公开(公告)号：US07864380B2

公开(公告)日：2011-01-04

申请号：US11711283

申请日：2007-02-27

申请人： Michael R. Descour ,  Artur G. Olszak ,  Andrew Lowe

发明人： Michael R. Descour ,  Artur G. Olszak ,  Andrew Lowe

IPC分类号： G06T5/50 ,  G02B21/18

CPC分类号： G02B21/34 ,  G01N2001/282 ,  G01N2035/00772

摘要： In a scanning microscope, slides are fed automatically from a magazine to the imaging system. Each slide is labeled in some fashion with information for selecting the appropriate modality of operation of the scanner for that slide and the modality is implemented automatically. The information is preferably tied to and defined by a laboratory information system (LIS). For example, the instructions may regard the type of microscopy (i.e., trans- or epi-illumination), multi-spectral imaging with particular spectral bands combined with a particular set of z-positions, alternative filters, settings for the numerical aperture of the condenser, alternative detector operation for different resolutions, and alternative post-scan analyses of the data, as deemed optimal for the scan. The label may also contain the slide's identity, a pathologist's name, desired post-scan handling protocol, etc. The preferred array microscope to carry out the invention is also described.

摘要翻译： 在扫描显微镜中，幻灯片自动从一个暗盒进给成像系统。 每个幻灯片都以某种方式被标记为具有用于选择用于该幻灯片的扫描器的适当操作模式的信息，并且该模式被自动实现。 该信息最好与实验室信息系统（LIS）相关联并由其定义。 例如，说明书可以将显微镜的类型（即透射或表面照明），具有与特定z轴位置组合的特定光谱带的多光谱成像，替代滤光片，数值孔径的设置 冷凝器，不同分辨率的替代检测器操作，以及数据的替代扫描后分析，被认为是扫描的最佳选择。 标签还可以包含幻灯片的身份，病理学家的名字，期望的扫描后处理协议等。还描述了实现本发明的优选阵列显微镜。

公开(公告)号：US07330574B2

公开(公告)日：2008-02-12

申请号：US10431937

申请日：2003-05-08

申请人： Artur G. Olszak

发明人： Artur G. Olszak

IPC分类号： G06K9/00

CPC分类号： G02B21/244 ,  Y10S128/922

摘要： The sample stage of an array microscope is tilted in the scanning direction such that the best-focus plane of the array microscope intersects the surface of the sample during the scan. As a result of the tilt, the distance from the sample surface of each miniaturized microscope spanning the array varies from point to point on the surface. Accordingly, the best focal distance for each such point on the sample surface is identified by tracking the quality of its focus as the sample surface travels across the rows of microscopes in the array. Best focus may be detected using any known technique, such as by measuring spatial frequency content and recording the scan position corresponding to maximum mid-range frequency content. This information is used to develop a best-focus axial-position map for use while performing a subsequent measurement scan.

摘要翻译： 阵列显微镜的样品台在扫描方向上倾斜，使得阵列显微镜的最佳聚焦平面在扫描期间与样品的表面相交。 作为倾斜的结果，跨越阵列的每个小型化显微镜的样品表面的距离随着表面上的点而变化。 因此，当样品表面穿过阵列中的显微镜行时，通过跟踪其焦点的质量来识别样品表面上每个这样的点的最佳焦距。 可以使用任何已知技术来检测最佳焦点，例如通过测量空间频率内容并记录对应于最大中档频率内容的扫描位置。 该信息用于开发最佳对焦轴位置图，供执行后续测量扫描时使用。

公开(公告)号：US08675205B2

公开(公告)日：2014-03-18

申请号：US13853864

申请日：2013-03-29

申请人： Artur G. Olszak

发明人： Artur G. Olszak

IPC分类号： G01B11/02

CPC分类号： G01B9/02002 ,  G01B9/02025 ,  G01B9/02057 ,  G01B9/0209

摘要： The time delay (and therefore the OPD) between object and reference beams in an interferometer is manipulated by changing the spectral properties of the source. The spectral distribution is tuned to produce a modulation peak at a value of OPD equal to the optical distance between the object and reference arms of a Fizeau interferometer, thereby enabling the use of its common-axis configuration to carry out white-light measurements free of coherence noise. Unwanted interferences from other reflections in the optical path are also removed by illuminating the object with appropriate spectral characteristics. OPD scanning is implemented without mechanical means by altering the source spectrum over time so as to shift the peak location by a predetermined scanning step between acquisition frames. The invention and its advantages are applicable to optical coherence tomography as well as conventional white light interferometry.

