公开(公告)号：US07701572B2

公开(公告)日：2010-04-20

申请号：US11918487

申请日：2005-04-08

Applicant: David Tuschel ,  Thomas C. Voigt

Inventor： David Tuschel ,  Thomas C. Voigt

IPC: G01N21/64 ,  G01N21/65 ,  G01J3/51 ,  G01J3/44

CPC classification number: G01J3/42 ,  G01J3/2823 ,  G01J3/44 ,  G01N21/253 ,  G01N21/6452 ,  G01N21/65

Abstract: The disclosure relates to systems and method for chemical imaging of microarrays. In one embodiment, the disclosure relates to a system for simultaneous spectral imaging of a plurality of samples arranged on an array. The system includes an illumination source for providing illuminating photons to said plurality of samples, the illuminating photons interacting with each of the plurality of samples to emit interacted photons; an array for receiving said plurality of samples, the array having an external dimension such that the samples are within a simultaneous field of view of the optical device; an optical device for collecting the interacted photons and directing the photons to an imaging device, the imaging device simultaneously forming a plurality of images corresponding to each of the plurality of samples.

Abstract translation: 本公开涉及用于微阵列的化学成像的系统和方法。 在一个实施例中，本公开涉及一种用于同时对阵列上布置的多个样本进行光谱成像的系统。 该系统包括用于向所述多个样本提供照明光子的照明源，所述照明光子与所述多个样本中的每一个相互作用以发射相互作用的光子; 用于接收所述多个样本的阵列，所述阵列具有使得所述样本在所述光学装置的同时视野内的外部尺寸; 用于收集相互作用的光子并将光子引导到成像装置的光学装置，成像装置同时形成对应于多个样本中的每一个的多个图像。

公开(公告)号：US07659978B2

公开(公告)日：2010-02-09

申请号：US11975403

申请日：2007-10-19

Applicant: David Tuschel ,  Arjun Bangalore

Inventor： David Tuschel ,  Arjun Bangalore

IPC: G01N21/65 ,  G01N1/00

CPC classification number: G01J3/44 ,  G01J3/10 ,  G01N21/274 ,  G01N21/65

Abstract: A pulse photobleaching methodology wherein a monochromatic illumination (e.g., laser illumination) having a higher power intensity (photobleaching power) just below the photodamage threshold of a luminescent sample is initially used to significantly attenuate sample luminescence without photothermally destroying the sample material. Thereafter, the laser power density may be reduced to a significantly lower level (analytical power level) to carry out spectroscopic measurements (e.g., collection of Raman scattered photons) on the sample. In one embodiment, the laser illumination wavelength remains the same despite changes in laser power intensity. Some figures-of-merit may be computed from optical measurements made at the analytical power level to guide the photobleaching process. Sample-dependent combinations of laser power density and short exposure times may be obtained to significantly expedite photobleaching to assist in collection of sample spectral data in the field without a long wait. Portable spectroscopy systems employing pulse photobleaching may be devised for expeditious collection of spectral data from luminescent samples in the field.

Abstract translation: 脉冲光漂白方法，其中最初使用具有刚好低于发光样品的光损伤阈值的较高功率强度（光漂白能力）的单色照明（例如，激光照明）来显着衰减样品发光而不光热地破坏样品材料。 此后，激光功率密度可以降低到显着较低的水平（分析能级），以对样品进行光谱测量（例如，拉曼散射光子的收集）。 在一个实施例中，激光照射波长保持相同，尽管激光功率强度的变化。 可以通过在分析功率级别进行的光学测量来计算一些数字值，以指导光漂白过程。 可以获得激光功率密度和短曝光时间的样品依赖组合，以显着加速光漂白，以帮助在现场收集样品光谱数据而不用长时间等待。 可以设计采用脉冲光漂白的便携式光谱系统，以便从现场的发光样品中快速收集光谱数据。

公开(公告)号：US07609370B2

公开(公告)日：2009-10-27

申请号：US12017409

申请日：2008-01-22

Applicant: Thomas Voigt ,  David Tuschel

Inventor： Thomas Voigt ,  David Tuschel

IPC: G01J3/44 ,  G01J3/443 ,  G01N21/64 ,  G01N21/65

CPC classification number: G01J3/02 ,  G01J3/0218 ,  G01J3/10 ,  G01J3/1838 ,  G01J3/2823 ,  G01N21/65

