公开(公告)号：US4753788A

公开(公告)日：1988-06-28

申请号：US696727

申请日：1985-01-31

Applicant: Ronald C. Gamble

Inventor： Ronald C. Gamble

IPC: A61K51/00 ,  A61K9/10 ,  A61K9/127 ,  A61K9/133 ,  A61K45/08 ,  B01J13/00 ,  B01J13/02 ,  A61K43/00 ,  A61K49/00

CPC classification number: A61K9/1277 ,  Y10S436/829

Abstract: A method is provided for preparing small (less than 2000 .ANG.) lipid vesicles in commercial quantities by microemulsifying lipid compositions using very high shear forces generated in a homogenizing apparatus operated at high pressures at a selected temperature. These vesicles are suitable for various biological applications including targeting of tumors in a body for diagnosis and treatment.

Abstract translation: 提供了一种通过使用在选定温度下以高压操作的均质化装置中产生的非常高的剪切力微乳化脂质组合物来制备商业量的小（小于2000安格姆）脂质囊泡的方法。 这些囊泡适用于各种生物学应用，包括靶向体内肿瘤用于诊断和治疗。

公开(公告)号：US07132650B1

公开(公告)日：2006-11-07

申请号：US10951255

申请日：2004-09-25

Applicant: Ronald C. Gamble ,  Stephen D. O'Connor ,  Bruce Wilcox ,  Matthew M. Gregori

Inventor： Ronald C. Gamble ,  Stephen D. O'Connor ,  Bruce Wilcox ,  Matthew M. Gregori

IPC: H01J49/42

CPC classification number: G01N30/7233 ,  G01N30/466 ,  G01N30/80 ,  G01N2030/8447 ,  H01J49/0018 ,  H01J49/0431 ,  H01J49/107 ,  Y10T137/86863 ,  Y10T137/86871 ,  Y10T436/115831

Abstract: High throughput analytical systems and methods employing multiple liquid phase separation process regions coupled to a common mass spectrometer are provided. Disclosed systems and methods permits parallel separation and parallel storage of discrete eluate fractions, followed by sequential discharge and ionization of previously stored eluate portions to yield a composite ion stream containing the sequential series of eluate portions, followed by mass analysis of the ion stream. A common manifold may receive ions and utilize pressurized gas or ion gating to direct ions within the manifold toward the mass spectrometer inlet.

Abstract translation: 提供了使用耦合到共同的质谱仪的多个液相分离工艺区域的高通量分析系统和方法。 公开的系统和方法允许离散洗脱液级分的并行分离和平行存储，随后顺序地排出和离子化先前储存的洗脱液部分，以产生含有顺序一系列洗脱液部分的复合离子流，随后对离子流进行质量分析。 常见的歧管可以接收离子并利用加压气体或离子门控来将歧管内的离子引向质谱仪入口。

公开(公告)号：US6001309A

公开(公告)日：1999-12-14

申请号：US79871

申请日：1998-05-15

Applicant: Ronald C. Gamble ,  Thomas P. Theriault ,  John Baldeschwieler

Inventor： Ronald C. Gamble ,  Thomas P. Theriault ,  John Baldeschwieler

IPC: C12N15/09 ,  B01J19/00 ,  B01L3/02 ,  C40B50/14 ,  C40B60/14 ,  G01N1/28 ,  G01N35/10

CPC classification number: B01L3/0268 ,  B01J19/0046 ,  B82Y30/00 ,  B01J2219/00378 ,  B01J2219/00531 ,  B01J2219/00533 ,  B01J2219/00536 ,  B01J2219/00605 ,  B01J2219/00612 ,  B01J2219/00637 ,  B01J2219/00659 ,  B01J2219/00675 ,  B01J2219/00677 ,  B01J2219/00691 ,  B01L2200/04 ,  C40B50/14 ,  C40B60/14 ,  G01N2001/282 ,  G01N2035/1041

Abstract: Devices and methods are provided for precise reduction of arrays of microspots. A pulse jetting device is employed having a capillary of micron dimensions, with a portion of the capillary proximal to the jetting orifice circumferentially surrounded by a piezoelectric transducer. By appropriate design of the capillary, orifice and piezoelectric transducer, droplets can be formed on a surface, separated by as little as 80 microns center-to-center, and having at least about a 15 micron spacing at the border. The subject substrate arrays can be used for providing miniaturized arrays of reagents, such as nucleic acids, for detecting the presence of homologous sequences in a sample.

