公开(公告)号：US20060250613A1

公开(公告)日：2006-11-09

申请号：US11404964

申请日：2006-04-14

申请人： Joseph Demuth ,  Patrick Treado ,  John Maier ,  David Tuschel

发明人： Joseph Demuth ,  Patrick Treado ,  John Maier ,  David Tuschel

IPC分类号： G01J3/44 ,  G01N21/65

CPC分类号： G01J3/44 ,  G01J3/32 ,  G01N21/658

摘要： A method and apparatus for imaging biological objects. A SERS surface is provided having enhancing structures uniformly distributed on the surface. The surface includes a two dimensional area of at least 5×105 nm. The enhancing structures may have a size, in at least one dimension of height, width and length, ranging from 100 nm to 1000 nm. A biological material is deposited on the SERS surface. The biological material on the SERS surface is illuminated using a monochromatic light source producing Raman scattered photons. The Raman scattered photons are filtered using a tunable filter into a plurality of predetermined wavelength bands. A two-dimensional array detector detects the filtered Raman scattered photons, in a spatially accurate manner. The results of filtering and detecting steps are combined to produce a plurality of spectrally resolved Raman images of the biological material.

摘要翻译： 一种用于成像生物体的方法和装置。 提供了具有均匀分布在表面上的增强结构的SERS表面。 该表面包括至少5×10 5 nm的二维区域。 增强结构可以在100nm至1000nm范围内的高度，宽度和长度的至少一个尺寸中具有尺寸。 生物材料沉积在SERS表面上。 使用产生拉曼散射光子的单色光源照射SERS表面上的生物材料。 使用可调滤波器将拉曼散射光子滤波成多个预定波长带。 二维阵列检测器以空间准确的方式检测经过滤波的拉曼散射光子。 滤波和检测步骤的结果被组合以产生生物材料的多个光谱分辨的拉曼图像。

公开(公告)号：US20060268267A1

公开(公告)日：2006-11-30

申请号：US11399032

申请日：2006-04-06

申请人： Thomas Voigt ,  David Tuschel ,  John Maier

发明人： Thomas Voigt ,  David Tuschel ,  John Maier

IPC分类号： G01J3/44

CPC分类号： G01N21/6456 ,  G01J3/12 ,  G01J3/1256 ,  G01J3/2823 ,  G01J3/32 ,  G01J3/44 ,  G01J2003/1269 ,  G01N21/3563 ,  G01N21/3577 ,  G01N21/65

摘要： A system and method for detecting dynamic changes that occur in a sample between a first time interval and a second time interval using a series of at least first and second sequential chemical images of the sample. During the first time interval: (i) the sample is illuminated with a plurality of photons to thereby produce photons scattered or emitted by the sample; (ii) a two-dimensional array of detection elements is used to simultaneously detect scattered or emitted photons in a first predetermined wavelength band from different locations on or within the sample; and (iii) the two-dimensional array of detection elements is thereafter used one or more further times to simultaneously detect scattered or emitted photons in one or more further predetermined wavelength band(s) from different locations on or within the sample. The outputs of the two-dimensional array of detection elements during the first time interval are then combined to generate the first chemical image of the sample. The process is repeated during the second time interval to generate the second chemical image of the sample. Dynamic changes occurring in the sample between the first time interval and the second time interval are detected based on one or more differences between the first and second chemical images.

摘要翻译： 一种系统和方法，用于使用所述样本的至少第一和第二顺序化学图像的一系列来检测在第一时间间隔和第二时间间隔之间在样本中发生的动态变化。 在第一时间间隔期间：（i）样品用多个光子照射，从而产生样品散射或发射的光子; （ii）检测元件的二维阵列用于同时从样品上或样品内的不同位置检测来自第一预定波长带的散射或发射的光子; 然后，（iii）检测元件的二维阵列此后再被使用一次或多次，以同时检测来自样品上或样品内的不同位置的一个或多个另外的预定波长带中的散射或发射的光子。 然后组合在第一时间间隔期间检测元件的二维阵列的输出以产生样本的第一化学图像。 该过程在第二时间间隔期间重复以产生样品的第二化学图像。 基于第一和第二化学图像之间的一个或多个差异来检测在第一时间间隔和第二时间间隔之间在样本中发生的动态变化。

