WO2003079089A1 - Microscope optique a haute stabilite - Google Patents

Microscope optique a haute stabilite Download PDF

Info

Publication number
WO2003079089A1
WO2003079089A1 PCT/JP2002/008935 JP0208935W WO03079089A1 WO 2003079089 A1 WO2003079089 A1 WO 2003079089A1 JP 0208935 W JP0208935 W JP 0208935W WO 03079089 A1 WO03079089 A1 WO 03079089A1
Authority
WO
WIPO (PCT)
Prior art keywords
optical system
optical
support
optical microscope
photometric
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2002/008935
Other languages
English (en)
French (fr)
Japanese (ja)
Inventor
Kazuhiko Kinoshita
Megumi Shio
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Japan Science and Technology Agency
Original Assignee
Japan Science and Technology Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Japan Science and Technology Corp filed Critical Japan Science and Technology Corp
Priority to DE60232196T priority Critical patent/DE60232196D1/de
Priority to EP02772834A priority patent/EP1486810B1/en
Priority to US10/506,107 priority patent/US7307784B2/en
Publication of WO2003079089A1 publication Critical patent/WO2003079089A1/ja
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • GPHYSICS
    • G02OPTICS
    • G02BOPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00Microscopes
    • G02B21/24Base structure
    • GPHYSICS
    • G02OPTICS
    • G02BOPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00Microscopes
    • G02B21/36Microscopes arranged for photographic purposes or projection purposes or digital imaging or video purposes including associated control and data processing arrangements
    • G02B21/362Mechanical details, e.g. mountings for the camera or image sensor, housings

