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1. 发明申请

WO2003082577A2 USE OF IMMISCIBLE FLUIDS IN DROPLET EJECTION THROUGH APPLICATION OF FOCUSED ACOUSTIC ENERGY 审中-公开
标题翻译：通过应用焦点声学能量在渗漏喷射中使用不可控流体
公开(公告)号：WO2003082577A2
公开(公告)日：2003-10-09
申请号：PCT/US2003/009490
申请日：2003-03-28
申请人： PICOLITER INC. , ELLSON, Richard, N. , MUTZ, Mitchell, W. , FOOTE, James, K.
发明人： ELLSON, Richard, N. , MUTZ, Mitchell, W. , FOOTE, James, K.
IPC分类号： B41J
CPC分类号： B41J2/14008 , B01J13/04 , B01J19/0046 , B01J2219/00351 , B01J2219/00527 , B01J2219/00529 , B01J2219/0059 , B01J2219/00596 , B01J2219/00605 , B01J2219/00608 , B01J2219/0061 , B01J2219/00612 , B01J2219/00626 , B01J2219/00637 , B01J2219/00641 , B01J2219/00659 , B01J2219/00722 , B01J2219/00725 , B05B17/0615 , B22F9/08 , B22F2009/0804 , B22F2999/00 , C40B40/06 , C40B40/10 , C40B60/14 , Y10T436/143333 , Y10T436/2575 , B22F2202/01
摘要： The invention provides a method for generating droplets. Extremely fine droplets may be generated (on the order of 1 picoliter or less) using focused acoustic energy to eject the droplets from a reservoir containing two or more immiscible fluids. The droplets may include immiscible fluids or a single fluid. Typically, the droplets are ejected onto discrete sites on a substrate surface so as to form an array thereon. In some instances, the reservoirs contain layers of immiscible fluids, wherein an upper layer exhibits a nonuniform thickness. In such a case, fluid from a lower fluid layer may be propelled through an aperture region of the upper layer.
摘要翻译：本发明提供了一种产生液滴的方法。可以使用聚焦声能产生非常细的液滴（大约1皮升或更小），以从含有两种或多种不混溶流体的储存器喷射液滴。液滴可以包括不混溶的流体或单一流体。通常，液滴被喷射到衬底表面上的离散位置上，以在其上形成阵列。在一些情况下，储存器包含不混溶流体层，其中上层表现出不均匀的厚度。在这种情况下，来自下部流体层的流体可以通过上层的开口区域被推进。

2. 发明申请

WO2003052403A2 ACOUSTIC ASSESSMENT OF FLUIDS IN A PLURALITY OF RESERVOIRS 审中-公开
标题翻译：流体在多个储层中的声学评估
公开(公告)号：WO2003052403A2
公开(公告)日：2003-06-26
申请号：PCT/US2002/038759
申请日：2002-12-04
申请人： PICOLITER INC. , MUTZ, Mitchell, W. , ELLSON, Richard, N. , FOOTE, James, K.
发明人： MUTZ, Mitchell, W. , ELLSON, Richard, N. , FOOTE, James, K.
IPC分类号： G01N29/00
CPC分类号： B01L3/0268 , B01J2219/00362 , B01J2219/00702 , B01L2200/143 , B01L2300/0819 , B01L2400/0436 , B01L2400/0439 , C40B60/14 , G01F23/296 , G01F23/2968 , G01N29/02 , G01N29/22 , G01N29/222 , G01N29/28 , G01N35/1016 , G01N2035/00158 , G01N2291/02818 , G01N2291/02836 , G01N2291/02881 , G01N2291/2695
摘要： Devices and methods are provided for acoustically assessing the contents in a plurality of reservoirs. Each reservoir has a portion adapted to contain a fluid, and an acoustic radiation generator is positioned in acoustic coupling relationship to each of the reservoirs. Acoustic radiation generated by the acoustic radiation generator is transmitted through at least the portion of each reservoir to an analyzer. In some instances, the acoustic generator is adapted to interrogate a single reservoir at one time. However, an acoustic radiation generator may be adapted to generate acoustic radiation having an image filed of a size sufficient to interrogate selected reservoirs of the plurality at one time. The analyzer is capable of analyzing a characteristic of the transmitted acoustic radiation and optionally correlating the characteristic to a property of the reservoirs' contents. This allows for greater accuracy and control over the dispensing of fluids from the reservoirs. Optionally, a means is provided for removing fluid acoustic coupling medium from the reservoir.
摘要翻译：提供了用于声学评估多个储存器中的内容物的装置和方法。每个储存器具有适于容纳流体的部分，并且声辐射发生器被定位成与每个储存器的声耦合关系。由声辐射发生器产生的声辐射通过至少每个储存器的部分传输到分析器。在一些情况下，声发生器适合于一次询问单个储存器。然而，声辐射发生器可以适于产生具有足以在一个时间询问多个选定的储存器的尺寸的图像场的声辐射。分析仪能够分析所发射的声辐射的特性，并且可选地将特征与储层内容物性相关联。这允许对来自储存器的流体分配的更高的精度和控制。可选地，提供了用于从储存器去除流体声学耦合介质的装置。

