CN102122063A - Inverted digital holographic microscope - Google Patents
Inverted digital holographic microscope Download PDFInfo
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- CN102122063A CN102122063A CN 201110057081 CN201110057081A CN102122063A CN 102122063 A CN102122063 A CN 102122063A CN 201110057081 CN201110057081 CN 201110057081 CN 201110057081 A CN201110057081 A CN 201110057081A CN 102122063 A CN102122063 A CN 102122063A
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Abstract
The invention discloses an inverted digital holographic microscope, which belongs to the digital holographic technical field, and can be used for three-dimensional real-time appearance measurement and biological cell imaging. In the inverted digital holographic microscope, an optical fiber coupler 4 is arranged in front of a laser 5 and connected with an optical fiber beam splitter 3 through an optical fiber; the optical fiber beam splitter 3 is connected with two paths of optical fibers respectively connected with an optical fiber collimator 1 and an optical fiber collimator 6, a sample stage 11 for placing a sample 13 is arranged under the optical fiber collimator 1, and the sample stage 11 is connected with a two-dimensional translation stage 12; a micro objective mounted on a one-dimensional translation stage 10 is located under the sample stage 11, and the micro objective 9 and the optical fiber collimator 6 are aligned with two mutually vertical sides of a beam combination crystal 8; and a CCD (charge-coupled device) camera 7 is located under the beam combination crystal 8. The inverted digital holographic microscope can be used for observing the living cell which is located at the bottom of a culture dish and grows along a wall of the culture dish with a high resolution ratio for long time, and is highly integrated and small in volume; moreover, with the optical fiber connection, the laser can be freely mounted on other parts of the system.
Description
Technical field
The invention discloses a kind of inversion type digital hologram microscope, belong to the digital holography techniques field, can be used for three-dimensional topography measurement in real time, the biological cell imaging.
Background technology
Biomedical Development has promoted the development of observation technology on the biological cell yardstick in recent years.Traditional optical microscope, the not three-dimensional appearance of energy measurement biological cell; Though and confocal microscope resolution is higher, owing to will do demarcation, can exert an influence to it to biological sample, be unfavorable for the needs of harmless observation.Digital hologram is as a kind of micro-imaging technique, and its characteristics harmless, real-time, that can obtain the quantitative phase distribution are its advantage in the biological sample imaging just.One is transparent configuration for the living body biological cell, so its phase image can provide the information of more uniquenesses.Be different from existing phase contrast imaging method, Digital Holography do not need to the living body biological sample carry out mark, processings such as fixing just can obtain quantitative amplitude of the object of observation and PHASE DISTRIBUTION, thereby realization is to the imaging of transparent organism sample and carry out quantitative test.Digital Holography can also realize the dynamic monitoring to the biological sample form, then may be used to obtain cell dynamic perfromance, intercellular interaction and the cell information such as reaction to medicine, expecting provides certain assay foundation for early stage medical diagnosis and drug design etc.The Lyncee Tec company of Switzerland is unique digital hologram microscope manufacturer, but its digital hologram microscope adopts upright structure, because the limited operating distance of microcobjective, particularly the very short operating distance of high magnification microcobjective can't be done real-time high resolution observations to the sample of growth bottom double dish or nutrient solution; Because existing microscopic system is to be made of space optical path, integral body weighs greatly, introduces fiber coupling system and can effectively reduce microscopical volume and weight, and can reduce the influence of the slight vibrations of laser instrument to the generation of measuring system precision
Summary of the invention
Big in order to solve digital hologram microscope volume and weight, and take upright structure can't observe the technical matters of active somatic cell in the double dish, the present invention proposes a kind of inversion type digital hologram microscope.
