公开(公告)号：US08073219B2

公开(公告)日：2011-12-06

申请号：US12369342

申请日：2009-02-11

申请人： Akira Maekawa ,  Toshiro Saito ,  Kiyoyuki Kagii ,  Takayuki Obara

发明人： Akira Maekawa ,  Toshiro Saito ,  Kiyoyuki Kagii ,  Takayuki Obara

IPC分类号： G06K9/18

CPC分类号： G01N21/6452 ,  G01N21/648 ,  G06T7/0004 ,  G06T7/136 ,  G06T2207/10064 ,  G06T2207/30024

摘要： The present invention provides a nucleic acid analyzing apparatus which achieves highly accurate analytical ability even in single molecule DNA analysis. The nucleic acid analyzing apparatus detects locations of fluorescent bright spots in image information about light emission, deletes defective bright spots, and thereby creates intensity trace data about proper bright spots.

摘要翻译： 本发明提供即使在单分子DNA分析中也能够获得高精度的分析能力的核酸分析装置。 核酸分析装置检测关于发光的图像信息中的荧光亮点的位置，删除有缺陷的亮点，从而生成关于适当的亮点的强度追踪数据。

公开(公告)号：US20090245604A1

公开(公告)日：2009-10-01

申请号：US12369342

申请日：2009-02-11

申请人： Akira MAEKAWA ,  Toshiro Saito ,  Kiyoyuki Kagii ,  Takayuki Obara

发明人： Akira MAEKAWA ,  Toshiro Saito ,  Kiyoyuki Kagii ,  Takayuki Obara

IPC分类号： G06K9/00

CPC分类号： G01N21/6452 ,  G01N21/648 ,  G06T7/0004 ,  G06T7/136 ,  G06T2207/10064 ,  G06T2207/30024

摘要： The present invention provides a nucleic acid analyzing apparatus which achieves highly accurate analytical ability even in single molecule DNA analysis. The nucleic acid analyzing apparatus detects locations of fluorescent bright spots in image information about light emission, deletes defective bright spots, and thereby creates intensity trace data about proper bright spots.

摘要翻译： 本发明提供即使在单分子DNA分析中也能够获得高精度的分析能力的核酸分析装置。 核酸分析装置检测关于发光的图像信息中的荧光亮点的位置，删除有缺陷的亮点，从而生成关于适当的亮点的强度追踪数据。

公开(公告)号：US20130309675A1

公开(公告)日：2013-11-21

申请号：US13981983

申请日：2012-01-26

申请人： Toshiro Saito ,  Kazumichi Imai ,  Takayuki Obara ,  Eri Tarasawa

发明人： Toshiro Saito ,  Kazumichi Imai ,  Takayuki Obara ,  Eri Tarasawa

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6869 ,  C12Q1/6806 ,  C12Q1/6834 ,  C12Q1/6876 ,  C12Q2525/131 ,  C12Q2525/197 ,  C12Q2535/122 ,  C12Q2537/125 ,  C12Q2537/159 ,  C12Q2563/155

摘要： A microparticle having a probe molecule able to capture a specific nucleic acid group to be analyzed is used to extract only the specific nucleic acid group to be analyzed from a nucleic acid sample and the microparticle is thereafter directly immobilized on a smooth plate, whereby a device for nucleic acid analysis is rapidly prepared. Immobilizing a single capture probe molecule onto an individual microparticle in advance and forming, at regular positions on the smooth substrate, an adhesion pad on which a functional group that binds to the microparticle has been introduced makes it possible to readily and rapidly prepare the device for nucleic analysis, where the nucleic acid sample to be analyzed is arranged molecule by molecule in a lattice shape on the smooth substrate.

