公开(公告)号：US08062841B2

公开(公告)日：2011-11-22

申请号：US12147440

申请日：2008-06-26

申请人： Xing Su ,  Lei Sun ,  Mineo Yamakawa ,  Jingwu Zhang ,  Qing Ma ,  Tae-Woong Koo ,  Richard Jones

发明人： Xing Su ,  Lei Sun ,  Mineo Yamakawa ,  Jingwu Zhang ,  Qing Ma ,  Tae-Woong Koo ,  Richard Jones

IPC分类号： C12Q1/68 ,  G01N33/53 ,  C07H21/02 ,  C07H21/04 ,  C07K14/00

CPC分类号： G01N33/53 ,  B82Y15/00 ,  B82Y30/00 ,  G01N33/54366 ,  G01N33/5438

摘要： Method and device to collect multiplex data simultaneously in analyte detection and analyze the data by experimentally trained software (machine-learning) is disclosed. Various ways (magnetic particles and microcoils) are disclosed to collect multiple reporter (tag) signals. Multiplex detection can increase the biomolecule analysis efficiency by using small sample size and saving assay reagents and time. Machine learning and data analysis schemes are also disclosed. Multiple affinity binding partners, each labeled by a unique reporter, are contacted with a sample and a single spectrum is taken to detect multiple reporter signals. The spectrum is deconvoluted by experimentally trained software to identify multiple analytes.

摘要翻译： 公开了通过实验训练的软件（机器学习）在分析物检测中同时收集多重数据并分析数据的方法和装置。 公开了各种方式（磁性颗粒和微型线圈）以收集多个报道（标签）信号。 多重检测可以通过使用小样本量和节省测定试剂和时间来增加生物分子分析效率。 还披露了机器学习和数据分析方案。 将多个亲和力结合配偶体（每个由唯一报道分子标记）与样品接触，并采用单个谱来检测多个报道信号。 通过实验训练的软件对光谱进行去卷积，以识别多个分析物。

公开(公告)号：US20090005260A1

公开(公告)日：2009-01-01

申请号：US12147440

申请日：2008-06-26

申请人： Xing Su ,  Lei Sun ,  Mineo Yamakawa ,  Jingwu Zhang ,  Qing Ma ,  Tae-Woong Koo ,  Richard Jones

发明人： Xing Su ,  Lei Sun ,  Mineo Yamakawa ,  Jingwu Zhang ,  Qing Ma ,  Tae-Woong Koo ,  Richard Jones

IPC分类号： C40B30/04

CPC分类号： G01N33/53 ,  B82Y15/00 ,  B82Y30/00 ,  G01N33/54366 ,  G01N33/5438

摘要： Method and device to collect multiplex data simultaneously in analyte detection and analyze the data by experimentally trained software (machine-learning) is disclosed. Various ways (magnetic particles and microcoils) are disclosed to collect multiple reporter (tag) signals. Multiplex detection can increase the biomolecule analysis efficiency by using small sample size and saving assay reagents and time. Machine learning and data analysis schemes are also disclosed. Multiple affinity binding partners, each labeled by a unique reporter, are contacted with a sample and a single spectrum is taken to detect multiple reporter signals. The spectrum is deconvoluted by experimentally trained software to identify multiple analytes.

摘要翻译： 公开了通过实验训练的软件（机器学习）在分析物检测中同时收集多重数据并分析数据的方法和装置。 公开了各种方式（磁性颗粒和微型线圈）以收集多个报道（标签）信号。 多重检测可以通过使用小样本量和节省测定试剂和时间来增加生物分子分析效率。 还披露了机器学习和数据分析方案。 将多个亲和力结合配偶体（每个由唯一报道分子标记）与样品接触，并采用单个谱来检测多个报道信号。 通过实验训练的软件对光谱进行去卷积，以识别多个分析物。