Definitions

  • the present invention relates to long-term image recording and measurement of optical instruments, optical measuring instruments, and optical microscopes.
  • the optical microscope may be displaced minutely, causing the object point (target object) to shift or become out of focus (a so-called drift phenomenon).
  • the present invention relates to a structure of a high-stability optical microscope which enables stable recording and measurement with a precision of nanometer unit for long-time image recording and measurement by preventing such a drift phenomenon from occurring.
  • the optical microscope method has a structure similar to a willow tree.
  • the main column (corresponding to the trunk) has the stage, illumination section, observation optical system, etc. of the sample positioning device attached to the optical axis, even in terms of weight and shape, with a great deal of asymmetricity and lacking balance.
  • the structure was unstable as shown in Figure 1. In FIG. 1
  • 1, 101 is a television camera, 102 is a relay lens, 103 is a connecting cylinder, 104 is a straight cylinder, 105 is an eyepiece, 106 is a binocular, and 10 ⁇ is a lens barrel, 1 08 is an illumination light source, 1 09 is an epi-illuminator, 1 1 0 is an arm, 1 1 1 is a revolver, 1 1 2 is an objective lens, 1 1 3 is a stage, 1 1 4 is A vertical movement mechanism, 115 is a condenser, 116 is a main pillar, 117 is a base and a lighting device.
  • the conventional optical microscope in FIG. 1 basically has a U-shape in which a main column is erected at one end of a base and an illumination device, and an arm is provided on an upper side of the main column.
  • the main column supports a vertical movement mechanism for vertically moving a stage on which a sample to be observed is mounted, and a condenser for guiding illumination light from the illumination device to the sample below the stage. — Is provided.
  • an objective lens and a revolver for changing the magnification of the objective lens are provided below the arm, and an epi-illumination device, a lens barrel, a straight cylinder, a relay lens, and a TV camera are provided above the arm, and Beside the fluorescent device Is provided with an illumination light source, a binocular portion and an eyepiece are provided on the side of the lens barrel, and an attached measuring device, a camera, and the like are attached like branches and leaves.
  • the main pillar is erected at one end of the base and the lighting device, and the cantilever structure, that is, the structure in which not only the branches and leaves sway in the willow but also the thin trunk sways,
  • illumination optical systems epifluorescence, total epifluorescence, transmitted fluorescence, reflected polarized light, transmitted polarized light, bright-field incident light, optical tweezers, etc.
  • the imaging lens shared a single imaging lens due to cost constraints.
  • the supporting hardware of the illumination system is integrated with the image optical system and the photometric optical system. Therefore, the illumination optical system and the monitor-optical system are affected by the instability of the shape and weight of the supporting hardware and the temperature dependence of the supporting hardware. The expansion and contraction affected the image optical system and the photometric optical system due to the deviation of the optical axis.
  • single-molecule physics A new field of research called “single-molecule physics” is emerging, in which one observes and manipulates how biological substances such as proteins work in single-molecule units.
  • An optical microscope is indispensable for this research, and the movement of biological materials is so small that analysis requires an accuracy of several nanometers.
  • the present invention aims to realize a highly stable optical microscope that does not cause defocusing of a sample during observation and does not cause movement (drift) of an object point (object).
  • the image forming lens and the subsequent optical system are arranged individually without using a common image forming lens.
  • the imaging lens TV camera is integrated even if displacement occurs in the X and Y directions as shown in Fig. 2b due to instability caused by the asymmetry of the shape and weight of the support metal from the ideal position in Fig. 2a. Therefore, the luminous flux is slightly biased, but the object is located at the center of the imaging lens and the focal position. An image is formed without displacement.
  • the technical means adopted by the present invention include, in an optical microscope, an objective lens, an imaging lens, an image optical system, and a photometric system on a linear guide mechanism and a support made symmetrically in shape and weight with respect to the optical axis.
  • the structure of an optical microscope with high stability is characterized by the fact that the optical systems are arranged in a straight line and supported without bias.
  • the support of the image optical system and the support of the photometric optical system have a highly stable optical microscope structure with a truncated pyramid or a truncated cone so that tilt displacement due to temperature change, vibration, etc. does not occur. That was done.
  • the illumination optical system (epifluorescence, total internal reflection epifluorescence, transmitted fluorescence, reflected polarized light, transmitted polarized light, bright-field epi-illumination, optical tweezers, etc.) and the introduction part of the monitor optical system in the infinity long optical microscope
  • a semi-transmission mirror including a dichroic mirror
  • an imaging lens are combined respectively, and the image optical system and the photometric optical system are affected by the instability caused by the asymmetrical shape and the temperature dependence of the support (metal). The instability was avoided by the principle of working on a telescope, and the structure of a highly stable optical microscope was adopted.
  • sample stage and the objective lens (sample section), whose shape and weight are symmetrical with respect to the optical axis, are integrated into a single unit, and all imaging lenses and independent supports are used.
  • the structure of the optical microscope is high.
  • FIG. 1 is an explanatory view of a conventional optical microscope.
  • Fig. 2 is a diagram for explaining the principle that the center of the imaging lens and the focal position are displaced by integrating the imaging lens and a TV camera, for example.
  • FIG. 3 is an explanatory diagram of an optical microscope configured according to the present invention.