Abstract translation: 提供了设备和方法来精确地减少微孢子体阵列。 使用脉冲喷射装置具有微米尺寸的毛细管，毛细管的一部分靠近喷射孔，周向地被压电换能器包围。 通过毛细管，孔口和压电换能器的适当设计，液滴可以形成在中心至中心微小至80微米的表面上，并且在边界处具有至少约15微米的间距。 主题衬底阵列可用于提供用于检测样品中同源序列的存在的小型试剂阵列，例如核酸。

公开(公告)号：US5981733A

公开(公告)日：1999-11-09

申请号：US714867

申请日：1996-09-16

Applicant: Ronald C. Gamble ,  Thomas P. Theriault ,  John D. Baldeschwieler

Inventor： Ronald C. Gamble ,  Thomas P. Theriault ,  John D. Baldeschwieler

IPC: B01J19/00 ,  C40B40/06 ,  C40B60/14 ,  C07H21/00

CPC classification number: B01J19/0046 ,  B01J2219/00378 ,  B01J2219/00391 ,  B01J2219/00475 ,  B01J2219/00527 ,  B01J2219/00585 ,  B01J2219/0059 ,  B01J2219/00596 ,  B01J2219/00605 ,  B01J2219/0061 ,  B01J2219/00617 ,  B01J2219/00626 ,  B01J2219/00637 ,  B01J2219/00659 ,  B01J2219/00689 ,  B01J2219/00722 ,  C40B40/06 ,  C40B60/14 ,  Y02P20/582

Abstract: An apparatus for the automated synthesis of molecular arrays. A jetting device is employed along with a reaction chamber to dispense reagents used in the synthesis onto the substrate. A positioning system moves the substrate from the jet to the reaction chamber. A controller controls the movement of the substrate and the application of the reagents so that the synthesis is carried out according to a pre-determined procedure. The apparatus will synthesize nucleotides in an array of micron-size spots according to a pattern selected by the operator immediately prior to synthesis.

Abstract translation: 用于自动合成分子阵列的装置。 喷射装置与反应室一起使用以将合成中使用的试剂分配到基材上。 定位系统将基板从射流移动到反应室。 控制器控制衬底的移动和试剂的应用，使得根据预定程序进行合成。 该装置将根据在合成前立即由操作者选择的图案在微米级斑点的阵列中合成核苷酸。

公开(公告)号：US5874554A

公开(公告)日：1999-02-23

申请号：US767233

申请日：1996-12-13

Applicant: Ronald C. Gamble ,  Thomas P. Theriault ,  Scott C. Winder

Inventor： Ronald C. Gamble ,  Thomas P. Theriault ,  Scott C. Winder

IPC: B01J19/00 ,  C07H21/00 ,  C40B40/06 ,  C40B60/14 ,  C07H19/00 ,  C08G63/48

CPC classification number: C07H21/00 ,  B01J19/0046 ,  B01J2219/00378 ,  B01J2219/00527 ,  B01J2219/0059 ,  B01J2219/00596 ,  B01J2219/00605 ,  B01J2219/00659 ,  B01J2219/00722 ,  C40B40/06 ,  C40B60/14

Abstract: Solvent vehicles and methods of their use in the pulse jet delivery of reagents in automated oligonucleotide synthesis by the solid-phase phosphoramidite method are provided. For pulse jet delivery of the activated monomer, acetonitrile in combination with at least one stabilizer co-solvent is employed as the solvent vehicle, where the stabilizer co-solvent is an inert, organic solvent having a boiling point of at least 100.degree. C. For pulse jet delivery of the detritylation reagent, a mono- or disubstituted methane is employed as the solvent vehicle, where substituents have a molecular weight greater than 36 daltons. Use of the solvent vehicles according to the subject invention provides for reduced reagent precipitation in the pulse jet tubes and improved results.

Abstract translation: 提供溶剂车辆及其在通过固相亚磷酰胺方法的自动寡核苷酸合成中脉冲喷射输送试剂中的方法。 对于活化单体的脉冲喷射输送，使用乙腈与至少一种稳定剂助溶剂组合作为溶剂载体，其中稳定剂助溶剂是沸点至少为100℃的惰性有机溶剂。 对于去离子试剂的脉冲喷射输送，使用单取代或二取代的甲烷作为溶剂载体，其中取代基的分子量大于36道尔顿。 根据本发明的溶剂载体的使用提供了脉冲喷射管中减少的试剂沉淀和改进的结果。

公开(公告)号：US5406832A

公开(公告)日：1995-04-18

申请号：US86592

申请日：1993-07-02

Applicant: Ronald C. Gamble ,  Paul E. West ,  Marc R. Schuman

Inventor： Ronald C. Gamble ,  Paul E. West ,  Marc R. Schuman

IPC: G01B21/30 ,  G01Q10/00 ,  G01Q10/06 ,  G01Q60/32 ,  G01B5/28 ,  G01N23/00

CPC classification number: G01Q10/06 ,  B82Y35/00 ,  Y10S977/85 ,  Y10S977/851

Abstract: The synchronous sampling scanning force microscope includes a reflective cantilever arm having a free end which is oscillated at a frequency different from the resonance frequency of the cantilever arm. The motion of the oscillating cantilever arm is measured, to generate a deflection signal indicative of the amplitude of deflection or phase shift of the cantilever arm. Selected portions of cycles of the output signal are sampled, for generating output signal data indicative of deflection of the near and far excursions of the probe. The method and apparatus permit monitoring of compliance of the surface of the specimen by multiple sampling at a rate greater than the period of oscillation of the cantilever probe of the microscope.