摘要翻译： 通过改变源的光谱特性来操纵干涉仪中对象和参考光束之间的时间延迟（因此OPD）。 频谱分布被调谐以产生等于Fizeau干涉仪的对象和参考臂之间的光学距离的OPD值的调制峰值，从而能够使用其共轴配置来进行白光测量 相干噪声 通过用适当的光谱特征照射物体也可以消除光路中其它反射的不希望的干扰。 通过随时间改变源频谱而实现无机械手段的OPD扫描，以便在采集帧之间将预定的扫描步骤移位峰值位置。 本发明及其优点适用于光学相干断层摄影以及常规白光干涉测量。

公开(公告)号：US07864379B2

公开(公告)日：2011-01-04

申请号：US11644564

申请日：2006-12-23

申请人： Artur G. Olszak ,  Chen Liang

发明人： Artur G. Olszak ,  Chen Liang

IPC分类号： G02B6/04 ,  H04N1/04

CPC分类号： G01J3/2803 ,  G01J3/02 ,  G01J3/0208 ,  G01J3/0235 ,  G01J3/0237 ,  G01J3/10 ,  G01J3/2823 ,  G01N21/253 ,  G01N21/31 ,  G02B21/367

摘要： An array microscope scans a slide in rapid sequence at different wavelengths to record multiple spectral images of the sample. Full spatial resolution of the image sensor is realized at each color because pixels are not shared between spectral bands. The object and detector are placed at conjugate distances selected to produce substantially equal magnification with minimum chromatic aberration at all wavelengths to ensure registration of all images. Spectral analysis is carried out by combining the images captured at each wavelength. The greater-than-RGB spectral resolution provided by the combination of images enables the isolation and display of the effects produced by the contemporaneous use of more than two stains on a tissue for improved pathological analysis.

摘要翻译： 阵列显微镜以不同波长的快速序列扫描载玻片以记录样品的多个光谱图像。 由于像素不在光谱带之间共享，因此在每种颜色下实现图像传感器的全空间分辨率。 物体和检测器被放置在所选择的共轭距离处以在所有波长处产生具有最小色差的基本相等的倍率，以确保所有图像的配准。 通过组合在每个波长处拍摄的图像进行光谱分析。 由图像组合提供的大于RGB的光谱分辨率使得能够隔离和显示由组织上同时使用两种以上污渍产生的效果，以改善病理分析。

公开(公告)号：US07193775B2

公开(公告)日：2007-03-20

申请号：US10158626

申请日：2002-05-30

申请人： Artur G. Olszak ,  Chen Liang

发明人： Artur G. Olszak ,  Chen Liang

IPC分类号： G02B21/06

CPC分类号： G02B21/125 ,  G02B21/002 ,  G02B21/082 ,  Y10S359/90

摘要： An epi-illumination system for an array microscope. For Kohler illumination, illumination light sources are placed, actually or virtually, at the pupils of respective individual microscope elements of an array microscope. In one Kohler illumination embodiment, the light source is a point source comprising the tip of an optical fiber placed on the optical axis at the pupil of its corresponding microscope element. In another Kohler illumination embodiment, the illumination light is provided by a reflective boundary placed on the optical axis of a corresponding microscope element. For critical illumination the light sources are placed at locations conjugate with their respective object planes so as to image the light sources thereon. For dark-field illumination, the support material around a microscope element lens, which is used to support an array of lenses, is fashioned to form an illumination optical element so that light from an off-axis source is directed by the illumination element toward the object plane at an angle such that light will not be reflected into the field of view of the imaging system, but scattered or fluorescence light will be within that field of view. The illumination optical element may be refractive element, a Fresnel element, a reflective element, a diffractive element, or some combination of one or more of these elements. An array of pinhole apertures may be provided to operate the array microscope in a confocal mode. All of the embodiments may be used for epi-fluorescence microscopy.

摘要翻译： 阵列显微镜的外照明系统。 对于科勒照明，照明光源实际上或虚拟地放置在阵列显微镜的各个显微镜元件的瞳孔处。 在一个科勒照明实施例中，光源是一个点源，其包括位于其对应的显微镜元件的光瞳处的光轴上的光纤的尖端。 在另一个科勒照明实施例中，照明光由放置在对应的显微镜元件的光轴上的反射边界提供。 对于临界照明，光源被放置在与它们各自的物平面共轭的位置处，以便在其上对光源进行成像。 对于暗场照明，用于支撑透镜阵列的显微镜元件透镜周围的支撑材料被形成为形成照明光学元件，使得来自离轴源的光被照明元件朝向 物体平面以使得光不会被反射到成像系统的视野中的角度，但散射或荧光将在该视场内。 照明光学元件可以是折射元件，菲涅尔元件，反射元件，衍射元件或这些元件中的一个或多个的某种组合。 可以提供针孔的阵列以以共焦模式操作阵列显微镜。 所有实施方案可用于外荧光显微镜。