The present invention adopts following technical scheme: the place ahead of laser instrument 5 is mounted with fiber coupler 4, fiber coupler 4 links to each other with fiber optic splitter 3 by optical fiber, fiber optic splitter 3 picks out two-way optical fiber and is connected with optical fiber collimator 1 and optical fiber collimator 6 respectively, optical fiber collimator 1 below is equipped with the sample stage 11 that is used to hold sample 13, sample stage 11 is connected on the 12. two-dimension translational platforms, sample stage 11 belows are equipped with the microcobjective 9 that is installed on the one dimension translation stage 10, and microcobjective 9 is aimed at two perpendicular sides of closing Shu Jingti 8 with optical fiber collimator 6.Close Shu Jingti 8 belows and be equipped with CCD camera 7, CCD camera 7 links to each other with computing machine 14.
The light of laser instrument 5 outgoing is through fiber coupler 4 coupled into optical fibres, and be divided into two-way by fiber optic splitter 3: the first via is a thing light, by an optical fiber collimator 1 spherical light wave of dispersing of optical fiber outgoing is collimated into directional light, directional light is radiated on the sample 13 of horizontal positioned straight down, pass sample stage 11, microcobjective 9, and by being radiated at behind the beam cementing prism 8 on the CCD camera 7; Another road is a reference light, is shaped to directional light by optical fiber collimator 6, and level is radiated on the beam cementing prism 8, and the reflection back forms hologram by CCD camera 7. records with the thing optical interference; Above-mentioned two-way light has angle.
Above-mentioned thing light is 5mm through the diameter of the directional light that optical fiber collimator 1 is collimated into.
Above-mentioned reference light is 2cm through the directional light diameter that optical fiber collimator 6 is collimated into.
The present invention can obtain following beneficial effect:
The invention of this cover can be done long-time high resolution observations to the active somatic cell of double dish bottom adherent growth, is not placed in the handtailor container and observes and do not need that living cells is broken away from its culture environment.
The level of integrated system height, volume is little, and optics lacks than common system, and makes laser instrument can be installed in other positions of system arbitrarily owing to adopt optical fiber to connect, and has avoided the influence of the slight vibrations of laser instrument to system accuracy.
Description of drawings
The microscopical structure principle chart of Fig. 1 inversion type digital hologram;
The hologram that Fig. 2 CCD camera is adopted
The partial enlarged drawing of Fig. 3 hologram
The 3-D display figure that in computer, is generated behind the sample process inversion type digital hologram microscope among Fig. 4 embodiment;
The gray scale displayed map that in computer, is generated behind the sample process inversion type digital hologram microscope among Fig. 5 embodiment;
Among the figure: 1,6, optical fiber collimator, 2, optical fiber, 3, fiber optic splitter, 4, fiber coupler, 5, laser instrument, 7, CCD camera, 8, close Shu Jingti, 9 microcobjectives, 10, the one dimension translation stage, 11 sample stage, 12 two-dimension translational platforms, 13, sample, 14, computing machine.
Embodiment
Be described further for the present invention below in conjunction with the drawings and specific embodiments:
The arrangement of present embodiment is as shown in Figure 1:
The place ahead of laser instrument 5 is mounted with fiber coupler 4, fiber coupler 4 links to each other with fiber optic splitter 3 by optical fiber, fiber optic splitter 3 picks out two-way optical fiber and is connected with optical fiber collimator 1 and optical fiber collimator 6 respectively, optical fiber collimator 1 below is equipped with the sample stage 10 that is used to hold sample 11, sample stage 10 belows are equipped with microcobjective 9, and microcobjective 9 is aimed at two perpendicular sides of closing Shu Jingti 8 with optical fiber collimator 6.Close Shu Jingti 8 belows and be equipped with CCD camera 7.
The light of laser instrument 5 outgoing is through fiber coupler 4 coupled into optical fibres, and be divided into two-way by fiber optic splitter 3: the first via is a thing light, by an optical fiber collimator 1, the spherical light wave of dispersing of optical fiber outgoing is collimated into directional light, directional light is radiated on the sample 11 of horizontal positioned straight down, pass sample stage 10, microcobjective 9, and by being radiated at behind the beam cementing prism 8 on the CCD camera 7; Another road is a reference light, is shaped to directional light by optical fiber collimator 6, and level is radiated on the beam cementing prism 8, and the reflection back forms hologram by CCD camera 7 records with the thing optical interference.
