公开(公告)号：US06441894B1

公开(公告)日：2002-08-27

申请号：US09430418

申请日：1999-10-29

Applicant: Bala S. Manian ,  David M. Heffelfinger ,  Edward M. Goldberg

Inventor： Bala S. Manian ,  David M. Heffelfinger ,  Edward M. Goldberg

IPC: G01J100

CPC classification number: G02B21/34 ,  G01N21/6452 ,  G02B21/241

Abstract: A method and apparatus for autofocus on a target layer contained within a microplate well is provided. The instrument is capable of optically sensing a reference point on the underside of a microplate. This reference point is then used to focus light onto a target layer within the microplate well, the target layer having a location that is in defined relation to the reference point. The reference point is either a surface of the bottom of the microplate well or is an optically detectable mark on the underside of the microplate. In an alternate embodiment, a light position sensitive detector is used to enable deterministic autofocus for a plurality of wells on a microplate.

Abstract translation: 提供了一种用于在微孔板中包含的靶层上的自动聚焦的方法和装置。 该仪器能够光学感测微孔板底面上的参考点。 然后将该参考点用于将光聚焦到微孔板内的目标层上，目标层具有与参考点限定的位置。 参考点是微孔板底部的表面，或者是微孔板下面的光学可检测标记。 在替代实施例中，使用光位置敏感检测器来使得微孔板上的多个孔的确定性自动聚焦。

公开(公告)号：US5591981A

公开(公告)日：1997-01-07

申请号：US405468

申请日：1995-03-16

Applicant: David M. Heffelfinger ,  Franklin R. Witney

Inventor： David M. Heffelfinger ,  Franklin R. Witney

IPC: G01N21/25 ,  G01N21/64

CPC classification number: G01N21/6456 ,  G01N21/64 ,  G01N2021/6419 ,  G01N2021/6421

Abstract: A method and apparatus to detect fluorescence from a sample is provided. The optical system allows the user to continuously tune the wavelengths and bandwidths of the excitation source and the emission detection system. A peaking function automatically peaks the detected fluorescent signal by fine tuning the excitation and emission detection systems. A look-up table allows the fluorescent signal for a specific wavelength to be corrected for the wavelength dependence of the optical train. In one embodiment of the system the sample is simultaneously irradiated in more than one wavelength band, each wavelength band being independently tunable.

Abstract translation: 提供了一种从样品中检测荧光的方法和装置。 光学系统允许用户连续调节激发源和发射检测系统的波长和带宽。 峰值功能通过微调激发和发射检测系统自动使检测到的荧光信号达到峰值。 查找表允许针对光学列车的波长依赖性校正特定波长的荧光信号。 在系统的一个实施例中，样本同时在多于一个波长带中照射，每个波长带是独立可调谐的。

公开(公告)号：US5266803A

公开(公告)日：1993-11-30

申请号：US845107

申请日：1991-03-03

Applicant: David M. Heffelfinger

Inventor： David M. Heffelfinger

IPC: G02B6/04 ,  G02B6/32 ,  G02B6/38 ,  G02B6/40 ,  H04N1/028 ,  G03B42/02

CPC classification number: H04N1/0281 ,  G02B26/103 ,  G02B6/32 ,  G02B6/403 ,  G02B6/3861

Abstract: A novel fiber optic cable having a bifurcated bundle of optical fibers comprised of emitter fiber(s) and collecting fiber(s), a means for focusing light into the proximal end of the emitter fiber(s), a means for focusing light out of the distal end of the emitter fiber(s), and a means for collecting light in the distal end of the collecting fiber(s) is used to increase the sensitivity and specificity of storage phosphor imaging plate scanning. The novel fiber optic cable is used in a storage phosphor imaging plate scanner to transmit light from a light source to the phosphors on the storage phosphor imaging plate and to collect any phosphorescence induced by the light. Use of the bifurcated fiber bundle with the means for focusing light into the emitter fiber(s), focus light out of the emitter fiber(s), and collect light in the collecting fiber(s) provides a method to scan storage phosphor imaging plates with high sensitivity and specificity.

