公开(公告)号：WO1996029571A1

公开(公告)日：1996-09-26

申请号：PCT/US1996003841

申请日：1996-03-22

Applicant: BECKMAN INSTRUMENTS, INC.

Inventor： BECKMAN INSTRUMENTS, INC. ,  KAYE, Wilbur ,  PENTONEY, Stephen, L., Jr.

IPC: G01B11/27

CPC classification number: G01N27/44782 ,  G01N21/65 ,  G01N27/44704 ,  G01N27/44721 ,  G01N30/74

Abstract: A system and method are disclosed for optically aligning a capillary tube and an excitation laser beam for fluorescence detection applications by utilizing the Raman scatter signals of the capillary tube's contents. For example, Raman scatter by an electrophoretic separation matrix may be used for alignment in a capillary electrophoresis system. Fluorescent material may be present and may also be used for alignment purposes, but is not necessary. The invention employs a parabolic reflector, having apertures through which the capillary tube and the laser beam are guided so that they intersect, preferably at right angles and at the focal point of the reflector. The Raman scatter signals of the material within the capillary tube are collected via a series of filters and this information is used to reposition, if necessary, a focusing lens that directs the excitation beam into the reflector and the capillary tube, so that the Raman scatter signals are maximized. Maximal Raman scatter signals indicate proper alignment of the capillary tube and the excitation beam. Other signals, such as fluorescence emission from the sample, may then be gathered. Adjustment of the focusing lens may be automated so that alignment of the capillary tube and the beam is maintained throughout analysis of the tube's contents. Sequential alignment of an array of capillary tubes with an excitation beam is also disclosed.

Abstract translation: 公开了一种用于通过利用毛细管内容物的拉曼散射信号将毛细管和激发激光束用于荧光检测应用的系统和方法。 例如，通过电泳分离基质的拉曼散射可以用于毛细管电泳系统中的比对。 荧光材料可以存在并且也可以用于对准目的，但不是必需的。 本发明采用抛物面反射器，其具有孔，毛细管和激光束通过该孔具有孔，使得它们优选地以直角相交，并在反射器的焦点处相交。 毛细管内的材料的拉曼散射信号通过一系列滤光片收集，并且该信息用于重新定位（如果需要的话）将激发光束引导到反射器和毛细管中的聚焦透镜，使得拉曼散射 信号最大化。 最大拉曼散射信号表示毛细管和激发光束的正确对准。 然后可以收集其它信号，例如来自样品的荧光发射。 聚焦透镜的调整可以是自动化的，以便在分析管的内容物期间保持毛细管和束的对准。 还公开了具有激发束的毛细管阵列的顺序对准。

公开(公告)号：WO1996006948A1

公开(公告)日：1996-03-07

申请号：PCT/US1995010226

申请日：1995-08-10

Applicant: BECKMAN INSTRUMENTS, INC.

Inventor： BECKMAN INSTRUMENTS, INC. ,  REDDY, M., Parameswara ,  STERNBERG, James, C.

IPC: C12Q01/68

CPC classification number: C12Q1/6825 ,  C12Q1/6804 ,  C12Q1/6813 ,  C12Q1/6816 ,  C12Q1/6834

Abstract: Double stranded nucleic acid duplexes serve as universal harvestable and cleavable link systems in a variety of different types of immnuoassays (e.g., sandwich, competitive, etc.). Depending upon the type of assay, at least one specific component involved in the assay system is attached to a first member of a pair of sequences forming a double stranded nucleic acid (i.e., two oligonucleotides comprising substantially complementary sequences). The assay is carried out in the presence of a support to which is attached an oligonucleotide which is the other member of the pair of sequences forming a double-stranded nucleic acid duplex under hybridization conditions. Upon the hybridization of the two complementary oligonucleotides to form a duplex, the component of the assay system to which the first member of the pair of oligonucleotides is attached may thereby be effectively removed from the solution phase and harvested onto the support. Oligonucleotides bound to a support are reusable in multiple successive assays. Moreover, any given support-bound oligonucleotide can be used in accordance with the present invention for the analysis of a variety of different analytes. In many cases, the assay system includes a label to facilitate quantifying the amount of analyte; in others, the amount of analyte may be determined without the use of any extraneous label.

