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1. 发明授权

US07884324B2 Nanopillar arrays for electron emission 有权
标题翻译：用于电子发射的纳米柱阵列
公开(公告)号：US07884324B2
公开(公告)日：2011-02-08
申请号：US12130103
申请日：2008-05-30
申请人： Robert H. Blick , Michael S. Westphall , Hua Qin , Lloyd M. Smith
发明人： Robert H. Blick , Michael S. Westphall , Hua Qin , Lloyd M. Smith
IPC分类号： G01N23/00 , G01N13/10 , H01J49/08
CPC分类号： H01J1/32 , H01J29/023 , H01J43/246 , Y10S977/762
摘要： The present invention provides systems, devices, device components and structures for modulating the intensity and/or energies of electrons, including a beam of incident electrons. In some embodiments, for example, the present invention provides nano-structured semiconductor membrane structures capable of generating secondary electron emission. Nano-structured semiconductor membranes of this aspect of the present invention include membranes having an array of nanopillar structures capable of providing electron emission for amplification, filtering and/or detection of incident radiation, for example secondary electron emission and/or field emission. Nano-structured semiconductor membranes of the present invention are useful as converters wherein interaction of incident primary electrons and nanopillars of the nanopillar array generates secondary emission. Nano-structured semiconductor membranes of this aspect of the present invention are also useful as directed charge amplifiers wherein secondary emission from a nanopillar array provides gain functionality for increasing the intensity of radiation comprising incident electrons.
摘要翻译：本发明提供了用于调制包括入射电子束的电子的强度和/或能量的系统，装置，器件组件和结构。在一些实施例中，例如，本发明提供能够产生二次电子发射的纳米结构的半导体膜结构。本发明该方面的纳米结构半导体膜包括具有能够提供用于放射，滤波和/或检测入射辐射的电子发射的纳米柱结构阵列的膜，例如二次电子发射和/或场发射。本发明的纳米结构半导体膜可用作其中纳米柱阵列的入射一次电子和纳米柱的相互作用产生二次发射的转换器。本发明该方面的纳米结构半导体膜也可用作定向电荷放大器，其中来自纳米柱阵列的二次发射提供了用于增加包括入射电子的辐射强度的增益功能。

2. 发明授权

US07303869B2 Solid-phase reactions 有权
标题翻译：固相反应
公开(公告)号：US07303869B2
公开(公告)日：2007-12-04
申请号：US10269222
申请日：2002-10-11
申请人： Priscilla Wilkins Stevens , David Kelso , Victor Lyamichev , Jeff Hall , Bruce P. Neri , Robert W. Kwiatkowski, Jr. , Lloyd M. Smith
发明人： Priscilla Wilkins Stevens , David Kelso , Victor Lyamichev , Jeff Hall , Bruce P. Neri , Robert W. Kwiatkowski, Jr. , Lloyd M. Smith
IPC分类号： C12Q1/68 , C12P19/34 , C07H21/02 , C07H21/04
CPC分类号： C12Q1/683 , C12Q2561/109 , C12Q2565/101
摘要： The present invention relates to systems, compositions, and methods for the detection and characterization of nucleic acid sequences and variations in nucleic acid sequences. The present invention relates to methods for attaching nucleic acids to solid supports and modifying nucleic acids. For example, in some embodiments, the 5′ nuclease activity of a cleavage agent is used to cleave a cleavage structure formed on the solid support, the occurrence of the cleavage event indicating the presence of specific nucleic acid sequences.
摘要翻译：本发明涉及核酸序列的检测和表征以及核酸序列变异的系统，组合物和方法。本发明涉及将核酸连接到固体支持物和修饰核酸的方法。例如，在一些实施方案中，切割剂的5'核酸酶活性用于切割在固体支持物上形成的切割结构，裂解事件的发生表明存在特定的核酸序列。

3. 发明授权

US5228971A Horizontal gel electrophoresis apparatus 失效
标题翻译：水平凝胶电泳仪
公开(公告)号：US5228971A
公开(公告)日：1993-07-20
申请号：US878632
申请日：1992-05-04
申请人： Robert L. Brumley, Jr. , Lloyd M. Smith
发明人： Robert L. Brumley, Jr. , Lloyd M. Smith
IPC分类号： G01N27/447
CPC分类号： G01N27/44704 , G01N27/44756
摘要： A horizontal electrophoresis assembly is described which is designed to utilize very thin gels of polyacrylamide. The assembly allows for water cooling of the gel during electrophoresis so that higher voltages can be applied to the gel without polymer degradation. The gel mold is made from a set of glass plates which are clamped into place defining a gel mold between them. In one embodiment, the site of field introduction is separated from the site of sample introduction so that the electric field is generally linear at the region of sample introduction.
摘要翻译：描述了一种设计用于使用非常薄的聚丙烯酰胺凝胶的水平电泳组件。该组件允许在电泳期间水冷却凝胶，使得更高的电压可以施加到凝胶上而没有聚合物降解。凝胶模具由一组玻璃板制成，这些玻璃板被夹紧就位，在它们之间限定凝胶模具。在一个实施例中，场引入位置与样品引入位置分离，使得电场在样品引入区域通常是线性的。

