公开(公告)号：WO2005081801A2

公开(公告)日：2005-09-09

申请号：PCT/US2005/004055

申请日：2005-02-09

Applicant: BLUESHIFT BIOTECHNOLOGIES, INC. ,  CROMWELL, Evan, F. ,  MILLER, Steven, C. ,  SHUMATE, Christopher, B. ,  COMITA, Paul, B.

Inventor： CROMWELL, Evan, F. ,  MILLER, Steven, C. ,  SHUMATE, Christopher, B. ,  COMITA, Paul, B.

IPC: B01L3/00 ,  G01N1/10 ,  G01N21/25 ,  G01N21/64 ,  G01N35/02

CPC classification number: G01N21/253 ,  B01L3/5085 ,  B01L2300/0806 ,  G01N21/6408 ,  G01N21/6445 ,  G01N21/6452 ,  G01N35/028

Abstract: Methods and apparatus for assaying biological materials employ multi-well substrates as described herein. The substrates include a plurality of wells, typically each of several nanoliters volume or smaller having consistent dimensions and formed in a rigid substrate such as a glass disk. Each well may be provided with a circumferential lip to minimize crosstalk between wells and/or facilitate optical location of the individual wells during interrogation. Samples are provided to the individual wells and assayed by an optical technique employing fluorescence, polarization, reflectance, or the like. A scanning laser system may be employed for this purpose. The substrate may rotate during the scan to allow consistent interrogation of the wells without stopping and starting the rotation. Multiple rotations may also be employed repeatedly interrogate the samples for use in a kinetic study, for example.

Abstract translation: 用于测定生物材料的方法和装置采用本文所述的多孔底物。 衬底包括多个孔，通常具有一定尺寸的几个纳升体积或更小的孔，并形成在诸如玻璃盘的刚性衬底中。 每个孔可以设置有圆周唇缘，以最小化井之间的串扰和/或促使询问期间各个孔的光学定位。 将样品提供给各个孔，并通过使用荧光，极化，反射率等的光学技术进行测定。 为此目的可以采用扫描激光系统。 衬底可以在扫描期间旋转，以允许孔的一致询问，而不停止和开始旋转。 例如，也可以多次旋转重复地询问用于动力学研究的样品。

公开(公告)号：WO2005081801A3

公开(公告)日：2005-11-10

申请号：PCT/US2005004055

申请日：2005-02-09

Applicant: BLUESHIFT BIOTECHNOLOGIES INC ,  CROMWELL EVAN F ,  MILLER STEVEN C ,  SHUMATE CHRISTOPHER B ,  COMITA PAUL B

Inventor： CROMWELL EVAN F ,  MILLER STEVEN C ,  SHUMATE CHRISTOPHER B ,  COMITA PAUL B

IPC: B01L3/00 ,  G01N1/10 ,  G01N21/25 ,  G01N21/64 ,  G01N35/02

CPC classification number: G01N21/253 ,  B01L3/5085 ,  B01L2300/0806 ,  G01N21/6408 ,  G01N21/6445 ,  G01N21/6452 ,  G01N35/028

Abstract: Methods and apparatus for assaying biological materials employ multi-well substrates as described herein. The substrates (102) include a plurality of wells (201) typically each of several nanoliters volume or smaller having consistent dimensions and formed in a rigid substrate (102) s a glass disk. Each well (201) provided with a circumferential lip to minimize crosstalk between wells and/or facilitate optical location of the individual wells during interrogation. Samples are provided to the individual wells and assayed by an optical technique (119) employing fluorescence, polarization, reflectance, or the like. A scanning laser system (111) may be employed for this purpose. The substrate may rotate during the scan to allow consistent interrogation of the wells without stopping and starting the rotation. Multiple rotations may also be employed repeatedly interrogate the samples for use in a kinetic study, for example.

Abstract translation: 用于测定生物材料的方法和装置采用本文所述的多孔底物。 衬底（102）包括通常具有一定尺寸的几个纳升体积或更小的多个孔（201），并形成在刚性基底（102）玻璃盘中。 每个井（201）设置有圆周唇缘，以在询问期间最小化井之间的串扰和/或促进各个井的光学定位。 将样品提供给各个孔，并通过使用荧光，偏振，反射率等的光学技术（119）进行测定。 为此目的可以采用扫描激光系统（111）。 衬底可以在扫描期间旋转，以允许孔的一致询问，而不停止和开始旋转。 例如，也可以多次旋转重复地询问用于动力学研究的样品。