公开(公告)号：US08513002B2

公开(公告)日：2013-08-20

申请号：US13185712

申请日：2011-07-19

申请人： Andrew Arthur Berlin ,  Christopher Marc Gerth ,  Tae-Woong Koo

发明人： Andrew Arthur Berlin ,  Christopher Marc Gerth ,  Tae-Woong Koo

IPC分类号： C12M1/34 ,  G01N33/00 ,  G01N33/553 ,  C12Q1/68 ,  C12M3/00

CPC分类号： G01N21/65 ,  G01N21/658 ,  G01N2021/052 ,  G01N2021/653 ,  G01N2021/655 ,  Y10T436/143333

摘要： Spectroscopic analysis systems and methods for analyzing samples are disclosed. An analysis system may contain an electromagnetic radiation source to provide radiation, a spectroscopic analysis chamber to perform a coherent Raman spectroscopy (e.g., stimulated Raman or coherent anti-Stokes Raman spectroscopy), and a radiation detector to detect radiation based on the spectroscopy. The chamber may have a resonant cavity to contain a sample for analysis, at least one window to the cavity to transmit the first radiation into the cavity and to transmit a second radiation out, a plurality of reflectors affixed to a housing of the cavity to reflect radiation of a predetermined frequency, the plurality of reflectors separated by a distance that is sufficient to resonate the radiation. The spectroscopic analysis system may be coupled with a nucleic acid sequencing system to receive a single nucleic acid derivative in solution and identify the derivative to sequence the nucleic acid.

摘要翻译： 公开了用于分析样品的光谱分析系统和方法。 分析系统可以包含用于提供辐射的电磁辐射源，用于执行相干拉曼光谱（例如，受激拉曼或相干反斯托克斯拉曼光谱）的光谱分析室，以及基于光谱检测辐射的辐射检测器。 腔室可以具有一个谐振腔，以容纳用于分析的样本，至少一个窗口，用于将腔室中的第一辐射传输到腔体中并将第二辐射透射出来，多个反射器固定到空腔的壳体以反射 预定频率的辐射，多个反射器分开足以使辐射共振的距离。 光谱分析系统可以与核酸测序系统结合以在溶液中接受单个核酸衍生物，并鉴定衍生物以对核酸进行排序。

公开(公告)号：US20120034686A1

公开(公告)日：2012-02-09

申请号：US13220214

申请日：2011-08-29

申请人： Andrew Arthur Berlin ,  Christopher Marc Gerth ,  Tae-Woong Koo

发明人： Andrew Arthur Berlin ,  Christopher Marc Gerth ,  Tae-Woong Koo

IPC分类号： C12M1/34

CPC分类号： G01N21/65 ,  G01N21/658 ,  G01N2021/052 ,  G01N2021/653 ,  G01N2021/655 ,  Y10T436/143333

摘要： Spectroscopic analysis systems and methods for analyzing samples are disclosed. An analysis system may contain an electromagnetic radiation source to provide radiation, a spectroscopic analysis chamber to perform a coherent Raman spectroscopy (e.g., stimulated Raman or coherent anti-Stokes Raman spectroscopy), and a radiation detector to detect radiation based on the spectroscopy. The chamber may have a resonant cavity to contain a sample for analysis, at least one window to the cavity to transmit the first radiation into the cavity and to transmit a second radiation out, a plurality of reflectors affixed to a housing of the cavity to reflect radiation of a predetermined frequency, the plurality of reflectors separated by a distance that is sufficient to resonate the radiation. The spectroscopic analysis system may be coupled with a nucleic acid sequencing system to receive a single nucleic acid derivative in solution and identify the derivative to sequence the nucleic acid.

摘要翻译： 公开了用于分析样品的光谱分析系统和方法。 分析系统可以包含用于提供辐射的电磁辐射源，用于执行相干拉曼光谱（例如，受激拉曼或相干反斯托克斯拉曼光谱）的光谱分析室，以及基于光谱检测辐射的辐射检测器。 腔室可以具有一个谐振腔，以容纳用于分析的样本，至少一个窗口，用于将腔室中的第一辐射传输到腔体中并将第二辐射透射出来，多个反射器固定到空腔的壳体以反射 预定频率的辐射，多个反射器分开足以使辐射共振的距离。 光谱分析系统可以与核酸测序系统结合以在溶液中接受单个核酸衍生物，并鉴定衍生物以对核酸进行排序。

公开(公告)号：US07476501B2

公开(公告)日：2009-01-13

申请号：US10108128

申请日：2002-03-26

申请人： Selena Chan ,  Xing Su ,  Tae-Woong Koo

发明人： Selena Chan ,  Xing Su ,  Tae-Woong Koo

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6869 ,  B01L3/5027 ,  C12Q2565/60 ,  C12Q2565/631 ,  C12Q2565/632 ,  G01N21/658 ,  G01N33/587 ,  G01N2021/653 ,  G01N2021/656

