EP1537401A1 - Dispositif support destine a une preparation biologique pouvant etre decoupee par microdissection laser - Google Patents

Dispositif support destine a une preparation biologique pouvant etre decoupee par microdissection laser

Info

Publication number
EP1537401A1
EP1537401A1 EP03792171A EP03792171A EP1537401A1 EP 1537401 A1 EP1537401 A1 EP 1537401A1 EP 03792171 A EP03792171 A EP 03792171A EP 03792171 A EP03792171 A EP 03792171A EP 1537401 A1 EP1537401 A1 EP 1537401A1
Authority
EP
European Patent Office
Prior art keywords
laser
carrier device
petri dish
preparation
laser light
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Withdrawn
Application number
EP03792171A
Other languages
German (de)
English (en)
Inventor
Werner Wittke
Christian May
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.)
Leica Microsystems CMS GmbH
Original Assignee
Leica Microsystems Wetzlar GmbH
Leica Microsystems CMS GmbH
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 Leica Microsystems Wetzlar GmbH, Leica Microsystems CMS GmbH filed Critical Leica Microsystems Wetzlar GmbH
Publication of EP1537401A1 publication Critical patent/EP1537401A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/02—Form or structure of the vessel
    • C12M23/10—Petri dish
    • 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
    • G02B21/34—Microscope slides, e.g. mounting specimens on microscope slides
    • 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
    • G01N1/2813—Producing thin layers of samples on a substrate, e.g. smearing, spinning-on
    • G01N2001/2833—Collecting samples on a sticky, tacky, adhesive surface
    • G01N2001/284—Collecting samples on a sticky, tacky, adhesive surface using local activation of adhesive, i.e. Laser Capture Microdissection
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T428/00—Stock material or miscellaneous articles
    • Y10T428/31504—Composite [nonstructural laminate]
    • Y10T428/31786—Of polyester [e.g., alkyd, etc.]