公开(公告)号：WO2004082003A2

公开(公告)日：2004-09-23

申请号：PCT/US2004006408

申请日：2004-03-01

Applicant: APPLIED MATERIALS INC ,  VATUS JEAN R ,  SCUDDER LANCE A ,  COMITA PAUL B

Inventor： VATUS JEAN R ,  SCUDDER LANCE A ,  COMITA PAUL B

IPC: C30B25/02 ,  H01L21/00 ,  H01L21/20 ,  H01L21/205 ,  H01L21/28 ,  H01L21/336

CPC classification number: H01L21/02381 ,  H01L21/02532 ,  H01L21/02576 ,  H01L21/02579 ,  H01L21/0262 ,  H01L21/02639

Abstract: A method of making a substantially facet-free epitaxial film is disclosed. A substrate having predetermined regions is first provided. An epitaxial film forming process gas and a carrier gas are introduced into a reactor chamber. The epitaxial film forming process gas and the carrier have a flow ratio between 1:1 and 1:200. The epitaxial film is deposited into the predetermined regions of the substrate wherein the substrate has a temperature between about 350°C and about 900°C when the epitaxial film is being deposited.

Abstract translation: 公开了一种制造基本无小面外延膜的方法。 首先提供具有预定区域的基板。 将外延膜形成处理气体和载气引入反应室中。 外延膜形成工艺气体和载体的流量比在1：1和1：200之间。 当沉积外延膜时，将外延膜沉积到衬底的预定区域中，其中衬底具有在大约350℃和大约900℃之间的温度。

公开(公告)号：WO2006014351A2

公开(公告)日：2006-02-09

申请号：PCT/US2005023520

申请日：2005-07-01

Applicant: BLUESHIFT BIOTECHNOLOGIES INC ,  COMITA PAUL B ,  SHUMATE CHRISTOPHER B ,  MILLER STEVEN C ,  CROMWELL EVAN F

Inventor： COMITA PAUL B ,  SHUMATE CHRISTOPHER B ,  MILLER STEVEN C ,  CROMWELL EVAN F

IPC: C12Q1/70 ,  C12Q1/68 ,  G01N33/53

CPC classification number: G01N33/582 ,  B82Y5/00 ,  B82Y10/00 ,  C12Q1/6816 ,  G01N21/6408 ,  G01N21/6428 ,  G01N21/6445 ,  G01N2021/6419 ,  G01N2021/6421 ,  G01N2021/6432 ,  G01N2021/6441 ,  G01N2021/6478 ,  G01N2021/6484 ,  G01N2201/067 ,  G01N2201/0697 ,  G01N2201/0833 ,  C12Q2563/107 ,  C12Q2561/119

Abstract: Methods, apparatus, and system, implementing and using techniques for detecting a presence of one or more target analytes in particular regions of interest of one or more samples. One or more samples including objects and one or more target analytes are provided. Some of the target analytes are labeled with a fluorophore and are bound to some of the objects in the samples. The samples are illuminated with fluorescence inducing light and fluorescent light is collected from one or more regions of the one or more samples. At least one anisotropy measurement of the samples is performed to identify regions of interest where one or more target analytes are bound to the objects. The collected fluorescent light from the regions of interest is analyzed to determine a presence of target analytes that are bound to the objects in the one or more samples.

Abstract translation: 方法，装置和系统，实施和使用用于检测一个或多个样品的特定感兴趣区域中一种或多种目标分析物的存在的技术。 提供一个或多个样品，包括物体和一种或多种目标分析物。 一些目标分析物用荧光团标记，并且与样品中的某些对象结合。 用荧光诱导光照射样品，并从一个或多个样品的一个或多个区域采集荧光。 进行样品的至少一个各向异性测量以识别一个或多个目标分析物与物体结合的感兴趣区域。 分析来自感兴趣区域的收集的荧光以确定与一个或多个样品中的物体结合的目标分析物的存在。

公开(公告)号：WO2005019811A2

公开(公告)日：2005-03-03

申请号：PCT/US2004/027890

申请日：2004-08-26

Applicant: BLUESHIFT BIOTECHNOLOGIES, INC. ,  CROMWELL, Evan, F. ,  ADAM, Johann, F. ,  BRUNFELD, Andrei ,  COMITA, Paul, B. ,  SEIPERT, Christopher, J.

Inventor： CROMWELL, Evan, F. ,  ADAM, Johann, F. ,  BRUNFELD, Andrei ,  COMITA, Paul, B. ,  SEIPERT, Christopher, J.

IPC: G01N21/64

CPC classification number: G01N21/6452 ,  G01N21/6408 ,  G01N21/6445 ,  G01N21/6458 ,  G01N2021/6484 ,  G02B21/0048 ,  G02B21/0068 ,  G02B21/0076 ,  G02B21/16

Abstract: Methods and apparatus, including computer program products, implementing and using techniques for collecting optical data pertaining to one or more characteristics of a sample. The apparatus has a light source, one or more illumination optical elements, a scanner, one or more collection optical elements, and a device forming an aperture that limits detection of light from the sample. The illumination optical elements direct a light beam from the light source onto the sample. The scanner scans the light beam across the sample. The collection optical elements collect light from the sample and transmit the collected light to a detector. None of the collection optical elements are included among the illumination optical elements. The device forming an aperture limits detection of light from the sample to light associated with a limited vertical depth within the sample, and is one of the collection optical elements.