Abstract translation: 同步采样扫描力显微镜包括反射悬臂，其具有以与悬臂的共振频率不同的频率振荡的自由端。 测量振荡悬臂的运动，以产生指示悬臂的偏转或相移幅度的偏转信号。 对输出信号的周期的选定部分进行采样，以产生指示探针的近距离和远距偏移的输出信号数据。 该方法和装置允许以大于显微镜的悬臂探头的振荡周期的速率进行多次采样来监测样品表面的顺应性。

公开(公告)号：US4581222A

公开(公告)日：1986-04-08

申请号：US465360

申请日：1983-02-09

Applicant: John D. Baldeschwieler ,  Ronald C. Gamble ,  Albert M. Lin ,  George W. Tin

Inventor： John D. Baldeschwieler ,  Ronald C. Gamble ,  Albert M. Lin ,  George W. Tin

IPC: G01N33/534 ,  A61K43/00 ,  G01T1/00

CPC classification number: G01N33/534 ,  Y10S436/804 ,  Y10S436/827

Abstract: An immunoassay method for detection of antigen is disclosed. The method employs complement mediated lysis of vesicles loaded with In-111 or other gamma-emitting cation, and quantitative detection of the lysis by gamma-ray perturbed angular correlation (PAC) spectroscopy. The vesicles are labeled with a substance competitive to the antigen to be measured, and the concentration of the antigen in the sample measured by assessing the diminution in lysis due to the presence of the competing antigen.The method may also be used to assess the immunologic competence of a subject by injecting suitably sensitized vesicles and monitoring the in vivo lysis pattern by (PAC).

Abstract translation: 公开了一种用于检测抗原的免疫测定方法。 该方法使用负载有In-111或其他γ发射阳离子的囊泡的补体介导的裂解，以及通过γ射线扰动角度相关（PAC）光谱定量检测裂解。 囊泡用与要测量的抗原竞争的物质标记，并且通过评估由于竞争性抗原的存在引起的裂解减少来测量样品中抗原的浓度。 该方法还可以用于通过注射适当敏化的囊泡和通过（PAC）监测体内裂解模式来评估受试者的免疫能力。

公开(公告)号：US4310505A

公开(公告)日：1982-01-12

申请号：US92342

申请日：1979-11-08

Applicant: John D. Baldeschwieler ,  Ronald C. Gamble ,  Marcia R. Mauk ,  Tsung-Ying Shen ,  Mitree M. Ponpipom

Inventor： John D. Baldeschwieler ,  Ronald C. Gamble ,  Marcia R. Mauk ,  Tsung-Ying Shen ,  Mitree M. Ponpipom

IPC: A61K51/00 ,  A61K9/127 ,  A61K47/00 ,  A61K49/00 ,  A61K43/00 ,  B01J13/00

CPC classification number: A61K9/1272 ,  A61K9/127 ,  A61K9/1271 ,  Y10T428/2984

Abstract: Lipid vesicles comprising a lipid bilayer which includes analogs of cell-surface receptors such as dicetyl phosphate; stearylamine; 6-(5-cholesten-3.beta.-yloxy) hexyl 1-thio-.beta.-L-fucopyranoside; 6-(5-cholesten-3.beta.-yloxy) hexyl 1-thio-.beta.-D-galactopyranoside; 6-(5-cholesten-3.beta.-yloxy)hexyl 1-thio-.alpha.-D-mannopyranoside; 6-(5-cholesten-3-yloxy)hexyl 2-acetamido-2-deoxy-1-thio-.beta.-D-galactopyranoside; 6-(5-cholesten-3.beta.-yloxy)hexyl 6-amino-6-deoxy-1-thio-.beta.-D-galactopyranoside; or 6-(5-cholesten-3.beta.-yloxy)hexyl 6-amino-6-deoxy-1-thio-.alpha.-D-mannopyranoside; cholesterol and distearoyl phospatidylcholine, and an effective amount of physiologically compatible radioactive tracer, cytotoxic or therapeutic agent as a part of the vesicles. The vesicles of this invention can be administered to the human host and have been found to release the contents of the vesicles in a predetermined manner, i.e., controlled release, and in some cases, to be rapidly concentrated in the lymphatic system and/or liver, lungs or spleen of the host.

