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1. 发明授权

US06532061B2 Measuring the velocity of small moving objects such as cells 有权
公开(公告)号：US06532061B2
公开(公告)日：2003-03-11
申请号：US09939292
申请日：2001-08-24
申请人： William E. Ortyn , David A. Basiji , Richard A. Bauer , Keith L. Frost , David J. Perry , James K. Riley
发明人： William E. Ortyn , David A. Basiji , Richard A. Bauer , Keith L. Frost , David J. Perry , James K. Riley
IPC分类号： G01P336
CPC分类号： G02B27/0012 , G01N15/1012 , G01N15/1459 , G01N15/147 , G01N2015/1018 , G01N2015/1025 , G01N2015/1075 , G01N2015/144 , G01N2015/1443 , G01N2015/1447 , G01N2015/1452 , G01N2015/1497 , G06T7/20
摘要： Frequency domain velocity measurements and time domain velocity measurements are made using light from cells or other objects. An optical grating is used to modulate the light from an object so that it has a frequency proportional to the velocity of the object. Depending upon the embodiment, the pitch of the optical grating is uniform or varying. The modulated light is detected and various signal processing techniques, such as a Fast Fourier Transform function, are used to indicate the velocity of the object. Preferably, the velocity measured is applied in determining a timing signal employed for synchronization of an image of the object and an detector signal in an optical analysis system that uses a time delay integration detector to determine characteristics of the object in response to light from the object.

2. 发明授权

US06507391B2 Measuring the velocity of small moving objects such as cells 有权
公开(公告)号：US06507391B2
公开(公告)日：2003-01-14
申请号：US09939049
申请日：2001-08-24
申请人： James K. Riley , David A. Basiji , Richard A. Bauer , Keith L. Frost , William E. Ortyn , David J. Perry
发明人： James K. Riley , David A. Basiji , Richard A. Bauer , Keith L. Frost , William E. Ortyn , David J. Perry
IPC分类号： G01P336
CPC分类号： G02B27/0012 , G01N15/1012 , G01N15/1459 , G01N15/147 , G01N2015/1018 , G01N2015/1025 , G01N2015/1075 , G01N2015/144 , G01N2015/1443 , G01N2015/1447 , G01N2015/1452 , G01N2015/1497 , G06T7/20
摘要： Frequency domain velocity measurements and time domain velocity measurements are made using light from cells or other objects. An optical grating is used to modulate the light from an object so that it has a frequency proportional to the velocity of the object. Depending upon the embodiment, the pitch of the optical grating is uniform or varying. The modulated light is detected, producing an analog signal that is then digitally sampled. Time domain signal processing techniques are used to determine the velocity of the object from the digital samples. Preferably, the velocity measured is applied in determining a timing signal employed for synchronization of an image of the object and an detector signal in an optical analysis system that uses a time delay integration (TDI) detector to determine characteristics of the object in response to light from the object.

3. 发明授权

US07567695B2 Method and apparatus for reading reporter labeled beads 失效
公开(公告)号：US07567695B2
公开(公告)日：2009-07-28
申请号：US11078009
申请日：2005-03-11
申请人： Keith L. Frost , David A. Basiji , Richard A. Bauer , Rosalynde J. Finch , William E. Ortyn , David J. Perry
发明人： Keith L. Frost , David A. Basiji , Richard A. Bauer , Rosalynde J. Finch , William E. Ortyn , David J. Perry
IPC分类号： G06K9/00
CPC分类号： G02B27/148 , C12Q1/6816 , C40B20/04 , C40B30/04 , C40B40/08 , C40B60/10 , G01N15/147 , G01N15/1475 , G01N2015/1447 , G01N2015/1472 , G01N2015/1479 , G01N2015/1497 , G02B7/28 , G02B27/0012 , G02B27/1013 , G02B27/126 , G02B27/144 , G02B27/145 , C12Q2563/179 , C12Q2563/155 , C12Q2563/107
摘要： Combinatorially-synthesized deoxyribonucleic acid (DNA) oligonucleotides attached to encoded beads that are hybridized to amplified and labeled genomic DNA or ribonucleic acid (RNA) are analyzed using a flow imaging system. Oligonucleotides and corresponding reporters are bound to the surfaces of a plurality of small beads such that different beads bear different oligo sequences. Each bead bears a unique optical signature comprising a predefined number of unique reporters, where each reporter comprises a predefined combination of different fluorochromes. The composite spectral signature in turn identifies the unique nucleotide sequence of its attached oligo chains. This optical signature is rapidly decoded using an imaging system to discriminate the different reporters attached to each bead in a flow in regard to color and spatial position on the bead.