公开(公告)号：US07130115B2

公开(公告)日：2006-10-31

申请号：US10666990

申请日：2003-09-19

申请人： Artur G. Olszak ,  Chen Liang ,  Michael R. Descour

发明人： Artur G. Olszak ,  Chen Liang ,  Michael R. Descour

IPC分类号： G02B21/18

CPC分类号： G02B21/002 ,  G02B21/367

摘要： A multi-mode scanning imaging system. The system includes a plurality of sets of optical elements and a scanning mechanism. Each set is disposed with respect to a corresponding image plane and configured to image respective portions of an object. A scanning mechanism produces relative translation between the sets and the object so as to scan the object. Sets of image sensors corresponding to the sets of optical elements are adapted to capture image data representative of the respective portions of the object. A mode implementation system coordinates the image data according to one or more desired modes of operation of the imaging system.

摘要翻译： 多模扫描成像系统。 该系统包括多组光学元件和扫描机构。 每个组相对于对应的图像平面设置并且被配置为对对象的各个部分进行成像。 扫描机制产生组和对象之间的相对平移，以扫描对象。 对应于这些光学元件组的图像传感器的组适于捕获表示对象的各个部分的图像数据。 模式实现系统根据成像系统的一个或多个期望的操作模式来协调图像数据。

公开(公告)号：US06987259B2

公开(公告)日：2006-01-17

申请号：US10158633

申请日：2002-05-30

申请人： Artur G. Olszak ,  Chen Liang

发明人： Artur G. Olszak ,  Chen Liang

IPC分类号： H01L27/00

CPC分类号： G02B21/0004 ,  G02B21/0032 ,  G02B21/0036 ,  G02B21/004 ,  G02B21/0068 ,  G02B21/0076 ,  G02B21/008 ,  G02B21/0096 ,  G02B21/365 ,  H01L27/14625

摘要： An imaging system with an integrated source and detector array. A plurality of light detectors are arranged in a detector array and a plurality of light sources corresponding to detectors in the detector array are arranged in a source array in an epi-illumination system so that light radiated from a point on the object illuminated by a given source is detected by a corresponding detector. An optical system is disposed with respect to the source array and the detector array so as to illuminate an object with light from the source array and image the object on the detector array. Ordinarily, the sources and detectors are coplanar and, preferably, are fabricated or at least mounted on the same substrate. One or more sources in the source array may have a corresponding plurality of detectors, and one or more detectors in the detector array may have a corresponding plurality of sources. In one embodiment the Airy pattern of the point response of the optical system encompasses both a detector and its corresponding light sources. In another embodiment, the optical pathway is split by a diffractive element to produce conjugate points corresponding to light sources and their respective detectors. In a further embodiment, the pathway is split by a Wollaston prism. In yet another embodiment where the illumination and image light have different wavelengths, the pathway is split by dispersion. The system is particularly suited for fluorescence imaging, confocal microscopy and array microscopes.

公开(公告)号：US06958464B2

公开(公告)日：2005-10-25

申请号：US10666445

申请日：2003-09-19

申请人： Artur G. Olszak ,  Chen Liang

发明人： Artur G. Olszak ,  Chen Liang

IPC分类号： G02B21/00 ,  G02B21/36 ,  H01L27/00 ,  H01L27/146 ,  G01J1/32

CPC分类号： G02B21/0004 ,  G02B21/0032 ,  G02B21/0036 ,  G02B21/004 ,  G02B21/0068 ,  G02B21/0076 ,  G02B21/008 ,  G02B21/0096 ,  G02B21/365 ,  H01L27/14625

摘要： An imaging system with an integrated source and detector array. A plurality of light detectors are arranged in an array and a corresponding plurality of light sources are arranged in an array in an epi-illumination system so that light radiated from a point on the object illuminated by a given source is detected by a corresponding detector. An optical system is disposed so as to illuminate an object with light from the source array and image the object on the detector array. Ordinarily, the sources and detectors are coplanar and, preferably, are fabricated or at least mounted on the same substrate. In one embodiment the Airy pattern of the point response of the optical system encompasses both a detector and corresponding light sources. In another embodiment, the optical pathway is split by a diffractive element to produce conjugate points corresponding to light sources and their respective detectors. In a further embodiment, the pathway is split by a Wollaston prism. In yet another embodiment where the illumination and image light have different wavelengths, the pathway is split by dispersion. Another embodiment comprises a power supply connected to the plurality of light sources, a signal conditioning circuit for receiving and digitizing output signals from the light detectors so as to produce a respective set of output values, and an equalizing system for equalizing the output values for a given input radiance.