Abstract translation: 双链核酸双链体在各种不同类型的免疫测定（例如，三明治，竞争性等）中用作通用可收获和可切割的连锁系统。 根据测定的类型，参与测定系统的至少一个特定组分连接到形成双链核酸的一对序列的第一个成员（即，包含基本上互补序列的两个寡核苷酸）。 所述测定在载体的存在下进行，其中连接寡核苷酸，其是在杂交条件下形成双链核酸双链体的一对序列的另一个成员。 当两个互补寡核苷酸杂交以形成双链体时，可以从溶液相中有效地从溶液相中除去与该对寡核苷酸的第一个成员所连接的测定系统的组分并收获到载体上。 结合支持物的寡核苷酸可在多次连续测定中重复使用。 此外，根据本发明，可以使用任何给定的支持结合寡核苷酸来分析各种不同的分析物。 在许多情况下，测定系统包括有助于量化分析物量的标签; 在其他方面，可以在不使用任何外来标签的情况下确定分析物的量。

公开(公告)号：WO1995014029A1

公开(公告)日：1995-05-26

申请号：PCT/US1994013331

申请日：1994-11-16

Applicant: BECKMAN INSTRUMENTS, INC.

Inventor： BECKMAN INSTRUMENTS, INC. ,  REDDY, M., P. ,  FAROOQUI, Firdous

IPC: C07H19/06

CPC classification number: C07H19/06 ,  C07H19/10 ,  C07H19/16 ,  C07H19/20 ,  C07H21/00 ,  Y02P20/55

Abstract: Disclosed herein are protecting groups for exocyclic amino groups of the base cytosine for use in the synthesis of oligonucleotides and oligonucleoside phosphorothioates, the protecting groups being represented by the formula: -CO-(CH2)0-9-CH3. In a particularly preferred embodiment, the base cytosine is protected with acetyl (-CO-CH3), and the oligonucleotide or oligonucleoside phosphorothioate incorporating the protected cytosine is subjected to a cleavage/deprotection reagent comprising methylamine and ammonia.

Abstract translation: 本文公开了用于合成寡核苷酸和寡核苷酸硫代磷酸酯的碱基胞嘧啶的环外氨基的保护基团，保护基由式-CO-（CH 2）0-9 -CH 3表示。 在一个特别优选的实施方案中，用乙酰基（-CO-CH 3）保护碱基胞嘧啶，并将含有保护的胞嘧啶的寡核苷酸或寡核苷硫代磷酸酯进行包含甲胺和氨的切割/去保护试剂。

公开(公告)号：WO1994029713A1

公开(公告)日：1994-12-22

申请号：PCT/US1994004514

申请日：1994-04-25

Applicant: BECKMAN INSTRUMENTS, INC.

Inventor： BECKMAN INSTRUMENTS, INC. ,  GOODALE, David, L. ,  REEVES, George, I.

IPC: G01N27/447

CPC classification number: G01N27/44782 ,  G01N27/44704

Abstract: A capillary and capillary retaining system including a capillary assembly (20) having first and second end holders (32, 36). The first and second end holders (32, 36) are adapted to be received by first and second retainers (22, 24). The first end holder (32) may include protruding portions (48, 50) and the first end retainer includes clips to receive the protruding portions. The second end holder may include opposite recesses and the second retainer is adapted to receive optical cables that are received within the recesses to retain the second end holder. Locks retained by the second end retainer cooperate with grooves in the optical cables to retain the optical cables.

Abstract translation: 毛细管和毛细管保持系统，其包括具有第一和第二端部保持器（32,36）的毛细管组件（20）。 第一和第二端部保持器（32,36）适于被第一和第二保持器（22,24）接收。 第一端部支架（32）可以包括突出部分（48,50），并且第一端部保持器包括用于容纳突出部分的夹子。 第二端保持器可以包括相对的凹部，并且第二保持器适于容纳容纳在凹部内以保持第二端保持器的光缆。 由第二端保持器保持的锁与光缆中的凹槽配合以保持光缆。

公开(公告)号：WO1994022585A1

公开(公告)日：1994-10-13

申请号：PCT/US1994003596

申请日：1994-04-01

Applicant: BECKMAN INSTRUMENTS, INC.

