EP1272887A1 - Vorrichtung zum laserschneiden von präparaten und mikroskop - Google Patents
Vorrichtung zum laserschneiden von präparaten und mikroskopInfo
- Publication number
- EP1272887A1 EP1272887A1 EP01925307A EP01925307A EP1272887A1 EP 1272887 A1 EP1272887 A1 EP 1272887A1 EP 01925307 A EP01925307 A EP 01925307A EP 01925307 A EP01925307 A EP 01925307A EP 1272887 A1 EP1272887 A1 EP 1272887A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- holder
- microscope
- plate
- table surface
- optical axis
- 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.)
- Withdrawn
Links
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/02—Devices for withdrawing samples
- G01N1/04—Devices for withdrawing samples in the solid state, e.g. by cutting
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/286—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q involving mechanical work, e.g. chopping, disintegrating, compacting, homogenising
-
- G—PHYSICS
- G02—OPTICS
- G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
- G02B21/00—Microscopes
- G02B21/32—Micromanipulators structurally combined with microscopes
Definitions
- the invention relates to a device for laser cutting preparations.
- the invention comprises an xy table that defines a table surface, a holder for receiving a specimen slide, the specimen slide being seated in the holder such that the specimen lies opposite the table surface, and a collecting device with at least one container for catching a cut-out specimen part ,
- the invention further relates to a microscope which is used together with the device for laser cutting of specimens.
- the microscope comprises an xy table, which defines a table surface, a holder for receiving a specimen slide, the specimen slide being seated in the holder such that the specimen lies opposite the table surface, and a collecting device with at least one container for collecting a cut-out specimen part.
- DE 196 16 216 A1 describes a method and a device for laser dissection of biological objects. It has a microscope arrangement for viewing thin sections of the objects on a slide, the slide lying on a holder integrated in the xy table and the thin section being on the underside of the slide. A laser arrangement generates a focused laser beam for cutting out sample material from the thin sections. The laser arrangement and the slide can be displaced relative to one another. A collecting device for receiving the cut-out sample material is arranged below the xy table. The collecting device consists of one or more containers.
- the disadvantage of the arrangement described is that the collecting device from below into the table recess in the area below the Preparation must be introduced. This area is difficult for the user to see or to reach. This area is particularly difficult to access with xy tables, which are constructed as three-table tables and therefore have a higher design. Even with motorized xy tables, the area is difficult to access because the drive motors make access to the area below the preparation difficult. In particular, collecting devices consisting of arrays of individual containers are in most cases not to be used.
- the invention is based on the object of designing a device for laser cutting microscopic specimens in such a way that the handling of a collecting device for holding the cut-out specimen part can be carried out safely, simply and conveniently. Furthermore, the contamination of the containers of the collecting device with particles released during the cutting should be reduced to a minimum.
- a collecting device (10) with at least one container (12) for collecting a cut-out preparation part which is characterized in that - the holder (14) is arranged above the table surface (4) and thus connected to the xy table (2) is that it is adjustable in the y direction (20a) and in the x direction (22a),
- a free work space (16) is defined, in which the collecting device (10) can be fed.
- Another object of the invention is to provide a microscope which can be used to cut out specimen parts from a specimen with a laser, a safe and simple transfer into the collecting container being ensured. This problem is solved by a microscope, which is characterized in that
- the holder (14) is arranged above the table surface (4) and is connected to the xy table (2) in such a way that it can be adjusted in the x direction (22a) and in the y direction (20a),
- a free working space (16) is defined between the holder (14) and the table surface (4), into which the collecting device (10) can be fed.
- a safe and easy-to-use receptacle of the cut-out preparation parts is ensured in containers of a collecting device provided for this purpose. Due to the special arrangement of the holder for the specimen slide above the xy table, which creates a spatial separation between the specimen slide and the table surface of the xy table, a suitable collecting device can be supplied in the free working space that is created as a result. It is possible in a particularly simple way to bring the collecting device with its at least one container into such a position that cut-out preparation parts get into the containers provided for this purpose. The user of the device or of the microscope does not have to undertake any complicated manipulations. The collecting device can be moved in the free work space on the table surface. This can be done manually or by motor.
- Another advantageous feature of the invention is that due to the special arrangement of the specimen slides in the holder, the specimen parts cut out by the laser beam get into the containers provided for this purpose due to the force of gravity. No additional action is required and the risk of contamination or product damage is almost eliminated.
- a contamination protection plate is provided directly under the holder for the specimen slide.