公开(公告)号：US20060001870A1

公开(公告)日：2006-01-05

申请号：US10882082

申请日：2004-06-30

申请人： Thomas Voigt ,  David Tuschel ,  John Maier

发明人： Thomas Voigt ,  David Tuschel ,  John Maier

IPC分类号： G01J3/44

CPC分类号： G01N21/6456 ,  G01J3/12 ,  G01J3/1256 ,  G01J3/2823 ,  G01J3/32 ,  G01J3/44 ,  G01J2003/1269 ,  G01N21/3563 ,  G01N21/3577 ,  G01N21/65

摘要： A system and method for detecting dynamic changes that occur in a sample between a first time interval and a second time interval using a series of at least first and second sequential chemical images of the sample. During the first time interval: (i) the sample is illuminated with a plurality of photons to thereby produce photons scattered or emitted by the sample; (ii) a two-dimensional array of detection elements is used to simultaneously detect scattered or emitted photons in a first predetermined wavelength band from different locations on or within the sample; and (iii) the two-dimensional array of detection elements is thereafter used one or more further times to simultaneously detect scattered or emitted photons in one or more further predetermined wavelength band(s) from different locations on or within the sample. The outputs of the two-dimensional array of detection elements during the first time interval are then combined to generate the first chemical image of the sample. The process is repeated during the second time interval to generate the second chemical image of the sample. Dynamic changes occurring in the sample between the first time interval and the second time interval are detected based on one or more differences between the first and second chemical images.

公开(公告)号：US20070182959A1

公开(公告)日：2007-08-09

申请号：US10556038

申请日：2005-06-30

申请人： John Maier ,  Patrick Treado ,  David Tuschel ,  Thomas Voigt

发明人： John Maier ,  Patrick Treado ,  David Tuschel ,  Thomas Voigt

IPC分类号： G01J3/44 ,  G01N21/65

CPC分类号： G01N21/6456 ,  G01J3/2803 ,  G01J3/32 ,  G01J3/36 ,  G01J3/44 ,  G01N21/359 ,  G01N21/6486 ,  G01N21/65 ,  G01N21/658 ,  G01N2021/656

摘要： The invention relates to methods of dynamic chemical imaging, including methods of cellular imaging. The method comprises illuminating at least a portion of a cell with substantially monochromatic light and assessing Raman-shifted light scattered from the illuminated portion at a plurality of discrete times. The Raman-shifted light can be assessed at a plurality of Raman shift (RS) values at each of the discrete times, and the RS values can be selected to be characteristic of a pre-selected component at each of the discrete times. Multivariate analysis of Raman spectral features of the images thus obtained can yield the location and chemical identity of components in the field of view. This information can be combined or overlaid with other spectral data (e.g., a visible microscopic image) obtained from the field of view.

摘要翻译： 本发明涉及动态化学成像方法，包括细胞成像方法。 该方法包括以基本上单色的光照亮电池的至少一部分，并且在多个离散时间评估从照射部分散射的拉曼偏移光。 可以在每个离散时间处以多个拉曼位移（RS）值评估拉曼移位的光，并且可以将每个离散时间的RS值选择为预选择的分量的特征。 如此获得的图像的拉曼光谱特征的多变量分析可以产生视场中部件的位置和化学特性。 该信息可以与从视野获得的其他光谱数据（例如，可见显微镜图像）组合或覆盖。

公开(公告)号：US20060274301A1

公开(公告)日：2006-12-07

申请号：US11433650

申请日：2006-05-15

申请人： David Tuschel ,  John Maier

发明人： David Tuschel ,  John Maier

IPC分类号： G01J3/44 ,  G01N21/64 ,  G01N21/65

CPC分类号： G01N21/6428 ,  G01J3/10 ,  G01J3/2823 ,  G01J3/4406 ,  G01N21/31 ,  G01N21/65 ,  G01N2021/6419 ,  G01N2021/6421 ,  G01N2021/6423

摘要： In one embodiment, the disclosure relates to a method for determining illumination parameters for a stained sample, the method may include providing a stained sample and obtaining an absorption band of the sample; obtaining an emission band of the sample and determining the illumination parameters for the sample as a function of the absorption band and the emission band of the sample.

