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1. 发明授权

US12001004B2 High-resolution, real-time imaging with adaptive optics and lattice light sheets 有权
公开(公告)号：US12001004B2
公开(公告)日：2024-06-04
申请号：US17644649
申请日：2021-12-16
申请人： Howard Hughes Medical Institute
发明人： Robert Eric Betzig , Tsung-Li Liu , Daniel E. Milkie , Kai Wang , Wesley Legant
IPC分类号： G02B21/36 , G01N21/64 , G02B21/00 , G02B21/06 , G02B26/06 , G02B27/00 , G02B27/58
CPC分类号： G02B21/361 , G01N21/64 , G01N21/6428 , G01N21/6458 , G02B21/0032 , G02B21/0072 , G02B21/0076 , G02B21/06 , G02B21/367 , G02B26/06 , G02B27/0025 , G02B27/58 , G02B2207/114
摘要： A microscope directs light through an excitation objective to generate a lattice light sheet (LLS) within a sample. A detection objective collects signal light from the sample in response to the LLS and images the collected light onto a detector. Second and third light beams are imaged onto focal planes of the excitation objective and detection objective, respectively. One or more wavefront detectors determine wavefronts of light emitted from the sample and through the excitation objective in response to the imaged second light beam and emitted from the sample through the detection objective in response to the imaged third light beam. A wavefront of the first light beam is modified to reduce a sample-induced aberration of the LLS within the sample, and a wavefront of the signal light emitted from the sample is modified to reduce a sample-induced aberration of the signal light at the detector.

2. 发明公开

US20230152561A1 Techniques for High-Speed Volumetric Sampling 审中-公开
公开(公告)号：US20230152561A1
公开(公告)日：2023-05-18
申请号：US17796295
申请日：2021-01-31
申请人： The Rockefeller University
发明人： Alipasha VAZIRI , Jeffrey Dakin DEMAS
IPC分类号： G02B21/00 , G02B27/28 , G02F1/01 , G02B17/08
CPC分类号： G02B21/0032 , G02B27/283 , G02F1/0136 , G02B17/0844 , G02B21/0076 , G02B21/0084 , G02B2207/114
摘要： A multiplexing module provided herein is configured to perform operations of receiving a plurality of laser pulses from a pulsed laser source; splitting each laser pulse into a plurality of beamlets; introducing a delay between each adjacent beamlet of the plurality of beamlets, such that the plurality of beamlets associated with a respective laser pulse of the plurality of laser pulses is distributed equally across a pulse repetition period associated with the pulsed laser source; changing a divergence of each subsequent beamlet of the plurality of beamlets associated with each respective laser pulse to introduce a distinguishing feature between each beamlet of the plurality of beamlet to cause each beamlet to focus on a different axial plane or lateral position of the sample; and outputting the plurality of beamlets associated with each respective laser pulse.

3. 发明申请

US20180196246A1 HYPERSPECTRAL MULTIPHOTON MICROSCOPE FOR BIOMEDICAL APPLICATIONS 审中-公开
公开(公告)号：US20180196246A1
公开(公告)日：2018-07-12
申请号：US15788778
申请日：2017-10-19
申请人： Cornell University
发明人： Amanda J. Bares , Chris B. Schaffer , Steven Tilley
IPC分类号： G02B21/00 , G02B27/14 , G02B26/00 , G01N21/64
CPC分类号： G02B21/0064 , G01J3/28 , G01J3/4406 , G01N21/6458 , G01N2021/6419 , G01N2021/6465 , G02B21/002 , G02B21/0032 , G02B21/0052 , G02B21/0076 , G02B21/16 , G02B26/007 , G02B26/105 , G02B27/141 , G02B2207/114
摘要： Optical sensing techniques and devices based on detection of fluorescent emissions at different optical wavelengths by nonlinear optical absorption of different excitation beams at different excitation wavelengths that interact with fluorescently-labeled structures within the sample to cause nonlinear optical absorption of two or more photons at each excitation wavelength. The fluorescent light at different fluorescent emission wavelengths by nonlinear optical absorption of excitation light at a particular excitation wavelength is spectrally separated into different optical channel output beams along different optical channel optical paths at different designated fluorescent imaging wavelength bands and the fluorescent light at different fluorescent imaging wavelengths within each designated fluorescent imaging wavelength is detected. This two-stage spectral separation in obtaining fluorescent images at different fluorescent imaging wavelengths in different fluorescent imaging wavelength bands enables highly sensitive hyperspectral imaging based on two-photo or multi-photon nonlinear absorption.