Abstract: A single detector based spectroscopy system using FAST (fiber array spectral translator) fibers and two excitation sources in conjunction with a holographic spectrum analyzer (HSA) to obtain simultaneous and selective display of spectroscopic regions of interest. A sample can be illuminated with different laser excitation wavelengths and resulting multiple spectra can be comparatively observed on a single display screen for more fruitful analysis of sample spectral responses (and, hence, sample chemical or physical properties) under different excitations. The HSA may be configured to focus on user-selected spectral regions of interest from different such spectra and a single CCD detector may be configured to collect spectral data from all selected spectral regions of interest in corresponding portions of the CCD pixel array, thereby allowing subsequent simultaneous display of such selected spectral regions of interest. The HSA may also allow simultaneous collection and display of portions of a single spectrum from a single excitation wavelength. A user can perform better comparative analysis when spectral regions of interest are juxtaposed with each other on a single electronic display.

Abstract translation: 基于单个检测器的光谱系统，使用FAST（光纤阵列光谱转换器）光纤和两个激光源与全息光谱分析仪（HSA）结合，以获得感兴趣的光谱区域的同时和选择性显示。 可以用不同的激光激发波长照射样品，并且可以在单个显示屏上比较观察到所得到的多个光谱，以便在不同激发下对样品光谱响应（以及因此的样品化学或物理性质）进行更有效的分析。 HSA可以被配置为聚焦于来自不同这样的光谱的用户选择的感兴趣的光谱区域，并且单个CCD检测器可以被配置为从CCD像素阵列的对应部分中的所有所选择的光谱区域收集光谱数据，从而允许随后的 同时显示所选择的所选择的光谱区域。 HSA还可以允许从单个激发波长同时收集和显示单个光谱的部分。 当感兴趣的光谱区域在单个电子显示器上彼此并置时，用户可以执行更好的比较分析。

公开(公告)号：US07564541B2

公开(公告)日：2009-07-21

申请号：US11393395

申请日：2006-03-30

Applicant: David Tuschel

Inventor： David Tuschel

IPC: G01N21/00 ,  G01J3/44

CPC classification number: G01J3/44 ,  G01J3/10 ,  G01J3/1256 ,  G01J3/26 ,  G01J3/32 ,  G01N21/21 ,  G01N21/23 ,  G01N21/31 ,  G01N21/35 ,  G01N21/3563 ,  G01N21/359 ,  G01N21/6456 ,  G01N21/6458 ,  G01N21/65 ,  G01N2021/6471 ,  G01N2021/6493

Abstract: An integrated system including one or more light sources, at least one processor, an optical lens, a two-dimensional tunable filter, one or more two-dimensional array of detection elements and instructions and a method using the integrated system. The system includes a plurality of modes: a Raman mode, an absorption mode, a luminescence mode, a crossed polarization mode, a crossed polarization absorption mode, bright field transmission or reflectance modes and a birefringence mode. The system includes instructions, executable by Sequential outputs from the two-dimensional array of detection elements is combined to generate a chemical image of the sample, wherein each of the sequential outputs from the first two-dimensional array of detection elements corresponds to spatially accurate wavelength-resolved images. The system is also used to detect dynamic changes in a sample over time by monitoring the sample using one or more of the modes.

Abstract translation: 包括一个或多个光源的集成系统，至少一个处理器，光学透镜，二维可调滤波器，检测元件和指令的一个或多个二维阵列以及使用该集成系统的方法。 该系统包括多种模式：拉曼模式，吸收模式，发光模式，交叉偏振模式，交叉偏振吸收模式，亮场透射或反射模式和双折射模式。 该系统包括可由来自检测元件的二维阵列的顺序输出执行的指令，以组合以产生样本的化学图像，其中来自检测元件的第一二维阵列的每个顺序输出对应于空间上准确的波长 解决的图像。 该系统还用于通过使用一种或多种模式监测样品来随时间检测样品中的动态变化。