摘要翻译： 使用具有能够捕获要分析的特定核酸组的探针分子的微粒从核酸样品中仅提取待分析的特异性核酸组，然后将微粒直接固定在光滑平板上， 用于核酸分析快速准备。 将单个捕获探针分子预先固定在单个微粒上，并且在光滑基底上的规则位置处形成粘附有与微粒结合的官能团的粘合垫，使得可以容易且快速地制备用于 核酸分析，其中要分析的核酸样品以平滑基底上的格子状分子排列。

公开(公告)号：US09957562B2

公开(公告)日：2018-05-01

申请号：US14002125

申请日：2012-01-24

申请人： Koshin Hamasaki ,  Toshiro Saito ,  Takayuki Obara

发明人： Koshin Hamasaki ,  Toshiro Saito ,  Takayuki Obara

IPC分类号： C12Q1/68 ,  G01N21/64 ,  C40B40/06

CPC分类号： C12Q1/6876 ,  C12Q1/6834 ,  C12Q1/6874 ,  C40B40/06 ,  G01N21/6452 ,  G01N21/648 ,  G01N2021/6439 ,  C12Q2521/543 ,  C12Q2535/122 ,  C12Q2563/149 ,  C12Q2565/513 ,  C12Q2523/308

摘要： In the conventional nucleic acid analysis devices and nucleic acid analyzers, there was no technique available for sequencing a single nucleic acid molecule easily and highly efficiently. The present invention enabled a highly efficient single molecule immobilization of nucleic acid with good reproductivity in a short time at a low price by providing small metallic bonding pads at predetermined positions on a support substrate, firmly fixing a hydrophobic linker on the bonding pads, and bonding on to the linker bulky microparticles onto which a single molecule of a nucleic acid sample fragment is immobilized. According to the present invention, in the nucleic acid analysis device which uses a nucleic acid analyzer, the nucleotide read length can be extended and many types of nucleic acid molecule to be analyzed can be analyzed at one time.

公开(公告)号：US20130157264A1

公开(公告)日：2013-06-20

申请号：US13818704

申请日：2011-07-19

申请人： Takayuki Obara ,  Kazumichi Imai ,  Toshiro Saito ,  Satoshi Takahashi

发明人： Takayuki Obara ,  Kazumichi Imai ,  Toshiro Saito ,  Satoshi Takahashi

IPC分类号： G01N21/64

CPC分类号： G01N21/6486 ,  C12Q1/6837 ,  G01N21/6428 ,  G01N21/6452 ,  G01N21/648 ,  C12Q2563/173

摘要： In a nucleic acid analysis device which detects a fluorescent dye on a nucleic acid sample immobilized on a surface of a substrate by exciting the fluorescent dye with an evanescent wave, the detection of a fluorescence signal with a high SN ratio is realized even for a long nucleic acid sample.The nucleic acid analysis device according to the invention is a nucleic acid analysis device in which a plurality of regions for immobilizing a nucleic acid sample are provided on a surface of a support base and a single molecule of a nucleic acid sample is immobilized on at least one of the regions, and which performs sequence determination by performing an extension reaction of the immobilized nucleic acid sample, wherein the immobilization of the single molecule of the nucleic acid sample on the support base is performed at two or more points.

摘要翻译： 在通过用ev逝波激发荧光染料来检测固定在基板表面上的核酸样品上的荧光染料的核酸分析装置中，即使长时间地实现高SN比的荧光信号的检测 核酸样品。 根据本发明的核酸分析装置是核酸分析装置，其中在支持基底的表面上提供用于固定核酸样品的多个区域，并且将至少一个核酸样品的单个分子固定在至少 其中一个区域，并且通过进行固定化的核酸样品的延伸反应进行序列测定，其中将核酸样品的单分子固定在载体基底上进行两点或更多点。