Use the 532nm green-light source in the experiment, the 20X microcobjective.Sample is the HELE tumour cell that is placed in the common plastics double dish.The hologram that the system of Figure 2 shows that adopts, Fig. 3 is its partial enlarged drawing, can be clearly seen that the interference fringe of inclination; Fig. 4 is the phase diagram that obtains after reproducing, and can know and see the cell pattern of growing in the nutrient solution; Fig. 5 is the gray scale displayed map of Fig. 4, and gray-scale value is represented elevation information, can clearerly see the distribution of cell in the visual field.
Claims (3)
1. inversion type digital hologram microscope comprises: optical fiber collimator (1,6), optical fiber (2), fiber optic splitter (3), fiber coupler (4), laser instrument (5), CCD camera (7), close Shu Jingti (8), microcobjective (9), one dimension translation stage (10), sample stage (11), two-dimension translational platform (12), sample (13); It is characterized in that:
The place ahead of laser instrument 5 is mounted with fiber coupler (4), fiber coupler (4) links to each other with fiber optic splitter (3) by optical fiber, fiber optic splitter (3) picks out two-way optical fiber and is connected with optical fiber collimator (1) and optical fiber collimator (6) respectively, optical fiber collimator (1) below is equipped with the sample stage (11) that is used to hold sample (13), sample stage (11) is connected (12). on the two-dimension translational platform, sample stage (11) below is equipped with the microcobjective (9) that is installed on the one dimension translation stage (10), microcobjective (9) is aimed at two perpendicular sides of closing Shu Jingti (8) with optical fiber collimator (6), close Shu Jingti (8) below and be equipped with C C D camera (7); CCD camera (7) links to each other with computing machine (14);
The light of laser instrument 5 outgoing is through fiber coupler (4) coupled into optical fibres, and be divided into two-way by fiber optic splitter (3): the first via is a thing light, by an optical fiber collimator (1) spherical light wave of dispersing of optical fiber outgoing is collimated into directional light, directional light is radiated on the sample (13) of horizontal positioned straight down, pass sample stage (11), microcobjective (9), and by being radiated at behind the beam cementing prism 8 on the CCD camera (7); Another road is a reference light, is shaped to directional light by optical fiber collimator (6), and level is radiated on the beam cementing prism (8), and the reflection back forms hologram by CCD camera (7) record with the thing optical interference; Above-mentioned two-way light has angle.
2. inversion type digital hologram microscope according to claim 1 is characterized in that: above-mentioned thing light is 5mm through the diameter of the directional light that optical fiber collimator (1) is collimated into.
3. inversion type digital hologram microscope according to claim 1 is characterized in that: above-mentioned reference light is 2cm through the directional light diameter that optical fiber collimator (6) is collimated into.