公开(公告)号：US20080272312A1

公开(公告)日：2008-11-06

申请号：US12148199

申请日：2008-04-17

Applicant: David Tuschel

Inventor： David Tuschel

IPC: G01J1/58

CPC classification number: G01J3/44 ,  G01N21/6452

Abstract: A system and method of hyperspectral chemical imaging (fluorescence or absorption based) to provide an automated approach for a more detailed analysis of disease status of a biological sample. When a biological sample is labeled with a fluorescent or light-absorbing contrast-enhancing agent, interactions between the contrast-enhancing agent and one or more constituents (or cellular components) of the biological sample may be manifested through spectral contents of a plurality of regions in a hyperspectral chemical image of the sample. Observations of such manifestations through analysis of corresponding spectral contents may greatly assist a user (e.g., a pathologist) in detecting and differentiating diseased portions of the stained sample. Hyperspectral chemical imaging may allow to identify multiple cellular components within a biological sample and to image their distribution within the sample, thereby assisting a pathologist to successfully and more accurately identify diseased portion(s) of the sample for further diagnosis and treatment.

Abstract translation: 一种高光谱化学成像（基于荧光或吸收）的系统和方法，为生物样品疾病状态的更详细分析提供一种自动化方法。 当生物样品用荧光或光吸收对比增强剂标记时，生物样品的对比度增强剂与一种或多种组分（或细胞组分）之间的相互作用可以通过多个区域的光谱含量来表现 在样品的高光谱化学图像中。 通过分析相应的光谱内容来观察这些表现可以极大地帮助用户（例如，病理学家）检测和区分染色样品的患病部分。 高光谱化学成像可以允许鉴定生物样品中的多种细胞组分并使其在样品内的分布成像，从而帮助病理学家成功且更准确地鉴定样品的患病部分以进行进一步的诊断和治疗。

公开(公告)号：US20080212079A1

公开(公告)日：2008-09-04

申请号：US12017409

申请日：2008-01-22

Applicant: Thomas VOIGT ,  David Tuschel

Inventor： Thomas VOIGT ,  David Tuschel

IPC: G01N21/00

CPC classification number: G01J3/02 ,  G01J3/0218 ,  G01J3/10 ,  G01J3/1838 ,  G01J3/2823 ,  G01N21/65

Abstract: A single detector based spectroscopy system using FAST (fiber array spectral translator) fibers and two excitation sources in conjunction with a holographic spectrum analyzer (HSA) to obtain simultaneous and selective display of spectroscopic regions of interest. A sample can be illuminated with different laser excitation wavelengths and resulting multiple spectra can be comparatively observed on a single display screen for more fruitful analysis of sample spectral responses (and, hence, sample chemical or physical properties) under different excitations. The HSA may be configured to focus on user-selected spectral regions of interest from different such spectra and a single CCD detector may be configured to collect spectral data from all selected spectral regions of interest in corresponding portions of the CCD pixel array, thereby allowing subsequent simultaneous display of such selected spectral regions of interest. The HSA may also allow simultaneous collection and display of portions of a single spectrum from a single excitation wavelength. A user can perform better comparative analysis when spectral regions of interest are juxtaposed with each other on a single electronic display.

Abstract translation: 基于单个检测器的光谱系统，使用FAST（光纤阵列光谱转换器）光纤和两个激光源与全息光谱分析仪（HSA）结合，以获得感兴趣的光谱区域的同时和选择性显示。 可以用不同的激光激发波长照射样品，并且可以在单个显示屏上比较观察到所得到的多个光谱，以便在不同激发下对样品光谱响应（以及因此的样品化学或物理性质）进行更有效的分析。 HSA可以被配置为聚焦于来自不同这样的光谱的用户选择的感兴趣的光谱区域，并且单个CCD检测器可以被配置为从CCD像素阵列的对应部分中的所有所选择的光谱区域收集光谱数据，从而允许随后的 同时显示所选择的所选择的光谱区域。 HSA还可以允许从单个激发波长同时收集和显示单个光谱的部分。 当感兴趣的光谱区域在单个电子显示器上彼此并置时，用户可以执行更好的比较分析。

公开(公告)号：US20080088844A1

公开(公告)日：2008-04-17

申请号：US11902874

申请日：2007-09-26

Applicant: Xinghua Wang ,  Thomas Voigt ,  David Tuschel ,  Chenhui Wang ,  Patrick Treado

Inventor： Xinghua Wang ,  Thomas Voigt ,  David Tuschel ,  Chenhui Wang ,  Patrick Treado

IPC: G01N21/25

CPC classification number: G01N21/65 ,  G01J3/02 ,  G01J3/0291 ,  G01J3/36 ,  G01J3/44 ,  G01N21/359 ,  G01N21/59 ,  G01N21/6458 ,  G01N2021/6419 ,  G01N2021/6421 ,  G01N2021/656