4. 发明授权

US5171534A Automated DNA sequencing technique 失效
标题翻译：自动DNA测序技术
公开(公告)号：US5171534A
公开(公告)日：1992-12-15
申请号：US558312
申请日：1990-10-15
申请人： Lloyd M. Smith , Leroy E. Hood , Michael W. Hunkapiller , Tim J. Hunkapiller
发明人： Lloyd M. Smith , Leroy E. Hood , Michael W. Hunkapiller , Tim J. Hunkapiller
IPC分类号： C12Q1/68 , G01N27/447
CPC分类号： G01N27/44726 , C12Q1/6869 , G01N27/44721 , Y10T436/143333
摘要： A system for the electrophoretic analysis of DNA fragments produced in DNA sequencing operations comprising: a source of chromophore or fluorescent tagged DNA fragments; a zone for contacting an electrophoresis gel; means for introducing said tagged DNA fragments to said zone; and photometric means for monitoring said tagged DNA fragments as they move through said gel.
摘要翻译：用于在DNA测序操作中产生的DNA片段的电泳分析系统，包括：发色团或荧光标记的DNA片段; 用于接触电泳凝胶的区域; 用于将所述标记的DNA片段引入所述区域的方法; 以及用于在所述标记的DNA片段移动通过所述凝胶时监测所述标记的DNA片段的光度装置

5. 发明授权

US5162654A Detection apparatus for electrophoretic gels 失效
标题翻译：电泳凝胶检测装置
公开(公告)号：US5162654A
公开(公告)日：1992-11-10
申请号：US650393
申请日：1991-02-01
申请人： Anthony J. Kostichka , Lloyd M. Smith
发明人： Anthony J. Kostichka , Lloyd M. Smith
IPC分类号： G01J3/12 , G01N21/64 , G01N27/447
CPC分类号： G01N21/645 , G01N27/44721 , G01J2003/1226 , G01N2021/6421 , G01N2021/6441
摘要： An apparatus is disclosed to optically determine which of four fluorophores is attached to a band of DNA molecules on an electrophoresis gel. The apparatus includes four separate band pass interference filters and four wedge prisms to create four discrete areas of light on a detector. Digital comparison of the relative intensity of light sensed in the four discrete areas determines the identity of the excited fluorophore.
摘要翻译：公开了一种用于光学确定四个荧光团中的哪一个附着到电泳凝胶上的DNA分子带上的装置。该装置包括四个单独的带通干涉滤光器和四个楔形棱镜，以在检测器上产生四个离散的光区域。在四个离散区域中感测的光的相对强度的数字比较确定激发的荧光团的身份。

6. 发明授权

US3935392A Dial pulse detection method and apparatus 失效
标题翻译：拨号脉冲检测方法和装置
公开(公告)号：US3935392A
公开(公告)日：1976-01-27
申请号：US434013
申请日：1974-01-17
申请人： Lloyd M. Smith , Robert E. Webb
发明人： Lloyd M. Smith , Robert E. Webb
IPC分类号： H04Q1/32 , H04Q1/36
CPC分类号： H04Q1/32
摘要： Apparatus and method for detecting the occurrence of a dial pulse signal in a telephone circuit. Transient signals within the frequency range of possible dial pulse signals are detected, and the amplitude of the detected signals are compared with a predetermined amplitude level. A first time period and a second time period are initiated in response to a first detected signal which exceeds a certain initial reference amplitude, with the duration of the first time period being less than the interval between the two consecutive transient pulse signals to be expected of a true dial pulse signal. The duration of the second time period is substantially equal to the period of a true dial pulse signal. A received signal resembling a dial pulse signal is detected during the first period only if the amplitude of such signal exceeds a second reference amplitude which is greater than the initial reference amplitude. A second apparent dial pulse transient signal condition, occurring after the termination of the first time period but before the termination of the second time period, is interpreted as the occurrence of a true dial pulse signal, in response to which a corresponding dial pulse output signal is produced. A second apparent dial pulse transient signal condition occurring in the first time period, however, merely extends the duration of the first time period and provides no dial pulse output signal. An amplitude comparison circuit automatically adjusts the reference amplitude in response to the signal level of the circuit providing input signals to the apparatus.
摘要翻译：用于检测电话电路中拨号脉冲信号的发生的装置和方法。检测可能的拨号脉冲信号的频率范围内的瞬态信号，并将检测到的信号的幅度与预定的振幅电平进行比较。响应于超过某一初始参考幅度的第一检测信号开始第一时间段和第二时间段，其中第一时间段的持续时间小于预期的两个连续瞬态脉冲信号之间的间隔真正的拨号脉冲信号。第二时间段的持续时间基本上等于真实拨号脉冲信号的周期。只有当这种信号的幅度超过大于初始参考幅度的第二参考幅度时，才在第一周期期间检测到类似于拨号脉冲信号的接收信号。在第一时间段结束之后但在第二时间段结束之前发生的第二表观拨号脉冲瞬态信号条件被解释为真实拨号脉冲信号的发生，响应于此，对应的拨号脉冲输出信号生产。然而，在第一时间段中发生的第二表观拨号脉冲瞬态信号条件仅延长了第一时间段的持续时间并且不提供拨号脉冲输出信号。振幅比较电路响应于向设备提供输入信号的电路的信号电平自动调整参考幅度。