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| CN 201110057081 CN102122063A (en) | 2011-03-09 | 2011-03-09 | Inverted digital holographic microscope |
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| CN 201110057081 CN102122063A (en) | 2011-03-09 | 2011-03-09 | Inverted digital holographic microscope |
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| CN102506746A (en) * | 2011-09-29 | 2012-06-20 | 北京工业大学 | Digital holography imaging system with speckle removing effect by multiple overlaying |
| CN102519976A (en) * | 2011-12-26 | 2012-06-27 | 上海大学 | Digital holographic detection device for subsurface defect of optical element |
| CN102591123A (en) * | 2012-03-13 | 2012-07-18 | 苏州大学 | Real-time three-dimensional display device and display method |
| CN103257441A (en) * | 2013-05-13 | 2013-08-21 | 北京工业大学 | Incoherent digital holography three-dimensional dynamic microscopic imaging system and method |
| CN103412398A (en) * | 2013-08-07 | 2013-11-27 | 桂林优利特医疗电子有限公司 | Double-lens-cone microscope device used in urinary sediment inspection equipment |
| CN103827889A (en) * | 2011-07-19 | 2014-05-28 | 奥维茨奥成像系统公司 | A method and system for detecting and/or classifying cancerous cells in a cell sample |
| CN104568753A (en) * | 2014-12-24 | 2015-04-29 | 天津大学 | Digital holography based sample drifting active compensation method and device |
| CN104729999A (en) * | 2015-03-20 | 2015-06-24 | 中国科学院近代物理研究所 | Device and method for measuring uniformity of nuclear track membrane by virtue of laser |
| CN106323469A (en) * | 2016-09-09 | 2017-01-11 | 华讯方舟科技有限公司 | Electronically controlled optical sampling system, method and terahertz time-domain spectrometer |
| CN106485779A (en) * | 2016-03-22 | 2017-03-08 | 智合新天（北京）传媒广告股份有限公司 | A kind of 3D virtual interacting display platform and the method for showing 3D animation |
| CN109827890A (en) * | 2019-01-29 | 2019-05-31 | 南京大学 | Utilize the devices and methods therefor of acoustic radiation force test biological cell mechanical characteristic |
| CN109975249A (en) * | 2017-12-28 | 2019-07-05 | 中山大学 | A kind of LSPR sensing device based on ordered nano-structure array |
| CN111865417A (en) * | 2019-04-24 | 2020-10-30 | 南京航星通信技术有限公司 | Satellite-ground satellite laser communication terminal facing cube star |
| US10876970B2 (en) | 2016-04-12 | 2020-12-29 | The Board Of Regents Of The University Of Texas System | Light-sheet microscope with parallelized 3D image acquisition |
| CN112198652A (en) * | 2020-09-09 | 2021-01-08 | 安徽九陆生物科技有限公司 | Inverted automatic slide scanner device and using method thereof |
| CN112268505A (en) * | 2020-10-22 | 2021-01-26 | 江苏集萃微纳自动化系统与装备技术研究所有限公司 | Microscopic operation system based on full-field optical coherence tomography technology |
| US10989661B2 (en) | 2015-05-01 | 2021-04-27 | The Board Of Regents Of The University Of Texas System | Uniform and scalable light-sheets generated by extended focusing |
| CN112945083A (en) * | 2021-01-29 | 2021-06-11 | 中国科学院长春光学精密机械与物理研究所 | Parallel phase shift digital holographic microscopic imaging system with optical fiber interconnection |
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| CN1971253A (en) * | 2006-10-19 | 2007-05-30 | 上海大学 | Digital holographic micro-measuring device |
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Patent Citations (2)
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| CN1971253A (en) * | 2006-10-19 | 2007-05-30 | 上海大学 | Digital holographic micro-measuring device |
| CN201382849Y (en) * | 2009-03-17 | 2010-01-13 | 西北工业大学 | Flow field display device based on digital holography |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103827889B (en) * | 2011-07-19 | 2018-01-02 | 奥维茨奥成像系统公司 | Method and system for the cancer cell in the cell sample that detects and/or classify |
