC. ,  REDDY, Meda, Parameswara ,  HANNA, Naeem, B. ,  FAROOQUI, Firdous

IPC: C07H19/06

CPC classification number: C07H19/06 ,  C07H19/04 ,  C07H19/16 ,  C07H21/00 ,  Y02P20/55

Abstract: Deoxyribonucleotide and ribonucleotide derivatives of general formula (I), wherein R represents -CR'R"-Ar, in which Ar is selected from the group consisting of unsubstituted or substituted aryl (as hereinafter defined) and R' and R" are independently selected from the group consisting of hydrogen and lower alkyl; one of -R and R is a hydroxyl-protecting group and the other is a group suitable for synthesis of polynucleotides or for attachment of the nucleotide to a solid support; R is selected from the group consisting of hydrogen, -OH and protected hydroxyl; and B represents a divalent radical corresponding to a purine or pyrimidine base. When synthesis is carried out using these derivatives, the deprotection procedure is reduced to an essentially instantaneous process. The derivatives have acceptable shelf life and are very stable to conventional DNA synthesis conditions. Particularly preferred are those compounds wherein Ar is mono- and dihalo-substituted phenyl.

Abstract translation: 通式（I）的脱氧核糖核苷酸和核糖核苷酸衍生物，其中R 1表示-CR'R“-Ar，其中Ar选自未取代或取代的芳基（如下文定义），R'和R” 独立地选自氢和低级烷基; -R 2和R 3之一是羟基保护基，另一个是适于合成多核苷酸或将核苷酸连接到固体支持物上的基团; R 4选自氢，-OH和被保护的羟基; B表示对应于嘌呤或嘧啶碱基的二价基团。 当使用这些衍生物进行合成时，脱保护程序减少到基本上即时的过程。 衍生物具有可接受的保质期，对于常规的DNA合成条件非常稳定。 特别优选的是其中Ar为单取代和二卤代取代的苯基的那些化合物。

公开(公告)号：WO1995020157A1

公开(公告)日：1995-07-27

申请号：PCT/US1995001019

申请日：1995-01-24

Applicant: BECKMAN INSTRUMENTS, INC.

Inventor： BECKMAN INSTRUMENTS, INC. ,  SHIEH, Chia-Hui

IPC: G01N27/447

CPC classification number: G01N27/44752 ,  G01N27/44704

Abstract: Coated capillary electrophoresis columns and methods for their use in electrophoretic separations are disclosed. The coated capillary columns include a length of tubing having an interior surface having an interconnected polymeric coating. The interconnected polymeric coating includes a hydrophobic polymeric functionality covalently bound to the interior surface and a hydrophilic polymer interconnected with the hydrophobic polymeric functionality. Exemplary columns are prepared by causing an Si-OH reactive compound, having a hydrophilic polymeric functionality, to react with Si-OH functionalities on the interior surface of capillary columns. Then causing a hydrophilic monomer to polymerize in contact with the hydrophobic polymeric functionality forms a coating of interconnecting hydrophilic and hydrophobic polymers.

Abstract translation: 公开了涂布毛细管电泳柱及其用于电泳分离的方法。 涂覆的毛细管柱包括具有内表面的一段长度的管，其具有互连的聚合物涂层。 相互连接的聚合物涂层包括与内表面共价结合的疏水性聚合物官能团和与疏水性聚合物官能团互连的亲水聚合物。 通过使具有亲水性聚合物官能团的Si-OH反应性化合物与毛细管柱内表面上的Si-OH官能团反应来制备示例性柱。 然后使亲水单体与疏水性聚合物官能团接触聚合形成相互连接的亲水和疏水聚合物的涂层。

公开(公告)号：WO1994024312A2

公开(公告)日：1994-10-27

申请号：PCT/US1994004275

申请日：1994-04-19

Applicant: BECKMAN INSTRUMENTS, INC.

Inventor： BECKMAN INSTRUMENTS, INC. ,  COASSIN, Peter, J. ,  KONRAD, Kenneth, D. ,  RAMPAL, Jang, B. ,  COOK, Ronald, M.

IPC: C12Q01/68

CPC classification number: C07H21/00 ,  C12N15/1034 ,  C12Q1/6853 ,  C12Q1/6862

Abstract: Disclosed herein, inter alia, are Inverse Linkage Oligonucleotides ("ILO") useful in enzymatic process. Particularly preferred ILOs are amenable to enzymatic elongation from either, or most preferably, both termini. In a particularly preferred embodiment, each terminus of an ILO has an enzymatically functional 3' group. Accordingly, under appropriate conditions and in the presence of, e.g., dNTPs, enzyme, sample DNA, and ILO comprising a first region complementary to a first region of the sample DNA and a second region complementary to a second, different region of the sample DNA, exponential amplification of the sample DNA can be effectuated.