Inventor： BECKMAN INSTRUMENTS, INC. ,  MOORE, Patrick, Q. ,  SCHIESSLER, David, L.

IPC: B04B05/04

CPC classification number: B65D39/0088 ,  B01L3/5021 ,  B04B5/0414 ,  B65D2539/006

Abstract: The present invention directed to a plug (16) for sealing a centrifuge tube (10). The plug (16) of the present invention is shaped and sized to provide an interference fit between the plug (16) and the tube stem (12) of the centrifuge tube. In the described embodiment, the plug is configured with a tapered body narrowing to a flared end (22). To facilitate the insertion and removal of the plug with moderate force, without compromising the restraining capability of the interference fit, the area of interference contact between the flared end and the filler stem is strategically reduced. An o-ring is provided in an annular groove (20) around the tapered body. The flared end (22) creates an interference fit with a tapered filler stem (12) whereby the plug (16) is secured in the filler stem (12) with a snapping action when the flared end (22) of the plug (16) extends into the tube beyond the tapered filler stem (12). In this snap-in position, the plug (16) is secured in the filler stem (12), providing an initial seal; such seal increases upon centrifugation by a self-sealing mechanism, either attributed to the internal hydrostatic pressure in the tube and/or the force of a support spacer on the plug. After centrifugation, the snap coupling between the filler stem and the plug securely retains the plug against any residual internal pressure built up within the tube created by deformation of the centrifuge tube either from centrifugation or through handling of the tube by the user.

Abstract translation: 本发明涉及用于密封离心管（10）的塞子（16）。 本发明的插头（16）的形状和尺寸被设计成提供离心管的插塞（16）和管杆（12）之间的过盈配合。 在所描述的实施例中，插头构造成具有朝向扩张端（22）变窄的锥形体。 为了有利于以适度的力插入和移除插头，在不影响过盈配合的约束能力的情况下，战略上减少了扩口端与加注杆之间的干涉接触面积。 O形圈设置在围绕锥形主体的环形槽（20）中。 扩口端（22）产生与锥形填充杆（12）的过盈配合，由此当插头（16）的扩口端（22）具有卡扣动作时，插头（16）固定在填充杆（12） 延伸到超过锥形填充杆（12）的管中。 在该卡入位置中，插头（16）固定在加注杆（12）中，提供初始密封; 这种密封通过自密封机构进行离心时增加，归因于管中的内部静水压力和/或插塞上的支撑间隔件的力。 离心后，填充杆和插塞之间的卡扣联结可以牢固地保持插塞抵抗由离心管变形而产生的管内的任何残余内部压力，或者离心或通过使用者处理管。

公开(公告)号：WO1994017401A1

公开(公告)日：1994-08-04

申请号：PCT/US1994000762

申请日：1994-01-19

Applicant: BECKMAN INSTRUMENTS, INC.

Inventor： BECKMAN INSTRUMENTS, INC. ,  HERRICK, Steven, S. ,  STERNBERG, James, C.

IPC: G01N27/447

CPC classification number: G01N27/44795 ,  G01N27/44752

Abstract: The present invention provides processes for isoelectric focusing ("IEF") and associated detection, which incorporates a dynamic means of electroosmotic flow ("EOF") control during IEF and/or after IEF to effect solute mobilization. In accordance with the present invention, the EOF control during IEF and/or solute mobilization after IEF are accomplished by applying an external electric field, relative to an internal electric field, to modify the electroosmotic flow in the capillary. This can be done by disposing a conductive member at one or more locations outside and along the buffer column in the capillary. The conductive member may be statically charged or caused to conduct a current to create the external required electric field. The applied external electric field may be adjusted, relative to the external electric field, during IEF necessary to reduce or completely suppress EOF to prevent flow of the buffer. Upon the completion of IEF (irrespective of the method of reducing or removing EOF during IEF), the external electric field is adjusted, relative to the internal electric field, such that the buffer carrying the focused solutes are moved electroosmotically through the capillary past a detection point. The present invention is applicable to internally coated capillary which suppresses EOF even in the absence of the external electric field.