4. 发明授权

US06934408B2 Method and apparatus for reading reporter labeled beads 失效
标题翻译：阅读报道标记珠粒的方法和装置
公开(公告)号：US06934408B2
公开(公告)日：2005-08-23
申请号：US09976237
申请日：2001-10-12
申请人： Keith L. Frost , David A. Basiji , Richard A. Bauer , Rosalynde J. Finch , William E. Ortyn , David J. Perry
发明人： Keith L. Frost , David A. Basiji , Richard A. Bauer , Rosalynde J. Finch , William E. Ortyn , David J. Perry
IPC分类号： C12Q1/68 , C40B20/04 , C40B30/04 , C40B40/08 , C40B60/10 , G01N15/14 , G02B7/28 , G02B27/00 , G02B27/14 , G06K9/00
CPC分类号： G02B27/148 , C12Q1/6816 , C40B20/04 , C40B30/04 , C40B40/08 , C40B60/10 , G01N15/147 , G01N15/1475 , G01N2015/1447 , G01N2015/1472 , G01N2015/1479 , G01N2015/1497 , G02B7/28 , G02B27/0012 , G02B27/1013 , G02B27/126 , G02B27/144 , G02B27/145 , C12Q2563/179 , C12Q2563/155 , C12Q2563/107
摘要： Combinatorially-synthesized deoxyribonucleic acid (DNA) oligonucleotides attached to encoded beads that are hybridized to amplified and labeled genomic DNA or ribonucleic acid (RNA) are analyzed using a flow imaging system. Oligonucleotides and corresponding reporters are bound to the surfaces of a plurality of small beads such that different beads bear different oligo sequences. Each bead bears a unique optical signature comprising a predefined number of unique reporters, where each reporter comprises a predefined combination of different fluorochromes. The composite spectral signature in turn identifies the unique nucleotide sequence of its attached oligo chains. This optical signature is rapidly decoded using an imaging system to discriminate the different reporters attached to each bead in a flow in regard to color and spatial position on the bead.
摘要翻译：使用流动成像系统分析与编码的珠偶联的与扩增和标记的基因组DNA或核糖核酸（RNA）杂交的组合合成的脱氧核糖核酸（DNA）寡核苷酸。寡核苷酸和相应的报道结合到多个小珠的表面，使得不同的珠具有不同的寡核苷酸序列。每个珠具有唯一的光学特征，其包含预定数量的唯一记录器，其中每个报告者包含不同荧光染料的预定组合。复合光谱特征依次识别其连接的寡链的唯一核苷酸序列。使用成像系统快速解码该光学特征，以便鉴别珠子上颜色和空间位置的流动中附着于每个珠粒的不同报告者。