Abstract translation: 本文公开的是在酶促过程中有用的反向连接寡核苷酸（“ILO”）。 特别优选的ILO适于从两末端或最优选两个末端的酶促延伸。 在特别优选的实施方案中，国际劳工组织的每个末端具有酶功能3'基团。 因此，在适当条件下和在例如dNTPs，酶，样品DNA和ILO的存在下，包含与样品DNA的第一区域互补的第一区域和与样品DNA的第二个不同区域互补的第二区域 ，可以实现样品DNA的指数扩增。

公开(公告)号：WO1994001446A2

公开(公告)日：1994-01-20

申请号：PCT/US1993006214

申请日：1993-06-29

Applicant: BECKMAN INSTRUMENTS, INC.

Inventor： BECKMAN INSTRUMENTS, INC. ,  REDDY, Parameswara, M. ,  MICHAEL, Maged, A.

IPC: C07H21/00

CPC classification number: C07H21/00

Abstract: A solid-phase nucleotide synthesis intermediate useful for chemical synthesis of oligodeoxyribonucleotides and oligoribonucleotides comprises: (1) a particulate support comprising a porous polymer whose backbone comprises optionally substituted acrylate or methacrylate moieties; (2) a nucleoside; and (3) a linker having a first and a second end, the first end being covalently attached to the particulate support and the second end being covalently attached to the nucleoside, the linker spacing the nucleoside at least 3 atoms away from the polymer. The linker can comprise at least one optionally substituted aliphatic diamine. Alternatively, the linker can comprise a polyethylene glycol moiety. Preferably, the porous polymer is a methacrylate-vinylidene polymer. The solid-phase support thus produced can be used for oligodeoxyribonucleotide synthesis by either the phosphite-triester or the phosphotriester processes.

Abstract translation: 用于寡脱氧核糖核苷酸和寡核糖核苷酸的化学合成的固相核苷酸合成中间体包括：（1）包含多孔聚合物的颗粒载体，其主链包含任选取代的丙烯酸酯或甲基丙烯酸酯部分; （2）核苷; 和（3）具有第一和第二端的接头，第一端共价连接到颗粒载体上，第二端共价连接到核苷上，连接体将核苷与聚合物隔开至少3个原子。 连接体可以包含至少一个任选取代的脂族二胺。 或者，连接体可以包含聚乙二醇部分。 优选地，多孔聚合物是甲基丙烯酸酯 - 亚乙烯基聚合物。 由此产生的固相载体可用于亚磷酸三酯或磷酸三酯方法的寡脱氧核糖核苷酸合成。

公开(公告)号：WO1994001215A1

公开(公告)日：1994-01-20

申请号：PCT/US1993006322

申请日：1993-07-02

Applicant: BECKMAN INSTRUMENTS, INC.

Inventor： BECKMAN INSTRUMENTS, INC. ,  COASSIN, Peter, J.

IPC: B01J19/00

CPC classification number: G01N35/1097 ,  B01J19/0046 ,  B01J2219/00353 ,  B01J2219/00391 ,  B01J2219/0059 ,  B01J2219/00722 ,  C07H21/00 ,  C07K1/045 ,  C40B40/06 ,  C40B60/14 ,  G01N1/31 ,  Y10T137/86566

Abstract: The present invention is directed to the implementation of a multi-port rotary valve in an automated chemistry processing instrument which reduces chemical reagent cross contamination and simplifies system design and control. One or more multi-port rotary valves are used in conjuction with isolation valves which are each dedicated for an associated reagent in the system. According to one embodiment of the present invention, the instrument utilizes a multi-port valve which defines several fluid branches each associated with a reagent. The valve has a common inlet and common outlet which are selectively brought into fluid communication with the branches in a controlled sequence. At each branch, there is a two-way three-port isolation valve which controls introduction of an associated reagent into the branch. When a branch is selected by the rotary valve, the reagent introduced into the branch is delivered out of the common outlet by the flow from the common inlet. According to another embodiment of the present invention, the reagents are introduced through isolation valves between two multi-port rotary valves.

Abstract translation: 本发明涉及一种减少化学试剂交叉污染并简化系统设计和控制的自动化学处​​理仪器中的多端口旋转阀的实现。 一个或多个多端口旋转阀与隔离阀结合使用，每个隔离阀专用于系统中的相关试剂。 根据本发明的一个实施例，仪器使用多端口阀，其限定了与试剂相关联的几个流体分支。 阀具有共同的入口和公共出口，其以受控的顺序选择性地与分支流体连通。 在每个分支处，存在一个双向三端口隔离阀，其控制将相关试剂引入分支中。 当通过旋转阀选择分支时，引入分支的试剂通过来自公共入口的流量从公共出口排出。 根据本发明的另一个实施方案，试剂通过两个多端口旋转阀之间的隔离阀引入。