公开(公告)号：US06806455B2

公开(公告)日：2004-10-19

申请号：US10240615

申请日：2002-09-30

申请人： Carlos Zarate ,  Paul Donders ,  Ahmad Yekta ,  Zahra Masoumi ,  Peter Ramm

发明人： Carlos Zarate ,  Paul Donders ,  Ahmad Yekta ,  Zahra Masoumi ,  Peter Ramm

IPC分类号： H01L2700

CPC分类号： G01N21/6408 ,  G01N2201/0648

摘要： The present invention relates to an apparatus and method for imaging time resolved fluorescence in biochemical and medical samples. In a primary aspect, the device includes a lens of large aperture, a flash lamp in the illumination path, a fast-acting solid state shutter or a gated detector in the emission path, a device for delivering homogenous monochromatic illumination to a plurality of wells distributed within a microwell plate, a digital camera of high quantum efficiency, and a computer under computer control, the lamp is pulsed at short intervals. The fast-acting emission shutter or gated detector operates to limit exposure of the camera to a period some microseconds after the extinction of each lamp pulse, during which only delayed fluorescence is transmitted to the camera. The invention achieves simultaneous time resolved imaging of a plurality of samples, with high sensitivity and high throughput.

摘要翻译： 本发明涉及用于在生物化学和医学样品中成像时间分辨荧光的装置和方法。 在主要方面，该装置包括大孔径的透镜，照明路径中的闪光灯，发射路径中的快速固态快门或门控检测器，用于将均匀单色照明传送到多个孔的装置 分布在微孔板内，高量子效率的数码相机和计算机在计算机控制下，以短时间间隔脉冲。 快速发射快门或门控检测器操作以将相机的曝光限制在每个灯脉冲消失之后几微秒的时段，在此期间仅将延迟的荧光传输到相机。 本发明实现多个样品的同时时间分辨成像，具有高灵敏度和高产量。

公开(公告)号：US06441973B1

公开(公告)日：2002-08-27

申请号：US09240649

申请日：1999-01-29

申请人： Peter Ramm ,  Gang Sun ,  Rolf Mueller ,  Timothy Ormsby ,  Kenneth R. Castle

发明人： Peter Ramm ,  Gang Sun ,  Rolf Mueller ,  Timothy Ormsby ,  Kenneth R. Castle

IPC分类号： G02B934

CPC分类号： G01N21/6452 ,  G01N21/6456 ,  G01N21/76 ,  G02B13/14 ,  G02B13/22 ,  G02B21/084 ,  G06T7/75 ,  G06T2207/10056 ,  G06T2207/30072

摘要： An electronic imaging system is disclosed, for assessing the intensity of colorimetric, fluorescent or luminescent signal in a matrix consisting of wells, microwells, hybridization dot blots on membranes, gels, or other specimens. The system includes a very sensitive area CCD detector, a fast, telecentric lens with epi-illumination, a reflective/transmissive illumination system, an illumination wavelength selection device, and a light-tight chamber. A computer and image analysis software are used to control the hardware, correct and calibrate the images, and detect and quantify targets within the images.

摘要翻译： 公开了一种电子成像系统，用于评估由孔，微孔，膜，凝胶或其它样品上的杂交点印迹组成的基质中的比色，荧光或发光信号的强度。 该系统包括非常敏感的区域CCD检测器，具有外部照明的快速远心透镜，反射/透射照明系统，照明波长选择装置和不透光室。 计算机和图像分析软件用于控制硬件，校正和校准图像，并检测和量化图像中的目标。

公开(公告)号：US06381058B2

公开(公告)日：2002-04-30

申请号：US09854035

申请日：2001-05-10

申请人： Peter Ramm ,  Gang Sun ,  Rolf Mueller ,  Timothy Ormsby ,  Kenneth R. Castle

发明人： Peter Ramm ,  Gang Sun ,  Rolf Mueller ,  Timothy Ormsby ,  Kenneth R. Castle

IPC分类号： G02F103

CPC分类号： G01N21/6452 ,  G01N21/6456 ,  G01N21/76 ,  G02B13/14 ,  G02B13/22 ,  G02B21/084 ,  G06T7/75 ,  G06T2207/10056 ,  G06T2207/30072

摘要： An electronic imaging system is disclosed, for assessing the intensity of calorimetric, fluorescent or luminescent signal in a matrix consisting of wells, microwells, hybridization dot blots on membranes, gels, or other specimens. The system includes a very sensitive area CCD detector, a fast, telecentric lens with epi-illumination, a reflective/transmissive illumination system, an illumination wavelength selection device, and a light-tight chamber. A computer and image analysis software are used to control the hardware, correct and calibrate the images, and detect and quantify targets within the images.