4. 发明申请

US20170082494A1 PHOTON ENTANGLEMENT ROUTER 有权
公开(公告)号：US20170082494A1
公开(公告)日：2017-03-23
申请号：US14824390
申请日：2015-08-12
申请人： GOVERNMENT OF THE UNITED STATES AS REPRESETNED BY THE SECRETARY OF THE AIR FORCE
发明人： DAVID H. HUGHES , REINHARD ERDMANN
IPC分类号： G01J4/04 , G02B5/30 , G02B27/28
CPC分类号： G01J4/02 , G01J4/04 , G02B5/3083 , G02B27/283 , G02B27/286 , G02B27/288 , G02B2207/114
摘要： A photon entanglement router comprises a modified birefringent spectral filter followed by a polarization beam splitter (PBS). Frequency degenerate or non-degenerate entangled photons, generated by a collinear laser source and incident on one input port of the photon entanglement router, are comprised of congruent photons and/or incongruent photons. The invention adds a plurality of additional filter stacks at each output port such that they invert the action of the first birefringent stack at the input port. Intermediate output photons from the invention is input to two ports of an additional PBS where they are spatially projected according to their frequencies and polarizations. Two congruent photons of an entangled photon pair exit as an entangled pair in one direction, while two incongruent photons exit as an entangled pair in the orthogonal direction. If one photon is congruent and the other photon incongruent, the photons remain entangled but are spectrally divided into orthogonal directions. The invention's birefringent spectral filter accepts specific input frequencies from the ITU optical C-band grid for proper operation.

5. 发明授权

US09001321B2 Microscope and observation method 有权
标题翻译：显微镜和观察方法
公开(公告)号：US09001321B2
公开(公告)日：2015-04-07
申请号：US13578164
申请日：2011-02-08
申请人： Katsumasa Fujita , Shogo Kawano , Masahito Yamanaka , Satoshi Kawata
发明人： Katsumasa Fujita , Shogo Kawano , Masahito Yamanaka , Satoshi Kawata
IPC分类号： G01J3/44 , G02B21/00 , G01N21/65
CPC分类号： G02B21/002 , G01N2021/653 , G01N2021/655 , G02B2207/114
摘要： Provided is a microscope and an observation method which can improve spatial resolution. A microscope according to an aspect of the invention includes a laser light source (10), an objective lens (16) that focuses light from the laser light source on a sample, and a detector (22) that detects the laser light as signal light from a sample (17) when the sample (17) is irradiated with the laser light. The light is applied to the sample with an intensity changed to obtain a nonlinear region where intensities of the light and the signal light have a nonlinear relation due to occurrence of saturation or nonlinear increase of the signal light when the light has a maximum intensity, and the detector (22) detects the signal light according to the intensity of the laser light to perform observation based on a saturation component or a nonlinear increase component of the signal light.
摘要翻译：提供了可以提高空间分辨率的显微镜和观察方法。根据本发明的一个方面的显微镜包括激光源（10），将来自激光光源的光聚焦在样本上的物镜（16）以及检测器（22），其将激光检测为信号光来自样品（17）当样品（17）被激光照射时。将光以强度变化的方式施加到样品，以获得非线性区域，其中当光具有最大强度时，光和信号光的强度由于饱和度的发生或信号光的非线性增加而具有非线性关系，以及检测器（22）根据激光的强度检测信号光，以基于信号光的饱和分量或非线性增加分量进行观察。