- the contamination protection plate is fastened to the fixed base plate of the xy table with holding elements in such a way that an approximately removed surface between the table surface and the contamination protection plate under the holder. closed space is created.
- the contamination protection plate has an opening that is fixed relative to the optical axis of the objective, through which the light for the specimen illumination passes and the cut specimen part falls into the container.
- Another advantage of the invention is that the preparation is moved with the existing operating elements of the xy table, which the user is familiar with from conventional microscope tables.
- the xy table can be moved both manually and by motor.
- Fig. 1 a perspective view of the device for holding a preparation for laser cutting
- FIG. 2 shows a cross section through the device in the plane spanned by the optical axis and the x-direction, the position of the collecting container also being shown, and
- Fig. 3 a second embodiment of the invention, the same view as in Fig. 2 is used.
- Fig. 1 shows a device for holding a preparation for laser cutting.
- the device has an xy table 2, which can be attached to a conventional microscope (not shown).
- the xy table can be moved manually or by means of motors (not shown).
- the microscope defines an optical axis 24, which is shown in FIG. 1 as a dashed line.
- the xy table 2 has a fixed base plate 18. On the fixed base plate 18 a movable plate 20 is attached, which in the illustrated embodiment can be moved in the y direction 20a.
- the y direction 20a is shown in FIG. 1 with a double arrow.
- a linear guide 22 which can be moved in the x direction 22a is attached to the movable plate 20.
- the x-direction 22a is shown in FIG. 1 by a further double arrow.
- a spacer element 15 is fastened on the linear guide 22, to which a holder 14 for a specimen slide 6 is connected.
- the plate 20 and the linear guide 22 can each be moved by means of roller bearings 23.
- the bracket 14 is releasably attached to the spacer 15 by means of two knurled screws 21.
- the xy table 2 defines a table surface 4.
- the holder 14 is spaced apart from the table surface 4 by the spacer 15 such that a free working space 16 is formed between the table surface 4 and the holder 14.
- the xy table 2 has a recess 26.
- the recess 26 is assigned with respect to the microscope in such a way that the optical axis 24 runs through the recess 26.
- the holder 14 is U-shaped, a first and a second leg 28 and 30 being formed.
- a free space 32 is formed between the first and the second leg 28 and 30 and is spanned by the specimen slide 6.
- the free space 32 is arranged with respect to the recess 26 such that the optical axis 24 runs through both. This arrangement of the recess 26 in the xy table 2 and the free space 32 enables transmitted light illumination of the preparation 8 applied to the specimen slide 6 (see FIG. 2).
- FIG. 2 shows a cross section through the device from FIG. 1 in the plane spanned by the optical axis and the x direction.
- the plate 20, which can be moved in the y direction, is arranged on the fixed base plate 18.
- the movable plate 20 defines the table surface 4 of the xy table 2.
- a collecting device 10 is provided, which can be provided with an adjusting device (see FIG. 3). It goes without saying that the collecting device 10 can also be moved manually in the free working space 16 defined by the spacer element 15.
- the specimen slide 6 is arranged above the free space 32 of the holder 14 in such a way that the specimen 8 is completely in the free space 32.
- the specimen 8 is arranged on a slide 6 located on the holder 14 in such a way that it is located directly opposite the table surface 4.
- a lens 36 of the microscope is assigned to the object carrier 6 on the optical axis 24 and generates an image of the specimen 8.
- a coupled-in laser beam 38 is directed onto the specimen 8 by the objective 36 in order to cut a small part out of the specimen 8.
- the collecting device 10 is located under the specimen 8 such that the cut-out part falls directly into a container 12 of the collecting device 10 due to gravity.
- the number of containers 12 of the collecting device 10 can be adapted to the conditions of use.
- FIG. 3 shows a further exemplary embodiment of the device for laser cutting of specimens 8.
- Two holding elements 40 are fastened to the fixed base plate 18.
- the holding elements 40 carry a contamination protection plate 42 which is fixed between the holder 14 and the collecting device 10 relative to the optical axis 24.
- the contamination protection plate 42 spans the entire table surface 4 and thus limits the free working space 16 upwards. It is provided with a cutout 44 around the optical axis 24.
- the collecting device 10 with containers 12 for receiving the cut-out preparation elements is arranged in the free working space 16.
- the collecting device 10 can have an array of containers 12.