Abstract translation: 方法和装置，包括计算机程序产品，用于收集与样品的一个或多个特征有关的光学数据的实施和使用技术。 该装置具有光源，一个或多个照明光学元件，扫描器，一个或多个收集光学元件，以及形成限制来自样品的光的检测的孔径的装置。 照明光学元件将来自光源的光束引导到样品上。 扫描仪扫描样品上的光束。 收集光学元件收集来自样品的光并将收集的光传输到检测器。 在照明光学元件中不包括收集光学元件。 形成孔径的装置将从样品的光的检测限制到与样品内的有限垂直深度相关联的光，并且是收集光学元件之一。

公开(公告)号：WO2006107864A1

公开(公告)日：2006-10-12

申请号：PCT/US2006/012292

申请日：2006-04-03

Applicant: BLUESHIFT BIOTECHNOLOGIES, INC. ,  MILLER, Steven, C. ,  COMITA, Paul, B. ,  SHUMATE, Christopher, B. ,  CROMWELL, Evan, F.

Inventor： MILLER, Steven, C. ,  COMITA, Paul, B. ,  SHUMATE, Christopher, B. ,  CROMWELL, Evan, F.

IPC: C12Q1/68 ,  G01N33/53

CPC classification number: G01N33/542 ,  G01N2500/00

Abstract: Methods and apparatus are described for detecting specific binding between first and second chemical entities. The first chemical entity in association with a first fluorophore is immobilized. The second chemical entity is allowed to bind with the immobilized first chemical entity. The second chemical entity is or becomes coupled to a second fluorophore, which forms a FRET pair with the first fluorophore. The bound chemical entities are exposed to radiation at an excitation frequency for either the first or the second fluorophore, and polarization anisotropy of a FRET fluorescent signal from the bound chemical entities is measured to detect specific binding between the first and second chemical entities. Techniques are also disclosed for detecting whether a FRET interaction is occurring between a first chemical entity including a donor fluorophore and a second chemical entity including an acceptor fluorophore, using simultaneous anisotropy measurements at the wavelengths of the donor and acceptor fluorophores.

Abstract translation: 描述了用于检测第一和第二化学实体之间的特异性结合的方法和装置。 与第一荧光团相关联的第一化学实体被固定化。 允许第二化学实体与固定化的第一化学实体结合。 第二化学实体是或连接到与第一荧光团形成FRET对的第二荧光团。 结合的化学实体以第一或第二荧光团的激发频率暴露于辐射，并且测量来自结合的化学实体的FRET荧光信号的偏振各向异性以检测第一和第二化学实体之间的特异性结合。 还公开了用于检测在包括供体荧光团的第一化学实体和包括受体荧光团的第二化学实体之间是否发生FRET相互作用的技术，其使用在供体和受体荧光团的波长处的同时各向异性测量。

公开(公告)号：WO2005019811A3

公开(公告)日：2006-03-02

申请号：PCT/US2004027890

申请日：2004-08-26

Applicant: BLUESHIFT BIOTECHNOLOGIES INC ,  CROMWELL EVAN F ,  ADAM JOHANN F ,  BRUNFELD ANDREI ,  COMITA PAUL B ,  SEIPERT CHRISTOPHER J

Inventor： CROMWELL EVAN F ,  ADAM JOHANN F ,  BRUNFELD ANDREI ,  COMITA PAUL B ,  SEIPERT CHRISTOPHER J

IPC: G01N21/64

CPC classification number: G01N21/6452 ,  G01N21/6408 ,  G01N21/6445 ,  G01N21/6458 ,  G01N2021/6484 ,  G02B21/0048 ,  G02B21/0068 ,  G02B21/0076 ,  G02B21/16

Abstract: Methods and apparatus, including computer program products, implementing and using techniques for collecting optical data pertaining to one or more characteristics of a sample. The apparatus has a light source, one or more illumination optical elements, a scanner, one or more collection optical elements, and a device forming an aperture that limits detection of light from the sample. The illumination optical elements direct a light beam from the light source onto the sample. The scanner scans the light beam across the sample. The collection optical elements collect light from the sample and transmit the collected light to a detector. None of the collection optical elements are included among the illumination optical elements. The device forming an aperture limits detection of light from the sample to light associated with a limited vertical depth within the sample, and is one of the collection optical elements.

