US20020079318A1 - Specimen holder for a high-pressure freezing device - Google Patents

Specimen holder for a high-pressure freezing device Download PDF

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Publication number
US20020079318A1
US20020079318A1 US10/022,528 US2252801A US2002079318A1 US 20020079318 A1 US20020079318 A1 US 20020079318A1 US 2252801 A US2252801 A US 2252801A US 2002079318 A1 US2002079318 A1 US 2002079318A1
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Prior art keywords
specimen holder
shaped
specimen
diamond
shaped parts
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Abandoned
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US10/022,528
Inventor
Paul Wurzinger
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Leica Mikrosysteme GmbH
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Leica Mikrosysteme GmbH
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Assigned to LEICA MICROSYSTEMS GMBH reassignment LEICA MICROSYSTEMS GMBH ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: WURZINGER, PAUL
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    • 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
    • G01N1/42—Low-temperature sample treatment, e.g. cryofixation

Definitions

  • the invention concerns a specimen holder for a high-pressure freezing device, according to the preamble of claim 1.
  • a “high-pressure freezing device” is understood to be a freezing system for rapid freezing (vitrification) of water-containing specimens under high pressure. Devices of this kind are described in DE Patent 18 06 741, EP 0 853 238 A1, and EP 0 637 741 A1.
  • a high-pressure freezing device of this kind is being successfully marketed by the Applicant under the name “Leica EM HPF,” and is depicted in the document “LEICA EM HPF, High Pressure Freezer, 1.K.-LEICA EM HPF-E-6/94, Juni 1994.”
  • the “Leica EM HPF” high-pressure freezing device makes it possible to vitrify conventional specimens under a pressure of approximately 2000 bar at a cooling rate of 10 3 -10 5 K/s.
  • the critical cooling phase from room temperature to ⁇ 100° C. lasts approximately 10 ms at the surface of the specimen (cooling rate of 10 4 K/s).
  • the cooling rate in the interior of the specimen depends exclusively on the physical properties of the specimen. In order to vitrify thicker biological or water-containing specimens, the specimen is exposed to high pressure.
  • the cooling rate for vitrification of biological specimens is approximate 10 5 -10 6 K/s at standard pressure, but at 2000 bar the cooling rate is only 10 3 -10 4 K/s; in other words, under high pressure biological specimens can still be vitrified at cooling rates that are a hundred times lower.
  • Metal holders that comprise at least two shaped parts detachably joinable to one another are used for freezing the specimens, the shaped parts joined to one another forming a chamber for reception of the specimens.
  • Specimen holders of this kind are depicted in the aforementioned document “LEICA EM HPF, High Pressure Freezer, 1.K.-LEICA EM HPF-E-6/94, Juni 1994” and in the document “Balzers, Hochdruck-Gefriermaschine [High-pressure freezing machine] HPM 010, Balzers Union Aktiengesellschaft, no publication date.”
  • the specimen holder In order to freeze the specimen, the specimen holder is clamped in the high-pressure freezing device in such a way that on the one hand specimen loss is prevented, and on the other hand a sufficient portion of the surface remains freely accessible for a cryogen, e.g. liquid nitrogen, to be sprayed onto it.
  • a cryogen e.g. liquid nitrogen
  • the cooling rate at the center of a biological specimen is determined only to a limited extent by the cooling rate at the surface.
  • the essential feature in this context is that with rapid cooling rates at the surface, a kind of “saturation effect” occurs, whereas lower cooling rates at the surface inevitably lead to poor freezing results. It is therefore essential that the cooling rate achievable by a unit be transferred in as undiminished a fashion as possible by the specimen holding system onto the surface of the biological specimen.
  • the invention is characterized in that one of the shaped parts is made of diamond or at least comprises a diamond.
  • Diamond possesses not only extreme hardness but also the advantage of low specific heat and very good thermal conductivity.
  • At least one of the shaped parts preferably the shaped part fabricated of diamond, is of disk-shaped configuration.
  • a spacer ring fabricated from metal, which determines the depression necessary for specimen reception, is provided between the two shaped parts. Said spacer ring can also assume the sealing function in this context.
