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1. 发明申请

US20070264640A1 Array-based assays using split-probe nucleic acid arrays 审中-公开
标题翻译：使用分裂探针核酸阵列的基于阵列的测定
公开(公告)号：US20070264640A1
公开(公告)日：2007-11-15
申请号：US11433876
申请日：2006-05-12
申请人： Michael T. Barrett , Nicholas M. Sampas
发明人： Michael T. Barrett , Nicholas M. Sampas
IPC分类号： C12Q1/68 , C12M3/00
CPC分类号： C12Q1/6837
摘要： Methods and compositions for performing array-based assays of a nucleic acid sample, such as genomic sample assays, e.g., comparative genomic (aCGH) assays, are provided. Aspects of the invention include arrays containing split-probe nucleic acids that include two linked domains that flank a nucleic acid region, such as a genomic region, of interest. The subject methods and compositions find use in a number of applications, including aCGH applications, e.g., identifying genomic copy number, evaluating the methylation status, etc. Also provided are kits that include the subject arrays.
摘要翻译：提供了用于进行核酸样品的基于阵列的测定的方法和组合物，例如基因组样品测定，例如比较基因组（aCGH）测定。本发明的方面包括含有分裂探针核酸的阵列，其包括位于感兴趣的核酸区域（例如基因组区域）的两个连接结构域。主题方法和组合物可用于许多应用，包括aCGH应用，例如识别基因组拷贝数，评估甲基化状态等。还提供了包括受试者阵列的试剂盒。

2. 发明申请

US20110301854A1 Method of Determining Allele-Specific Copy Number of a SNP 审中-公开
标题翻译：确定SNP的等位基因特异性拷贝数的方法
公开(公告)号：US20110301854A1
公开(公告)日：2011-12-08
申请号：US13073766
申请日：2011-03-28
申请人： Bo U. Curry , Nicholas M. Sampas
发明人： Bo U. Curry , Nicholas M. Sampas
IPC分类号： G06F19/00 , C40B30/04
CPC分类号： C12Q1/683 , C12Q1/6827 , G16B20/00 , G16B40/00 , C12Q2537/16 , C12Q2537/165
摘要： A method of estimating the allele-specific copy number of a SNP in a test genome is provided. In certain embodiments, the method involves: a) calculating a plurality of probability distribution functions that fit a plurality of log ratios indicating which alleles of a plurality of single nucleotide polymorphisms (SNPs) are present in diploid regions of a test and reference genome; and b) estimating the allele-specific copy number of a SNP of the test genome using said plurality of probability distribution functions.
摘要翻译：提供了一种估计测试基因组中SNP等位基因特异性拷贝数的方法。在某些实施方案中，所述方法包括：a）计算多个拟合多个对数比的概率分布函数，所述多个对数比指示在测试和参考基因组的二倍体区域中存在多个单核苷酸多态性（SNP）的哪些等位基因; 以及b）使用所述多个概率分布函数估计所述测试基因组的SNP的等位基因特异性拷贝数。

3. 发明授权

US08036835B2 Probe design methods and microarrays for comparative genomic hybridization and location analysis 有权
标题翻译：用于比较基因组杂交和位置分析的探针设计方法和微阵列
公开(公告)号：US08036835B2
公开(公告)日：2011-10-11
申请号：US12797521
申请日：2010-06-09
申请人： Nicholas M. Sampas , Bo Curry , Peter Tsang , Doron Lipson , Zohar H. Yakhini
发明人： Nicholas M. Sampas , Bo Curry , Peter Tsang , Doron Lipson , Zohar H. Yakhini
IPC分类号： G06F7/00
CPC分类号： C12Q1/6883 , B01J2219/00689 , B01J2219/00695 , B01J2219/00722 , G06F19/20
摘要： Methods and systems for identifying and selecting nucleic acid probes for detecting a target with a nucleic acid probe array or comparative genome hybridization microarray, comprising selecting a plurality of potential target sequences, generating a plurality of candidate probes from the target sequences, filtering the plurality of candidate probes by analyzing candidate probes for selected probe properties in silico. Microarrays comprising probes selected by the methods of the invention are particularly useful for comparative genome hybridization and location analysis.
摘要翻译：用于鉴定和选择用于用核酸探针阵列或比较基因组杂交微阵列检测靶的核酸探针的方法和系统，包括选择多个潜在靶序列，从靶序列产生多个候选探针，过滤多个通过分析选择的探针属性的候选探针在硅胶中的候选探针。包含通过本发明方法选择的探针的微阵列特别可用于比较基因组杂交和位置分析。