Abstract translation: 一种新颖的光纤电缆，其具有由发射光纤和收集光纤组成的光纤的分叉束，用于将光聚焦到发射光纤的近端的装置，用于将光聚焦到 发射光纤的远端和用于收集聚光纤的远端的光的装置用于增加存储荧光体成像板扫描的灵敏度和特异性。 新型光纤电缆用于存储磷光体成像板扫描器中，以将来自光源的光透射到存储荧光体成像板上的荧光体，并收集由光诱导的任何磷光。 将分叉的光纤束与用于将光聚焦到发射光纤中的装置一起使用，将光聚焦在发射光纤之外，并收集聚光中的光提供了一种扫描存储荧光体成像板的方法 具有高灵敏度和特异性。

公开(公告)号：US06853454B1

公开(公告)日：2005-02-08

申请号：US10758576

申请日：2004-01-15

Applicant: David M. Heffelfinger

Inventor： David M. Heffelfinger

IPC: G01N21/64 ,  G01N21/47

CPC classification number: G01N21/6456

Abstract: A system for optical detection of kinetic samples. The system includes a dual set of detectors linked to a single processor. The time of signal integration is different for each detector, allowing one detector to have a higher sensitivity by integrating over a longer time period while the second detector using shorter integration periods is able to measure kinetic events.

Abstract translation: 一种用于光学检测动力学样品的系统。 该系统包括连接到单个处理器的双组检测器。 信号整合时间对于每个检测器是不同的，允许一个检测器通过在更长的时间段内积分而具有更高的灵敏度，而使用较短积分期的第二检测器能够测量动力学事件。

公开(公告)号：US06750457B2

公开(公告)日：2004-06-15

申请号：US09942472

申请日：2001-08-29

Applicant: David M. Heffelfinger ,  Aram P. Schiffman ,  Bala S. Manian

Inventor： David M. Heffelfinger ,  Aram P. Schiffman ,  Bala S. Manian

IPC: G01N2100

CPC classification number: G01N21/6452 ,  G01J3/10 ,  G01J3/14 ,  G01J3/36 ,  G01J3/4406 ,  G01N27/44721 ,  G01N2021/6463

Abstract: An apparatus and method in which illumination light and collected emitted light share a pathway and subsequently are physically separated. The optical configuration is designed such that at the point of separation, the illumination light is at has a smaller cross sectional area than the collected light. Collected light is directed away from the pathway of the illumination light and to detection optics. This configuration is adaptable to illumination and light collection across a broad wavelength spectrum. This configuration is adaptable to scanning in a limited depth of field to allow high throughput optical analysis of samples.

Abstract translation: 照明光和收集的发射光共享通路并随后物理分离的装置和方法。 光学构造被设计成使得在分离点处，照明光具有比收集的光更小的横截面面积。 收集的光被引导离开照明光的路径和检测光学器件。 该配置适用于宽波长光谱下的照明和光采集。 该配置适用于在有限的景深中的扫描，以允许样品的高通量光学分析。

公开(公告)号：US6130745A

公开(公告)日：2000-10-10

申请号：US245782

申请日：1999-02-05

Applicant: Bala S. Manian ,  David M. Heffelfinger ,  Edward M. Goldberg

Inventor： Bala S. Manian ,  David M. Heffelfinger ,  Edward M. Goldberg

IPC: G01B11/00 ,  G01J1/00 ,  G01N21/03 ,  G01N21/55 ,  G01N21/64 ,  G01N33/483 ,  G02B7/28 ,  G02B21/24 ,  G02B21/34

CPC classification number: G02B21/34 ,  G01N21/6452 ,  G02B21/241

Abstract: A method and apparatus for autofocus on a target layer contained within a microplate well is provided. The instrument is capable of optically sensing a reference point on the underside of a microplate. This reference point is then used to focus light onto a target layer within the microplate well, the target layer having a location that is in defined relation to the reference point. The reference point is either a surface of the bottom of the microplate well or is an optically detectable mark on the underside of the microplate. In an alternate embodiment, a light position sensitive detector is used to enable deterministic autofocus for a plurality of wells on a microplate.