- the contamination protection plate 42 prevents dust or other particles from the ambient air from being deposited in the containers 12 of the collecting device 10. In addition, the contamination protection plate 42 prevents the precipitation of preparation parts, which are released from the preparation 8 during laser cutting, into the containers 12. It proves to be advantageous here that only one container 12 of the collecting device 10 is open through the cutout 44 in the contamination protection plate 42, while the other containers 12 are covered.
- An adjustment device 46 is connected to the collecting device 10, and both are arranged on the table surface 4.
- a motor 48 can also be provided on the table surface 4 for the motorized movement of the adjustment device 46 his.
- the motor 48 is connected to a computer 50, which is responsible for controlling the adjustment device 46.
- the computer 50 moves the collecting device 10 in such a way that the desired container 12 is located under the recess 44 and thus under the area of the specimen 8 which is currently undergoing the laser cutting process. When the laser cutting process is complete, the cut specimen element falls into the container 12 due to the force of gravity. If necessary, the computer 50 will position another or empty container 12 accordingly in order to catch a new cut specimen element.
- the computer 50 is also connected to a monitor 52. Via the monitor 52, e.g. using a mouse (not shown), the desired cutting line is selected by the user and the cutting process is observed. In the case of an image analysis system (not shown) installed in the computer 50, the cutting process can be regulated and monitored.
- the computer 50 automatically sets the parameters required for an optimal cut, for example intensity of the laser, width of the cutting line, travel speed of the xy table, illumination of the microscope.
- the contamination protection plate 42 is provided directly under the holder 14.
- the slide 6 placed on the holder 14 can be observed through an objective 34 of the microscope.
- the lens 34 is e.g. attached to a revolver (not shown) so that a user can choose between several magnifications for specimen viewing.
- optical elements are provided which couple the laser beam 38 into the microscope in such a way that the laser beam 38 runs essentially along the optical axis 24 of the objective 34. With one and the same lens 34, an image of the preparation 8 is generated for the user and at the same time the laser beam is imaged on the preparation 8 for cutting.
Landscapes
- Physics & Mathematics (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Optics & Photonics (AREA)
- Sampling And Sample Adjustment (AREA)
- Microscoopes, Condenser (AREA)
- Laser Beam Processing (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE10018251A DE10018251C2 (de) | 2000-04-13 | 2000-04-13 | Laserschneid-Vorrichtung mit Mikroskop |
DE10018251 | 2000-04-13 | ||
PCT/DE2001/001082 WO2001079911A1 (de) | 2000-04-13 | 2001-03-21 | Vorrichtung zum laserschneiden von präparaten und mikroskop |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1272887A1 true EP1272887A1 (de) | 2003-01-08 |
Family
ID=7638551
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP01925307A Withdrawn EP1272887A1 (de) | 2000-04-13 | 2001-03-21 | Vorrichtung zum laserschneiden von präparaten und mikroskop |
Country Status (7)
Country | Link |
---|---|
US (1) | US6907798B2 (ja) |
EP (1) | EP1272887A1 (ja) |
JP (1) | JP4146642B2 (ja) |
AU (1) | AU5210701A (ja) |
DE (1) | DE10018251C2 (ja) |
TW (1) | TW505788B (ja) |
WO (1) | WO2001079911A1 (ja) |
Families Citing this family (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE10015157A1 (de) † | 2000-03-27 | 2001-10-18 | P A L M Gmbh | Verfahren zur Bearbeitung einer biologischen Masse und Steuersystem für eine Vorrichtung zur Bearbeitung einer biologischen Masse |