4. 发明授权

US5774213A Techniques for measuring difference of an optical property at two wavelengths by modulating two sources to have opposite-phase components at a common frequency 失效
标题翻译：通过调制两个源以在相同频率处具有相位分量来测量两个波长的光学性质的差异的技术
公开(公告)号：US5774213A
公开(公告)日：1998-06-30
申请号：US518427
申请日：1995-08-23
申请人： Rick P. Trebino , Nicholas M. Sampas , Eric K. Gustafson
发明人： Rick P. Trebino , Nicholas M. Sampas , Eric K. Gustafson
IPC分类号： G01N21/31
CPC分类号： G01N21/3151
摘要： A technique for making precise spectrophotometric measurements illuminates a sample with two or more modulated light sources at two or more, typically closely spaced, wavelengths. Light from the sources is combined, homogenized, and directed to the sample, and the light from the sample is collected and detected by a photodetector. The optical output powers of two sources are modulated with the same periodicity and with a reversed amplitude. Variations in the concentrations of species in the sample affect the modulation amplitude representing the sum of the optical powers from two sources in such a way as to produce an output signal. That output signal, based on an electrical component varying with a periodicity at the fundamental frequency, provides a measure of the difference in the transmissions (or other optical properties) of the sample at the two wavelengths. Feedback methods, such as null-point detection, provide stable, sensitive measurements. Wavelength-division multiplexing--required for simultaneous measurements at many wavelengths--is achieved by modulating different pairs of sources at different frequencies.
摘要翻译：用于进行精确的分光光度测量的技术用两个或更多个通常紧密间隔的波长的两个或多个调制光源照射样品。来自源的光被组合，均质化并且被引导到样品，并且来自样品的光被光电检测器收集和检测。两个源的光输出功率以相同的周期性和相反的幅度进行调制。样品中物种浓度的变化影响表示来自两个光源的光功率之和的调制幅度，以产生输出信号。该输出信号基于以基频周期性变化的电子分量提供在两个波长处的样本的传输（或其他光学性质）的差异的度量。反馈方法，如零点检测，提供稳定，敏感的测量。通过在不同频率调制不同的源对来实现在许多波长下同时测量所需的波分复用。

5. 发明授权

US09255245B2 Sample probes and methods for sampling intracellular material 有权
标题翻译：用于取样细胞内物质的样品探针和方法
公开(公告)号：US09255245B2
公开(公告)日：2016-02-09
申请号：US13541478
申请日：2012-07-03
申请人： Kristin Briana Bernick , Nicholas M. Sampas
发明人： Kristin Briana Bernick , Nicholas M. Sampas
IPC分类号： C12M1/34 , C12M1/00 , G01Q60/38 , B01L3/02 , C12M1/26
CPC分类号： C12M47/06 , B01L3/021 , C12M33/04 , G01Q60/38 , G01Q80/00
摘要： A sample probe includes a tip including a distal end for penetrating a cellular membrane, an opening located at or proximal to the distal end, and tip microchannels extending through the tip and communicating with the opening; and a body adjoining the tip and including body microchannels, wherein at least one of the body microchannels communicates with at least one of the tip microchannels. A method for sampling intracellular material includes inserting a probe tip through a cellular membrane; aspirating intracellular material from the cell, through an opening of the tip, and into a first microchannel of the tip; flowing isolator fluid from a second microchannel of the tip into the first microchannel to form a plug of intracellular material; and aspirating the plug and the isolator fluid through the first microchannel.
摘要翻译：样品探针包括尖端，其包括用于穿透细胞膜的远端，位于远端或近端的开口，以及延伸穿过尖端并与开口连通的尖端微通道; 以及与所述尖端相邻并且包括身体微通道的主体，其中所述主体微通道中的至少一个与所述尖端微通道中的至少一个连通。用于取样细胞内物质的方法包括将探针尖端穿过细胞膜; 从细胞吸出细胞内物质，通过尖端的开口并进入尖端的第一微通道; 流动的隔离器流体从尖端的第二微通道进入第一微通道以形成细胞内物质的塞子; 并且通过第一微通道吸出塞子和隔离器流体。