  • the image optics which consists of a photometric aperture ps17, a relay lens support hardware Pk18, a relay lens pr19, a TV camera support hardware 20, and a television camera 21
  • a photometric optical system consisting of a straight tube 28, a photometric aperture ms 29, a relay lens hardware mk30, a relay lens m131, a photometric device support hardware 32, and a photometric device 33
  • an illumination optical system Epi-illumination illuminator 1 2, total reflection epi-fluorescence, transmitted fluorescence, reflected polarized light, transmitted polarized light, bright-field epi-illumination, optical tweezers 10 and 11, etc.
  • the length of the infinity barrel provided in the illumination optical system It consists of an objective lens 2 and an imaging lens p 1 16.
  • a hollow and frustoconical support base 7 is fixed to the vibration isolator 15 supported by the support legs 38, and an optical tweezer introduction optical system 10 is provided at an enlarged portion below the support base 7.
  • Epi-illumination illuminator 12, monitor—optical system (a) 13 ⁇ Provided toward the center.
  • the optical tweezer introduction optical system 10 is connected to an optical tweezer illumination system 11 provided on a vibration isolator 15.
  • a base 14 having an imaging lens p 1 16 in the center is provided below the hollow portion of the support base 7, and a flat part 39 of the base 14 is a vibration isolator
  • the leg portion 40 is placed on the surface of 15 and the leg portion 40 is inserted into the center of the vibration isolator 7.
  • On the base 14, a support 9 is erected, and on the board 8 at the upper end of the support 9, there are a fixed base 6, a Y-axis coarse movement base 5, an X-axis coarse movement base 4, and an XYZ axis fine movement.
  • the sample 1 to be observed is placed on the sample table 3 provided with the XYZ-axis fine movement provided sequentially with the sample table 3 having the XYZ-axis fine movement.
  • a transmission illumination device 23, a dark field illumination device 26, and a monitor optical system (b) 2 ⁇ ⁇ ⁇ ⁇ are mounted on the reduced portion above the support table 7 toward the center.
  • a condenser lens 22 is provided at the distal end of the condenser lens support hardware 24 fixed to the lens, and an illumination system imaging lens 25 is provided at the flat center of the distal end of the support 7. ing.
  • a hollow and inverted trapezoidal support 41 is attached to the lower surface of the vibration isolation table 15.
  • a photometric stop ps 17 and a relay lens support hardware pk 1 are provided in the hollow portion of the support 41.
  • a relay lens pr 19 is sequentially provided to form a video-side primary image 34 and a video-side secondary image 35.
  • the infinity barrel objective lens 2 imaging lens 16p1, illumination system imaging lens 25, image optical system (photometric aperture 17ps, relay lens support hardware pk18, relay —Lens pr 19, TV camera support hardware 20 and TV camera 21), photometric optical system (straight tube 28, photometric aperture ms 29, relay lens hardware mk30, relay lens hardware ml31, ), Consisting of a support for the photometric device 32 and a photometric device 33), which are arranged in a straight line on a linear guide mechanism that is symmetrical in shape and weight on the optical axis and supported without bias. High optical microscope structure.
  • the parallel movement causes no defocusing unless the tilt changes.
  • the principle of a telescope that does not cause movement (drift) of the (object) works.
  • An example of this linear guide mechanism consists of a cylinder and a cylinder, and the cylinder can move in the optical axis direction.
  • the sample focus mechanism is performed by the sample table 3 with XYZ axis fine movement.
  • the sample table 3 with XYZ axis fine movement is not only symmetrical about the center of the optical axis, but also has a built-in capacitance type sensor and is displaced by a piezo drive mechanism. The amount is fed back and the focus position is maintained.
  • a semi-transmissive mirror (dike) is installed at the entrance of the illumination optical system (epifluorescent illumination device 12, total reflection epifluorescence, transmitted fluorescence, reflected polarized light, transmitted polarized light, bright-field incident light, optical tweezers 10 and 11).
  • the image optical system and the photometric optical system are supported by an independent support, and the image optical system and the photometric optical system are affected by the asymmetry of the shape and weight.
  • the structure eliminates instability. Even if the image optical system, photometric optical system and illumination optical system fluctuate, the above-mentioned principle of working with the telescope is applied. ing.
  • heavy objects such as the optical tweezers illumination system are further separated and attached directly to the anti-vibration table 15 so that they do not become unstable elements such as unbalanced weights, and may cause tilting. It doesn't matter.
  • the sample 1 the objective lens at infinity lens barrel length 2
  • the sample stage 3 with XYZ axis fine movement 3 the X axis coarse movement stage 4
  • the Y axis coarse movement stage 5 the fixed stage 6 are fixed by vacuum suction etc. Perform integration.
  • Eliminating relative fluctuation between the sample and the objective lens by this integration is very effective for ensuring stability. Furthermore, the problem is solved by mounting these parts directly on the vibration isolator 15 and arranging them at a position with a low center of gravity.
  • the objective lens, the imaging lens, and the image optics are provided on the linear guide mechanism and the support that are formed symmetrically in shape and weight with respect to the optical axis.
  • the system and the photometric optical system are arranged in a straight line and are supported without bias.
  • the highly stable optical microscope is realized, and an extremely stable optical microscope is realized, which is used in molecular biology, biophysics, etc. Measuring distance and molecular momentum at the molecular position can be easily performed on the order of nanometers. Also, long-time image recording can be easily performed without causing drift.
  • the illumination optical system epifluorescence, total reflection epifluorescence, transmitted fluorescence, reflected polarized light, transmitted polarized light
  • a semi-transmissive mirror including a dichroic mirror
  • an imaging lens in the introduction part of the optical system, such as field light, optical tweezers, etc. Is born, and a highly stable optical microscope that can be developed as a system can be realized.