摘要翻译： 具有集成源和检测器阵列的成像系统。 多个光检测器被布置成阵列，并且对应的多个光源以外延照射系统排列成阵列，使得由相应的检测器检测由给定源照射的物体上的点辐射的光。 设置光学系统以便用来自源阵列的光来照射物体，并将物体成像在检测器阵列上。 通常，源极和检测器是共面的，并且优选地被制造或至少安装在相同的衬底上。 在一个实施例中，光学系统的点响应的艾里图案包括检测器和对应的光源。 在另一个实施例中，光学通路由衍射元件分裂以产生对应于光源及其相应检测器的共轭点。 在另一个实施例中，通过Wollaston棱镜将路径分开。 在照明和图像光具有不同波长的另一个实施例中，该通路被分散分裂。 另一个实施例包括连接到多个光源的电源，信号调节电路，用于接收和数字化来自光检测器的输出信号，以便产生相应的一组输出值;以及均衡系统，用于均衡输出值 给定的输入辐射。

公开(公告)号：US06842290B2

公开(公告)日：2005-01-11

申请号：US10425757

申请日：2003-04-29

申请人： Chen Liang ,  Artur G. Olszak ,  James Goodall

发明人： Chen Liang ,  Artur G. Olszak ,  James Goodall

IPC分类号： G02B21/00 ,  G02B21/24 ,  G02B27/10

CPC分类号： G02B21/002 ,  G02B21/241

摘要： A multiple-axis imaging system having individually-adjustable optical elements and a method for individually adjusting optical elements of the system. The system comprises a plurality of optical elements having respective optical axes and being individually disposed with respect to one another to image respective sections of an object, and a plurality of individually-operable positioning devices corresponding to respective optical elements for positioning the optical elements with respect to their respective optical axes. The positioning devices are specifically adapted to adjust the axial position, lateral position and angular orientation of the optical elements with respect to their respective optical axes. The system is particularly adapted for use as a microscope array, and the positioning devices may be micro-actuators.

摘要翻译： 具有可单独调节的光学元件的多轴成像系统和用于单独调节系统的光学元件的方法。 该系统包括具有各自的光轴的多个光学元件，并且相对于彼此单独地设置以对物体的各个部分进行成像，以及对应于各个光学元件的多个可单独操作的定位装置，用于将光学元件相对于 到它们各自的光轴。 定位装置特别适于调整光学元件相对于它们各自的光轴的轴向位置，横向位置和角度定向。 该系统特别适合用作显微镜阵列，并且定位装置可以是微致动器。

公开(公告)号：US07755841B2

公开(公告)日：2010-07-13

申请号：US12011818

申请日：2008-01-30

申请人： Todd R. Christenson ,  Michael R. Descour ,  Chen Liang ,  Artur G. Olszak

发明人： Todd R. Christenson ,  Michael R. Descour ,  Chen Liang ,  Artur G. Olszak

IPC分类号： G02B1/06 ,  G02B21/02 ,  B29D11/00

CPC分类号： B29D11/00028 ,  B29D11/00807 ,  G02B3/0012 ,  G02B3/0056 ,  G02B3/14 ,  G02B21/002 ,  G02B21/02

摘要： A liquid lens includes a segmented electrode that allows the simultaneous application of different potentials across the lens's meniscus to obtain a predetermined aberration correction condition and to adjust focal length as necessary to conform to the topography of the object being scanned. The lens also includes a gas plenum interfacing with one of the liquids of the lens to allow for volume changes in the lens cell due to temperature variations. This combination of features produces a liquid-lens cell capable of maintaining substantially constant transverse magnification and diffraction-limited image quality over a useful range of focal length. As such, the lens is particularly suitable for incorporation in an array of micro-objectives used in a scanning microscope.

摘要翻译： 液体透镜包括分段电极，其允许跨透镜的弯月面同时施加不同电位以获得预定的像差校正条件，并且根据需要调整焦距以符合被扫描物体的形貌。 透镜还包括与透镜的​​液体之一接口的气体增压室，以允许由于温度变化导致的透镜单元的体积变化。 特征的这种组合产生能够在有效的焦距范围内保持基本恒定的横向放大率和衍射受限图像质量的液体透镜单元。 因此，镜片特别适合于并入在扫描显微镜中使用的微观物镜的阵列中。