Abstract translation: 本发明提供等电聚焦（“IEF”）和相关检测的方法，其包括在IEF期间和/或在IEF之后的电渗流（“EOF”）控制的动态方式以进行溶质动员。 根据本发明，在IEF之间的IEF和/或溶质动员期间的EOF控制是通过相对于内部电场施加外部电场来实现的，以改变毛细管中的电渗流。 这可以通过在毛细管中的缓冲柱的外部和沿着一个或多个位置设置导电构件来实现。 导电构件可以被静电充电或导致电流以产生外部所需的电场。 在IEF期间，可以相对于外部电场调整所施加的外部电场，以减少或完全抑制EOF以防止缓冲器的流动。 在完成IEF（不管在IEF期间减少或去除EOF的方法）时，相对于内部电场调节外部电场，使得携带聚焦溶质的缓冲液通过毛细管电动移动通过检测 点。 本发明适用于即使没有外部电场也能抑制EOF的内部涂布毛细管。

公开(公告)号：WO1994015637A2

公开(公告)日：1994-07-21

申请号：PCT/US1993012187

申请日：1993-12-13

Applicant: BECKMAN INSTRUMENTS, INC.

Inventor： BECKMAN INSTRUMENTS, INC. ,  CERCEK, Boris ,  CERCEK, Lea

IPC: A61K39/395

CPC classification number: G01N33/5091 ,  A61K35/16 ,  A61K38/00 ,  A61K47/6845 ,  C07K7/08 ,  C07K14/4745 ,  C07K14/585 ,  C07K16/18 ,  G01N33/5011

Abstract: A method for blocking suppression of at least one of the natural killer (NK) and lymphocyte activated killer (LAK) immune defense mechanisms in lymphocytes of cancer patients comprises administering to a cancer patient an agent capable of blocking the immune defense suppressive activities of a peptide capable of inducing a detectable decrease in the structuredness of the cytoplasmic matrix in lymphocytes isolated from a patient with cancer (an SCM-factor peptide) in a quantity sufficient to block suppression of at least one of the natural killer (NK) and lymphocyte activated killer (LAK) immune defense mechanisms. The agent can comprise an antibody, an antisense peptide, or a factor present in blood plasma. The invention also includes pharmaceutical compositions for blocking suppression of immune defense and kits for stimulating immune response of cancer patients, as well as immunization methods to induce antibody to SCM-factor peptides.

Abstract translation: 抑制癌症患者淋巴细胞中的至少一种天然杀伤（NK）和淋巴细胞活化的杀伤（LAK）免疫防御机制的抑制方法包括向癌症患者施用能够阻断肽的免疫防御抑制活性的试剂 能够诱导分离自患有癌症的淋巴细胞（SCM-因子肽）中的足以阻断至少一种天然杀伤（NK）和淋巴细胞活化的杀伤剂的抑制的量的淋巴细胞的细胞质基质的结构化的可检测的降低 （LAK）免疫防御机制。 该试剂可以包含抗体，反义肽或存在于血浆中的因子。 本发明还包括用于阻断免疫防御的药物组合物和用于刺激癌症患者的免疫应答的试剂盒，以及用于诱导针对SCM-因子肽的抗体的免疫方法。

公开(公告)号：WO1994001214A1

公开(公告)日：1994-01-20

申请号：PCT/US1993006217

申请日：1993-06-29

Applicant: BECKMAN INSTRUMENTS, INC.

Inventor： BECKMAN INSTRUMENTS, INC. ,  KEENAN, Charles, A. ,  COASSIN, Peter, J. ,  HELPHREY, David, B. ,  WINER, Roger ,  DIH, Jiunn-Jye

IPC: B01J19/00

CPC classification number: C07H21/00 ,  B01J19/0046 ,  B01J2219/00353 ,  B01J2219/00391 ,  B01J2219/00689 ,  B01J2219/00698 ,  B01J2219/00722 ,  C07K1/045 ,  C40B40/06 ,  C40B60/14 ,  G01F1/708 ,  G01F1/7086 ,  Y10T436/11