Abstract translation: 包含脂质双层的脂质囊泡，其包括细胞表面受体的类似物，例如磷酸二鲸蜡酯; 硬脂胺 6-（5-胆甾烯-3β-氧代）己基1-硫代-β-L-吡喃葡萄糖苷; 6-（5-胆甾烯-3β-氧基）己基1-硫代-β-D-吡喃半乳糖苷; 6-（5-胆甾烯-3β-氧基）己基1-硫代-α-D-吡喃甘露糖苷; 6-（5-胆甾烯-3-基氧基）己基2-乙酰氨基-2-脱氧-1-硫代-β-D-吡喃半乳糖苷; 6-（5-胆甾烯-3β-氧基）己基6-氨基-6-脱氧-1-硫代-β-D-吡喃半乳糖苷; 或6-（5-胆甾烯-3β-氧基）己基6-氨基-6-脱氧-1-硫代-α-D-吡喃甘露糖苷; 胆固醇和二硬脂酰磷脂酰胆碱，以及有效量的生理相容的放射性示踪剂，细胞毒性剂或治疗剂作为囊泡的一部分。 本发明的囊泡可以施用于人宿主，并且已经被发现以预定的方式（即控制释放）释放囊泡的内容物，并且在一些情况下快速浓缩在淋巴系统和/或肝脏中 ，肺或脾脏的主机。

公开(公告)号：US5949070A

公开(公告)日：1999-09-07

申请号：US783416

申请日：1997-01-14

Applicant: Ronald C. Gamble

Inventor： Ronald C. Gamble

IPC: G01Q10/00 ,  G01Q60/04 ,  G01B7/34 ,  G01Q20/02 ,  G01Q30/14 ,  G01Q70/02 ,  H01J37/352

CPC classification number: G01B7/34 ,  B82Y35/00 ,  G01Q20/02 ,  G01Q30/14 ,  G01Q70/02 ,  Y10S977/87

Abstract: A scanning force microscope is disclosed which includes integrated optics for viewing the optical lever arm, probe and sample to be examined. The scanning force microscope includes a simplified mounting of laser and related adjustments and the locating of a detector independent of the scanner, to improve ease of handling and providing convenient locations for adjustments. In one preferred embodiment of the scanning force microscope, the surface of samples may be imaged while the cantilever portion of the scanner is immersed in liquids without special set-up or special adapters.

Abstract translation: 公开了一种扫描力显微镜，其包括用于观察光学杠杆臂，待检查的探针和样品的集成光学元件。 扫描力显微镜包括简化的激光安装和相关调整以及独立于扫描仪的检测器的定位，以提高操作的便利性并提供便于调节的位置。 在扫描力显微镜的一个优选实施例中，可以将扫描仪的悬臂部分浸没在没有特殊装置或特殊适配器的液体中的同时，将样品的表面进行成像。

公开(公告)号：US5811802A

公开(公告)日：1998-09-22

申请号：US720243

申请日：1996-09-26

Applicant: Ronald C. Gamble

Inventor： Ronald C. Gamble

IPC: G01Q10/00 ,  G01Q60/04 ,  G01B7/34 ,  G01Q20/02 ,  G01Q30/14 ,  G01Q70/02 ,  H01J37/00

CPC classification number: G01Q10/04 ,  B82Y35/00 ,  G01B7/34 ,  G01Q20/02 ,  G01Q30/14 ,  G01Q70/02 ,  Y10S977/86

Abstract: A scanning probe microscope is disclosed which includes a pivotally mounted scanning assembly for scanning a surface of a sample. A sensing assembly is mounted relative to the scanning assembly and is positioned for sensing the surface topography of the sample. The scanning assembly includes a bore extending vertically through the scanning assembly which allows direct overhead viewing of the sensing assembly and the sample. The scanning assembly is pivotally mounted by a hollow pivot assembly which permits both the sensing assembly and the sample to be viewed through the scanning assembly when aligning the sensing assembly with the sample. The hollow pivot assembly also allows a user to optically view the sample from directly overhead with an optical microscope or charge coupled device.

Abstract translation: 公开了一种扫描探针显微镜，其包括用于扫描样品表面的可枢转地安装的扫描组件。 感测组件相对于扫描组件安装并且被定位成用于感测样品的表面形貌。 扫描组件包括垂直延伸穿过扫描组件的孔，其允许感测组件和样品的直接俯视观察。 扫描组件通过中空枢轴组件可枢转地安装，当将感测组件与样品对准时，其允许通过扫描组件观察感测组件和样品。 中空枢轴组件还允许用户使用光学显微镜或电荷耦合装置从直接顶部光学地观察样品。