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1. 发明授权

US10407718B2 Optimization of gene expression analysis using immobilized capture probes 有权
公开(公告)号：US10407718B2
公开(公告)日：2019-09-10
申请号：US15491127
申请日：2017-04-19
申请人： BioArray Solutions, Ltd.
发明人： Michael Seul , Sukanta Banerjee , Jiacheng Yang , Tatiana Vener
IPC分类号： C12Q1/6832 , C12Q1/6809 , C12Q1/6834 , C12Q1/6837
摘要： Disclosed are methods of multiplexed analysis of oligonucleotides in a sample, including a method of preventing a significant reduction in duplexes detectable in a hybridization assay involving (i) selecting probe lengths for sets of oligonucleotide probes, wherein probes include different subsequences such that at least one subsequence is complementary to a subsequence in a cognate target; wherein probes for longer cognate targets are longer in length than probes for shorter cognate targets, (ii) selecting, for each set of probes, a density of oligonucleotides probes attached per unit area on a solid phase carrier which is below a limit at which the significant reduction in detectable duplexes is predicated to take place, (iii) producing the probes and affixing them to different solid phase carriers at the selected density, and (iv) annealing targets to the probes, wherein signal intensities of probes and targets of different lengths are about the same.

2. 发明申请

US20170218437A1 Optimization Of Gene Expression Analysis Using Immobilized Capture Probes 审中-公开
公开(公告)号：US20170218437A1
公开(公告)日：2017-08-03
申请号：US15491127
申请日：2017-04-19
申请人： BioArray Solutions, Ltd.
发明人： Michael SEUL , Sukanta Banerjee , Jiacheng YANG , Tatiana Vener
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6832 , B01J2219/00459 , B01J2219/00576 , B01J2219/00608 , B01J2219/00648 , B01J2219/00722 , C12Q1/6809 , C12Q1/6834 , C12Q1/6837 , C12Q2537/143 , C12Q2565/501 , C12Q2565/507 , C12Q2533/101 , C12Q2565/514 , C12Q2565/519
摘要： Disclosed are methods of multiplexed analysis of oligonucleotides in a sample, including: methods of probe and target “engineering”, as well as methods of assay signal analysis relating to the modulation of the probe-target affinity constant, K by a variety of factors including the elastic properties of target strands and layers of immobilized (“grafted”) probes; and assay methodologies relating to: the tuning of assay signal intensities including dynamic range compression and on-chip signal amplification; the combination of hybridization-mediated and elongation-mediated detection for the quantitative determination of abundance of messages displaying a high degree of sequence similarity, including, for example, the simultaneous determination of the relative expression levels, and identification of the specific class of, untranslated AU-rich subsequences located near the 3′ terminus of mRNA; and a new method of subtractive differential gene expression analysis which requires only a single color label.

3. 发明授权

US09709559B2 Multianalyte molecular analysis using application-specific random particle arrays 有权
公开(公告)号：US09709559B2
公开(公告)日：2017-07-18
申请号：US10032657
申请日：2001-12-28
申请人： Sukanta Banerjee , Michael Seul
发明人： Sukanta Banerjee , Michael Seul
IPC分类号： G01N33/543 , G01N33/58 , B01J19/00 , B82Y15/00
CPC分类号： G01N33/5434 , B01J19/0046 , B01J2219/005 , B01J2219/00545 , B01J2219/00576 , B82Y15/00 , C12Q1/6837 , C12Q1/6876 , G01N27/745 , G01N33/54326 , G01N33/54333 , G01N33/54346 , G01N33/587 , G01N33/588
摘要： The present invention provides a method for the generation of novel libraries of encoded magnetic particles from sub-libraries of by the generation of novel sub-libraries of magnetic nanoparticles and encoded particles. The sub-libraries are functionalized on demand are useful in the formation of arrays. The present invention is especially useful for performing multiplexed (parallel) assays for qualitative and/or quantitative analysis of binding interactions of a number of analyte molecules in a sample.