摘要： The methods and apparatus disclosed herein concern nucleic acid sequencing by enhanced Raman spectroscopy. In certain embodiments of the invention, exonuclease treatment of the nucleic acids 109 results in the release of nucleotides 110. The nucleotides may pass from a reaction chamber 101 through a microfluidic channel 102 and enter a nanochannel or microchannel 103. The nanochannel or microchannel 103 may be packed with nanoparticle 111 aggregates containing hot spots for Raman detection. As the nucleotides 110 pass through the nanoparticle 111 hot spots, they may be detected by surface enhanced Raman spectroscopy (SERS), surface enhanced resonance Raman spectroscopy (SERRS) and/or coherent anti-Stokes Raman spectroscopy (CARS). Identification of the sequence of nucleotides 110 released from the nucleic acid 109 provides the nucleic acid sequence. Other embodiments of the invention concern apparatus 100 for nucleic acid sequencing.

摘要翻译： 本文公开的方法和装置涉及通过增强拉曼光谱进行的核酸测序。 在本发明的某些实施方案中，核酸109的核酸外切酶处理导致核苷酸110的释放。核苷酸可以从反应室101通过微流体通道102并进入纳米通道或微通道103.纳米通道或微通道103可以 填充含有用于拉曼检测的热点的纳米颗粒111聚集体。 当核苷酸110通过纳米颗粒111热点时，它们可以通过表面增强拉曼光谱（SERS），表面增强共振拉曼光谱（SERRS）和/或相干抗斯托克斯拉曼光谱（CARS）来检测。 从核酸109释放的核苷酸序列110的鉴定提供了核酸序列。 本发明的其它实施方案涉及用于核酸测序的设备100。

公开(公告)号：US20070154881A1

公开(公告)日：2007-07-05

申请号：US11319791

申请日：2005-12-29

申请人： Tae-Woong Koo

发明人： Tae-Woong Koo

IPC分类号： C12Q1/70

CPC分类号： B82Y15/00 ,  B82Y30/00 ,  C12Q1/6823 ,  C12Q2565/629 ,  C12Q2565/501

摘要： The application relates to a method, system and device for performing biological assays. The method, system and device allow more accurate and specific detections of biomolecules in multiplex assays, such as immunoassays and DNA microarray assays. More specifically, the embodiments of the invention allow the detection of labels after their detachment or disassociation from a binding situation wherein interference from other labels or the background may reduce the accuracy of specificity of the detection. The embodiments of the invention further allow detection of individual labels.

摘要翻译： 本申请涉及用于进行生物测定的方法，系统和装置。 该方法，系统和装置允许在多重测定（例如免疫测定和DNA微阵列测定）中更准确和更具体地检测生物分子。 更具体地说，本发明的实施例允许在其与其他标签或背景的干扰可能降低检测的特异性的准确性的结合情况下分离或分离之后检测标签。 本发明的实施例还允许检测单个标签。

公开(公告)号：US07105301B2

公开(公告)日：2006-09-12

申请号：US10667776

申请日：2003-09-22

申请人： Xing Su ,  Selena Chan ,  Tae-Woong Koo ,  Mineo Yamakawa ,  Andrew A. Berlin

发明人： Xing Su ,  Selena Chan ,  Tae-Woong Koo ,  Mineo Yamakawa ,  Andrew A. Berlin

IPC分类号： C12Q1/68 ,  C12Q1/70 ,  G01N33/566 ,  G01N33/563

CPC分类号： C12Q1/6825 ,  B82Y5/00 ,  G01N33/54373 ,  G01N2800/52 ,  Y10S977/924 ,  C12Q2565/501

摘要： The present methods and apparatus concern the detection and/or identification of target analytes using probe molecules. In various embodiments of the invention, the probes or analytes are attached to one or more cantilevers. Binding of a probe to an analyte results in deflection of the cantilever, detected by a detection unit. A counterbalancing force may be applied to restore the cantilever to its original position. The counterbalancing force may be magnetic, electrical or radiative. The detection unit and the mechanism generating the counterbalancing force may be operably coupled to an information processing and control unit, such as a computer. The computer may regulate a feedback loop that maintains the cantilever in a fixed position by balancing the deflecting force and the counterbalancing force. The concentration of analytes in a sample may be determined from the magnitude of the counterbalancing force required to maintain the cantilever in a fixed position.