摘要翻译： 公开了一种电子成像系统，用于评估由孔，微孔，膜，凝胶或其它样品上的杂交点印迹组成的基质中的量热，荧光或发光信号的强度。 该系统包括非常敏感的区域CCD检测器，具有外部照明的快速远心透镜，反射/透射照明系统，照明波长选择装置和不透光室。 计算机和图像分析软件用于控制硬件，校正和校准图像，并检测和量化图像中的目标。

公开(公告)号：US5766984A

公开(公告)日：1998-06-16

申请号：US532367

申请日：1995-09-22

申请人： Peter Ramm ,  Reinhold Buchner

发明人： Peter Ramm ,  Reinhold Buchner

IPC分类号： H01L21/283 ,  H01L21/302 ,  H01L21/3065 ,  H01L21/768 ,  H01L21/822 ,  H01L27/00 ,  H01L27/06 ,  H01L21/18

CPC分类号： H01L27/0688 ,  H01L21/8221 ,  H01L25/0657 ,  H01L25/50 ,  H01L2225/06541 ,  H01L2924/0002 ,  Y10S438/975

摘要： A method of making a vertical integrated circuit by providing first and second substrates surfaces of which have layers with circuit structures and metallization planes therein, by providing an etching mask on a primary surface of the first substrate, forming via holes in the first substrate extending through the masking surface and the layers of the first substrate, reducing the thickness of the first substrate from a surface opposite its layer surface, alignedly connecting the first substrate by its reduced surface to the layer surface of the second substrate, subsequent deepening of the via holes to the metallization plane of the second substrate and forming electrical interconnection between the metallization planes in the first and second substrates through the via holes.

摘要翻译： 通过在第一基板的主表面上设置蚀刻掩模，通过在其中具有电路结构和金属化平面的第一和第二基板表面来制造垂直集成电路的方法，在第一基板上形成通孔， 所述掩蔽表面和所述第一基底的层，从与所述第一基底的表面相反的表面减小所述第一基底的厚度，将所述第一基底通过其还原表面对准地连接到所述第二基底的所述层表面， 到第二基板的金属化平面，并且通过通孔在第一和第二基板中的金属化平面之间形成电互连。

公开(公告)号：US09057701B2

公开(公告)日：2015-06-16

申请号：US12817422

申请日：2010-06-17

申请人： Peter Ramm ,  Yuriy Alexandrov ,  Paul Donders ,  Carlos Zarate ,  Bohdan J. Soltys

发明人： Peter Ramm ,  Yuriy Alexandrov ,  Jurich Cybuch ,  Paul Donders ,  Carlos Zarate ,  Bohdan J. Soltys

IPC分类号： G06K9/00 ,  G01N21/64 ,  G01N15/14 ,  G01N33/50 ,  G06T7/00

CPC分类号： G01N21/6458 ,  G01N15/1475 ,  G01N21/6428 ,  G01N33/5026 ,  G01N2015/1497 ,  G01N2333/4603 ,  G06K9/00127 ,  G06T7/0012 ,  G06T7/187 ,  G06T2207/10056 ,  G06T2207/30024

摘要： A system for performing automated cell screening in drug discovery, includes an automated microscope, a fast autofocus device, and a digital imaging system. Processes are implemented in software through which relevant cellular material is segmented and quantified with minimal user interaction. Improvements in the following areas: known methods for image processing are implemented in such a way that automated segmentation is achieved; sets of known measurements (pixel counting, etc.) are implemented as methods which demonstrate aspects of biology in a reliable fashion; components for automated positioning, focusing, imaging and processing of a multiplicity of samples are integrated as systems within which the segmentation and measurement methods may be mounted; and components and methods are adapted into systems which yield more highly automated and more rapid cell screening.