5. 发明授权

US06618140B2 Spectral deconvolution of fluorescent markers 有权
公开(公告)号：US06618140B2
公开(公告)日：2003-09-09
申请号：US10175543
申请日：2002-06-18
申请人： Keith L. Frost , James K. Riley , David A. Basiji , William E. Ortyn
发明人： Keith L. Frost , James K. Riley , David A. Basiji , William E. Ortyn
IPC分类号： G01J330
CPC分类号： G01J3/10 , G01J3/14 , G01J3/28 , G01J3/4406 , G01N15/147 , G01N21/6428 , G01N21/645 , G01N21/6456 , G01N2015/1472 , G01N2015/1486 , G01N2015/1497 , G01N2021/6423 , G01N2021/6441 , G01N2201/1293
摘要： In an instrument generating images from the fluorescent emissions of a plurality of fluorescent dyes carried by objects in a flow stream, spectral dispersion is used to expand the images of the objects along one axis of a two-dimensional photosensor array according to emission wavelength. The dispersion is unable to completely separate the emissions of a plurality of dyes because the emission spectra of the dyes overlap in wavelength. The method of the present invention accomplishes accurate estimation of the intensity of the light received from each of a plurality of dyes by decomposing the two dimensional spectrally dispersed images into a set of characteristic parameters using either an iterative curve fitting optimization method or a linear algebraic method.

6. 发明授权

US07087877B2 Auto focus for a flow imaging system 有权
标题翻译：流量成像系统的自动对焦
公开(公告)号：US07087877B2
公开(公告)日：2006-08-08
申请号：US11045675
申请日：2005-01-28
申请人： William E. Ortyn , Michael J. Seo , David A. Basiji , Keith L. Frost , David J. Perry
发明人： William E. Ortyn , Michael J. Seo , David A. Basiji , Keith L. Frost , David J. Perry
IPC分类号： G02B27/40
CPC分类号： G06T7/20 , G01N15/1459 , G01N15/1463 , G01N2015/1018 , G01N2015/1443 , G01N2015/1447 , G01N2015/1452 , G01N2015/1497 , G02B27/0012 , G06K9/00134
摘要： A pair of optical gratings are used to modulate light from an object, and the modulated light from either grating is used to determine the velocity of the object. Each optical grating is offset from a reference focal point by the same distance, one grating being offset in a positive direction, the other in a negative direction. Signals produced in response to the modulated light can be processed to determine a direction in which a primary collection lens should be moved in order to improve a focus of the imaging system on the object. The lens is moved incrementally in the direction so determined, and the process is repeated until an optimal focus is achieved. In a preferred embodiment, the signals are weighted, so that the optical grating disposed closest to the optimal focus position contributes the most to velocity detection.
摘要翻译：一对光栅用于调制来自物体的光，并且来自任一光栅的调制光用于确定物体的速度。每个光栅从参考焦点偏移相同的距离，一个光栅在正方向偏移，另一个光栅在负方向上偏移。可以处理响应于调制光产生的信号以确定主收集透镜应该移动的方向，以便改善成像系统对物体的焦点。透镜在如此确定的方向上逐渐移动，并重复该过程，直到达到最佳聚焦。在优选实施例中，对信号进行加权，使得最靠近最佳聚焦位置布置的光栅最有助于速度检测。

7. 发明授权

US06875973B2 Auto focus for a flow imaging system 有权
标题翻译：流量成像系统的自动对焦
公开(公告)号：US06875973B2
公开(公告)日：2005-04-05
申请号：US10822170
申请日：2004-04-09
申请人： William E. Ortyn , Michael J. Seo , David A. Basiji , Keith L. Frost , David J. Perry
发明人： William E. Ortyn , Michael J. Seo , David A. Basiji , Keith L. Frost , David J. Perry
IPC分类号： G01N15/10 , G01N15/14 , G02B27/00 , G06T7/20 , G02B27/40
CPC分类号： G06T7/20 , G01N15/1459 , G01N15/1463 , G01N2015/1018 , G01N2015/1443 , G01N2015/1447 , G01N2015/1452 , G01N2015/1497 , G02B27/0012 , G06K9/00134
摘要： A pair of optical gratings are used to modulate light from an object, and the modulated light from either optical is used to determine the velocity of the object. Each optical grating is offset from a reference focal point by the same distance, one grating being offset in a positive direction, the other in a negative direction. Signals produced in response to the modulated light can be processed to determine a direction in which a primary collection lens should be moved in order to improve a focus of the imaging system on the object. The lens is moved incrementally in the direction so determined, and the process is repeated until an optimal focus is achieved. In a preferred embodiment, the signals are weighted, so that the optical grating disposed closest to the optimal focus position contributes the most to velocity detection.
摘要翻译：一对光栅被用于调制来自物体的光，并且来自任一光学的调制光用于确定物体的速度。每个光栅从参考焦点偏移相同的距离，一个光栅在正方向偏移，另一个光栅在负方向上偏移。可以处理响应于调制光产生的信号以确定主收集透镜应该移动的方向，以便改善成像系统对物体的焦点。透镜在如此确定的方向上逐渐移动，并重复该过程，直到达到最佳聚焦。在优选实施例中，对信号进行加权，使得最靠近最佳聚焦位置布置的光栅最有助于速度检测。