  • the depression for specimen reception can be accomplished by the mount of the diamond or by a corresponding configuration of the other shaped part.
  • a preferred exemplary embodiment is a specimen holder having one disk-shaped shaped part made of diamond, and one disk-shaped one made of metal.
  • the metal shaped part has a circumferential shaped-on bead at the rim.
  • the diamond or one of the shaped parts can be equipped with an orifice for the delivery of high pressure.
  • both shaped parts are of planar configuration on their inwardly directed surfaces.
  • a spacer running around the surfaces is arranged between those surfaces as a seal and in order to constitute the specimen receptacle.
  • Differently dimensioned receptacles for the specimens can easily be produced by way of differently dimensioned spacers.
  • FIG. 1 shows a sectioned depiction of the specimen holder having two shaped parts manufactured from diamond and a circumferential metal ring;
  • FIG. 2 shows a sectioned depiction of the specimen holder having one shaped part made of diamond and one shaped part made of metal;
  • FIG. 3 shows a sectioned depiction of the specimen holder having two shaped parts made of diamond and an additional shaped part with a high pressure delivery line;
  • FIG. 4 shows a sectioned depiction of the specimen holder having one shaped part made of diamond and another shaped part with a high pressure delivery line;
  • FIG. 5 shows a sectioned depiction of the specimen holder having one shaped part made of diamond and a shaped part forming a sample receptacle and a seal.
  • FIG. 1 shows a specimen holder 1 having a shaped part 2 and a shaped part 3 arranged opposite the latter. Both shaped parts 2 and 3 are produced from diamond and are configured as disk-shaped plates.
  • a spacer ring 9 which preferably is made of metal, is provided between the two shaped parts 2 and 3 .
  • the metal used here is preferably gold, copper, or aluminum.
  • the size of spacer ring 9 determines the size of sample receptacle 6 . It is thus easy to achieve sample receptacles 6 of different sizes by way of differently dimensioned spacer rings 9 .
  • Specimen receptacle 6 is isolated via spacer ring 9 when clamped into a clamping device (not depicted) of a high-pressure freezing device.
  • FIG. 2 shows a further exemplary embodiment of specimen holder 1 having one shaped part 2 fabricated of diamond and an oppositely arranged shaped part 3 produced from metal.
  • Shaped part 3 has, at the rim, shaped-on beads 8 extending around the rim that assume the function of spacer ring 9 of FIG. 1.
  • Specimen receptacles 6 of different sizes can be implemented by different dimensioning of beads 8 .
  • a fixed specimen receptacle 6 is constituted by shaped-on beads 8 , thereby facilitating insertion and removal of the specimen.
  • FIG. 3 shows a specimen holder 1 corresponding to the embodiment of FIG. 1, an orifice 10 for a downstream high-pressure device (not depicted here) being provided in this case in shaped part 3 .
  • a further shaped part 4 having a high-pressure conduit 5 is associated with shaped part 3 .
  • High-pressure conduit 5 corresponds to orifice 10 , which terminates in specimen receptacle 6 . The necessary pressure can thereby be generated directly in specimen receptacle 6 .
  • FIG. 4 shows an exemplary embodiment of specimen holder 1 corresponding to FIG. 1, shaped part 4 here being directly joined to shaped part 2 via seal 9 .
  • shaped part 3 has been completely replaced.
  • FIG. 5 shows an exemplary embodiment of specimen holder 1 according to FIG. 4, the encircling spacer ring 9 for sealing having been replaced here by metal shaped part 3 having a bottom 8 and the circumferentially shaped-on beads 8 .
  • This shaped part corresponds to shaped part 3 of FIG. 2, bottom 7 being in this case of the thinnest possible configuration. Since shaped part 3 is, in this case as well, arranged removably in specimen holder 1 , shaped part 3 can be removed separately. It is thus easier for the specimens to be introduced into and removed from specimen holder 1 or specimen receptacle 6 .
  • the shaped parts described above and fabricated from diamond, preferably from a polycrystalline CVD diamond, can of course also comprise one or more mounted diamonds.

Abstract

A specimen holder (1) for water-containing specimens for high-pressure freezing is described, the specimen holder (1) comprising at least two shaped parts (2, 3) detachably joinable to one another, and the joined shaped parts (2, 3) forming a receptacle (6) for the specimen. At least one of the shaped parts (2; 3) comprises a diamond.