公开(公告)号：US07046359B2

公开(公告)日：2006-05-16

申请号：US10882082

申请日：2004-06-30

申请人： Thomas C. Voigt ,  David Tuschel ,  John Maier

发明人： Thomas C. Voigt ,  David Tuschel ,  John Maier

IPC分类号： G01J3/44 ,  G01N21/65

CPC分类号： G01N21/6456 ,  G01J3/12 ,  G01J3/1256 ,  G01J3/2823 ,  G01J3/32 ,  G01J3/44 ,  G01J2003/1269 ,  G01N21/3563 ,  G01N21/3577 ,  G01N21/65

摘要： A system and method for detecting dynamic changes that occur in a sample between a first time interval and a second time interval using a series of at least first and second sequential chemical images of the sample. During the first time interval: (i) the sample is illuminated with a plurality of photons to thereby produce photons scattered or emitted by the sample; (ii) a two-dimensional array of detection elements is used to simultaneously detect scattered or emitted photons in a first predetermined wavelength band from different locations on or within the sample; and (iii) the two-dimensional array of detection elements is thereafter used one or more further times to simultaneously detect scattered or emitted photons in one or more further predetermined wavelength band(s) from different locations on or within the sample. The outputs of the two-dimensional array of detection elements during the first time interval are then combined to generate the first chemical image of the sample. The process is repeated during the second time interval to generate the second chemical image of the sample. Dynamic changes occurring in the sample between the first time interval and the second time interval are detected based on one or more differences between the first and second chemical images.

公开(公告)号：US20080093539A1

公开(公告)日：2008-04-24

申请号：US11907613

申请日：2007-10-15

申请人： David Tuschel ,  John Maier

发明人： David Tuschel ,  John Maier

IPC分类号： G01N21/27 ,  G01N21/31

CPC分类号： G01N21/6428 ,  G01J3/10 ,  G01J3/2823 ,  G01J3/4406 ,  G01N21/31 ,  G01N21/65 ,  G01N2021/6419 ,  G01N2021/6421 ,  G01N2021/6423

摘要： In one embodiment, the disclosure relates to a method for determining illumination parameters for a stained sample, the method may include providing a stained sample and obtaining an absorption band of the sample; obtaining an emission band of the sample and determining the illumination parameters for the sample as a function of the absorption band and the emission band of the sample.

摘要翻译： 在一个实施方案中，本公开涉及一种用于确定染色样品的照明参数的方法，所述方法可包括提供染色样品并获得样品的吸收带; 获得样品的发射带，并根据样品的吸收带和发射带确定样品的照射参数。

公开(公告)号：US07045757B1

公开(公告)日：2006-05-16

申请号：US11097161

申请日：2005-04-04

申请人： David Tuschel ,  John Maier ,  Joseph Demuth

发明人： David Tuschel ,  John Maier ,  Joseph Demuth

IPC分类号： H01L27/00

CPC分类号： G01N21/6428 ,  G01J3/02 ,  G01J3/027 ,  G01J3/10 ,  G01N21/65 ,  G01N2021/6417 ,  G01N2021/6471 ,  G01N2201/067

摘要： In one embodiment, the disclosure relates to a method for determining illumination parameters for a stained sample, the method may include providing a stained sample and obtaining an absorption band of the sample; obtaining an emission band of the sample and determining the illumination parameters for the sample as a function of the absorption band and the emission band of the sample.