Abstract: The disclosure generally relates to a multimode imaging apparatus for simultaneously obtaining multiple wavelength-discriminative spectral images of a sample. In one embodiment, the apparatus includes an image selector having a rotator assembly, the rotator assembly housing a first plurality of optical components, the image selector adapted to receive a illuminating photons having a first wavelength and direct the illuminating photons to the sample, the image selector adapted to receive illuminating photons interacted with the sample and selectively direct said interacted photons to one of a plurality of detection sources; a microscope turret housing a second plurality of components, the microscope turret adapted to receive illuminating photons having a second wavelength and direct the photons to the sample; the microscopic turret adapted to receive illuminating photons interacted with the sample and selectively direct said interacted photons to one of a plurality of detection sources; wherein substantially all of the interacted photons are selectively directed one of a plurality of detection sources to form multiple wavelength discriminative spectral images of the sample simultaneously.

公开(公告)号：US07317526B2

公开(公告)日：2008-01-08

申请号：US11399032

申请日：2006-04-06

Applicant: Thomas C. Voigt ,  David Tuschel ,  John S. Maier

Inventor： Thomas C. Voigt ,  David Tuschel ,  John S. Maier

IPC: G01J3/44 ,  G01N21/65

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

Abstract: 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.

Abstract translation: 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：US07283241B2

公开(公告)日：2007-10-16

申请号：US11045080

申请日：2005-01-31

Applicant: Xinghua Wang ,  Thomas C. Voigt ,  David Tuschel ,  Chenhui Wang ,  Patrick J. Treado

Inventor： Xinghua Wang ,  Thomas C. Voigt ,  David Tuschel ,  Chenhui Wang ,  Patrick J. Treado

IPC: G01N21/25

CPC classification number: G01N21/65 ,  G01J3/02 ,  G01J3/0291 ,  G01J3/36 ,  G01J3/44 ,  G01N21/359 ,  G01N21/59 ,  G01N21/6458 ,  G01N2021/6419 ,  G01N2021/6421 ,  G01N2021/656

Abstract: The disclosure generally relates to a multimode imaging apparatus for simultaneously obtaining multiple wavelength-discriminative spectral images of a sample. In one embodiment, the apparatus includes an image selector having a rotator assembly, the rotator assembly housing a first plurality of optical components, the image selector adapted to receive a illuminating photons having a first wavelength and direct the illuminating photons to the sample, the image selector adapted to receive illuminating photons interacted with the sample and selectively direct said interacted photons to one of a plurality of detection sources; a microscope turret housing a second plurality of components, the microscope turret adapted to receive illuminating photons having a second wavelength and direct the photons to the sample; the microscopic turret adapted to receive illuminating photons interacted with the sample and selectively direct said interacted photons to one of a plurality of detection sources; wherein substantially all of the interacted photons are selectively directed one of a plurality of detection sources to form multiple wavelength discriminative spectral images of the sample simultaneously.

Abstract translation: 本公开总体上涉及用于同时获得样本的多个波长鉴别光谱图像的多模式成像装置。 在一个实施例中，该装置包括具有旋转器组件的图像选择器，旋转体组件容纳第一多个光学部件，图像选择器适于接收具有第一波长的照明光子并将照射光子引导到样本，图像 选择器，适于接收与样本相互作用的照明光子，并选择性地将所述相互作用的光子引导到多个检测源之一; 显微镜转台，其容纳第二多个部件，所述显微镜转台适于接收具有第二波长并且将所述光子引导到所述样品的照明光子; 适于接收与样品相互作用的照明光子并且选择性地将所述相互作用的光子引导到多个检测源中的一个的微观炮塔; 其中基本上所有相互作用的光子被选择性地指向多个检测源中的一个，以同时形成样品的多个波长鉴别光谱图像。

公开(公告)号：US20070182959A1

公开(公告)日：2007-08-09

申请号：US10556038

申请日：2005-06-30

Applicant: John Maier ,  Patrick Treado ,  David Tuschel ,  Thomas Voigt

Inventor： John Maier ,  Patrick Treado ,  David Tuschel ,  Thomas Voigt

IPC: G01J3/44 ,  G01N21/65

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

Abstract: 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.

Abstract translation: 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。