Abstract translation: 方法和装置，包括计算机程序产品，用于收集与样品的一个或多个特征有关的光学数据的实施和使用技术。 该装置具有光源，一个或多个照明光学元件，扫描器，一个或多个收集光学元件，以及形成限制来自样品的光的检测的孔径的装置。 照明光学元件将来自光源的光束引导到样品上。 扫描仪扫描样品上的光束。 收集光学元件收集来自样品的光并将收集的光传输到检测器。 在照明光学元件中不包括收集光学元件。 形成孔径的装置将从样品的光的检测限制到与样品内的有限垂直深度相关联的光，并且是收集光学元件之一。

公开(公告)号：WO2007084704A1

公开(公告)日：2007-07-26

申请号：PCT/US2007/001512

申请日：2007-01-19

Applicant: BLUESHIFT BIOTECHNOLOGIES, INC. ,  CROMWELL, Evan, F. ,  MILLER, Steven, C. ,  TRUJILLO, Robert, T. ,  COMITA, Paul, B.

Inventor： CROMWELL, Evan, F. ,  MILLER, Steven, C. ,  TRUJILLO, Robert, T. ,  COMITA, Paul, B.

IPC: G01N21/00 ,  B01L3/00

CPC classification number: B01L3/50853 ,  B01L2200/0684 ,  B01L2300/0654 ,  B01L2300/0829 ,  G01N21/0303 ,  G01N21/49

Abstract: Methods and apparatus for performing scatterometry measurements of biological samples as described herein. A substrate having formed therein one or more sample wells is provided. Each sample well is configured to hold a sample solution containing objects that are to be characterized based on their light scattering properties. One or more sample solutions are dispensed into the sample wells. A specular reflection reducing element is applied to at least some of the sample solutions in the sample wells to reduce a curvature of the meniscus of the sample solution and, therefore, to decrease reflections of light into one or more detectors. A light beam is directed from a light source onto the objects in the sample wells. Light scattered by the objects in the sample wells is collected and transmitted to one or more detectors. The signal from the detectors is analyzed to detect the one or more characteristics of the one or more samples .

Abstract translation: 如本文所述进行生物样品的散射测量的方法和装置。 提供了其中形成有一个或多个样品阱的衬底。 每个样品孔构造成容纳含有根据其光散射性质进行表征的物体的样品溶液。 将一种或多种样品溶液分配到样品孔中。 将镜面反射减少元件应用于样品阱中的至少一些样品溶液以减少样品溶液的弯月面的曲率，并因此减少光到一个或多个检测器中的反射。 将光束从光源引导到样品孔中的物体上。 被样品孔中的物体散射的光被收集并传输到一个或多个检测器。 分析来自检测器的信号以检测一个或多个样品的一个或多个特性。

公开(公告)号：WO2006014351A3

公开(公告)日：2006-02-09

申请号：PCT/US2005/023520

申请日：2005-07-01

Applicant: BLUESHIFT BIOTECHNOLOGIES, INC. ,  COMITA, Paul, B. ,  SHUMATE, Christopher, B. ,  MILLER, Steven, C. ,  CROMWELL, Evan, F.

Inventor： COMITA, Paul, B. ,  SHUMATE, Christopher, B. ,  MILLER, Steven, C. ,  CROMWELL, Evan, F.

IPC: C12Q1/68 ,  G01N33/53

Abstract: Methods, apparatus, and system, implementing and using techniques for detecting a presence of one or more target analytes in particular regions of interest of one or more samples. One or more samples including objects and one or more target analytes are provided. Some of the target analytes are labeled with a fluorophore and are bound to some of the objects in the samples. The samples are illuminated with fluorescence inducing light and fluorescent light is collected from one or more regions of the one or more samples. At least one anisotropy measurement of the samples is performed to identify regions of interest where one or more target analytes are bound to the objects. The collected fluorescent light from the regions of interest is analyzed to determine a presence of target analytes that are bound to the objects in the one or more samples.

公开(公告)号：WO2004082003A3

公开(公告)日：2004-09-23

申请号：PCT/US2004/006408

申请日：2004-03-01

Applicant: APPLIED MATERIALS, INC. ,  VATUS, Jean, R. ,  SCUDDER, Lance, A. ,  COMITA, Paul, B.

Inventor： VATUS, Jean, R. ,  SCUDDER, Lance, A. ,  COMITA, Paul, B.

IPC: H01L21/205

Abstract: A method of making a substantially facet-free epitaxial film is disclosed. A substrate having predetermined regions is first provided. An epitaxial film forming process gas and a carrier gas are introduced into a reactor chamber. The epitaxial film forming process gas and the carrier have a flow ratio between 1:1 and 1:200. The epitaxial film is deposited into the predetermined regions of the substrate wherein the substrate has a temperature between about 350°C and about 900°C when the epitaxial film is being deposited.