Definitions

  • Carrier device for a biological preparation that can be cut by laser microdissection
  • the invention relates to a carrier device for a biological preparation which can be cut by laser microdissection and which is arranged on a freely stretched laser-light-absorbing film which is applied to a frame-shaped holder.
  • microdissection refers to a process with which a small piece is cut out of a generally flat preparation (for example cells or a tissue section) with a fine, focused laser beam. The cut piece is then available for further biological or medical (e.g. histological) examinations.
  • the type of preparation depends, among other things, on the laser microdissection method used to process the preparation.
  • a carrier device for a preparation in particular for a biological preparation, is known from DE 201 00 866.1, the preparation being provided for cutting out a preparation area by means of a focused laser beam.
  • the carrier device has a laser light-absorbing and thus laser-cutable film for receiving the preparation, the
  • Foil is applied to a frame-shaped holder, so that it is spanned, that is, it is not supported or carried by further carrier means below the foil.
  • This carrier device for a preparation is specially designed to be used in a method for laser microdissection, in which the cutting, focused laser beam is directed onto the Preparation is directed and the cut-out preparation area falls after the cutting process.
  • a focused laser beam from a pulsed UV laser is directed from above onto a, preferably biological, preparation and a preparation region of interest is circumnavigated by the focused laser beam along a closed cutting line, so that the preparation region of interest is completely out of it
  • the environment is separated out and falls down into a collecting device.
  • DE 100 39 979 A1 describes a carrier device and a laser microdissection method for separating a preparation area of interest from a biological live preparation, in which the preparation area of interest is cut out with a laser beam generating a cutting line.
  • the live preparation is applied to a laser-cut film that is supported by a carrier.
  • the preparation area cut out together with a film part remains on the carrier means and is catapulted upwards to a collecting device only by a further, additionally required laser pulse. Since the nutrient liquid over the preparation hinders catapulting, the nutrient liquid usually has to be poured off before catapulting, which significantly shortens the survival time of the live preparation.
  • a focused laser beam is directed from above onto a, preferably biological, preparation.
  • a specimen area of interest is bypassed with the focused laser beam along an open cutting line that largely closes the specimen area of interest, with between
  • a stable web remains, over which the preparation area of interest is connected to the surrounding sample.
  • the web is cut through with a single focused laser pulse directed at the web, the cutting width having previously been adjusted, ie enlarged, to the width of the web.
  • the preparation area of interest is completely separated from its surroundings and falls down.
  • the method has the advantage over the previously mentioned method that it prevents the almost cut preparation area from folding away or twisting towards the end of the cutting process.
  • This method has the disadvantage that the cells can only be kept alive for a short time after the carrier device has been removed from the Petri dish.
  • the film of the carrier devices can be damaged during handling.
  • contamination can occur on the device for laser microdissection, since the carrier device also comes into contact with culture medium in the area of its frame or its underside, so that colonization with cells can also occur there.
  • pathogens therefore, there is not only a handling problem, but also a hygienic problem. It is therefore an object of the present invention to provide a carrier device which allows laser microdissection on living cell cultures in a convenient and hygienic manner, in particular with a laser beam directed onto the specimen from above.
  • a carrier device for a biological preparation which can be cut by laser microdissection and which is arranged on a spanned laser light-absorbing film which is applied to a frame-shaped holder
  • the carrier device according to the invention being characterized in that the frame-shaped holder is essentially as Wall of a Petri dish is designed with a completely or partially missing bottom and that instead of the missing bottom, only the laser light-absorbing film is arranged.
  • the carrier device according to the invention has the advantage that the carrier device itself is used for pre-culture of the cells, which simplifies cell pre-cultivation. After culturing, the cells are also under optimized, reliable growth conditions during laser microdissection. The handling problem is eliminated since, as before, it is no longer necessary to remove the cell cultures from the Petri dish. Contamination of the device used for laser microdissection is also excluded.
  • the entire bottom of the Petri dish can be formed by the laser light-absorbing film.
  • the laser light-absorbing film it is also conceivable to form only a part of the bottom of the petri dish by the laser light-absorbing film.
  • the wall of the petri dish and an edge area of the base can be made of plastic and only a remaining opening of the bottom of the petri dish is closed by the film. It is crucial that the film is laser-absorbing, i.e. laser-cut, and that the film is stable enough not to sag in the spanned bottom opening and to carry the culture medium including cells. The layer thickness of the film must therefore be chosen sufficiently thick.
  • the laser light-absorbing film of the carrier device has having a polyethylene naphthalate film (PEN), preferably • a thickness of 1, 35 microns or 2.5 microns. Depending on the application, other film thicknesses can also be used.
  • PEN polyethylene naphthalate film
  • connection between the wall of the Petri dish and the laser light absorbing film can be realized in different ways.
  • the laser light-absorbing film can be welded to the lower edge of the wall of the petri dish or the edge area of the opening in the bottom of the petri dish.
  • the wall of the petri dish is glued to the laser light absorbing film.
  • the gluing can be carried out using an adhesive tape.
  • the adhesive tape is preferably designed in the form of a template such that the
  • Adhesive tape is glued on one side to the wall of the petri dish and on the other side to the laser light absorbing film.
  • the film can already be prepared on ring-shaped holding elements, that is to say applied by means of welding or adhesive technology.
  • the diameter of the annular holding elements is matched to the cylindrical wall of the petri dish.
  • the annular holding elements have locking grooves which allow the wall of the petri dish to snap into place, so that a liquid-tight, releasable connection between the wall of the