| CN103827889A (en) * | 2011-07-19 | 2014-05-28 | 奥维茨奥成像系统公司 | A method and system for detecting and/or classifying cancerous cells in a cell sample |
| CN102506746A (en) * | 2011-09-29 | 2012-06-20 | 北京工业大学 | Digital holography imaging system with speckle removing effect by multiple overlaying |
| CN102519976A (en) * | 2011-12-26 | 2012-06-27 | 上海大学 | Digital holographic detection device for subsurface defect of optical element |
| CN102591123A (en) * | 2012-03-13 | 2012-07-18 | 苏州大学 | Real-time three-dimensional display device and display method |
| CN102591123B (en) * | 2012-03-13 | 2014-12-10 | 苏州大学 | Real-time three-dimensional display device and display method |
| CN103257441B (en) * | 2013-05-13 | 2016-10-26 | 北京工业大学 | A kind of dynamic micro imaging system of incoherent digital holography three-dimensional and method |
| CN103257441A (en) * | 2013-05-13 | 2013-08-21 | 北京工业大学 | Incoherent digital holography three-dimensional dynamic microscopic imaging system and method |
| CN103412398A (en) * | 2013-08-07 | 2013-11-27 | 桂林优利特医疗电子有限公司 | Double-lens-cone microscope device used in urinary sediment inspection equipment |
| CN103412398B (en) * | 2013-08-07 | 2015-06-10 | 桂林优利特医疗电子有限公司 | Double-lens-cone microscope device used in urinary sediment inspection equipment |
| CN104568753A (en) * | 2014-12-24 | 2015-04-29 | 天津大学 | Digital holography based sample drifting active compensation method and device |
| CN104568753B (en) * | 2014-12-24 | 2017-08-22 | 天津大学 | Sample drift active compensation method and device based on digital hologram |
| CN104729999A (en) * | 2015-03-20 | 2015-06-24 | 中国科学院近代物理研究所 | Device and method for measuring uniformity of nuclear track membrane by virtue of laser |
| CN104729999B (en) * | 2015-03-20 | 2016-05-11 | 中国科学院近代物理研究所 | The method of the laser measurement nucleopore membranes uniformity |
| US10989661B2 (en) | 2015-05-01 | 2021-04-27 | The Board Of Regents Of The University Of Texas System | Uniform and scalable light-sheets generated by extended focusing |
| CN106485779A (en) * | 2016-03-22 | 2017-03-08 | 智合新天（北京）传媒广告股份有限公司 | A kind of 3D virtual interacting display platform and the method for showing 3D animation |
| CN106485779B (en) * | 2016-03-22 | 2019-05-03 | 智合新天（北京）传媒广告股份有限公司 | A kind of 3D virtual interacting display platform and the method for showing 3D animation |
| US10876970B2 (en) | 2016-04-12 | 2020-12-29 | The Board Of Regents Of The University Of Texas System | Light-sheet microscope with parallelized 3D image acquisition |
| CN106323469A (en) * | 2016-09-09 | 2017-01-11 | 华讯方舟科技有限公司 | Electronically controlled optical sampling system, method and terahertz time-domain spectrometer |
| CN106323469B (en) * | 2016-09-09 | 2019-05-03 | 华讯方舟科技有限公司 | The automatically controlled smooth sampling system of one kind, method and terahertz time-domain spectroscopy instrument |
| CN109975249A (en) * | 2017-12-28 | 2019-07-05 | 中山大学 | A kind of LSPR sensing device based on ordered nano-structure array |
| CN109827890A (en) * | 2019-01-29 | 2019-05-31 | 南京大学 | Utilize the devices and methods therefor of acoustic radiation force test biological cell mechanical characteristic |
| CN111865417A (en) * | 2019-04-24 | 2020-10-30 | 南京航星通信技术有限公司 | Satellite-ground satellite laser communication terminal facing cube star |
| CN112198652A (en) * | 2020-09-09 | 2021-01-08 | 安徽九陆生物科技有限公司 | Inverted automatic slide scanner device and using method thereof |
| CN112268505A (en) * | 2020-10-22 | 2021-01-26 | 江苏集萃微纳自动化系统与装备技术研究所有限公司 | Microscopic operation system based on full-field optical coherence tomography technology |
| CN112945083A (en) * | 2021-01-29 | 2021-06-11 | 中国科学院长春光学精密机械与物理研究所 | Parallel phase shift digital holographic microscopic imaging system with optical fiber interconnection |
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Application publication date: 20110713 |