6. 发明申请

US20140285873A1 Laser Illumination Systems and Methods for Dual-Excitation Wavelength Non-Linear Optical Microscopy and Micro-Spectroscopy Systems 有权
标题翻译：激光照明系统和双激发波长非线性光学显微镜和微光谱系统的方法
公开(公告)号：US20140285873A1
公开(公告)日：2014-09-25
申请号：US14297082
申请日：2014-06-05
申请人： President and Fellows of Harvard College , The Arizona Board of Regents on Behalf of the University of Arizona
发明人： Khanh Kieu , Nasser Peyghambarian , Xiaoliang Sunney Xie , Christian W. Freudiger , Dan Fu
IPC分类号： G02B21/16 , G02F1/37 , H01S3/10
CPC分类号： G02B21/16 , G01J3/0218 , G01J3/10 , G01J3/44 , G01N2021/653 , G01N2021/655 , G02B21/002 , G02B21/008 , G02B2207/114 , G02F1/353 , G02F1/37 , G02F2001/354 , H01S3/0057 , H01S3/0092 , H01S3/06754 , H01S3/06791 , H01S3/10023 , H01S3/1118 , H01S3/1608 , H01S3/1618 , H01S3/2391
摘要： An illumination system is disclosed for providing dual-excitation wavelength illumination for non-linear optical microscopy and micro-spectroscopy. The illumination system includes a laser system, an optical splitting means, a frequency shifting system, and a picosecond amplifier system. The laser system includes a laser for providing a first train of pulses at a center optical frequency ω1. The optical splitting means divides the first train of pulses at the center optical frequency ω1 into two trains of pulses. The frequency shifting system shifts the optical frequency of one of the two trains of pulses to provide a frequency shifted train of pulses. The picosecond amplifier system amplifies the frequency shifted train of pulses to provide an amplified frequency-shifted train of pulses having a pulse duration of at least 0.5 picoseconds.
摘要翻译：公开了用于为非线性光学显微镜和微光谱提供双激发波长照明的照明系统。照明系统包括激光系统，光分离装置，变频系统和皮秒放大器系统。激光系统包括用于以中心光频率ω1提供第一脉冲串的激光器。光分路装置将中心光频率ω1处的第一脉冲串划分成两列脉冲。频移系统移动两列脉冲之一的光频，以提供频移的脉冲串。皮秒放大器系统放大脉冲串的频移列，以提供具有至少0.5皮秒的脉冲持续时间的经脉冲放大的频移列。

7. 发明授权

US08508849B2 Multiphoton fluorescence filters 有权
标题翻译：多光子荧光滤光片
公开(公告)号：US08508849B2
公开(公告)日：2013-08-13
申请号：US12839040
申请日：2010-07-19
申请人： Craig Hodgson , Turan Erdogan , Ligang Wang
发明人： Craig Hodgson , Turan Erdogan , Ligang Wang
IPC分类号： G02B5/28
CPC分类号： G02B5/285 , G02B2207/114
摘要： An optical filter is provided which includes a plurality of hard coating layers of alternating high and low refractive index provided on a substrate and has an associated first transmission band. The filter also includes at least one additional plurality of hard coating layers including high and low refractive index layers and Herpin equivalent layers sandwiched therebetween. The additional plurality of layers has an associated second transmission band that substantially coincides with the first transmission band, but provides additional blocking at wavelengths outside the first transmission band. Relatively wide transmission bands and high blocking over an extended range of wavelengths can be achieved such that the filter is suitable for use in multiphoton fluorescence systems.
摘要翻译：提供了一种滤光器，其包括设置在基板上的具有交替的高折射率和低折射率的多个硬涂层，并且具有相关联的第一传输带。过滤器还包括至少一个附加的多个硬涂层，包括高折射率层和低折射率层以及夹在其间的Herpin等效层。附加的多个层具有与第一传输频带基本一致的相关联的第二传输频带，但在第一传输频带外的波长处提供附加的阻塞。可以实现相对宽的传输带和在扩展的波长范围上的高阻挡，使得滤波器适用于多光子荧光系统。

8. 发明授权

US07943889B2 Apparatus for improving detection efficiency of multiphoton microscopy systems by focus compensation, pupil image division, and parallel pupil rearrangement 有权
标题翻译：用于通过聚焦补偿，瞳孔图像分割和平行光瞳重排来提高多光子显微镜系统的检测效率的装置
公开(公告)号：US07943889B2
公开(公告)日：2011-05-17
申请号：US12052766
申请日：2008-03-21
申请人： William I. Vogt
发明人： William I. Vogt
IPC分类号： H01J3/14
CPC分类号： G02B21/16 , G01J3/02 , G01J3/0208 , G01J3/021 , G01J3/0229 , G01J3/36 , G01J3/4406 , G02B21/002 , G02B2207/114
摘要： Disclosed is an apparatus for division and rearrangement of light from a source object. The apparatus splits the light from the source object, or image of the source object, and recombines it in a parallel, fashion to increase the efficiency of multiphoton microscopy in general and harmonic or fluorescence emission microscopy in particular. The apparatus includes a beam splitter configured to split a light beam into at least two independent light paths to yield a first light path and a second light path; a first beam focuser configured to direct and focus the first light path onto a focal plane; and a second beam focuser configured to direct and focus the second light path onto the same or different focal plane to which the first light path is focused; and wherein the first and second light paths may be superimposed upon one another at a common focal plane or directed independently to different positions.
摘要翻译：公开了一种用于从源物体分离和重排光的装置。该装置分离来自源对象的光或源对象的图像，并且以平行的方式重新组合，以增加一般的多光子显微镜的效率，特别是谐波或荧光发射显微镜。该装置包括分束器，其配置成将光束分成至少两个独立光路以产生第一光路和第二光路; 第一光束聚焦器，被配置为将第一光路引导和聚焦到焦平面上; 以及第二光束聚焦器，被配置为将所述第二光路引导和聚焦到所述第一光路被聚焦到的相同或不同的焦平面上; 并且其中所述第一和第二光路可以在公共焦平面上彼此重叠或独立于不同位置引导。