4. 发明申请

US20160340723A1 Multiplexed Analysis Of Polymorphic Loci By Concurrent Interrogation And Enzyme-Mediated Detection 审中-公开
标题翻译：通过并发询问和酶介导检测多态位点的多重分析
公开(公告)号：US20160340723A1
公开(公告)日：2016-11-24
申请号：US15228377
申请日：2016-08-04
申请人： BioArray Solutions, Ltd.
发明人： Alice Xiang Li , Ghazala Hashmi , Michael SEUL
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6827 , C12Q1/6837 , C12Q1/6858 , C12Q1/6883 , C12Q2600/156 , C12Q2600/16 , C12Q2565/537 , C12Q2535/125 , C12Q2527/107
摘要： The invention provides methods and processes for the identification of polymorphisms at one ore more designated sites, without interference from non-designated sites located within proximity of such designated sites. Probes are provided capable of interrogation of such designated sites in order to determine the composition of each such designated site. By the methods of this invention, one ore more mutations within the CFTR gene and the HLA gene complex can be identified.
摘要翻译：本发明提供了在一个或多个指定地点识别多态性的方法和过程，而不受位于该指定位点附近的非指定位点的干扰。提供能够询问这些指定地点的探测器，以确定每个这样的指定地点的组成。通过本发明的方法，可以鉴定CFTR基因和HLA基因复合体之间一个以上的突变。

5. 发明申请

US20160267650A1 ANALYSIS, SECURE ACCESS TO, AND TRANSMISSION OF ARRAY IMAGES 有权
标题翻译：分析，安全访问和传输阵列图像
公开(公告)号：US20160267650A1
公开(公告)日：2016-09-15
申请号：US15010597
申请日：2016-01-29
申请人： BioArray Solutions, Ltd.
发明人： Michael SEUL , Xiongwu Xia , Chiu CHAU , Scott DETERMAN
IPC分类号： G06T7/00 , G01N33/566 , G06K9/00
CPC分类号： G06T7/0012 , G01N33/566 , G06K9/00 , G06K9/00147 , G06K2209/07 , G06T7/11 , G06T7/155 , G06T7/33 , G06T2207/10064 , G06T2207/20152 , G06T2207/30072
摘要： Systems and methods are provided the autocentering, autofocusing, acquiring, decoding, aligning, analyzing and exchanging among various parties, images, where the images are of arrays of signals associated with ligand-receptor interactions, and more particularly, ligand-receptor interactions where a multitude of receptors are associated with microparticles or microbeads. The beads are encoded to indicate the identity of the receptor attached, and therefore, an assay image and decoding image are aligned to effect the decoding. The images or data extracted from such images can be exchanged between de-centralized assay locations and a centralized location where the data are analyzed to indicate assay results. Access to data can be restricted to authorized parties in possession of certain encoding information, so as to preserve confidentiality.
摘要翻译：系统和方法提供了各方之间的自动对中，自动聚焦，获取，解码，对齐，分析和交换，其中图像是与配体 - 受体相互作用相关联的信号阵列，更具体地，配体 - 受体相互作用，其中许多受体与微粒或微珠相关。编码珠子以指示所连接的受体的身份，因此，分析图像和解码图像被对准以影响解码。从这样的图像提取的图像或数据可以在非集中测定位置和数据被分析以指示测定结果的集中位置之间交换。访问数据可以限于拥有某些编码信息的授权方，以保护机密性。

6. 发明申请

US20160002714A1 AUTOMATED ANALYSIS OF MULTIPLEXED PROBE-TARGET INTERACTION PATTERNS: PATTERN MATCHING AND ALLELE IDENTIFICATION 审中-公开
标题翻译：多重探测目标相互作用模式的自动分析：模式匹配与识别
公开(公告)号：US20160002714A1
公开(公告)日：2016-01-07
申请号：US14851844
申请日：2015-09-11
申请人： BioArray Solutions, Ltd.
发明人： Xiongwu XIA , Michael SEUL
IPC分类号： C12Q1/68 , G06F19/22
CPC分类号： C12Q1/6827 , G16B20/00 , G16B30/00
摘要： Disclosed are methods and algorithms (and their implementation) supporting the automated analysis and interactive review and refinement (“redaction”) of the analysis within an integrated software environment, for automated allele assignments. The implementation, preferably with a software system and a program referred to as the Automated Allele Assignment (“AAA”) program, provides a multiplicity of functionalities including: data management by way of an integrated interface to a portable database to permit visualizing, importing, exporting and creating customizable summary reports; system configuration (“Set-up”) including user authorization, training set analysis and probe masking; Pattern Analysis including string matching and probe flipping; and Interactive Redaction combining real-time database computations and “cut-and-paste” editing, generating “warning” statements and supporting annotation. It also includes a thresholding function, a method of setting thresholds, a method of refining thresholds by matching an experimental binary string (“reaction pattern”) setting for that probe, probe masking of signals produced by probes which do not contribute significantly to discriminating among alleles.
摘要翻译：公开的方法和算法（及其实现）支持在集成软件环境中进行自动化等位基因分配的自动分析和交互式审查和细化（“编辑”）分析。优选地使用软件系统和称为自动等位基因分配（“AAA”）程序的程序的实现提供了多种功能，包括：通过与便携式数据库的集成接口的数据管理，以允许可视化，导入，出口和创建可定制的汇总报告; 系统配置（“设置”），包括用户授权，训练集分析和探测屏蔽; 模式分析包括字符串匹配和探针翻转; 和Interactive Redaction将实时数据库计算和“剪切和粘贴”编辑相结合，生成“警告”语句和支持注释。它还包括阈值功能，设置阈值的方法，通过匹配用于该探针的实验二进制串（“反应模式”）设置来精确化阈值的方法，探针对由探针产生的信号进行探针掩蔽，所述探针不对显着区别于等位基因