7. 发明授权

US08563777B2 Ionizable isotopic labeling reagents for relative quantification by mass spectrometry 有权
标题翻译：用于质谱相对定量的可离子化同位素标记试剂
公开(公告)号：US08563777B2
公开(公告)日：2013-10-22
申请号：US13155682
申请日：2011-06-08
申请人： Lloyd M. Smith , Michael R. Shortreed , Brian L. Frey , Margaret F. Phillips , Joshua J. Coon , Shane M. Lamos , Casey J. Krusemark , Peter J. Belshaw , Madhusudan Patel , Neil L. Kelleher
发明人： Lloyd M. Smith , Michael R. Shortreed , Brian L. Frey , Margaret F. Phillips , Joshua J. Coon , Shane M. Lamos , Casey J. Krusemark , Peter J. Belshaw , Madhusudan Patel , Neil L. Kelleher
IPC分类号： C07C211/10 , C07C211/11 , G01N33/58
CPC分类号： C07B59/001 , C07B59/00 , C07B59/008 , G01N30/7233 , G01N2458/15 , Y10T436/163333 , Y10T436/17
摘要： Relative quantification of metabolites by Electrospray Ionization Mass Spectrometry (ESI-MS) requiring a mechanism for simultaneous analysis of multiple analytes in two or more samples. Labeling reagents that are reactive to particular compound classes and differ only in their isotopic compositions facilitate relative quantification. Heavy and light isotopic forms of methylacetimidate were synthesized and used as labeling reagents for quantification of amine-containing molecules. Heavy and light isotopic forms of formaldehyde and cholamine were also synthesized and used independently as labeling reagents for quantification of amine-containing and carboxylic acid-containing molecules, such as found in biological samples. The labeled end-products are positively charged under normal acidic conditions involving conventional Liquid Chromatography Mass Spectrometry (LC/MS) applications. Labeled primary and secondary amine and carboxylic acid end-products generated higher signals concerning mass-spectra than pre-cursor molecules and improved sensitivity. Improved accuracy concerning relative quantification was demonstrated by mixing heavy and light labeled Arabidopsis extracts in different ratios.
摘要翻译：通过电喷雾离子化质谱（ESI-MS）对代谢物进行相对定量，其需要同时分析两个或多个样品中多种分析物的机制。对特定化合物类别具有反应性且仅在其同位素组成上不同的标记试剂便于相对定量。合成了甲基乙酰亚胺酸的重和轻同位素形式，并用作定量含胺分子的标记试剂。还合成了重和轻的同位素形式的甲醛和胆胺，并且独立地用作用于定量含胺和含羧酸的分子的标记试剂，例如在生物样品中发现的。标记的最终产物在常规的液相色谱质谱（LC / MS）应用的正常酸性条件下带正电。标记的伯胺和仲胺和羧酸终产物产生比前体分子更高的质谱信号，提高了灵敏度。通过以不同的比例混合重和轻标记的拟南芥提取物来证明相对定量的改进的准确性。