3. 发明申请

WO2003106179A1 ACOUSTIC ASSESSMENT AND/OR CONTROL OF FLUID CONTENT IN A RESERVOIR 审中-公开
标题翻译：液体含量在储层中的声学评估和/或控制
公开(公告)号：WO2003106179A1
公开(公告)日：2003-12-24
申请号：PCT/US2003/019490
申请日：2003-06-18
申请人： PICOLITER INC. , ELLSON, Richard, N. , MUTZ, Mitchell, W. , FOOTE, James, K.
发明人： ELLSON, Richard, N. , MUTZ, Mitchell, W. , FOOTE, James, K.
IPC分类号： B41J2/14
CPC分类号： G01N29/0681 , B01J2219/00315 , B01J2219/00362 , B01J2219/00722 , B01J2219/00725 , B01L3/0268 , B01L3/5085 , B01L2400/0436 , B65D90/48 , C40B40/06 , C40B40/10 , C40B60/14 , G01F23/2962 , G01N29/222 , G01N35/1016 , G01N2035/00237 , G01N2035/1025 , G01N2035/1034 , G01N2291/02836
摘要： The invention provides devices and methods for acoustically assessing fluid content in a reservoir. When used to assess the contents of a plurality of reservoirs, the reservoirs are typically provided as an array. An acoustic radiation generator is employed for generating acoustic radiation having an image field of a size sufficient to interrogate a plurality of selected reservoirs at one time. The generator is placed in acoustic coupling relationship via a fluid acoustic coupling medium to the selected reservoirs, and acoustic radiation generated by the generator is transmitted through the coupling medium, an exterior surface of the selected reservoirs, and the selected reservoirs. A characteristic of the transmitted acoustic radiation is analyzed so as to assess the contents of each of the selected reservoirs. Fluid may be ejected from the selected reservoirs based on the assessment. Optionally, a means is provided for removing fluid acoustic coupling medium from the exterior surface after acoustic assessment. Also provided are devices and methods for controlling the composition and/or volume of a fluid within a reservoir that include means for introducing additional fluid into the reservoir.
摘要翻译：本发明提供用于声学评估储层中的流体含量的装置和方法。当用于评估多个储存器的内容物时，储存器通常被提供为阵列。声辐射发生器用于产生具有足以在一个时间询问多个所选择的储层的尺寸的图像场的声辐射。发电机通过流体声耦合介质放置到声学耦合关系到所选择的储存器，并且由发生器产生的声辐射通过耦合介质，所选择的储存器的外表面和所选择的储存器传输。分析所发射的声辐射的特征，以便评估每个所选择的储层的内容物。基于评估，流体可能从所选择的储层中排出。可选地，提供了用于在声学评估之后从外表面去除流体声学耦合介质的装置。还提供了用于控制储存器内的流体的组成和/或体积的装置和方法，其包括用于将附加流体引入储存器的装置。