7. 发明申请

US20140358446A1 Selection of Genotyped Transfusion Donors by Cross-Matching to Genotyped Recipients 审中-公开
标题翻译：通过与基因型受体的交叉匹配选择基因型输血供体
公开(公告)号：US20140358446A1
公开(公告)日：2014-12-04
申请号：US14256579
申请日：2014-04-18
申请人： BIOARRAY SOLUTIONS, LTD.
发明人： Yi Zhang , Michael Seul
IPC分类号： G06F19/00
CPC分类号： G06F19/3456 , G06F19/3481 , G16B20/00 , G16B25/00 , G16B30/00 , G16B40/00 , G16H10/60 , G16H50/70
摘要： Disclosed are methods for establishing the compatibility between two blood types on the basis of cross-matching (under a designated rule of stringency) the minor blood group genotypes of recipient and prospective donors. To determine compatibility, the blood group genotypes are mapped to corresponding phenotypes according to the expression states associated with a set of underlying haplotypes, and compatibility is established by establishing the compatibility of blood types constructed as a combination of constituent phenotypes. The bit strings are matched, preferably using an algorithm expression. Where ambiguity in mapping genotypes to haplotypes exists, it can be reduced based on frequency of occurrence of the haplotypes in the sample population, or resolved by gametic phasing. Such reduction or resolution of ambiguity is particularly desirable where mismatches in the antigens expressed by the constituent haplotypes have greater clinical significance.
摘要翻译：公开的是基于接受者和潜在供体的次要血型基因型的交叉匹配（在指定的严格规则）的基础上建立两种血型之间的相容性的方法。为了确定相容性，根据与一组潜在单倍型相关联的表达状态，将血型基因型映射到相应的表型，并且通过建立构成为构成表型的组合的血型相容性建立相容性。比特串匹配，最好使用算法表达式。如果存在将基因型映射到单倍型的歧义，则可以根据样本群体中单倍型的发生频率来减少，或者通过配子定相来解决。在组成单元型表达的抗原中的错配具有更大的临床意义的情况下，这种模糊的减少或解决是特别理想的。

8. 发明授权

US08691754B2 Microparticles with enhanced covalent binding capacity and their uses 有权
标题翻译：具有增强的共价结合能力的微粒及其用途
公开(公告)号：US08691754B2
公开(公告)日：2014-04-08
申请号：US12795198
申请日：2010-06-07
申请人： Xinwen Wang , Sukanta Banerjee
发明人： Xinwen Wang , Sukanta Banerjee
IPC分类号： C07K14/00
CPC分类号： C12Q1/6834 , C07H21/04 , G01N33/54353 , C12Q2563/119
摘要： A polyelectrolyte having multiple exposed functional groups, each such group being capable of covalently bonding to a molecule, is immobilized on a surface for the purpose of bonding to a biomolecule. The biomolecule can be, for example, a nucleic acid, e.g., an amine functionalized oligonucleotide. The polyelectrolyte can include, e.g., BSA (Bovine Serum Albumin) which is bound to a functionalized surface using a covalent immobilization strategy, e.g., reaction with the surface of a tosyl-activated microparticle. Following such reaction, exposed reactive functional groups on the protein, such as amine, carboxyl, thiol, hydroxyl groups can further be utilized to covalently couple the oligonucleotide of interest using suitable chemistry.
摘要翻译：具有多个暴露的官能团的聚电解质，每个这样的基团能够共价键合到分子，固定在表面上用于与生物分子结合的目的。生物分子可以是例如核酸，例如胺官能化的寡核苷酸。聚电解质可以包括例如BSA（牛血清白蛋白），其使用共价固定策略结合到官能化表面，例如与甲苯磺酰基活化的微粒的表面反应。在这样的反应之后，蛋白质上暴露的反应性官能团如胺，羧基，硫醇，羟基可进一步用于使用合适的化学物质共价连接感兴趣的寡核苷酸。