公开(公告)号：US20060134667A1

公开(公告)日：2006-06-22

申请号：US11274314

申请日：2005-11-16

申请人： Masatoshi Narahara ,  Toshiro Saito ,  Takayuki Obara ,  Kenji Yasuda

发明人： Masatoshi Narahara ,  Toshiro Saito ,  Takayuki Obara ,  Kenji Yasuda

IPC分类号： C12Q1/68 ,  C12P19/34

CPC分类号： C12Q1/6806 ,  C12Q1/6827 ,  C12Q1/6834 ,  C12Q1/6886 ,  C12Q2600/158 ,  C12Q2525/143 ,  C12Q2521/119 ,  C12Q2525/149

摘要： The present invention relates to a method for detecting fusion gene transcripts resulting from chromosomal translocation. Specifically, the method of the present invention comprises allowing at least two or more probes, each of which contains a partial base sequence of exons which sandwich the breakpoint of a fusion gene or complementary base sequence thereof, and each of which immobilized on a support, to hybridize with a sample containing a nucleic acid derived from a fusion gene, thereby allowing the detection of two or more fusion genes at a time.

摘要翻译： 本发明涉及一种检测由染色体易位引起的融合基因转录物的方法。 具体地说，本发明的方法包括允许至少两个或更多个探针，每个探针含有夹心融合基因或其互补碱基序列的断点的外显子的部分碱基序列，并且每个探针固定在载体上， 与含有衍生自融合基因的核酸的样品杂交，从而一次检测两个或更多个融合基因。

公开(公告)号：US09290804B2

公开(公告)日：2016-03-22

申请号：US13981983

申请日：2012-01-26

申请人： Toshiro Saito ,  Kazumichi Imai ,  Takayuki Obara ,  Eri Tarasawa

发明人： Toshiro Saito ,  Kazumichi Imai ,  Takayuki Obara ,  Eri Tarasawa

IPC分类号： C12Q1/68 ,  C12P19/34

CPC分类号： C12Q1/6869 ,  C12Q1/6806 ,  C12Q1/6834 ,  C12Q1/6876 ,  C12Q2525/131 ,  C12Q2525/197 ,  C12Q2535/122 ,  C12Q2537/125 ,  C12Q2537/159 ,  C12Q2563/155

摘要： A microparticle having a probe molecule able to capture a specific nucleic acid group to be analyzed is used to extract only the specific nucleic acid group to be analyzed from a nucleic acid sample and the microparticle is thereafter directly immobilized on a smooth plate, whereby a device for nucleic acid analysis is rapidly prepared. Immobilizing a single capture probe molecule onto an individual microparticle in advance and forming, at regular positions on the smooth substrate, an adhesion pad on which a functional group that binds to the microparticle has been introduced makes it possible to readily and rapidly prepare the device for nucleic analysis, where the nucleic acid sample to be analyzed is arranged molecule by molecule in a lattice shape on the smooth substrate.

公开(公告)号：US20130338041A1

公开(公告)日：2013-12-19

申请号：US14002125

申请日：2012-01-24

申请人： Koshin Hamasaki ,  Toshiro Saito ,  Takayuki Obara

发明人： Koshin Hamasaki ,  Toshiro Saito ,  Takayuki Obara

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6876 ,  C12Q1/6834 ,  C12Q1/6874 ,  C40B40/06 ,  G01N21/6452 ,  G01N21/648 ,  G01N2021/6439 ,  C12Q2521/543 ,  C12Q2535/122 ,  C12Q2563/149 ,  C12Q2565/513 ,  C12Q2523/308

摘要： In the conventional nucleic acid analysis devices and nucleic acid analyzers, there was no technique available for sequencing a single nucleic acid molecule easily and highly efficiently. The present invention enabled a highly efficient single molecule immobilization of nucleic acid with good reproductivity in a short time at a low price by providing small metallic bonding pads at predetermined positions on a support substrate, firmly fixing a hydrophobic linker on the bonding pads, and bonding on to the linker bulky microparticles onto which a single molecule of a nucleic acid sample fragment is immobilized. According to the present invention, in the nucleic acid analysis device which uses a nucleic acid analyzer, the nucleotide read length can be extended and many types of nucleic acid molecule to be analyzed can be analyzed at one time.