公开(公告)号：US5784152A

公开(公告)日：1998-07-21

申请号：US729111

申请日：1996-10-11

Applicant: David M. Heffelfinger ,  Franklin R. Witney ,  Chris Cunanan

Inventor： David M. Heffelfinger ,  Franklin R. Witney ,  Chris Cunanan

IPC: G01N21/64 ,  G01N21/03 ,  G01N21/25 ,  G01N21/27 ,  G01N21/75

CPC classification number: G01N21/64 ,  G01N21/253 ,  G01N21/6456 ,  G01N2021/6419 ,  G01N2021/6421

Abstract: A method and apparatus of analyzing samples contained in a microplate is provided. The instrument is capable of measuring fluorescence, luminescence, and/or absorption within multiple locations within a sample well. The instrument is tunable over the excitation and/or detection wavelengths. Neutral density filters are used to extend the sensitivity range of the absorption measuring aspect of the instrument. Due to the wavelength tuning capabilities of the instrument, the spectral dependence of the measured fluorescence, luminescence, and absorption of the materials in question can be analyzed. The combination of a data processor and a look-up table improve the ease of operation of the instrument. Several different formats are available for the output data including creation of a bit map of the sample.

Abstract translation: 提供了分析微孔板中包含的样品的方法和装置。 该仪器能够测量样品井内多个位置的荧光，发光和/或吸收。 仪器可以在激发和/或检测波长上调谐。 中性密度滤波器用于扩展仪器吸收测量方面的灵敏度范围。 由于仪器的波长调谐能力，可以分析所测材料的测量荧光，发光和吸收的光谱依赖性。 数据处理器和查找表的组合可以提高仪器的操作性。 输出数据可以使用几种不同的格式，包括创建样本的位图。

公开(公告)号：US07016087B2

公开(公告)日：2006-03-21

申请号：US09925124

申请日：2001-08-08

Applicant: David M. Heffelfinger ,  Aram P. Schiffman ,  Bala S. Manian

Inventor： David M. Heffelfinger ,  Aram P. Schiffman ,  Bala S. Manian

IPC: H04N1/04

CPC classification number: G01N21/6452 ,  G01N21/6428 ,  G01N2021/6419 ,  G01N2021/6421

Abstract: A system for optical interrogation of a sample adaptable for multiple wavelength illumination and multiple wavelength fluorescent or luminescent light collection, wherein the illumination wavelength profile and the light collection profile may overlap. In the system, coherent light from one or more lasers is focused onto a target layer on a sample to excite fluorescent or luminescent light from the target layer. Emitted light is collected from a selected depth by a reflective light collector that transmits the collected light to detection optics. The reflective light collector directs collected light at an angle to the optical axis of the illumination light, thereby separating collected emitted light from illumination light. The light collector may collect light from a focus, whereby the focused illumination light combined with the focused light collection aid in limitation of the depth of field to a selected depth. Additionally, a spatial filter positioned between the light collector and the detection optics may be used to confine the depth of field to a selected depth. This device may be incorporated into an optical scanner by scanning of illumination light in a first direction and translation of the sample in a tangent direction. Alternatively, the illumination and detection optics may remain stationary and the detectable targets moved past a scanning location (e.g. as in electrophoretic analysis).

公开(公告)号：US06995901B2

公开(公告)日：2006-02-07

申请号：US10758140

申请日：2004-01-15

Applicant: David M. Heffelfinger

Inventor： David M. Heffelfinger

IPC: G02B21/00

CPC classification number: G02B21/16

Abstract: A system for the optical analysis of a sample. An illumination source illuminates the sample, exciting fluorescence. The fluorescence is collected by an objective lens, which transmits the collected illumination light onto an imaging lens, which focuses the collected light onto an area array detector. Collected light rays between the objective lens and the imaging lens are parallel and pass through an emission filter. Both the objective lens and the imaging lens are positioned on a mount that allows an alternative objective or imaging lens to be positioned to collect or image the emitted light. Any objective lens/imaging lens pair is optically symmetrical, greatly reducing the optically degrading effects.