  • This embodiment has the advantage that the ring-shaped holding element with the laser-cut film base can be separated again from the wall of the petri dish, so that the cell culture can either be further processed or, for example, can be archived or frozen to save space.
  • the laser light-absorbing film is designed to be hydrophilic, since this facilitates the application of a cell culture medium to the laser-cut film.
  • a nutrient liquid is usually used as the nutrient medium.
  • Culture media for cell culture are commercially available, for example DMEM (Dulbeco's Modified Eagle's Medium) or RPMI (Rosewell Park Memorial Institute Medium) or MEM.
  • Nutrient fluid seeps through the microscopic holes created in the laser-cut film by laser microdissection. It therefore proves to be particularly advantageous if the nutrient medium is designed as a nutrient gel which is sufficiently firm or at least very viscous so that it "remains" around the holes created by microdissection in the laser-cutable film.
  • the desired preparation area can be separated out by moving the focused preparation area with the focused laser beam along a closed cutting line. After the preparation area of interest has been completely separated from its surroundings by means of the laser beam, it falls down and can be collected in a collecting device.
  • a specimen area of interest is bypassed with the focused laser beam along an open cutting line that largely closes the specimen area of interest.
  • a stable bridge remains between the beginning and end of the cutting line, via which the preparation area of interest is connected to the surrounding sample.
  • the web is focussed with a single, focused laser pulse directed at the web Cutting width adapted to the web, cut through. As a result, the preparation area of interest is completely separated from its surroundings and falls down.
  • the carrier device allows the use of a method for laser microdissection on living biological cell cultures, in which a focused laser beam is directed from above onto a living biological preparation.
  • the cells are treated particularly gently because they fall into a collecting vessel by gravity. This eliminates the need for mechanical or laser-induced transport of the cells, which carries the risk of cell damage.
  • Areas of application are the selection of preferably living cells or organisms from pure cultures or mixed cultures, in order to pass them on for further analysis or cultivation.
  • cancer cells can be separated from a cluster of healthy cells, from colored cells from cultures, from microorganisms from mixed cultures (or cultures) or from parasites from cultures.
  • a device for laser microdissection with a carrier device with a full-surface foil bottom 1 shows a first embodiment of a carrier device 1 with a full-surface foil base.
  • 1a shows the carrier device 1 in a vertical section.
  • 1b shows the carrier device 1 from below.
  • the carrier device 1 has a frame-shaped holder which is designed as a wall 2 of a petri dish, which typically consists of plastic.
  • the petri dish has no bottom.
  • the missing bottom of the Petri dish is replaced by a laser light-absorbing and thus laser-cut film 3, which is glued to the lower edge 4 of the wall 2.
  • the adhesive is only applied in a thin layer and is therefore not shown. It is crucial that the adhesive connection is resistant to a nutrient solution to be applied later or a viscous nutrient gel for the cell culture to be grown. In addition, it must be ensured that the adhesive is not cytotoxic so that the biological preparation is not damaged.
  • the absorption of the laser-cutable film 3 is adapted to the wavelength of the laser provided for cutting, preferably using a pulsed UV laser for laser microdissection. It has therefore proven useful for the laser light-absorbing film 3 of the carrier device 1 to use a polyethylene naphthalate film (PEN) which preferably has a thickness of 1.35 ⁇ m or 2.5 ⁇ m. Depending on the application, other film thicknesses can also be used.
  • PEN polyethylene naphthalate film
  • the film must be applied exactly flat and without undulation. Only then is it possible, after the focus of the laser beam has been adjusted once, to be able to cut at different locations on the film by simply moving the laser beam and the carrier device relative to one another, so that a closed cutting line can arise.
  • a biological preparation 5 is applied to the laser-cut film 3.
  • it is a live biological preparation. This was obtained by using the laser-cut film 3
  • Carrier device 1 was wetted or coated with culture medium. The desired cells were then sown. It is decisive here that the thickness of the laser-cutable film 3 is sufficient to carry the preparation and the culture medium without sagging. Only then, as described above, is it possible later to precisely cut the flat film 3 in a single focus setting of the laser beam.
  • the preparation 5 resulted from the growth of the cell culture. Now the carrier device 1 together with the preparation 5, ie the cell culture, can be inserted into a device for laser microdissection.
  • Fig. 2 shows a second embodiment of a carrier device 1 with a non-full-surface foil bottom.
  • 2a shows the carrier device 1 in a vertical section.
  • the carrier device 1 has a frame-shaped holder which is designed as a wall 2 of a petri dish and also forms an outer annular part 6 of the bottom of the petri dish.
  • FIG. 2b shows the carrier device 1 from below.
  • the petri dish has no closed bottom. Instead, there is only an outer annular part 6 of the bottom of the Petri dish, which encloses a free opening 7.
  • the opening 7 is spanned and thus closed by a laser light-absorbing and thus laser-cut film 3, which is glued to the underside of the annular part 6 of the bottom of the petri dish. In this way, the laser-cut film 3 replaces the missing bottom of the petri dish.
  • the adhesive was realized using an appropriately shaped adhesive film 8.
  • FIG. 2c shows a top view of an embodiment of this suitably shaped adhesive film 8. It is pre-shaped in the form of a template in such a way that it completely surrounds the free opening 7. A small tab 9 makes handling easier.
  • the adhesive film 8 can preferably be a double-sided adhesive tape, on which on a solid, non-detachable carrier material adhesive applied on both sides, each of which is covered on the outside with a cover film. After peeling off the first cover film, the adhesive tape with the exposed adhesive can be placed at the desired location on the underside of the annular part 6 of the bottom of the petri dish. The second cover film is then also removed, so that the adhesive tape with its carrier material remains on the annular part 6 of the base. The laser-cutable film 3 can then be applied to the exposed adhesive of the adhesive tape and glued to it.
  • a firm adhesive film can be used as the adhesive film 8, which is applied between two stable cover films.
  • the adhesive film can be placed at the desired location on the underside of the annular part 6 of the bottom of the petri dish.
  • the second cover film is then also pulled off, so that only the adhesive film remains on the annular part 6 of the base.