Description

    CROSS REFERENCE TO RELATED APPLICATIONS
  • This invention claims priority of the German patent application 100 65 143.7 which is incorporated by reference herein. [0001]
    • FIELD OF THE INVENTION
  • The invention concerns a specimen holder for a high-pressure freezing device, according to the preamble of [0002] claim 1.
    • BACKGROUND OF THE INVENTION
  • For purposes of the invention, a “high-pressure freezing device” is understood to be a freezing system for rapid freezing (vitrification) of water-containing specimens under high pressure. Devices of this kind are described in DE Patent 18 06 741, EP 0 853 238 A1, and EP 0 637 741 A1. [0003]
  • A high-pressure freezing device of this kind is being successfully marketed by the Applicant under the name “Leica EM HPF,” and is depicted in the document “LEICA EM HPF, High Pressure Freezer, 1.K.-LEICA EM HPF-E-6/94, Juni 1994.”[0004]
  • The “Leica EM HPF” high-pressure freezing device makes it possible to vitrify conventional specimens under a pressure of approximately 2000 bar at a cooling rate of 10[0005] 3-105 K/s. With this known unit, the critical cooling phase from room temperature to −100° C. lasts approximately 10 ms at the surface of the specimen (cooling rate of 104 K/s).
  • The cooling rate in the interior of the specimen depends exclusively on the physical properties of the specimen. In order to vitrify thicker biological or water-containing specimens, the specimen is exposed to high pressure. [0006]
  • Because of the elevation in pressure, a slower cooling rate is sufficient for vitrification. The cooling rate for vitrification of biological specimens is approximate 10[0007] 5-106 K/s at standard pressure, but at 2000 bar the cooling rate is only 103-104 K/s; in other words, under high pressure biological specimens can still be vitrified at cooling rates that are a hundred times lower.
  • Metal holders that comprise at least two shaped parts detachably joinable to one another are used for freezing the specimens, the shaped parts joined to one another forming a chamber for reception of the specimens. Specimen holders of this kind are depicted in the aforementioned document “LEICA EM HPF, High Pressure Freezer, 1.K.-LEICA EM HPF-E-6/94, Juni 1994” and in the document “Balzers, Hochdruck-Gefriermaschine [High-pressure freezing machine] HPM 010, Balzers Union Aktiengesellschaft, no publication date.”[0008]
  • In order to freeze the specimen, the specimen holder is clamped in the high-pressure freezing device in such a way that on the one hand specimen loss is prevented, and on the other hand a sufficient portion of the surface remains freely accessible for a cryogen, e.g. liquid nitrogen, to be sprayed onto it. An arrangement of this kind is depicted and described in unpublished DE 100 15 773. [0009]
  • From the known art of refrigeration and from the physical processes, it is also known that the cooling rate at the center of a biological specimen is determined only to a limited extent by the cooling rate at the surface. The essential feature in this context is that with rapid cooling rates at the surface, a kind of “saturation effect” occurs, whereas lower cooling rates at the surface inevitably lead to poor freezing results. It is therefore essential that the cooling rate achievable by a unit be transferred in as undiminished a fashion as possible by the specimen holding system onto the surface of the biological specimen. [0010]
    • SUMMARY OF THE INVENTION
  • It is therefore the object of the present invention to create a specimen holder for a high-pressure freezing device that transfers the achievable cooling rate in as undiminished a fashion as possible onto the surface of the specimen. [0011]
  • According to the present invention, this object is achieved by the features recited in the characterizing portion of [0012] claim 1. Advantageous developments of the invention are the subject matter of the dependent claims.
  • The invention is characterized in that one of the shaped parts is made of diamond or at least comprises a diamond. Diamond possesses not only extreme hardness but also the advantage of low specific heat and very good thermal conductivity. [0013]
  • In a further embodiment of the invention, at least one of the shaped parts, preferably the shaped part fabricated of diamond, is of disk-shaped configuration. A spacer ring fabricated from metal, which determines the depression necessary for specimen reception, is provided between the two shaped parts. Said spacer ring can also assume the sealing function in this context. [0014]
  • Provision can, of course, also be made for only one of the shaped parts to be fabricated of diamond or for the shaped part to comprise a mounted diamond. In this case the depression for specimen reception can be accomplished by the mount of the diamond or by a corresponding configuration of the other shaped part. A preferred exemplary embodiment is a specimen holder having one disk-shaped shaped part made of diamond, and one disk-shaped one made of metal. The metal shaped part has a circumferential shaped-on bead at the rim. [0015]