Abstract: The present invention makes use of a single detector to monitor several process functions, e.g. reaction efficiency, reagent flow rates, the presence of empty reagent reservoirs, the absence of a chemical reactor column in the system, blockage of flow system, etc., at a single location in the flow system. In accordance with the detection scheme of the present invention, only one detector is required to accomplish the same, if not more, functions as many detectors in the prior art instruments. In the described embodiment, an optical detector is positioned downstream of a chemical reaction chamber. This detector monitors the effluent from the reaction chamber to monitor the reaction efficiency. It also monitors the system functions upstream of the reaction chamber. System flow rate is monitored by detecting the presence of a gas bubble which has been introduced into the system at a known instance. Depletion of reagents in the reservoirs can be detected by monitoring the absence of the reagents at the detector at times when the reagents are expected. The flow system may be periodically diagnosed to check for flow blockage or missing flow component, by monitoring the flow past the detector which corresponds to a predetermined succession of reagents introduced into the system. Any deviation from a predictable succession of changes in the flow monitored by the detector indicates possible blockage of the flow delivery system or missing flow components.

Abstract translation: 本发明利用单个检测器来监视多个过程功能，例如， 反应效率，试剂流量，空试剂储存器的存在，系统中没有化学反应器塔，堵塞流动系统等，在流动系统的单个位置。 根据本发明的检测方案，仅需要一个检测器来实现与现有技术的仪器相同的（如果不是更多的）功能的检测器。 在所描述的实施例中，光学检测器位于化学反应室的下游。 该检测器监测来自反应室的流出物以监测反应效率。 它还监控反应室上游的系统功能。 通过检测在已知情况下已经引入到系统中的气泡的存在来监测系统流量。 可以通过在预期的时候监测检测器处的​​试剂的不存在来检测储存器中试剂的消耗。 可以通过监测通过检测器的流量来对应于引入到系统中的预定的一系列试剂，周期性地诊断流量系统来检查流体阻塞或缺少流动成分。 由检测器监测的流量的可预测的连续变化的任何偏差表明流量输送系统或缺少流动分量的可能的阻塞。

公开(公告)号：WO1993025899A1

公开(公告)日：1993-12-23

申请号：PCT/US1993005809

申请日：1993-06-17

Applicant: BECKMAN INSTRUMENTS, INC.

Inventor： BECKMAN INSTRUMENTS, INC. ,  GUTTMAN, Andras

IPC: G01N27/447

CPC classification number: G01N27/44773

Abstract: The present invention is directed to a technique that provides enhanced separation resolution in electrophoresis. This technique involves the use of a time-varying field strength, which may be progressively increasing or decreasing, constant or otherwise, as a function of time. The shape of the field strength with respect to time may be continuous or stepwise over time, monotonic or otherwise. Because the mobility of different size species is a function of the applied electric field, the use of a nonuniform (time varying) electric field increases the resolving power of electrophoresis. This technique has been found to provide enhanced resolution of double-stranded DNA molecules in capillary polyacrylamide gel electrophoresis. It has been found that enhanced separation of DNA restriction fragments of 1 to more than 1000 base pairs in size has been achieved employing the technique of the present invention.

公开(公告)号：WO1989004216A1

公开(公告)日：1989-05-18

申请号：PCT/US1988003681

申请日：1988-10-20

Applicant: BECKMAN INSTRUMENTS, INC.

Inventor： BECKMAN INSTRUMENTS, INC. ,  PENHASI, Harry, Aron

IPC: B04B09/08

CPC classification number: B04B9/08

Abstract: The present invention provides a mechanism for bolting a rotor to a hub without introducing excessive radial stress around the bolt holes when the rotor is operating at high speed. The rotor (1) has a slot cut (35) through its center to eliminate radial stress perpendicular to the slot and thereby avoid the problems of stress cracking of the otherwise weak section. The mounting bolts (501) are necked down and not threaded at the surface of the hub. The bolts are threaded into the hub (501A) at a substantial distance from the top surface of the hub (503) so that they can flex and so that the center of the rotor (1) can move out relative to the hub (32). The hub rotor interface (503) is lubricated to facilitate radial motion of the center of the rotor.