公开(公告)号：WO2003095986A1

公开(公告)日：2003-11-20

申请号：PCT/IB2003/001821

申请日：2003-05-09

Applicant: IMAGING RESEARCH, INC. ,  RAMM, Peter ,  ALEXAMDROV, Yuriy ,  CYBUCH, Jerry ,  DONDERS, Paul ,  ZARATE, Carlos

Inventor： RAMM, Peter ,  ALEXAMDROV, Yuriy ,  CYBUCH, Jerry ,  DONDERS, Paul ,  ZARATE, Carlos

IPC: G01N15/14

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

Abstract: A system for performing automated cell screening in drug discovery includes an automated microscope (100), a fast autofocus device, and a digital imaging system (500). 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.

Abstract translation: 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（100），快速自动聚焦装置和数字成像系统（500）。 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：WO2002068942A2

公开(公告)日：2002-09-06

申请号：PCT/IB2002/000590

申请日：2002-02-27

Applicant: IMAGING RESEARCH INC. ,  ZARATE, Carlos ,  DONDERS, Paul ,  YEKTA, Ahmed ,  MASOUMI, Zahra ,  RAMM, Peter

Inventor： ZARATE, Carlos ,  DONDERS, Paul ,  YEKTA, Ahmed ,  MASOUMI, Zahra ,  RAMM, Peter

IPC: G01N21/64

CPC classification number: G01N21/6408 ,  G01N2201/0648

Abstract: 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.

Abstract translation: 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，高量子效率的数码相机和计算机中。 在计算机控制下，灯以短时间脉冲。 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：EP1078256A1

公开(公告)日：2001-02-28

申请号：EP99915966.8

申请日：1999-04-22

Applicant: Imaging Research, Inc.

Inventor： RAMM, Peter ,  NADON, Robert

IPC: G01N33/00 ,  C12Q1/68

CPC classification number: G06F19/24 ,  G01N33/50 ,  G06F19/20

Abstract: 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：EP1002297A1

公开(公告)日：2000-05-24

申请号：EP98939995.1

申请日：1998-08-07

Applicant: Imaging Research, Inc.

Inventor： RAMM, Peter ,  SUN, Gang

IPC: G06T7/00

CPC classification number: G06T7/73 ,  G06T2207/30072

Abstract: A method and apparatus are disclosed for use in an area digital imaging system for assays to extract targets on a specimen containing an array of targets that may not be arranged in perfect regularity. A matrix is defined of nominal target locations including a probe template of predefined, two-dimensional size and shape at each of a plurality of fixed, predefined grid points on the specimen, and a determination is made of the most probable location of the probe template corresponding to a specific target by sensing both pixel intensity and the spatial distribution of pixel intensities in an image of the specimen at a plurality of locations in the vicinity of a nominal target location.

Abstract translation: 公开了一种用于区域数字成像系统中的方法和装置，用于在包含可能未以完全规则排列的目标阵列的样本上提取目标的测定。 矩阵定义为标称目标位置，包括在样本上的多个固定的预定网格点中的每一个上的预定义的二维尺寸和形状的探针模板，并且确定探针模板的最可能的位置 通过检测在标称目标位置附近的多个位置处的样本的图像中的像素强度的像素强度和像素强度的空间分布来对应于特定目标。

公开(公告)号：EP1078256B1

公开(公告)日：2002-11-27

申请号：EP99915966.8

申请日：1999-04-22

Applicant: Imaging Research, Inc.

Inventor： RAMM, Peter ,  NADON, Robert

IPC: G01N33/00 ,  C12Q1/68

CPC classification number: G06F19/24 ,  G01N33/50 ,  G06F19/20

公开(公告)号：EP1259928A2

公开(公告)日：2002-11-27

申请号：EP01908045.6

申请日：2001-03-02

Applicant: Imaging Research, Inc.

Inventor： NADON, Robert ,  SHI, Peide ,  RAMM, Peter

IPC: G06F19/00

CPC classification number: G06F19/20 ,  C12Q1/6837 ,  G06F19/24

Abstract: 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 hybridisation 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：EP1366351A2

公开(公告)日：2003-12-03

申请号：EP02700526.3

申请日：2002-02-27

Applicant: Imaging Research, Inc.

Inventor： ZARATE, Carlos ,  DONDERS, Paul ,  YEKTA, Ahmed ,  MASOUMI, Zahra ,  RAMM, Peter

IPC: G01N21/64

CPC classification number: G01N21/6408 ,  G01N2201/0648

Abstract: 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.

公开(公告)号：EP1200620A2

公开(公告)日：2002-05-02

申请号：EP00935427.5

申请日：2000-06-19

Applicant: Imaging Research, Inc.

Inventor： RAMM, Peter ,  NADON, Robert ,  SHI, Peide

IPC: C12Q1/68 ,  G01N33/00

CPC classification number: G06F19/20 ,  G06F19/24

Abstract: A method for improving the reliability and/or accuracy of physical measurements obtained from array hybridization studies performed on an array having a large number of genomic samples uses a small number of replicates insufficient for making precise and valid statistical inferences. This is overcome by estimating an error in measurement of a sample by averaging errors obtained when measuring the large number of samples or a subset of the large number of samples. The estimated sample error is utilized as a standard for accepting or rejecting the measurement of the respective sample. The samples may be independent or dependant in that correlated across two or more conditions.

公开(公告)号：EP1019705A1

公开(公告)日：2000-07-19

申请号：EP97940695.6

申请日：1997-08-12

Applicant: Imaging Research, Inc.

Inventor： RAMM, Peter ,  SUN, Gang ,  MUELLER, Rolf ,  ORMSBY, Timothy ,  CASTLE, Kenneth, R.

IPC: G01N21/64

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

Abstract: 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 (18), a fast, telecentric lens (22) with epi-illumination (44), a reflective/transmissive illumination system, an illumination wavelength selection device (34), and a light-tight chamber (24). 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.

Abstract translation: 公开了一种用于评估由孔，微孔，膜，凝胶或其它样品上的杂交点印迹的基质中的比色，荧光或发光信号的强度的电子成像系统。 该系统包括非常敏感的区域CCD检测器（18），具有外露照明（44）的快速远心透镜（22），反射/透射照明系统，照明波长选择装置（34）和不透光 室（24）。 用于控制硬件的计算机和图像分析软件区域，校正和校准图像，以及检测和量化图像中的目标。