8. 发明授权

US06707551B2 Multipass cavity for illumination and excitation of moving objects 有权
标题翻译：多光腔用于照明和激发移动物体
公开(公告)号：US06707551B2
公开(公告)日：2004-03-16
申请号：US10355653
申请日：2003-01-29
申请人： William E. Ortyn , David A. Basiji , Keith L. Frost , N. Robert McRuer
发明人： William E. Ortyn , David A. Basiji , Keith L. Frost , N. Robert McRuer
IPC分类号： G01N2100
CPC分类号： G02B27/126 , G01J3/2803 , G01J3/2823 , G01N15/1434 , G01N15/147 , G01N21/031 , G01N21/6428 , G01N21/645 , G01N21/85 , G01N2015/0294 , G01N2015/1006 , G01N2015/1472 , G01N2015/1486 , G02B7/28
摘要： An illumination system for increasing a light signal from an object passing through a reflection cavity. The reflection cavity is disposed between spaced-apart, opposed first and second surfaces disposed on opposite sides of a moving stream of objects. A light collection system is disposed substantially orthogonal to a plane passing through the surfaces and the stream so as to collect light that is scattered from or emitted by the objects as they pass through a field of view disposed between the first and second surfaces. A beam of light from a laser source is directed through the stream of moving objects in a direction nearly orthogonal to the stream (but slightly inclined) and lying in the plane that extends through the surfaces and the stream. Due to the reflection angle and the distance between the stream and the first surface, the point at which the light reflected from the first surface intersects the stream on a second pass is displaced from where it passed though the stream on its initial pass. The light is reflected back and forth between the surfaces a plurality of times, illuminating a different portion of the field of view with each pass until, having ranged over the field of view, the light exits the reflection cavity. The “recycling” of the light beam in this manner substantially improves the SNR of the detection system by increasing an average illumination intensity experienced by the objects in the stream.
摘要翻译：一种用于增加来自穿过反射腔的物体的光信号的照明系统。反射腔设置在位于物体的移动物流的相对侧上的间隔开的相对的第一和第二表面之间。光采集系统设置成基本上垂直于穿过表面和流的平面，以便收集当物体经过设置在第一表面和第二表面之间的视野时从物体散射或发射的光。来自激光源的光束被引导通过几何垂直于流（但稍微倾斜）并且位于延伸穿过表面和流的平面中的移动物体流。由于反射角度和流与第一表面之间的距离，从第一表面反射的光在第二遍上与流相交的点从其在其初始通过时通过流的位置偏移。光在表面之间反复反射多次，每次通过照射视场的不同部分，直到在视场范围内，光离开反射腔。以这种方式，光束的“回收”通过增加物流在物流中经历的平均照明强度，大大提高了检测系统的信噪比。