6. 发明授权

US07122303B2 Arrays comprising background features that provide for a measure of a non-specific binding and methods for using the same 失效
标题翻译：包含提供非特异性结合度量的背景特征的数组和使用该特征的方法
公开(公告)号：US07122303B2
公开(公告)日：2006-10-17
申请号：US09398399
申请日：1999-09-17
申请人： Glenda C. Delenstarr , Steven M. Lefkowitz , Kevin J. Luebke , Leslie B. Overman , Nicholas M. Sampas , Jeffery R. Sampson , Paul K. Wolber
发明人： Glenda C. Delenstarr , Steven M. Lefkowitz , Kevin J. Luebke , Leslie B. Overman , Nicholas M. Sampas , Jeffery R. Sampson , Paul K. Wolber
IPC分类号： C12Q1/68 , C12M1/34 , C07H21/02 , C07H21/04
CPC分类号： C12Q1/6837 , Y10T436/143333 , C12Q2545/107
摘要： Methods for substantially improved detection and analysis in nucleic acid hybridization assays are described. The methods provide the reliable estimation of background signal which derives primarily from nonspecific hybridization. The invention is useful in chemical, biological, medical and diagnostic techniques, as well as for drug discovery.
摘要翻译：描述了在核酸杂交测定中基本上改进的检测和分析的方法。该方法提供了主要来自非特异性杂交的背景信号的可靠估计。本发明可用于化学，生物，医学和诊断技术以及用于药物发现。

7. 发明授权

US07006927B2 Method and system for extracting data from surface array deposited features 有权
公开(公告)号：US07006927B2
公开(公告)日：2006-02-28
申请号：US10086839
申请日：2002-02-28
申请人： Zohar Yakhini , Cynthia Y. Enderwick , Glenda C. Delenstarr , Paul K. Wolber , Nicholas M. Sampas , Herbert F. Cattell , Scott D. Connell
发明人： Zohar Yakhini , Cynthia Y. Enderwick , Glenda C. Delenstarr , Paul K. Wolber , Nicholas M. Sampas , Herbert F. Cattell , Scott D. Connell
IPC分类号： G06F11/32
CPC分类号： G06T7/73 , G06T2207/30072
摘要： A method and system for extracting data signals from a scanned image resulting from optical, radiometric, or other types of analysis of a molecular array. The positions of corner features are first located. Then, an initial feature coordinate grid is determined from the positions of the corner features. A refined feature coordinate grid is then calculated based on the positions of strong features, and is used to identify the positions of weak features and the positions of the local background regions surrounding all features. Finally, signal intensity values are extracted from the features and their respective local background regions in the scanned image, and background-subtracted signal intensity values, background-subtracted and normalized signal intensity ratios, and variability information and confidence intervals are determined based on the extracted values.

8. 发明授权

US06750963B2 Imaging systems for signals on a surface 有权
标题翻译：用于表面信号的成像系统
公开(公告)号：US06750963B2
公开(公告)日：2004-06-15
申请号：US10153128
申请日：2002-05-21
申请人： Nicholas M. Sampas
发明人： Nicholas M. Sampas
IPC分类号： G01N2164
CPC分类号： G01N21/6452 , G01N21/6428
摘要： Apparatus and methods are disclosed for imaging surfaces that comprise a sample. One embodiment of the present invention is an imaging apparatus comprising a holder for a surface, a light source adapted to illuminate the surface, a diffractive element between the holder and the light source and an imaging detector adapted to receive light from the surface. In a method for imaging a surface comprising a plurality of discrete features, light is selectively diffracted on to one or more predetermined features of the surface at a predetermined point in time. This step is repeated until substantially all of the features on the surface are illuminated. Light is detected from the surface to thereby image the surface.
摘要翻译：公开了用于对包含样品的表面进行成像的装置和方法。本发明的一个实施例是一种成像设备，其包括用于表面的保持器，适于照亮表面的光源，保持器和光源之间的衍射元件以及适于接收来自表面的光的成像检测器。在用于成像包括多个离散特征的表面的方法中，光在预定的时间点被选择性地衍射到表面的一个或多个预定特征。重复该步骤直到基本上表面上的所有特征被照亮。从表面检测光，从而对表面进行成像。