Abstract translation: 用于样品光学分析的系统。 照明源照亮样品，激发荧光。 荧光被物镜收集，物镜将收集的照明光透射到成像透镜上，该成像透镜将收集的光聚焦到区域阵列检测器上。 物镜和成像透镜之间的收集的光线平行并通过发射滤光片。 物镜和成像透镜都位于允许替代物镜或成像透镜被定位以收集或成像发射光的安装座上。 任何物镜/成像透镜对都是光学对称的，大大降低了光学降解效果。

公开(公告)号：US6043506A

公开(公告)日：2000-03-28

申请号：US1254

申请日：1997-12-30

Applicant: David M. Heffelfinger ,  Rebecca Ann Batterson ,  Renato Salgado

Inventor： David M. Heffelfinger ,  Rebecca Ann Batterson ,  Renato Salgado

IPC: G01N21/64 ,  C12M1/00 ,  C12M1/34 ,  C12N15/09 ,  C12Q1/68 ,  G01N21/75 ,  G01N21/78 ,  G01N33/53 ,  G01N37/00 ,  G03B42/00 ,  G03B42/02

CPC classification number: G03B42/00 ,  G01N2021/6419 ,  G01N2021/6421 ,  G01N2021/6471 ,  G01N2021/6484 ,  G01N2201/024

Abstract: An apparatus capable of measuring quantities of biological or other types of samples that have been labeled using any of a variety of techniques including fluorescence, radioisotopes, enzyme activated light emitting chemicals, and enzyme activated fluorescent materials is provided. The apparatus allows for either simultaneous or sequential acquisition of signals from multiple sample types. The apparatus is not restricted to a particular source or wavelength of excitation or readout light, nor is the apparatus restricted to a particular emission wavelength. The provided scanner includes a source module that preferably contains an internal laser emitting two different wavelengths of approximately the same intensity. An optional external light source may be coupled to the source module, thus adding further flexibility through the addition of other wavelengths (e.g., V, visible, mid-IR, and IR). The scanner also includes a detection module. Within the detection module are two detectors, thus allowing the simultaneous detection of multiple wavelengths. A bifurcated optical cable is used to transfer the excitation and/or readout light from the source module to the sample and subsequently transfer the emitted and/or scattered light from the sample to the detection module. The scanning stage of the scanner is designed to accommodate a variety of samples, ranging from phosphor screens, gels, and fluorescent samples to microtiter plates. An internal microprocessor is used to control the various aspects of the scanner, preferably including translation stage control, source filters, and detection filters. The internal microprocessor may be coupled to an external computer. The external computer may be used to change the programming of the microprocessor, provide a user interface to the microprocessor, process and store test results, and display sample images.

Abstract translation: 提供了一种能够测量使用包括荧光，放射性同位素，酶活化的发光化学物质和酶激活的荧光材料在内的各种技术中的任何一种进行标记的生物样品或其他类型样品的量的装置。 该装置允许同时或顺序地采集来自多个样本类型的信号。 该装置不限于激发或读出光的特定源或波长，也不限于特定发射波长的装置。 所提供的扫描器包括源模块，其优选地包含发射具有大致相同强度的两个不同波长的内部激光器。 可选的外部光源可以耦合到源模块，从而通过添加其它波长（例如，V，可见，中IR和IR）来增加更多的灵活性。 扫描仪还包括检测模块。 在检测模块内是两个检测器，从而允许同时检测多个波长。 使用分叉光缆将激励和/或读出光从源模块传送到样品，随后将发射和/或散射的光从样品转移到检测模块。 扫描仪的扫描阶段设计为适应各种样品，从荧光屏，凝胶和荧光样品到微量滴定板。 内部微处理器用于控制扫描仪的各个方面，最好包括平移台控制，源滤波器和检测滤波器。 内部微处理器可以耦合到外部计算机。 外部计算机可用于改变微处理器的编程，向微处理器提供用户界面，处理和存储测试结果以及显示样本图像。