8. 再颁专利

USRE43096E1 Tagged extendable primers and extension products 有权
标题翻译：标签可扩展引物和扩展产物
公开(公告)号：USRE43096E1
公开(公告)日：2012-01-10
申请号：US10389663
申请日：2003-03-13
申请人： Lloyd M. Smith , Leroy E. Hood , Michael W. Hunkapiller , Timothy Hunkapiller , Charles R. Connell
发明人： Lloyd M. Smith , Leroy E. Hood , Michael W. Hunkapiller , Timothy Hunkapiller , Charles R. Connell
IPC分类号： C12Q1/68 , G01N27/447
CPC分类号： G01N27/44726 , C12Q1/6816 , C12Q1/6869 , G01N27/44721 , C12Q2563/107 , C12Q2535/101
摘要： This invention provides a duplex comprising an oligonucleotide primer and a template, wherein the primer is coupled chemically to a chromophore or fluorophore so as to allow chain extension by a polymerase. In one embodiment, the primer is extended by a polymerase to generate the complement of the template. In a further embodiment, the extended primer is separated from the template for use in a number of methods, including sequencing reactions. Methods of generating these compositions of matter are further provided.
摘要翻译：本发明提供了一种双链体，其包含寡核苷酸引物和模板，其中引物与发色团或荧光团化学偶联，以允许通过聚合酶进行链延伸。在一个实施方案中，引物通过聚合酶延伸以产生模板的补体。在另一个实施方案中，将延伸的引物与模板分离以用于多种方法，包括测序反应。进一步提供产生这些物质组合物的方法。

9. 发明申请

US20090141376A1 SURFACE PLASMON RESONANCE COMPATIBLE CARBON THIN FILMS 有权
标题翻译：表面等离子体共混碳薄膜
公开(公告)号：US20090141376A1
公开(公告)日：2009-06-04
申请号：US12037332
申请日：2008-02-26
申请人： Lloyd M. Smith , Matthew R. Lockett , Michael R. Shortreed , Robert M. Corn , Stephen Weibel , Robert J. Hamers , Bin Sun
发明人： Lloyd M. Smith , Matthew R. Lockett , Michael R. Shortreed , Robert M. Corn , Stephen Weibel , Robert J. Hamers , Bin Sun
IPC分类号： G02B5/04 , G01N21/55 , H01J49/00 , B32B38/00 , B05D5/06 , C23C14/34
CPC分类号： G01N21/553 , G02B5/04
摘要： SPR-compatible substrates for high density microarray fabrication and analyses are provided. Novel carbon-on-metal thin film substrate architecture permits the integration of surface plasmon resonance detection with photolithographically fabricated biomolecule arrays for the analysis of biomolecular interactions. The utility of the technology is shown in the analysis of specific DNA-DNA, DNA-RNA and DNA-protein binding interactions. These new substrates may be used to determine the secondary structure of RNA molecules, to probe the sequence-specific binding kinetics and affinity of proteins and small molecules, and as substrates for small-molecule combinatorial chemistry platforms for drug discovery applications.
摘要翻译：提供了用于高密度微阵列制造和分析的SPR兼容基板。新的碳 - 金属薄膜基板架构允许将表面等离子体共振检测与光刻制造的生物分子阵列整合以用于生物分子相互作用的分析。该技术的实用性在特异性DNA-DNA，DNA-RNA和DNA-蛋白结合相互作用的分析中显示。这些新的底物可用于确定RNA分子的二级结构，以探测序列特异性结合动力学和蛋白质和小分子的亲和力，以及作为用于药物发现应用的小分子组合化学平台的底物。

10. 发明授权

US07518108B2 Electrospray ionization ion source with tunable charge reduction 有权
标题翻译：具有可调电荷还原的电喷雾离子源
公开(公告)号：US07518108B2
公开(公告)日：2009-04-14
申请号：US11272450
申请日：2005-11-10
申请人： Brian L. Frey , Lloyd M. Smith , Michael S. Westphall
发明人： Brian L. Frey , Lloyd M. Smith , Michael S. Westphall
IPC分类号： B01D59/44 , H01J49/00
CPC分类号： H01J49/165 , H01J49/0045
摘要： This invention provides methods, devices and device components for preparing ions from liquid samples containing chemical species and methods and devices for analyzing chemical species in liquid samples. The present invention provides an ion source for generating analyte ions having a selected charge state distribution, such as a reduced charged state distribution, that may be effectively interfaced with a variety of charged particle analyzers, including virtually any type of mass spectrometer.
摘要翻译：本发明提供用于从含有化学物质的液体样品制备离子的方法，装置和装置组件以及用于分析液体样品中的化学物质的方法和装置。本发明提供了一种用于产生具有选定的电荷状态分布的分析离子的离子源，所述电荷状态分布例如降低的充电状态分布，其可以有效地与包括实际上任何类型的质谱仪在内的各种带电粒子分析仪接口。

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