4. 发明申请

WO2003082577A3 USE OF IMMISCIBLE FLUIDS IN DROPLET EJECTION THROUGH APPLICATION OF FOCUSED ACOUSTIC ENERGY 审中-公开
公开(公告)号：WO2003082577A3
公开(公告)日：2003-10-09
申请号：PCT/US2003/009490
申请日：2003-03-28
申请人： PICOLITER INC. , ELLSON, Richard, N. , MUTZ, Mitchell, W. , FOOTE, James, K.
发明人： ELLSON, Richard, N. , MUTZ, Mitchell, W. , FOOTE, James, K.
IPC分类号： B01L3/02
摘要： Methods of gengerating droplets (47) from a reservoir (13) containing two or more immiscible fluids (10, 12) using a focused acoustic energy generator (35, 37, 41). An upper layer (12) may have a nonuniform thickness for ejection of a droplet (47) of a predetermined volume of fluid form the lower layer (10) through a minimum thickness aperture (17), or a droplet (47) may contain both fluids (10, 12) to produce a feature of reduced size.

5. 发明申请

WO2003075307A1 METHODS, DEVICES, AND SYSTEMS USING ACOUSTIC EJECTION FOR DEPOSITING FLUID DROPLETS ON A SAMPLE SURFACE FOR ANALYSIS 审中-公开
标题翻译：使用声学喷射在样品表面上沉积流体滴的方法，装置和系统用于分析
公开(公告)号：WO2003075307A1
公开(公告)日：2003-09-12
申请号：PCT/US2003/006427
申请日：2003-03-03
申请人： PICOLITER INC. , ELLSON, Richard, N. , MUTZ, Mitchell, W. , CAPRIOLI, Richard, M.
发明人： ELLSON, Richard, N. , MUTZ, Mitchell, W. , CAPRIOLI, Richard, M.
IPC分类号： H01J49/04
CPC分类号： H01J49/0454 , G01N33/54393 , G01N35/1011 , H01J49/0004 , Y10T436/2575
摘要： Provided is a method for preparing a sample surface (51) for analysis that involves placing a sample surface (51) in droplet-receiving relationship to a reservoir (13,15) containing a fluid (14, 16). Typically, the sample is a cellular sample (45) that exhibits a nonuniform surface, the fluid (14, 16) is an analysis-enhancing fluid comprised of a mass spectrometry matrix material and a carrier fluid, and the carrier fluid is comprised of a low volatility solvent. A droplet (49) of fluid is ejected from the reservoir (13, 15) such that the droplet (49) is deposited on the sample surface (51) at a designated site (55, 57). Such ejection is typically, but not necessarily carried out through the application of focused acoustic energy. Then, the sample (45) is subjected to conditions sufficient to allow the fluid (14, 16) to interact with the sample surface (51) and to render the sample surface (51) suitable for analysis. Optionally, the sample (45) is analyzed at the designated site (55,57). Also provided are systems and devices for preparing a sample surface (51) for analysis.
摘要翻译：提供一种用于制备用于分析的样本表面（51）的方法，该方法包括将样本表面（51）以液滴接收关系放置到包含流体（14,15）的储存器（13,15） 16）。典型地，样品是呈现不均匀表面的细胞样品（45），流体（14,16）是由质谱基质材料和载体流体组成的分析增强流体，并且载体流体由低挥发性溶剂。流体的液滴（49）从贮存器（13,15）喷出，使得液滴（49）在指定的位置（55,57）沉积在样本表面（51）上。这种喷射通常是通过聚焦声能的应用来实现的，但不是必须的。然后，样品（45）经受足以允许流体（14,16）与样品表面（51）相互作用并使样品表面（51）适于分析的条件。可选地，样品（45）在指定地点进行分析（55,57）。还提供了用于制备用于分析的样品表面（51）的系统和设备。