摘要翻译： 用于在药物发现中进行自动细胞筛选的系统包括自动显微镜，快速自动对焦装置和数字成像系统。 过程在软件中实现，通过该软件，相关的细胞材料通过最小的用户交互被分段和量化。 以下领域的改进：图像处理的已知方法以实现自动分割的方式实现; 已知测量的集合（像素计数等）被实现为以可靠的方式示出生物学方面的方法; 将多个样本的自动定位，聚焦，成像和处理的组件集成为其中可以安装分割和测量方法的系统; 并且组件和方法被适应成产生更高度自动化和更快速的细胞筛选的系统。

公开(公告)号：US20100289146A1

公开(公告)日：2010-11-18

申请号：US12678473

申请日：2008-09-17

申请人： Peter Ramm ,  Armin Klumpp

发明人： Peter Ramm ,  Armin Klumpp

IPC分类号： H01L23/538 ,  H01L21/768 ,  H01L23/48

CPC分类号： H01L23/538 ,  H01L21/76898 ,  H01L23/481 ,  H01L25/50 ,  H01L2224/05573 ,  H01L2224/13025 ,  H01L2224/16 ,  H01L2924/13091 ,  H01L2924/00

摘要： A method for manufacturing a three-dimensional, electronic system includes: providing a first integrated circuit structure in a first substrate, wherein the first integrated circuit structure has a contact pad at a first main side of the first substrate; providing a second substrate with a main side; forming a vertical contact area in the second substrate; after step (c) forming a semiconductor layer on the main side of the second substrate; forming a semiconductor device of a second integrated circuit structure in the second substrate with the semiconductor layer; removing the substrate material from a side of the second substrate opposite the main side, so that the vertical contact area at the opposite side is electrically exposed; arranging the first and second substrates on top of each other aligning the vertical contact area with the contact pad, so that an electrical connection between the first and second integrated circuit structures is produced via the vertical contact area and the contact pad.

摘要翻译： 一种制造三维电子系统的方法包括：在第一基板中提供第一集成电路结构，其中第一集成电路结构在第一基板的第一主侧具有接触焊盘; 提供具有主侧的第二基板; 在所述第二基板中形成垂直接触区域; （c）在第二基板的主面上形成半导体层; 在所述第二基板中形成具有所述半导体层的第二集成电路结构的半导体器件; 从第二基板的与主侧相反的一侧去除基板材料，使得相对侧的垂直接触面电暴露; 将第一和第二基板布置在彼此的顶部上，使与垂直接触区域的接触面对准，使得通过垂直接触区域和接触垫片产生第一和第二集成电路结构之间的电连接。

公开(公告)号：US20090074283A1

公开(公告)日：2009-03-19

申请号：US12253275

申请日：2008-10-17

申请人： PETER RAMM ,  Yuriy Alexandrov ,  Jurich Cybuch ,  Paul Donders ,  Carlos Zarate ,  Bohdan J. Soltys

发明人： PETER RAMM ,  Yuriy Alexandrov ,  Jurich Cybuch ,  Paul Donders ,  Carlos Zarate ,  Bohdan J. Soltys

IPC分类号： G06K9/00

CPC分类号： G01N21/6458 ,  G01N15/1475 ,  G01N21/6428 ,  G01N33/5026 ,  G01N2015/1497 ,  G01N2333/4603 ,  G06K9/00127 ,  G06T7/0012 ,  G06T7/187 ,  G06T2207/10056 ,  G06T2207/30024

摘要： A system for performing automated cell screening in drug discovery, includes an automated microscope, a fast autofocus device, and a digital imaging system. Processes are implemented in software through which relevant cellular material is segmented and quantified with minimal user interaction. Improvements in the following areas: known methods for image processing are implemented in such a way that automated segmentation is achieved; sets of known measurements (pixel counting, etc.) are implemented as methods which demonstrate aspects of biology in a reliable fashion; components for automated positioning, focusing, imaging and processing of a multiplicity of samples are integrated as systems within which the segmentation and measurement methods may be mounted; and components and methods are adapted into systems which yield more highly automated and more rapid cell screening.