摘要翻译： 本方法和装置涉及使用探针分子检测和/或鉴定目标分析物。 在本发明的各种实施方案中，探针或分析物附着到一个或多个悬臂。 将探针与分析物结合导致由检测单元检测到的悬臂的偏转。 可以应用平衡力将悬臂恢复到其原始位置。 平衡力可以是磁性的，电的或辐射的。 生成平衡力的检测单元和机构可以可操作地耦合到诸如计算机的信息处理和控制单元。 计算机可以通过平衡偏转力和平衡力来调节将悬臂维持在固定位置的反馈回路。 样品中分析物的浓度可以从将悬臂维持在固定位置所需的平衡力的大小来确定。

公开(公告)号：US20060199193A1

公开(公告)日：2006-09-07

申请号：US11226696

申请日：2005-09-13

申请人： Tae-Woong Koo ,  Selena Chan ,  Xing Su ,  Zhang Jingwu ,  Mineo Yamakawa ,  Val Dubin

发明人： Tae-Woong Koo ,  Selena Chan ,  Xing Su ,  Zhang Jingwu ,  Mineo Yamakawa ,  Val Dubin

IPC分类号： C12Q1/68 ,  C12M1/34

CPC分类号： C12Q1/6874 ,  B01J2219/00317 ,  B01J2219/00511 ,  B01J2219/00605 ,  B01J2219/00612 ,  B01J2219/00621 ,  B01J2219/00626 ,  B01J2219/0063 ,  B01J2219/00641 ,  B01J2219/00722 ,  B01L3/5085 ,  B82Y30/00 ,  C12Q1/6869 ,  G01N27/414 ,  G01N27/4145 ,  G01N27/4148

摘要： Embodiments of the present invention provide devices methods for sequencing DNA using arrays of reaction cavities containing sensors to monitor changes in solutions contained in the reaction cavities. Additional embodiments provide devices and methods for sequencing DNA using arrays of reaction cavities that allow for optical monitoring of solutions in the reaction cavities. Test and fill reaction schemes are disclosed that allow DNA to be sequenced. By sequencing DNA using parallel reactions contained in large arrays, DNA can be rapidly sequenced.

公开(公告)号：US20060181702A1

公开(公告)日：2006-08-17

申请号：US11388345

申请日：2006-03-24

申请人： Tae-Woong Koo ,  Mineo Yamakawa

发明人： Tae-Woong Koo ,  Mineo Yamakawa

IPC分类号： G01J3/44 ,  G01N21/65

CPC分类号： G01N21/65

摘要： Disclosed herein are a Raman spectroscopy structure comprising a porous material substrate, and a method of performing Raman spectroscopy of a sample disposed adjacent to the structure comprising the porous material substrate. Generally, the substrate includes one or more layers of a porous material such as porous silicon, porous polysilicon, porous ceramics, porous silica, porous alumina, porous silicon-germanium, porous germanium, porous gallium arsenide, porous gallium phosphide, porous zinc oxide, and porous silicon carbide. It has been discovered that such a substrate material, when excited with near-infrared light, does not exhibit undesired background fluorescence characteristic of other known Raman spectroscopy substrates.

公开(公告)号：US07019828B2

公开(公告)日：2006-03-28

申请号：US10387080

申请日：2003-03-12

申请人： Xing Su ,  Lei Sun ,  Tae-Woong Koo ,  Selena Chan

发明人： Xing Su ,  Lei Sun ,  Tae-Woong Koo ,  Selena Chan

IPC分类号： G01J3/44

CPC分类号： G01N21/658 ,  B82Y10/00 ,  B82Y20/00

摘要： Briefly, in accordance with one embodiment of the invention, the intensity of the signals from surface enhanced Raman spectroscopy may be increased by using lithium chloride as an enhancer to activate a metallic structure used for surface enhanced Raman spectroscopy. The increased signal intensity may allow surface enhanced Raman spectroscopy to be utilized to detect individual analytes such as nucleotides, for example in DNA sequencing without requiring a dye or radioactive label.

摘要翻译： 简而言之，根据本发明的一个实施例，可以通过使用氯化锂作为增强剂激活用于表面增强拉曼光谱的金属结构来增加来自表面增强拉曼光谱的信号的强度。 增加的信号强度可以允许使用表面增强拉曼光谱来检测单个分析物例如核苷酸，例如在DNA测序中，而不需要染料或放射性标记。