公开(公告)号：US5401632A

公开(公告)日：1995-03-28

申请号：US915245

申请日：1992-07-16

申请人： Renfeng Wang ,  Lloyd M. Smith ,  Xinchun E. Tong

发明人： Renfeng Wang ,  Lloyd M. Smith ,  Xinchun E. Tong

IPC分类号： C12N15/10 ,  C12Q1/68 ,  C12Q1/70 ,  C07H21/04 ,  C12P19/34

CPC分类号： C12Q1/6813 ,  C12N15/1006 ,  C12Q1/6869

摘要： Disclosed herein are methods, kits, and equipment for purifying single stranded circular DNA and then using the DNA for DNA sequencing purposes. Templates are provided with an insert having a hybridization region. An elongated oligonucleotide has two regions that are complementary to the insert and the oligo is bound to a magnetic anchor. The oligo hybridizes to the insert on two sides to form a stable triple helix complex. The anchor can then be used to drag the template out of solution using a magnet. The system can purify sequencing templates, and if desired the triple helix complex can be opened up to a double helix so that the oligonucleotide will act as a primer for further DNA synthesis.

摘要翻译： 本文公开了用于纯化单链环状DNA然后使用DNA进行DNA测序目的的方法，试剂盒和设备。 提供了具有杂交区域的插入物的模板。 细长的寡核苷酸具有与插入物互补的两个区域，寡聚体结合到磁性锚定体上。 寡核苷酸与两侧的插入物杂交以形成稳定的三螺旋复合物。 然后可以使用锚来使用磁体将模板从溶液中拖出。 该系统可以纯化测序模板，如果需要，三螺旋复合物可以打开至双螺旋，使得寡核苷酸将作为进一步DNA合成的引物。

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。

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。

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。

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

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。

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。

公开(公告)号：US09651487B2

公开(公告)日：2017-05-16

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 ,  G01N21/552

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.

公开(公告)号：US07982070B2

公开(公告)日：2011-07-19

申请号：US11726307

申请日：2007-03-21

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 kit facilitating relative quantification and providing tangible evidence for the existence of specific functional groups. Heavy and light isotopic forms of methylacetimidate were synthesized and used as labeling reagents for quantification of amine-containing molecules, such as biological samples. 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. Advantageously, 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 also generated higher signals concerning mass-spectra than pre-cursor molecules and improved sensitivity. Improved accuracy concerning relative quantification was achieved by mixing heavy and light labeled Arabidopsis extracts in different ratios. Labeling strategy was further employed to ascertain differences in the amounts of amine-containing metabolites for two strains of Arabidopsis seeds.

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。 标记对特定化合物类别具有反应性的试剂，仅在其同位素试剂盒中有所不同，便于相对定量，并为特定官能团的存在提供有形证据。 合成了甲基亚酰亚胺酸的重和轻同位素形式，并用作定量含胺分子（如生物样品）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。 有利地，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荷。 标记的伯胺和仲胺和羧酸终产物也产生了比前体分子更高的质谱信号，提高了灵敏度。 通过以不同比例混合重和轻标记的拟南芥提取物，提高了相对定量的准确性。 进一步使用标记策略来确定两种拟南芥种子的含胺代谢物的量的差异。

公开(公告)号：US5258538A

公开(公告)日：1993-11-02

申请号：US734575

申请日：1991-10-29

申请人： Steven Fung ,  Sam L. Woo ,  Lloyd M. Smith

发明人： Steven Fung ,  Sam L. Woo ,  Lloyd M. Smith

IPC分类号： A61K47/48 ,  C07F9/24 ,  C07F9/6584 ,  C07H21/00 ,  C07F9/00

CPC分类号： C07H21/00 ,  A61K47/48023 ,  A61K47/48061 ,  A61K47/48084 ,  C07F9/2408 ,  C07F9/65842

摘要： The compounds of the invention include novel linking agents comprising 2-substituted-3-protected-1,3,2-oxazaphosphacycloalkanes and their phosphoramidite precursors. The compounds of the invention further include conjugates of the above linking agents with oligonucleotides and polymer supports. The compounds of the present invention are useful for linking organic moieties, such as fluorescent or chromogenic dyes, to polymer supports and oligonucleotides, particularly single- and double-stranded DNA and RNA fragments.

摘要翻译： 本发明的化合物包括包含2-取代-3-保护的1,3,2-氧杂氮杂环烷烃及其亚磷酰胺前体的新型交联剂。 本发明的化合物还包括上述连接剂与寡核苷酸和聚合物载体的缀合物。 本发明的化合物可用于将有机部分如荧光或显色染料与聚合物载体和寡核苷酸，特别是单链和双链DNA和RNA片段连接。