Landscapes

  • Physics & Mathematics (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Optics & Photonics (AREA)
  • Engineering & Computer Science (AREA)
  • Multimedia (AREA)
  • Microscoopes, Condenser (AREA)
PCT/JP2002/008935 2002-03-18 2002-09-03 Microscope optique a haute stabilite Ceased WO2003079089A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
DE60232196T DE60232196D1 (de) 2002-03-18 2002-09-03 Hochstabiles optisches mikroskop
EP02772834A EP1486810B1 (en) 2002-03-18 2002-09-03 High-stability optical microscope
US10/506,107 US7307784B2 (en) 2002-03-18 2002-09-03 High-stability optical microscope

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2002073455A JP4084061B2 (ja) 2002-03-18 2002-03-18 高安定性光学顕微鏡
JP2002-73455 2002-03-18

Publications (1)

Publication Number Publication Date
WO2003079089A1 true WO2003079089A1 (fr) 2003-09-25

Family

ID=28035240

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2002/008935 Ceased WO2003079089A1 (fr) 2002-03-18 2002-09-03 Microscope optique a haute stabilite

Country Status (6)

Country Link
US (1) US7307784B2 (https=)
EP (1) EP1486810B1 (https=)
JP (1) JP4084061B2 (https=)
CN (1) CN100559228C (https=)
DE (1) DE60232196D1 (https=)
WO (1) WO2003079089A1 (https=)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1582904A1 (en) * 2004-03-30 2005-10-05 Olympus Corporation System microscope

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102005001102B4 (de) * 2005-01-08 2021-04-29 Carl Zeiss Microscopy Gmbh Temperierbares Objektiv für Mikroskope
WO2007011844A1 (en) * 2005-07-19 2007-01-25 Physical Sciences, Inc. Side view imaging microwell array
US7854524B2 (en) * 2007-09-28 2010-12-21 Anorad Corporation High stiffness low mass supporting structure for a mirror assembly
EP2246725A3 (en) * 2009-04-30 2011-01-26 Olympus Corporation Microscope with fixed imaging unit and movable objective lens
DE202009010772U1 (de) 2009-08-11 2009-11-26 Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts Anordnung zur Abbildungsstabilisierung
EP3358387A1 (en) 2010-08-27 2018-08-08 The Board of Trustees of The Leland Stanford Junior University Microscopy imaging device with advanced imaging properties
US9428384B2 (en) * 2011-01-18 2016-08-30 Jizhong He Inspection instrument
WO2015029032A1 (en) 2013-08-26 2015-03-05 Parasight Ltd. Digital microscopy systems, methods and computer program products
JP6849405B2 (ja) * 2016-11-14 2021-03-24 浜松ホトニクス株式会社 分光計測装置及び分光計測システム
CN108414446A (zh) * 2018-03-30 2018-08-17 广东顺德墨赛生物科技有限公司 微流控芯片荧光检测设备、方法以及装置
AU2020370212B2 (en) 2019-10-22 2025-09-25 S.D. Sight Diagnostics Ltd Accounting for errors in optical measurements
CN110888230A (zh) * 2019-11-28 2020-03-17 天津职业技术师范大学(中国职业培训指导教师进修中心) 一种智能生物显微镜
CN114787625B (zh) 2019-12-12 2026-01-13 思迪赛特诊断有限公司 检测血液样品中的血小板
BR112022011312A2 (pt) * 2019-12-12 2022-08-23 S D Sight Diagnostics Ltd Análise de um analito disposto dentro de um meio

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH08114750A (ja) * 1994-10-14 1996-05-07 Olympus Optical Co Ltd 倒立形顕微鏡用保温装置
US5764409A (en) * 1996-04-26 1998-06-09 Alpha Innotech Corp Elimination of vibration by vibration coupling in microscopy applications
US20010028510A1 (en) * 1996-08-16 2001-10-11 Imaging Research, Inc. Digital imaging system for assays in well plates, gels and blots