摘要翻译： 在一个实施方案中，本公开涉及一种用于确定染色样品的照明参数的方法，所述方法可包括提供染色样品并获得样品的吸收带; 获得样品的发射带，并根据样品的吸收带和发射带确定样品的照射参数。

公开(公告)号：US20120078524A1

公开(公告)日：2012-03-29

申请号：US13136366

申请日：2011-07-29

申请人： Shona Stewart ,  Jeffrey Cohen ,  Amy Drauch ,  John Maier

发明人： Shona Stewart ,  Jeffrey Cohen ,  Amy Drauch ,  John Maier

IPC分类号： G01N33/48 ,  G01N21/64 ,  G01J3/44

CPC分类号： A61B5/0059 ,  A61B5/417 ,  G01J3/02 ,  G01J3/0291 ,  G01J3/0294 ,  G01J3/10 ,  G01J3/2823 ,  G01J3/32 ,  G01J3/44 ,  G01J2003/2826 ,  G01N21/6458 ,  G01N21/65 ,  G01N21/658 ,  G01N2021/656 ,  G01N2201/1293 ,  G01N2201/1296 ,  G02B21/16 ,  G02B21/365 ,  G06F19/325 ,  G16H50/70

摘要： A system and method for determining a diagnosis of a test biological sample. A system comprising a first illumination source to illuminate a sample, a first detector for generating a fluorescence data set of said sample, a means for determining a region of interest, a second illumination source to illuminate said region of interest, a second detector to generate a Raman data set of said region of interest, and a means for determining a diagnosis of said sample. A method comprising illuminating a sample, generating a fluorescence data set of said sample, and assessing the fluorescence data set to identify a region of interest, illuminating a region of interest, and generating Raman data set. This Raman data set may be assessed to determine a diagnosis of the sample. A diagnosis may include a metabolic state, a clinical outcome, a disease progression, a disease state, and combinations thereof.

摘要翻译： 用于确定测试生物样品的诊断的系统和方法。 一种系统，包括用于照亮样品的第一照明源，用于产生所述样品的荧光数据集的第一检测器，用于确定感兴趣区域的装置，用于照亮所述感兴趣区域的第二照明源，产生 所述感兴趣区域的拉曼数据集，以及用于确定所述样本的诊断的装置。 一种方法，包括照亮样品，产生所述样品的荧光数据集，以及评估所述荧光数据集以识别感兴趣区域，照亮感兴趣区域，以及产生拉曼数据集。 可以评估该拉曼数据集以确定样品的诊断。 诊断可以包括代谢状态，临床结果，疾病进展，疾病状态及其组合。

公开(公告)号：US07956996B2

公开(公告)日：2011-06-07

申请号：US12206500

申请日：2008-09-08

申请人： John Maier ,  Jeffrey Cohen ,  Shona Stewart

发明人： John Maier ,  Jeffrey Cohen ,  Shona Stewart

IPC分类号： G01J3/44 ,  G01N21/65

CPC分类号： G01J3/02 ,  A61B5/0059 ,  A61B5/417 ,  G01J3/0291 ,  G01J3/0294 ,  G01J3/28 ,  G01J3/2823 ,  G01J3/36 ,  G01J3/44 ,  G01J2003/2826 ,  G01N21/65 ,  G01N33/57415 ,  G01N2021/656 ,  G01N2201/1293 ,  G01N2201/1296 ,  Y02A90/26

摘要： A system and method to provide a diagnosis of the breast disease state of a test breast sample. A database containing a plurality of reference Raman data sets is provided where each reference Raman data set has an associated known breast sample and an associated known breast disease state. A test breast sample is irradiated with substantially monochromatic light to generate scattered photons resulting in a test Raman data set. The test Raman data set is compared to the plurality of reference Raman data sets using a chemometric technique. Based on the comparison, a diagnosis of a breast disease state of the test breast sample is provided. The breast disease state includes invasive ductal carcinoma or invasive lobular carcinoma disease state.

摘要翻译： 一种用于提供测试乳房样品的乳腺疾病状态诊断的系统和方法。 提供了包含多个参考拉曼数据集的数据库，其中每个参考拉曼数据集具有相关联的已知乳房样本和相关联的已知乳腺疾病状态。 用基本上单色的光照射测试乳样品以产生散射的光子，得到测试拉曼数据集。 使用化学计量技术将测试拉曼数据集与多个参考拉曼数据集进行比较。 基于比较，提供了测试乳房样品的乳腺疾病状态的诊断。 乳腺疾病状态包括浸润性导管癌或侵袭性小叶癌疾病状态。