6. 发明申请

WO2002071051A2 ACOUSTIC SAMPLE INTRODUCTION FOR ANALYSIS AND/OR PROCESSING 审中-公开
标题翻译：声学样本介绍分析和/或处理
公开(公告)号：WO2002071051A2
公开(公告)日：2002-09-12
申请号：PCT/US2002/004912
申请日：2002-02-14
申请人： PICOLITER, INC. , ELLSON, Richard, N. , MUTZ, Mitchell, W.
发明人： ELLSON, Richard, N. , MUTZ, Mitchell, W.
IPC分类号： G01N30/00
CPC分类号： H01J49/0454 , G01N33/54393 , Y10T436/2575
摘要： The invention relates to the efficient transport of a small volume of fluid, such as may be required by mass spectrometers and other devices configured to process and/or analyze small samples of biomolecular fluids. Such transport involves nozzleless acoustic ejection. In some instances, sample molecules contained in droplets of fluid are introduced from a reservoir into an ionization chamber of a analytical device. In other instances, sample molecules are introduced into a small capillary by directing focused acoustic radiation at a focal point near the surface of a fluid sample. In still other instances, acoustic ejection is used to form an array on a surface, wherein the features of the array are ionized for analysis. The invention may be used with microfluidic devices. Thus, the invention facilitates the processing and/or analysis of various types of samples, such as biomolecules having high molecular weights.
摘要翻译：本发明涉及小体积流体的有效输送，例如质谱仪可能需要的，以及被配置为处理和/或分析生物分子流体的小样品的其它装置。这种运输涉及喷嘴无声弹射。在一些情况下，包含在流体液滴中的样品分子从储器引入分析装置的电离室。在其他情况下，通过将聚焦声辐射引导到流体样品表面附近的焦点处，将样品分子引入小毛细管中。在其他情况下，使用声弹出来在表面上形成阵列，其中阵列的特征被电离以便分析。本发明可以与微流体装置一起使用。因此，本发明有助于各种类型的样品（例如具有高分子量的生物分子）的加工和/或分析。

7. 发明申请

WO2006039700A2 ACOUSTIC ASSESSMENT OF CHARACTERISTICS OF A FLUID RELEVANT TO ACOUSTIC EJECTION 审中-公开
标题翻译：流体与声音喷射相关的特征的声学评估
公开(公告)号：WO2006039700A2
公开(公告)日：2006-04-13
申请号：PCT/US2005/035683
申请日：2005-10-03
申请人： LABCYTE INC. , ELLSON, Richard, N. , MUTZ, Mitchell, W. , QURESHI, Shehrzad, Ahmed , STEARNS, Richard, G.
发明人： ELLSON, Richard, N. , MUTZ, Mitchell, W. , QURESHI, Shehrzad, Ahmed , STEARNS, Richard, G.
IPC分类号： B41J2/14
CPC分类号： G01N29/4418 , B01J2219/00362 , B01J2219/00702 , B01L3/0268 , B01L2200/143 , B01L2300/0819 , B01L2300/0829 , B01L2300/1888 , B01L2400/0436 , B01L2400/0439 , B41J2/14008 , C40B60/14 , G01F23/296 , G01F23/2968 , G01N29/02 , G01N29/024 , G01N29/22 , G01N29/222 , G01N29/28 , G01N29/4427 , G01N29/46 , G01N35/1016 , G01N2035/00158 , G01N2291/02818 , G01N2291/02836 , G01N2291/02881 , G01N2291/2695
摘要： Methods are provided for analyzing characteristics of fluids in the context of an acoustic ejection system. Such a system has a controller, an acoustic radiation generator, and a coupling medium coupling the radiation to a reservoir holding fluid. The methods can use acoustic radiation to both perturb a surface of the fluid in the reservoir and analyze the effect of the perturbation. The methods may use information about prior fluids. The methods of the invention can determine physical characteristics such as speed of sound and viscosity. The methods also include ways to determine a level of acoustic energy suitable to eject a droplet. Preferably the methods are executed automatically under control of programming of a controller of an acoustic ejection system.
摘要翻译：提供了用于在声弹射系统的上下文中分析流体特性的方法。这种系统具有控制器，声辐射发生器和将辐射耦合到储存器保持流体的耦合介质。这些方法可以使用声辐射来扰乱储层中流体的表面并分析扰动的影响。这些方法可以使用关于现有流体的信息。本发明的方法可以确定诸如声速和粘度的物理特性。所述方法还包括确定适于喷射液滴的声能水平的方法。优选地，这种方法在声学弹射系统的控制器的编程的控制下自动执行。