  • In a further embodiment of the specimen holder, the diamond or one of the shaped parts can be equipped with an orifice for the delivery of high pressure. [0016]
  • It has proven to be advantageous in the context of such specimen holders to use gold or aluminum or copper as the metal, and to utilize a commercially available polycrystalline CVD industrial diamond as the diamond. [0017]
  • In a further embodiment of the invention, both shaped parts are of planar configuration on their inwardly directed surfaces. A spacer running around the surfaces is arranged between those surfaces as a seal and in order to constitute the specimen receptacle. Differently dimensioned receptacles for the specimens can easily be produced by way of differently dimensioned spacers.[0018]
    • BRIEF DESCRIPTION OF THE DRAWINGS
  • The invention is depicted and explained in more detail, in several exemplary embodiments, on the basis of the schematic drawings in which: [0019]
  • FIG. 1 shows a sectioned depiction of the specimen holder having two shaped parts manufactured from diamond and a circumferential metal ring; [0020]
  • FIG. 2 shows a sectioned depiction of the specimen holder having one shaped part made of diamond and one shaped part made of metal; [0021]
  • FIG. 3 shows a sectioned depiction of the specimen holder having two shaped parts made of diamond and an additional shaped part with a high pressure delivery line; [0022]
  • FIG. 4 shows a sectioned depiction of the specimen holder having one shaped part made of diamond and another shaped part with a high pressure delivery line; [0023]
  • FIG. 5 shows a sectioned depiction of the specimen holder having one shaped part made of diamond and a shaped part forming a sample receptacle and a seal. [0024]
    • DETAILED DESCRIPTION OF THE INVENTION
  • FIG. 1 shows a [0025] specimen holder 1 having a shaped part 2 and a shaped part 3 arranged opposite the latter. Both shaped parts 2 and 3 are produced from diamond and are configured as disk-shaped plates. A spacer ring 9, which preferably is made of metal, is provided between the two shaped parts 2 and 3. The metal used here is preferably gold, copper, or aluminum. The size of spacer ring 9 determines the size of sample receptacle 6. It is thus easy to achieve sample receptacles 6 of different sizes by way of differently dimensioned spacer rings 9.
  • [0026] Specimen receptacle 6 is isolated via spacer ring 9 when clamped into a clamping device (not depicted) of a high-pressure freezing device.
  • FIG. 2 shows a further exemplary embodiment of [0027] specimen holder 1 having one shaped part 2 fabricated of diamond and an oppositely arranged shaped part 3 produced from metal. Shaped part 3 has, at the rim, shaped-on beads 8 extending around the rim that assume the function of spacer ring 9 of FIG. 1. Specimen receptacles 6 of different sizes can be implemented by different dimensioning of beads 8. A fixed specimen receptacle 6 is constituted by shaped-on beads 8, thereby facilitating insertion and removal of the specimen.
  • FIG. 3 shows a [0028] specimen holder 1 corresponding to the embodiment of FIG. 1, an orifice 10 for a downstream high-pressure device (not depicted here) being provided in this case in shaped part 3. A further shaped part 4 having a high-pressure conduit 5 is associated with shaped part 3. High-pressure conduit 5 corresponds to orifice 10, which terminates in specimen receptacle 6. The necessary pressure can thereby be generated directly in specimen receptacle 6.
  • FIG. 4 shows an exemplary embodiment of [0029] specimen holder 1 corresponding to FIG. 1, shaped part 4 here being directly joined to shaped part 2 via seal 9. In this exemplary embodiment, shaped part 3 has been completely replaced.
  • FIG. 5 shows an exemplary embodiment of [0030] specimen holder 1 according to FIG. 4, the encircling spacer ring 9 for sealing having been replaced here by metal shaped part 3 having a bottom 8 and the circumferentially shaped-on beads 8. This shaped part corresponds to shaped part 3 of FIG. 2, bottom 7 being in this case of the thinnest possible configuration. Since shaped part 3 is, in this case as well, arranged removably in specimen holder 1, shaped part 3 can be removed separately. It is thus easier for the specimens to be introduced into and removed from specimen holder 1 or specimen receptacle 6.
  • The shaped parts described above and fabricated from diamond, preferably from a polycrystalline CVD diamond, can of course also comprise one or more mounted diamonds. [0031]
  • It is of course also within the context of the invention if the external surface of the shaped elements is of irregular configuration, so as thereby to constitute a greater area for spraying on liquid nitrogen. [0032]
  • Parts List [0033]
  • [0034] 1 Specimen holder
  • [0035] 2 Shaped part
  • [0036] 3 Shaped part
  • [0037] 4 Shaped part
  • [0038] 5 High-pressure conduit
  • [0039] 6 Specimen receptacle
  • [0040] 7 Bottom
  • [0041] 8 Bead
  • [0042] 9 Spacer ring
  • [0043] 10 Orifice