  • the laser-cutable film 3 can be applied to the adhesive film and glued to it.
  • the bond is resistant to a nutrient solution to be applied later or a viscous nutrient gel for the cell culture to be grown.
  • the adhesive connection must withstand the weight of film 3, nutrient medium and cell culture. In addition, it must be ensured that the adhesive film is not cytotoxic so that the biological preparation is not damaged.
  • 3 shows a further embodiment of a carrier device 1 with a reversibly attachable full-surface film base.
  • 3a shows the carrier device 1 in a vertical section.
  • the carrier device has a frame-shaped holder which is designed as a wall 2 of a petri dish.
  • the petri dish has no bottom.
  • the missing bottom of the Petri dish is replaced by a laser light-absorbing and thus laser-cut film 3.
  • the laser-cutable film 3 is not glued directly to the lower edge of the wall 2.
  • the carrier device additionally has an annular holding element 10, on the underside of which the laser-cut film 3 is glued.
  • the annular holding element 10 On its upper side, the annular holding element 10 has a circumferential locking groove 11, into which the lower edge of the wall 2 of the petri dish is engaged.
  • the diameter of the annular holding element 10 and the locking groove 11 are adapted to the cylindrical wall of the Petri dish.
  • FIG. 3b shows the carrier device 1 from below. Visible is the annular holding element 10, on the underside of which the laser-cut film 3 is glued.
  • the gluing can be carried out according to one of the methods that have been described for FIGS. 1 and 2.
  • 3c shows the ring-shaped holding element 10 in a top view with the locking groove 11 running around on the top.
  • the locking connection is liquid-tight, so that the laser-cutable film 3 can be covered with liquid nutrient medium without liquid passing through the locking connection.
  • the snap-in connection forms a releasable connection between the wall 2 of the petri dish and the annular holding element 10 with the laser-cut films 3.
  • FIG. 4 shows a device for laser microdissection with a carrier device 1 according to the invention.
  • the device for laser microdissection comprises a microscope 12 with a microscope stand 18 and a motor-driven xy table 13.
  • the xy table 13 is used to hold the carrier device 1.
  • the carrier device 1 has a frame-shaped holder which is designed as a wall 2 of a petri dish, which typically consists of plastic.
  • the petri dish has no bottom.
  • the missing bottom of the Petri dish is replaced by a laser light-absorbing and thus laser-cut film 3, which is glued to the lower edge 4 of the wall 2.
  • the adhesive is only applied in a thin layer and is therefore not shown.
  • a biological live preparation 5 has been applied or has already been grown on the laser light-absorbing and thus laser-cut film 3.
  • the xy table 13 has a frame-shaped table opening 15.
  • the microscope 12 shown is a transmitted light microscope.
  • an illumination system 15 and a condenser 21, which illuminates the sample 4 is arranged under the xy table 13 and thus also below the specimen 5.
  • At least one collecting container 29 is arranged below the preparation 5 for collecting the cut-out preparation region of interest.
  • the light penetrating the specimen 5 arrives at the objective 19 of the microscope 12.
  • the light is supplied via at least one eyepiece 22 via lenses and mirrors, not shown, through which an operator can view the specimen 5 arranged on the xy table 13.
  • a laser 16 which in this example is a UV laser, emits a laser beam 17, which is coupled into an incident light illumination beam path with an optical axis 20.
  • a laser scan device 30 is arranged in the illumination beam path.
  • the laser beam 17 passes through the laser scanning device 30 and arrives via an optical system 23 at a lens 19 which focuses the laser beam 17 on the specimen 5.
  • the optical system 23 is preferably designed as a dichromatic splitter, through which an imaging beam path proceeding from the specimen 5 through the objective 19 reaches at least one eyepiece 22.
  • the optical system 23 can consist of several optical components. This is the case, for example, when the laser beam 17 has to be deflected several times.
  • an aperture 24 is provided in the laser beam 17, with which the diameter of the laser beam 17 can be adjusted.
  • the aperture 24 can e.g. be designed as a fixed aperture.
  • a plurality of fixed diaphragms can be arranged on a turret disk or a linear slide in order to introduce one of these fixed diaphragms into the beam path as the respectively required diaphragm 24.
  • the introduction into the laser beam 17 is carried out manually by the user or by motor.
  • the setting of the laser scan device 30 and thus the adjustment of the laser beam 17 to the specimen 5 takes place with a motor 31 assigned to the laser scan device 30, a control unit 32 and a computer 26.
  • the motor 31 is included connected to the control unit 32, which the control signals for
  • Control of the motor 31 delivers.
  • the control unit 32 is connected to the computer 26, to which a monitor 28 is connected.
  • the image of the preparation 5 recorded by a camera 27 is displayed on the monitor 28.
  • the system of computer 26, camera 27 and monitor 28 serves to observe and monitor the cutting process.
  • the computer can emit trigger signals to trigger the laser pulses and to control the laser power, control the diaphragm motor 25 and control an auto-focus device (not shown) for the laser 16.
  • the computer 26 is connected to the laser 16 and supplies it with trigger signals for triggering laser pulses when a cutting process is carried out.
  • the sample area of the preparation 5 of interest to be cut out is bypassed on the monitor 28 by means of a mouse pointer.
  • a desired target cutting line is defined on the monitor 28 in the camera image.
  • the laser scan device 30 itself serves as a cutting line control unit, which moves the laser beam 17 focused on the biological specimen 5 over the fixed specimen 5 during the cutting process.
  • the xy table 13 is not moved horizontally, that is to say in the x direction and in the y direction, during the cutting process.
  • the laser beam 17 can be focused on the biological specimen 5 by manually adjusting the height of the xy table 13 while simultaneously checking the camera image visually by a user.
  • an embodiment of the device which comprises an autofocus device (not shown) for the laser beam 17 is more user-friendly.
  • the laser beam 17 can be guided to any positions on the specimen 5.
  • the biological preparation 5 can be kept alive throughout the preparation of the cut and also during the cut itself, since the growth conditions in the carrier device 1 are always maintained.
  • the focused laser beam 17 is moved over the specimen 5 by suitable control of the laser scanning device 30, thereby producing a closed cutting line around the specimen area of interest.
  • the preparation area of interest itself is never irradiated with the laser radiation, so that a damaging effect of the