8. 发明申请

WO2004063029A3 DROPLET DISPENSATION FROM A RESERVOIR WITH REDUCTION IN UNCONTROLLED ELECTROSTATIC CHARGE 审中-公开
公开(公告)号：WO2004063029A3
公开(公告)日：2004-07-29
申请号：PCT/US2004/000522
申请日：2004-01-09
申请人： PICOLITER INC. , MUTZ, Mitchell, W. , LEE, David, Soong-Hua , MCLENDON, George
发明人： MUTZ, Mitchell, W. , LEE, David, Soong-Hua , MCLENDON, George
IPC分类号： B41J2/14
摘要： Devices and methods are provided for reducing uncontrolled electrostatic charge that can alter the volume and/or trajectory of a droplet, which may be ejected through the application of focused acoustic radiation. Also provided are reservoirs and substrates, e.g., well plates formed from a material that is at least partially nonmetallic or polymeric and either has an electrical resistivity of no more than about 10 11 ohm-cm, has a surface electrical resistivity of no more than about 10 12 ohm/sq, or both.

9. 发明申请

WO2010132852A2 PROTEASE INHIBITORS 审中-公开
标题翻译： PROTEASE抑制剂
公开(公告)号：WO2010132852A2
公开(公告)日：2010-11-18
申请号：PCT/US2010/035025
申请日：2010-05-14
申请人： AMPLYX PHARMACEUTICALS INC. , WEBB, Robert, R., III , MUTZ, Mitchell, W. , BARR, Kenneth, Jay
发明人： WEBB, Robert, R., III , MUTZ, Mitchell, W. , BARR, Kenneth, Jay
IPC分类号： C07D403/10 , C07D405/02 , A61P31/18 , A61K31/4433
CPC分类号： C07D498/18 , C07D211/60
摘要： Compounds useful as protease inhibitors are provided, as are methods of use and preparation of such compounds and compositions containing such compounds. In one embodiment, the compounds are useful for inhibiting HIV protease enzymes, and are therefore useful in slowing the proliferation of HIV.
摘要翻译：提供了可用作蛋白酶抑制剂的化合物，以及这些化合物和含有这些化合物的组合物的使用方法和制备方法。在一个实施方案中，所述化合物可用于抑制HIV蛋白酶，因此可用于减缓HIV的增殖。

10. 发明申请

WO2007053792A2 IMPROVING THE PHARMACOKINETICS OF PROTEASE INHIBITORS AND OTHER DRUGS 审中-公开
标题翻译：改善蛋白酶抑制剂和其他药物的药代动力学
公开(公告)号：WO2007053792A2
公开(公告)日：2007-05-10
申请号：PCT/US2006/043400
申请日：2006-11-06
申请人： AMPLYX PHARMACEUTICALS, INC. , MUTZ, Mitchell, W. , GESTWICKI, Jason, E.
发明人： MUTZ, Mitchell, W. , GESTWICKI, Jason, E.
IPC分类号： A61K38/55
CPC分类号： A61K47/55 , A61K47/54
摘要： A method for modulating at least one pharmacokinetic property of a protease inhibitor upon administration to a host is provided. One administers to the host an effective amount of a bifunctional compound of less than about 5000 daltons comprising the protease inhibitor or an active derivative thereof and a pharmacokinetic modulating moiety. The pharmacokinetic modulating moiety binds to at least one intracellular protein. The bifunctional compound has at least one modulated pharmacokinetic property upon administration to the host as compared to a free drug control that comprises the protease inhibitor.
摘要翻译：提供了一种在向宿主给药时调节蛋白酶抑制剂的至少一种药代动力学性质的方法。一个向宿主施用有效量的小于约5000道尔顿的双功能化合物，其包含蛋白酶抑制剂或其活性衍生物和药代动力学调节部分。药代动力学调节部分与至少一种细胞内蛋白结合。与包含蛋白酶抑制剂的游离药物对照相比，双官能化合物在给予宿主时具有至少一种调节的药代动力学性质。

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