9. 发明授权

US08206953B2 Message abundance and allele copy number determination using IVT with single-stranded primer-promoter-selector constructs 有权
标题翻译：使用IVT与单链引物启动子选择构建体的消息丰度和等位基因拷贝数确定
公开(公告)号：US08206953B2
公开(公告)日：2012-06-26
申请号：US11525064
申请日：2006-09-21
申请人： Nataliya Korzheva , Michael Seul
发明人： Nataliya Korzheva , Michael Seul
IPC分类号： C12P19/34
CPC分类号： C12Q1/6837 , C12N15/1096 , C12Q1/6858 , C12Q1/6865 , C12Q1/6876 , C12Q2521/107 , C12Q2525/143 , C12Q2563/179 , C12Q2565/137 , C12Q2545/114 , C12Q2531/113
摘要： Disclosed is a single stranded primer-promoter-selector construct comprising (in 3′ to 5′ orientation) a primer subsequence annealing to the target, a T7 or other promoter subsequence (the template strand), and a selector subsequence. The primer can be extended by template mediated elongation, including reverse transcription, or ligation to another oligonucleotide. The promoter sequence is oriented to direct the in-vitro transcription (IVT) opposite to that of primer extension, where the selector subsequence serves as a template for IVT. The selector is associated with the target subsequence of interest and it, and the amplified product are unique subsequences, dissimilar to other sequence present in the sample. The construct's is useful for determination of the presence and relative abundance of designated subsequences in the sample, multiplex gene expression analysis, multiplex allele counting, determination of polymorphic/mutation site, and loss of heterozygosity.
摘要翻译：公开了一种单链引物 - 启动子选择构建体，其包含（靶向3'至5'取向）引物亚序列退火，T7或其它启动子亚序列（模板链）和选择子序列。引物可通过模板介导的延伸扩增，包括逆转录或连接至另一寡核苷酸。启动子序列被定向以引导与引物延伸相反的体外转录（IVT），其中选择子序列用作IVT的模板。选择器与感兴趣的目标子序列相关联，并且扩增产物是与样本中存在的其他序列不同的唯一子序列。该构建体可用于确定样品中指定的子序列的存在和相对丰度，多重基因表达分析，多重等位基因计数，多态/突变位点的确定和杂合性的丧失。

10. 发明申请

US20120157346A1 Programmable illumination pattern for transporting microparticles 有权
标题翻译：用于运输微粒的可编程照明图案
公开(公告)号：US20120157346A1
公开(公告)日：2012-06-21
申请号：US13332715
申请日：2011-12-21
申请人： Michael Seul , Chiu Wo Chau
发明人： Michael Seul , Chiu Wo Chau
IPC分类号： C40B40/00
CPC分类号： B01L3/502792 , B01L3/502715 , B01L3/50273 , B01L3/502753 , B01L3/502761 , B01L2200/0668 , B01L2300/0819 , B01L2300/089 , B01L2400/0454 , C12Q1/6837 , G01N15/0266 , G01N30/0005 , G01N33/54313 , G01N2015/0288 , G01N2015/149 , C12Q2565/607 , C12Q2563/155
摘要： The present application provides a set of fundamental operations enabling interactive control over the creation and placement of planar arrays of several types of particles and biomolecules and the manipulation of array shape and size. The present invention enables sample preparation and handling for diagnostic assays and biochemical analysis in an array format, and the functional integration of these operations. In addition, the present invention provides a procedure for the creation of material surfaces with desired properties and for the fabrication of surface-mounted optical components.
摘要翻译：本申请提供了一组基本操作，使得能够对几种类型的颗粒和生物分子的平面阵列的创建和放置以及阵列形状和尺寸的操纵进行交互式控制。本发明使得能够以阵列格式进行诊断测定和生化分析的样品制备和处理以及这些操作的功能整合。此外，本发明提供了用于产生具有所需性质的材料表面和用于制造表面安装光学部件的步骤。

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