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Biochemistry (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Clinical Laboratory Science (AREA)
  • General Physics & Mathematics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Sustainable Development (AREA)
  • Pathology (AREA)
  • Immunology (AREA)
  • Biomedical Technology (AREA)
  • Genetics & Genomics (AREA)
  • Optics & Photonics (AREA)
  • Hematology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

L'invention concerne un dispositif support (1) destiné à une préparation biologique (5) pouvant être découpée par microdissection laser, ladite préparation (5) étant disposée sur une feuille (3) en porte-à-faux, absorbant la lumière laser, logée sur un support en forme de cadre. Selon l'invention, le support en forme de cadre est essentiellement conçu en tant que paroi (2) d'une boîte de Pétri dont le fond est partiellement ou entièrement supprimé, la feuille (3) absorbant la lumière laser remplaçant ledit fond manquant. L'invention concerne également un dispositif de microdissection laser dans lequel un objectif (19) dirige un faisceau laser focalisé, tranchant (17), par le haut, sur une préparation biologique (5), une zone d'intérêt de la préparation étant contournée avec une ligne de coupe fermée et séparée de son environnement. Ledit dispositif de microdissection peut être employé pour la microdissection laser de cultures biologiques vivantes lorsqu'il est pourvu d'un dispositif support selon l'invention supportant une préparation biologique vivante (5).
EP03792171A 2002-07-30 2003-07-02 Dispositif support destine a une preparation biologique pouvant etre decoupee par microdissection laser Withdrawn EP1537401A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE10234755 2002-07-30
DE2002134755 DE10234755A1 (de) 2002-07-30 2002-07-30 Trägervorrichtung für ein biologisches, mittels Laser-Mikrodissektion schneidbares Präparat
PCT/EP2003/007054 WO2004019007A1 (fr) 2002-07-30 2003-07-02 Dispositif support destine a une preparation biologique pouvant etre decoupee par microdissection laser

Publications (1)

Publication Number Publication Date
EP1537401A1 true EP1537401A1 (fr) 2005-06-08

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
EP03792171A Withdrawn EP1537401A1 (fr) 2002-07-30 2003-07-02 Dispositif support destine a une preparation biologique pouvant etre decoupee par microdissection laser

Country Status (5)

Country Link
US (1) US20060121298A1 (fr)
EP (1) EP1537401A1 (fr)
JP (1) JP2005534941A (fr)
DE (1) DE10234755A1 (fr)
WO (1) WO2004019007A1 (fr)

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DE10234755A1 (de) 2004-02-26
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US20060121298A1 (en) 2006-06-08

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