Claims (10)

What is claimed is:
1. A specimen holder (1) for water-containing specimens for high-pressure freezing, the specimen holder (1) comprising at least two shaped parts (2, 3; 2, 4) detachably joinable to one another, and the joined shaped parts (2, 3; 2, 4) forming a receptacle (6) for the specimen, wherein at least one of the shaped parts (2; 3) comprises a diamond.
2. The specimen holder (1) as defined in claim 1, wherein at least one of the shaped parts (2; 3) is of disk-shaped configuration.
3. The specimen holder (1) as defined in claim 1 or 2, wherein a spacer ring (9) fabricated from metal is provided between the shaped parts (2; 3).
4. The specimen holder (1) as defined in claim 3, wherein both shaped parts (2; 3) are configured as disk-shaped diamonds.
5. The specimen holder (1) as defined in claim 1 or 2, wherein the other shaped part (3) [is] fabricated from metal, [is] of disk-shaped configuration, and comprises a shaped-on bead (8) running around the rim.
6. The specimen holder (1) as defined in claim 1, wherein the diamond comprises an orifice (10) for the delivery of high pressure.
7. The specimen holder (1) as defined in claim 3 or 5, wherein gold or aluminum or copper is used the metal.
8. The specimen holder (1) as defined in claim 1, wherein both shaped parts (2; 3) are of planar configuration on their inwardly directed surfaces, and a spacer (9) running around the surfaces is arranged between those surfaces as a seal and in order to constitute the specimen receptacle (6).
9. The specimen holder (1) as defined in at least one of the foregoing claims, wherein the diamond is configured as polycrystalline CVD diamond.
10. The specimen holder (1) as defined in at least one of the foregoing claims, wherein at least one of the shaped parts (2, 3, 4) is configured with an irregularly shaped surface.
US10/022,528 2000-12-23 2001-12-20 Specimen holder for a high-pressure freezing device Abandoned US20020079318A1 (en)

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Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050035156A1 (en) * 2003-08-11 2005-02-17 Michael Hersch Fluid dispensing apparatus
US20060070392A1 (en) * 2004-10-05 2006-04-06 Washington University Apparatus for freezing a biological sample
US20060169719A1 (en) * 2003-08-11 2006-08-03 Bui Xuan S Manifold assembly
US20060171857A1 (en) * 2003-08-11 2006-08-03 Stead Ronald H Reagent container and slide reaction and retaining tray, and method of operation
US20060173575A1 (en) * 2003-08-11 2006-08-03 Gilles Lefebvre Automated reagent dispensing system and method of operation
US20060255520A1 (en) * 2005-05-12 2006-11-16 Fritz Bierleutgeb Specimen Holder For Specimens For High-Pressure Freezing And High-Pressure Freezing Device Having A Specimen Holder
US20100151570A1 (en) * 2008-06-18 2010-06-17 The Cleveland Clinic Foundation Systems and methods for vitrifying tissue
US8459509B2 (en) 2006-05-25 2013-06-11 Sakura Finetek U.S.A., Inc. Fluid dispensing apparatus
US8580568B2 (en) 2011-09-21 2013-11-12 Sakura Finetek U.S.A., Inc. Traceability for automated staining system
US8752732B2 (en) 2011-02-01 2014-06-17 Sakura Finetek U.S.A., Inc. Fluid dispensing system
US8932543B2 (en) 2011-09-21 2015-01-13 Sakura Finetek U.S.A., Inc. Automated staining system and reaction chamber

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102004041965B4 (en) * 2004-08-31 2009-08-13 Leica Mikrosysteme Gmbh Device and method for freeze substitution and embedding of biological samples
EP3287775B1 (en) 2016-08-26 2019-04-03 Leica Mikrosysteme GmbH Modular specimen holders for high pressure freezing and x-ray crystallography of a specimen