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3259012A (en) * 1960-09-12 1966-07-05 Inv S Finance Corp Microscope having bridge type support arm for body tube and focusing mechanism
GB1260653A (en) * 1968-01-25 1972-01-19 Watson W & Sons Ltd Improvements in or relating to optical apparatus
US3830560A (en) * 1970-09-14 1974-08-20 R Onanian Microscope apparatus
JPS5524566Y2 (https=) * 1975-10-28 1980-06-12
US5317153A (en) * 1991-08-08 1994-05-31 Nikon Corporation Scanning probe microscope
JP2966311B2 (ja) * 1995-03-10 1999-10-25 科学技術振興事業団 顕微測光装置
DE19530136C1 (de) * 1995-08-16 1997-02-13 Leica Mikroskopie & Syst Einrichtung zur Fokusstabilisierung in einem Mikroskop
JP3221823B2 (ja) * 1995-11-24 2001-10-22 キヤノン株式会社 投影露光装置およびこれを用いた露光方法ならびに半導体製造方法
US6091911A (en) * 1996-08-30 2000-07-18 Nikon Corporation Microscope photographing unit with brightness control for observation optical system
JP3437406B2 (ja) * 1997-04-22 2003-08-18 キヤノン株式会社 投影露光装置
US5970260A (en) * 1997-09-10 1999-10-19 Konica Corporation Camera equipped with zoom lens
CA2243090A1 (en) * 1998-07-10 2000-01-10 Timothy M. Richardson Inverted darkfield contrast microscope and method

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH08114750A (ja) * 1994-10-14 1996-05-07 Olympus Optical Co Ltd 倒立形顕微鏡用保温装置
US5764409A (en) * 1996-04-26 1998-06-09 Alpha Innotech Corp Elimination of vibration by vibration coupling in microscopy applications
US20010028510A1 (en) * 1996-08-16 2001-10-11 Imaging Research, Inc. Digital imaging system for assays in well plates, gels and blots

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP1486810A4 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1582904A1 (en) * 2004-03-30 2005-10-05 Olympus Corporation System microscope

Also Published As

Publication number Publication date
EP1486810A4 (en) 2007-05-23
CN1623110A (zh) 2005-06-01
EP1486810B1 (en) 2009-04-29
EP1486810A1 (en) 2004-12-15
JP2003270537A (ja) 2003-09-25
DE60232196D1 (de) 2009-06-10
JP4084061B2 (ja) 2008-04-30
US7307784B2 (en) 2007-12-11
US20050117204A1 (en) 2005-06-02
CN100559228C (zh) 2009-11-11

Similar Documents

Publication Publication Date Title
JP4084061B2 (ja) 高安定性光学顕微鏡
US7042638B2 (en) Device for coupling light into a microscope
US6980360B2 (en) Focus stabilizing apparatus
EP0488023A1 (en) Microscope having a focus-adjusting mechanism
EP3776054B1 (en) Improved scanning optical microscope
JP2003270537A5 (https=)
US6975409B2 (en) Illumination device; and coordinate measuring instrument having an illumination device
JP7025530B2 (ja) 広領域の共焦点及び多光子顕微鏡で用いる動的フォーカス・ズームシステム
JP4205321B2 (ja) 顕微鏡等のフォーカス安定性機構
US8964287B2 (en) Device for focusing a microscope objective on a sample
JP2003043373A5 (https=)
EP1582904A1 (en) System microscope
JP4914537B2 (ja) 倒立型顕微鏡に適用される試料支持装置
US7936502B2 (en) Microscope
JP4792163B2 (ja) 顕微鏡装置
US20090116103A1 (en) Microscope apparatus
JP2004530948A (ja) 顕微鏡鏡筒
McAllister et al. Design and optimization of a high-speed, high-sensitivity, spinning disk confocal microscopy system
US12135412B2 (en) Non-linear optical scanning microscope having kinematic flexure mechanism
JPH09145721A (ja) 光学顕微鏡一体型走査型プローブ顕微鏡
JPH11160627A (ja) 倒立顕微鏡
JPH0835973A (ja) 走査型プローブ顕微鏡
JP2002162570A (ja) 正立顕微鏡
JP2004286855A (ja) 実体顕微鏡

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): CN US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR IE IT LU MC NL PT SE SK TR

121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 10506107

Country of ref document: US

WWE Wipo information: entry into national phase

Ref document number: 20028285794

Country of ref document: CN

WWE Wipo information: entry into national phase

Ref document number: 2002772834

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 2002772834

Country of ref document: EP