摘要翻译： 用于在药物发现中进行自动细胞筛选的系统包括自动显微镜，快速自动对焦装置和数字成像系统。 过程在软件中实现，通过该软件，相关的细胞材料通过最少的用户交互被分段和量化。 以下领域的改进：图像处理的已知方法以实现自动分割的方式实现; 已知测量的集合（像素计数等）被实现为以可靠的方式示出生物学方面的方法; 将多个样本的自动定位，聚焦，成像和处理的组件集成为其中可以安装分割和测量方法的系统; 并且组件和方法被适应成产生更高度自动化和更快速的细胞筛选的系统。

公开(公告)号：US20060257013A1

公开(公告)日：2006-11-16

申请号：US10514925

申请日：2003-05-09

申请人： Peter Ramm ,  Yuriy Alexandrov ,  Jurich Cybuch ,  Paul Donders ,  Carlos Zarate ,  Bohdan Soltys

发明人： Peter Ramm ,  Yuriy Alexandrov ,  Jurich Cybuch ,  Paul Donders ,  Carlos Zarate ,  Bohdan Soltys

IPC分类号： G06K9/00

CPC分类号： G01N21/6458 ,  G01N15/1475 ,  G01N21/6428 ,  G01N33/5026 ,  G01N2015/1497 ,  G01N2333/4603 ,  G06K9/00127 ,  G06T7/0012 ,  G06T7/187 ,  G06T2207/10056 ,  G06T2207/30024

摘要： A system for performing automated cell screening in drug discovery, including an automated microscope, a fast autofocus device and a digital imaging system. Processes are implemented in software through which relevant cellular material is segmented and quantified with minimal user interaction. Improvements in the following areas: known methods for image processing are implemented in such a way that automated segmentation is achieved; sets of known measurements (pixel counting, etc.) are implemented as methods which demonstrate aspects of biology in a reliable fashion; components for automated positioning, focusing, imaging and processing of a multiplicity of samples are integrated as systems within which the segmentation and measurement methods may be mounted; and components and methods are adapted into systems which yield more highly automated and more rapid cell screening.

摘要翻译： 一种用于在药物发现中进行自动细胞筛选的系统，包括自动显微镜，快速自动对焦装置和数字成像系统。 过程在软件中实现，通过该软件，相关的细胞材料通过最小的用户交互被分段和量化。 以下领域的改进：图像处理的已知方法以实现自动分割的方式实现; 已知测量的集合（像素计数等）被实现为以可靠的方式示出生物学方面的方法; 将多个样本的自动定位，聚焦，成像和处理的组件集成为其中可以安装分割和测量方法的系统; 并且组件和方法被适应成产生更高度自动化和更快速的细胞筛选的系统。

公开(公告)号：US06567750B1

公开(公告)日：2003-05-20

申请号：US09693623

申请日：2000-10-20

申请人： Robert Nadon ,  Peter Ramm

发明人： Robert Nadon ,  Peter Ramm

IPC分类号： G06F1900

CPC分类号： G06F19/24 ,  G01N33/50 ,  G06F19/20

摘要： An analytical process is disclosed, for discriminating data acquired from samples with overlapping distributions, and for improving and assessing the statistical validity of hybridization signal in arrays of assays. The process includes method of convolving data into two or more discrete probability density functions representing signal and nonsignal, discrete fluors, or other convolved independent variables. The system uses the probability density functions to assign hybridization signals, objectively, to one of the modeled distributions. Subsequent processes assess variability inherent to the arrays, and use this assessed variation to establish reliability scores and confidence limits for complete hybridization arrays, and for discrete hybridization assays within arrays.

公开(公告)号：US06498690B2

公开(公告)日：2002-12-24

申请号：US10091697

申请日：2002-03-05

申请人： Peter Ramm ,  Gang Sun ,  Rolf Mueller ,  Timothy Ormsby ,  Kenneth R. Castle

发明人： Peter Ramm ,  Gang Sun ,  Rolf Mueller ,  Timothy Ormsby ,  Kenneth R. Castle

IPC分类号： G02B936

CPC分类号： G01N21/6452 ,  G01N21/6456 ,  G01N21/76 ,  G02B13/14 ,  G02B13/22 ,  G02B21/084 ,  G06T7/75 ,  G06T2207/10056 ,  G06T2207/30072

摘要： An electronic imaging system is disclosed, for assessing the intensity of calorimetric, fluorescent or luminescent signal in a matrix consisting of wells, microwells, hybridization dot blots on membranes, gels, or other specimens. The system includes a very sensitive area CCD detector, a fast, telecentric lens with epi-illumination, a reflective/transmissive illumination system, an illumination wavelength selection device, and a light-tight chamber. A computer and image analysis software are used to control the hardware, correct and calibrate the images, and detect and quantify targets within the images.