DE10018255C2 (de) * | 2000-04-13 | 2003-08-28 | Leica Microsystems | Laserschneid-Verfahren und Laserschneid-Vorrichtung zum Laserschneiden mit mikroskopischer Proben |
DE10057292C2 (de) * | 2000-11-17 | 2003-02-13 | Leica Microsystems | Vorrichtung zum Aufnehmen von Mirodissektaten |
DE10102134A1 (de) * | 2001-01-18 | 2002-08-01 | Christoph Viebahn | Glasschneidegerät für Objektträger |
AU2003223079A1 (en) * | 2002-05-24 | 2003-12-12 | Koninklijke Philips Electronics N.V. | Method suitable for transferring a component supported by a carrier to a desired position on a substrate, and a device designed for this |
EP1473107A1 (en) * | 2003-05-02 | 2004-11-03 | Kba-Giori S.A. | Machine and process for cutting openings in a substrate |
DE102004051508B4 (de) * | 2003-10-21 | 2006-09-21 | Leica Microsystems Cms Gmbh | Verfahren zur automatischen Erzeugung von Laser-Schnittlinien in der Laser-Mikrodissektion |
US9217694B2 (en) | 2003-10-21 | 2015-12-22 | Leica Microsystems Cms Gmbh | Method for automatically generating laser cutting lines in laser microdissection processes |
DE102004021904B4 (de) * | 2004-05-04 | 2011-08-18 | Carl Zeiss Microlmaging GmbH, 07745 | Verfahren und Vorrichtung zur Erzeugung einer Analyseanordnung mit diskreten, separaten Messbereichen zur biologischen, biochemischen oder chemischen Analyse |
DE102005039833A1 (de) * | 2005-08-22 | 2007-03-01 | Rowiak Gmbh | Vorrichtung und Verfahren zur Materialtrennung mit Laserpulsen |
DE102007016301A1 (de) * | 2007-04-04 | 2008-10-09 | P.A.L.M. Microlaser Technologies Gmbh | Laser-Mikrodissektionsverfahren und Laser-Mikrodissektionsvorrichtung |
DE102009016512B4 (de) | 2009-04-08 | 2011-05-12 | Forschungszentrum Jülich GmbH | Verfahren und Vorrichtung zur Durchführung einer quantitativen ortsaufgelösten Lokal- und Verteilungsanalyse chemischer Elemente und in-situ Charakterisierung der ablatierten Oberflächenregionen |
KR101193857B1 (ko) * | 2010-06-29 | 2012-10-24 | 현대제철 주식회사 | 슈라우드 노즐 교체 장치 |
US8497138B2 (en) | 2010-09-30 | 2013-07-30 | Genetix Limited | Method for cell selection |
DE102010061167B3 (de) * | 2010-12-10 | 2012-05-31 | Leica Microsystems Cms Gmbh | Mikroskoptisch |
DE102011001474A1 (de) * | 2011-03-22 | 2012-09-27 | Carl Zeiss Microimaging Gmbh | Laser-Mikrodissektionsverfahren und Laser-Mikrodissektionsvorrichtung |
CN102628758B (zh) * | 2012-03-01 | 2014-04-16 | 麦克奥迪实业集团有限公司 | 一种激光显微切割后收集细胞的收集装置、方法及系统 |
US20140168405A1 (en) * | 2012-12-17 | 2014-06-19 | National Taiwan University | Sampling assembly, microscope module, and microscope apparatus |
DE102013209880A1 (de) | 2013-05-28 | 2014-12-04 | Leica Microsystems Cms Gmbh | Verfahren zur Lasermikrodissektion und Lasermikrodissektionssystem |
DE102013209881A1 (de) | 2013-05-28 | 2014-12-04 | Leica Microsystems Cms Gmbh | Lasermikrodissektionssystem mit Visualisierungseinrichtung, Visualisierungseinrichtung für Lasermikrodissektionssystem und Verfahren zur Lasermikrodissektion |
DE102013212811A1 (de) * | 2013-07-01 | 2015-01-08 | Leica Microsystems Cms Gmbh | Lasermikrodissektionssystem und Untersuchungsverfahren für nukleinsäurehaltige Proben |
US20150040688A1 (en) * | 2013-08-09 | 2015-02-12 | University Of Washington Through Its Center For Commercialization | Systems for touchless processing of dried blood spots and methods of using same |
DE102014202860B4 (de) | 2014-02-17 | 2016-12-29 | Leica Microsystems Cms Gmbh | Bereitstellen von Probeninformationen mit einem Lasermikrodissektionssystem |
DE102016111781B3 (de) * | 2016-06-28 | 2017-06-29 | Leica Microsystems Cms Gmbh | Kontaminationsschutzeinrichtung für ein Lasermikrodissektionssystem und Lasermikrodissektionssystem |
CN110268108B (zh) | 2016-12-12 | 2022-09-06 | 埃克切拉生物科学公司 | 用于使用微毛细管阵列进行筛选的方法和系统 |
US11085039B2 (en) | 2016-12-12 | 2021-08-10 | xCella Biosciences, Inc. | Methods and systems for screening using microcapillary arrays |
JP7208902B2 (ja) | 2016-12-30 | 2023-01-19 | エクセラ・バイオサイエンシーズ・インコーポレイテッド | マルチステージサンプル回収システム |