9. 发明授权

US07773300B2 Multiphoton fluorescence filters 有权
标题翻译：多光子荧光滤光片
公开(公告)号：US07773300B2
公开(公告)日：2010-08-10
申请号：US11650441
申请日：2007-01-08
申请人： Craig Hodgson , Turan Erdogan , Ligang Wang
发明人： Craig Hodgson , Turan Erdogan , Ligang Wang
IPC分类号： G02B1/10
CPC分类号： G02B5/285 , G02B2207/114
摘要： An optical filter is provided which includes a plurality of hard coating layers of alternating high and low refractive index provided on a substrate and has an associated first transmission band. The filter also includes at least one additional plurality of hard coating layers including high and low refractive index layers and Herpin equivalent layers sandwiched therebetween. The additional plurality of layers has an associated second transmission band that substantially coincides with the first transmission band, but provides additional blocking at wavelengths outside the first transmission band. Relatively wide transmission bands and high blocking over an extended range of wavelengths can be achieved such that the filter is suitable for use in multiphoton fluorescence systems.
摘要翻译：提供了一种滤光器，其包括设置在基板上的具有交替的高折射率和低折射率的多个硬涂层，并且具有相关联的第一传输带。过滤器还包括至少一个附加的多个硬涂层，包括高折射率层和低折射率层以及夹在其间的Herpin等效层。附加的多个层具有与第一传输频带基本一致的相关联的第二传输频带，但在第一传输频带外的波长处提供附加的阻塞。可以实现相对宽的传输带和在扩展的波长范围上的高阻挡，使得滤波器适用于多光子荧光系统。

10. 发明授权

US07667210B2 Wide-area fluorescence detection system for multi-photon microscopy 有权
标题翻译：用于多光子显微镜的广域荧光检测系统
公开(公告)号：US07667210B2
公开(公告)日：2010-02-23
申请号：US11979600
申请日：2007-11-06
申请人： Robert S. Balaban , Christian A. Combs , Jay R. Knutson
发明人： Robert S. Balaban , Christian A. Combs , Jay R. Knutson
IPC分类号： G01J1/58
CPC分类号： G02B21/06 , G02B2207/114
摘要： A multi-photon microscope has an illumination source, an objective lens unit arranged in an optical path of the illumination source, a first light collection system arranged to collect a first portion of light emitted from a sample when the sample is illuminated by light from the illumination source, and a second light collection system arranged to collect a second portion of light emitted from the sample when the sample is illuminated by light from the illumination source. The first portion of light when collected by the first light collection system and the second portion of light when collected by the second light collection system, together provide a means of collecting as much light from as many angles as possible emanating from an emitting point source. This collection scheme has the potential to approach the total emission collection of light from an emitting point source depending on the optical properties of the sample being imaged.
摘要翻译：多光子显微镜具有照明源，布置在照明源的光路中的物镜单元，第一光收集系统，被布置成当样品被来自光源的光照射时，收集从样品发射的光的第一部分照明源和第二光收集系统，其被布置成当样品被来自照明源的光照射时收集从样品发射的光的第二部分。由第一光收集系统收集的第一部分光和第二光收集系统收集的第二部分光一起提供了从发射点源发出的尽可能多的角度收集尽可能多的光的装置。该采集方案具有取决于正在成像的样品的光学性质来接近来自发射点源的光的总发射收集的潜力。

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