9. 发明授权

US06591196B1 Method and system for extracting data from surface array deposited features 有权
公开(公告)号：US06591196B1
公开(公告)日：2003-07-08
申请号：US09589046
申请日：2000-06-06
申请人： Zohar Yakhini , Cynthia Y. Enderwick , Glenda C. Delenstarr , Paul K. Wolber , Nicholas M. Sampas
发明人： Zohar Yakhini , Cynthia Y. Enderwick , Glenda C. Delenstarr , Paul K. Wolber , Nicholas M. Sampas
IPC分类号： G01J102
CPC分类号： G06K9/3275 , G06T7/73 , G06T2207/30072
摘要： A method and system for extracting data signals from a scanned image resulting from optical, radiometric, or other types of analysis of a molecular array. The positions of corner features are first located. Then, an initial feature coordinate grid is determined from the positions of the corner features. A refined feature coordinate grid is then calculated based on the positions of strong features, and is used to identify the positions of weak features and the positions of the local background regions surrounding all features. Finally, signal intensity values are extracted from the features and their respective local background regions in the scanned image, and background-subtracted signal intensity values, background-subtracted and normalized signal intensity ratios, and variability information and confidence intervals are determined based on the extracted values.

10. 发明授权

US06218118B1 Method and mixture reagents for analyzing the nucleotide sequence of nucleic acids by mass spectrometry 失效
标题翻译：用于通过质谱分析核酸核苷酸序列的方法和混合试剂
公开(公告)号：US06218118B1
公开(公告)日：2001-04-17
申请号：US09112437
申请日：1998-07-09
申请人： Jeffrey R. Sampson , Zohar H. Yakhini , Peter G. Webb , Nicholas M. Sampas , Anna M. Tsalenko , Joel Myerson
发明人： Jeffrey R. Sampson , Zohar H. Yakhini , Peter G. Webb , Nicholas M. Sampas , Anna M. Tsalenko , Joel Myerson
IPC分类号： C12Q168
CPC分类号： C12Q1/6872 , B01J2219/00454 , B01J2219/00497 , B01J2219/00605 , B01J2219/0061 , B01J2219/00612 , B01J2219/00626 , B01J2219/00637 , B01J2219/00641 , B01J2219/00722 , C12Q1/6874 , C40B40/00 , C12Q2537/143 , C12Q2533/101 , C12Q2533/107
摘要： Methods and reagents are disclosed which satisfy the need for more sensitive, more accurate and higher through-put analyses of target nucleic acid sequences. The methods and reagents may be generically applied to generally any target nucleic acid sequence and do not require a priori information about the presence, location or identity of mutations in the target nucleic acid sequence. The reagents of the invention are mixtures of natural and mass-modified oligonucleotide precursors having a high level of coverage and mass number complexity. A method is also disclosed for analyzing a target nucleic acid sequence employing the mixtures of natural and mass-modified oligonucleotide precursors and chemical or enzymatic assays to alter the mass of the oligonucleotide precursors prior to mass spectral analysis, generally via MALDI-TOF. The enzymatic assay may be a polymerase extension assay or a ligase assay. The kits for carrying out the methods of the invention are also disclosed.
摘要翻译：公开了满足对靶核酸序列的更灵敏，更准确和更高的通过分析的需要的方法和试剂。方法和试剂通常可以一般地应用于任何靶核酸序列，并且不需要关于靶核酸序列中突变的存在，位置或特征的先验信息。本发明的试剂是具有高覆盖率和质量数复杂性的天然和质量修饰的寡核苷酸前体的混合物。还公开了一种使用天然和质量修饰寡核苷酸前体的混合物分析目标核酸序列的方法，以及通常通过MALDI-TOF在质谱分析之前改变寡核苷酸前体的质量以进行化学或酶学测定。酶测定可以是聚合酶延伸测定或连接酶测定。还公开了用于实施本发明的方法的试剂盒。

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