Family Cites Families (18)
Publication number | Priority date | Publication date | Assignee | Title |
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DE245501C (ja) | ||||
DD245501A1 (de) * | 1985-12-31 | 1987-05-06 | Zeiss Jena Veb Carl | Objekttisch mit objekthaltersystem fuer mikroskope |
DE9110075U1 (de) * | 1991-08-14 | 1991-12-12 | Luigs & Neumann Feinmechanik und Elektronik GmbH, 4030 Ratingen | Mikroskoptisch-Einheit |
US5337178A (en) * | 1992-12-23 | 1994-08-09 | International Business Machines Corporation | Titlable optical microscope stage |
DE4300698A1 (de) | 1993-01-13 | 1994-07-14 | Raimund Schuetze | Vorrichtung und Verfahren zur Handhabung, Bearbeitung und Beobachtung kleiner Teilchen, insbesondere biologischer Teilchen |
US5587833A (en) * | 1993-07-09 | 1996-12-24 | Compucyte Corporation | Computerized microscope specimen encoder |
US5843644A (en) | 1994-03-01 | 1998-12-01 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Isolation of cellular material under microscopic visualization using an adhesive/extraction reagent tipped probe |
US5843657A (en) | 1994-03-01 | 1998-12-01 | The United States Of America As Represented By The Department Of Health And Human Services | Isolation of cellular material under microscopic visualization |
US5523941A (en) * | 1994-10-04 | 1996-06-04 | Burton; Gary L. | X-Y-theta positioning mechanism |
JPH08194162A (ja) * | 1995-01-17 | 1996-07-30 | Nikon Corp | ステージの駆動装置 |
DE19603996C2 (de) | 1996-02-05 | 2002-08-29 | P A L M Gmbh Mikrolaser Techno | Sortierverfahren für planar ausgebrachte biologische Objekte mit Laserstrahlen |
WO1997029354A1 (de) | 1996-02-05 | 1997-08-14 | Bayer Aktiengesellschaft | Verfahren und vorrichtung zum sortieren und zur gewinnung von planar ausgebrachten biologischen objekten wie biologische zellen bzw. zellorganellen, histologischen schnitten, chromosomenteilchen etc. mit laserstrahlen |
DE19616216A1 (de) * | 1996-04-23 | 1997-10-30 | P A L M Gmbh | Verfahren und Vorrichtung zur Gewinnung von laserdissektierten Partikeln wie biologische Zellen bzw. Zellorganellen, Chromosomenteilchen etc. |
US6469779B2 (en) * | 1997-02-07 | 2002-10-22 | Arcturus Engineering, Inc. | Laser capture microdissection method and apparatus |
US5859699A (en) | 1997-02-07 | 1999-01-12 | Arcturus Engineering, Inc. | Laser capture microdissection analysis vessel |
US6495195B2 (en) | 1997-02-14 | 2002-12-17 | Arcturus Engineering, Inc. | Broadband absorbing film for laser capture microdissection |
US6100051A (en) | 1997-06-27 | 2000-08-08 | The United States Of America As Represented By The Department Of Health And Human Services | Method utilizing convex geometry for laser capture microdissection |
ATE259057T1 (de) | 1997-10-01 | 2004-02-15 | Arcturus Eng Inc | Verbrauchseinheit für laseranheftung- mikrodissektion |
-
2000
- 2000-04-13 DE DE10018251A patent/DE10018251C2/de not_active Expired - Lifetime
-
2001
- 2001-03-21 JP JP2001576518A patent/JP4146642B2/ja not_active Expired - Lifetime
- 2001-03-21 AU AU52107/01A patent/AU5210701A/en not_active Abandoned
- 2001-03-21 EP EP01925307A patent/EP1272887A1/de not_active Withdrawn
- 2001-03-21 WO PCT/DE2001/001082 patent/WO2001079911A1/de not_active Application Discontinuation
- 2001-03-21 US US10/257,153 patent/US6907798B2/en not_active Expired - Lifetime
- 2001-05-04 TW TW090108913A patent/TW505788B/zh not_active IP Right Cessation
Non-Patent Citations (1)
Title |
---|
See references of WO0179911A1 * |
Also Published As
Publication number | Publication date |
---|---|
US6907798B2 (en) | 2005-06-21 |
US20030075530A1 (en) | 2003-04-24 |
DE10018251A1 (de) | 2001-10-25 |
WO2001079911A1 (de) | 2001-10-25 |
JP2004510955A (ja) | 2004-04-08 |
TW505788B (en) | 2002-10-11 |
AU5210701A (en) | 2001-10-30 |
JP4146642B2 (ja) | 2008-09-10 |
DE10018251C2 (de) | 2003-08-14 |
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