9. 发明授权

US06906792B2 Methods of calibrating an imaging system using calibration beads 有权
标题翻译：使用校准珠校准成像系统的方法
公开(公告)号：US06906792B2
公开(公告)日：2005-06-14
申请号：US10865664
申请日：2004-06-10
申请人： William E. Ortyn , David A. Basiji , Keith L. Frost , Brian E. Hall , Michael J. Seo
发明人： William E. Ortyn , David A. Basiji , Keith L. Frost , Brian E. Hall , Michael J. Seo
IPC分类号： G01N15/10 , G01N15/14 , G02B27/00 , G06T7/20 , G01P3/36
CPC分类号： G01N15/1012 , G01N15/1459 , G01N15/1463 , G01N15/147 , G01N15/1475 , G01N2015/1018 , G01N2015/1025 , G01N2015/1075 , G01N2015/144 , G01N2015/1443 , G01N2015/1447 , G01N2015/1452 , G01N2015/1465 , G01N2015/1472 , G01N2015/1477 , G01N2015/1497 , G02B27/0012 , G06T7/20
摘要： When utilized in a flow imaging instrument, calibration beads provide a known data source that can be employed in various self-diagnostic, calibration and quality metric applications for the both the optical system of the flow imaging instrument, as well as the flow cell of the flow imaging instrument. Such data can be used to determine point spread functions associated with an imaging system, to determine a sensitivity of an imaging system, and to determine a focal point of the imaging system. Imagery collected from calibration beads can be used to determine core size and stability and TDI/flow speed synchronization. Calibration beads can be beneficially employed to enable stable system operation, even when very low sample concentration, or very small sample sizes are to be analyzed.
摘要翻译：当在流动成像仪器中使用时，校准珠粒提供已知的数据源，其可以用于流动成像仪器的光学系统的各种自我诊断，校准和质量度量应用，以及流量单元流量成像仪。这样的数据可用于确定与成像系统相关联的点扩散功能，以确定成像系统的灵敏度，并确定成像系统的焦点。从校准珠收集的图像可用于确定核心尺寸和稳定性以及TDI /流速同步。即使要分析非常低的样品浓度或非常小的样品量，也可以有利地使用校准珠来实现稳定的系统操作。

10. 发明授权

US06947136B2 Multipass cavity for illumination and excitation of moving objects 有权
标题翻译：多光腔用于照明和激发移动物体
公开(公告)号：US06947136B2
公开(公告)日：2005-09-20
申请号：US10691292
申请日：2003-10-21
申请人： William E. Ortyn , David A. Basiji , Keith L. Frost , N. Robert McRuer
发明人： William E. Ortyn , David A. Basiji , Keith L. Frost , N. Robert McRuer
IPC分类号： G01J3/28 , G01N15/02 , G01N15/10 , G01N15/14 , G01N21/03 , G01N21/64 , G01N21/85 , G02B7/28 , G02B27/00 , G02B27/14 , G01N21/00
CPC分类号： G02B27/126 , G01J3/2803 , G01J3/2823 , G01N15/1434 , G01N15/147 , G01N21/031 , G01N21/6428 , G01N21/645 , G01N21/85 , G01N2015/0294 , G01N2015/1006 , G01N2015/1472 , G01N2015/1486 , G02B7/28
摘要： An illumination system for increasing a light signal from an object passing through a reflection cavity. The reflection cavity is defined by spaced-apart, opposed first and second surfaces disposed on opposite sides of a central volume. Preferably the first reflecting surface forms an acute angle with the second reflecting surface. A beam of light is directed into the reflection cavity so that light is reflected back and forth between the first and second surfaces a plurality of times, illuminating a different portion of the central volume with each pass until, having ranged over the central volume, the light exits the reflection cavity. The “recycling” of the light beam in this manner substantially improves the signal to noise ratio of a detection system used in conjunction with the reflection cavity by increasing an average illumination intensity in the central volume.
摘要翻译：一种用于增加来自穿过反射腔的物体的光信号的照明系统。反射空腔由设置在中心体积的相对侧上的间隔开的相对的第一和第二表面限定。优选地，第一反射表面与第二反射表面形成锐角。光束被引导到反射腔中，使得光在第一和第二表面之间多次反复地反射，每次通过照射中心体积的不同部分，直到超过中心体积，光离开反射腔。以这种方式“回收”光束通过增加中心体积中的平均照明强度，大大提高了与反射腔结合使用的检测系统的信噪比。

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