摘要翻译： 在常规核酸分析装置和核酸分析仪中，没有技术可以容易且高效率地测序单个核酸分子。 本发明通过在支撑衬底上的预定位置处提供小的金属粘合垫，在接合焊盘上牢固地固定疏水性接头，并且在接合焊盘上牢固地固定疏水性接头，从而能够以低价格在短时间内以高效率的单分子固定具有良好繁殖力的核酸 在其上固定有单个分子的核酸样品片段的连接体庞大的微粒上。 根据本发明，在使用核酸分析仪的核酸分析装置中，可以延长核苷酸读取长度，并且可以一次分析多种类型的要分析的核酸分子。

公开(公告)号：US20130053280A1

公开(公告)日：2013-02-28

申请号：US13697019

申请日：2011-05-09

申请人： Koshin Hamasaki ,  Toshiro Saito

发明人： Koshin Hamasaki ,  Toshiro Saito

IPC分类号： C40B60/12 ,  C40B40/10 ,  C40B50/14 ,  C40B40/06

CPC分类号： C12Q1/6806 ,  C12Q1/6834 ,  G01N21/05 ,  G01N21/554 ,  G01N21/648 ,  G01N33/54346 ,  C12Q2565/518 ,  C12Q2565/507 ,  C12Q2563/155

摘要： Disclosed is a technique for binding microparticles to patterned bonding pads of a metal (e.g., gold) formed on a support. The microparticles each carry a nucleic acid synthetase or DNA probe immobilized thereon for capturing a nucleic acid sample fragment. The technique involves forming, on a support surface, a film having a thickness equivalent to that of the bonding pads; controlling the size of microparticles with respect to the size of bonding pads; and thereby immobilizing microparticles each bearing a single nucleic acid sample fragment to the bonding pads in a one-to-one manner in a grid form. This allows high-density regular alignment and immobilization of many types of nucleic acid fragment samples on a support and enables high-throughput analysis of nucleic acid samples. Typically, immobilization of microparticles at 1-micrometer intervals easily provides a high density of 106 nucleic acid fragments per square millimeter.

公开(公告)号：US08228505B2

公开(公告)日：2012-07-24

申请号：US12233184

申请日：2008-09-18

申请人： Masatoshi Narahara ,  Satoshi Takahashi ,  Toshiro Saito

发明人： Masatoshi Narahara ,  Satoshi Takahashi ,  Toshiro Saito

IPC分类号： G01N21/55

CPC分类号： G01N21/648 ,  G01N21/6428

摘要： An object of the present invention relates to detecting a target substance with high contrast. The invention relates to analysis of a target substance using a light-transmitting substrate and a metal for inducing plasmon resonance, and further using a low refractive index layer with an opening portion, which forms an interface with the substrate, and which has a lower refractive index than the substrate. Light emitted from a substrate side is totally reflected at the interface to irradiate the metal arranged in the opening portion with evanescent light. Light generated from the target substance by plasmon resonance of the evanescent light is detected. According to the invention, the radiation of evanescent light to a material other than the target substance can be reduced, and thereby light emission from the martial other than the target substance, e.g., a molecule floating around the target substance, can be reduced.

摘要翻译： 本发明的目的是检测具有高对比度的目标物质。 本发明涉及使用透光基板和用于诱导等离子体共振的金属的目标物质的分析，并且还使用具有与基板形成界面的开口部分的低折射率层，并且具有较低的折射率 指数比底物。 从基板侧发射的光在界面处被全反射，以照射具有ev逝光的开口部中的金属。 检测由目标物质通过ev逝光的等离子体共振产生的光。 根据本发明，可以减少对目标物质以外的材料的ev逝光的照射，从而可以减少来自目标物质以外的武器例如悬浮在目标物质周围的分子的发光。