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US5044165A (en) * 1986-12-03 1991-09-03 Board Of Regents, The University Of Texas Cryo-slammer
US5255783A (en) * 1991-12-20 1993-10-26 Fluoroware, Inc. Evacuated wafer container
US5493865A (en) * 1993-08-03 1996-02-27 Wohlwend; Martin Method and apparatus for vitrification of water or moisture-containing test samples, particularly biological samples

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EP0853238B1 (en) * 1997-01-13 2002-09-18 Daniel Dr. Studer Sample holder for water-containing samples and method for use thereof

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US5044165A (en) * 1986-12-03 1991-09-03 Board Of Regents, The University Of Texas Cryo-slammer
US5255783A (en) * 1991-12-20 1993-10-26 Fluoroware, Inc. Evacuated wafer container
US5493865A (en) * 1993-08-03 1996-02-27 Wohlwend; Martin Method and apparatus for vitrification of water or moisture-containing test samples, particularly biological samples

Cited By (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7744817B2 (en) 2003-08-11 2010-06-29 Sakura Finetek U.S.A., Inc. Manifold assembly
US20060169719A1 (en) * 2003-08-11 2006-08-03 Bui Xuan S Manifold assembly
US20060171857A1 (en) * 2003-08-11 2006-08-03 Stead Ronald H Reagent container and slide reaction and retaining tray, and method of operation
US20060173575A1 (en) * 2003-08-11 2006-08-03 Gilles Lefebvre Automated reagent dispensing system and method of operation
US20050035156A1 (en) * 2003-08-11 2005-02-17 Michael Hersch Fluid dispensing apparatus
US9518899B2 (en) 2003-08-11 2016-12-13 Sakura Finetek U.S.A., Inc. Automated reagent dispensing system and method of operation
US7767152B2 (en) 2003-08-11 2010-08-03 Sakura Finetek U.S.A., Inc. Reagent container and slide reaction retaining tray, and method of operation
US20060070392A1 (en) * 2004-10-05 2006-04-06 Washington University Apparatus for freezing a biological sample
US7293426B2 (en) 2004-10-05 2007-11-13 Washington University Apparatus for freezing a biological sample
US20060255520A1 (en) * 2005-05-12 2006-11-16 Fritz Bierleutgeb Specimen Holder For Specimens For High-Pressure Freezing And High-Pressure Freezing Device Having A Specimen Holder
US7632469B2 (en) 2005-05-12 2009-12-15 Leica Mikrosysteme Gmbh Specimen holder for specimens for high-pressure freezing and high-pressure freezing device having a specimen holder
US8459509B2 (en) 2006-05-25 2013-06-11 Sakura Finetek U.S.A., Inc. Fluid dispensing apparatus
US9914124B2 (en) 2006-05-25 2018-03-13 Sakura Finetek U.S.A., Inc. Fluid dispensing apparatus
US20100151570A1 (en) * 2008-06-18 2010-06-17 The Cleveland Clinic Foundation Systems and methods for vitrifying tissue
US8030063B2 (en) * 2008-06-18 2011-10-04 The Cleveland Clinic Foundation Systems and methods for vitrifying tissue
US8752732B2 (en) 2011-02-01 2014-06-17 Sakura Finetek U.S.A., Inc. Fluid dispensing system
US9016526B2 (en) 2011-02-01 2015-04-28 Sakura Finetek U.S.A., Inc. Fluid dispensing system
US8580568B2 (en) 2011-09-21 2013-11-12 Sakura Finetek U.S.A., Inc. Traceability for automated staining system
US8932543B2 (en) 2011-09-21 2015-01-13 Sakura Finetek U.S.A., Inc. Automated staining system and reaction chamber
US9005980B2 (en) 2011-09-21 2015-04-14 Sakura Finetek U.S.A., Inc. Traceability for automated staining system
US10295444B2 (en) 2011-09-21 2019-05-21 Sakura Finetek U.S.A., Inc. Automated staining system and reaction chamber

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JP2002277365A (en) 2002-09-25
DE10065143A1 (en) 2002-06-27
JP4146638B2 (en) 2008-09-10
DE10065143B4 (en) 2007-12-27

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Owner name: LEICA MICROSYSTEMS GMBH, AUSTRIA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:WURZINGER, PAUL;REEL/FRAME:012400/0846

Effective date: 20011120

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION