• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    Apparatus (1) for freezing or cryogenic substitution, with a holder (3) which can be inserted into a cooling chamber (4) for arranging a sample carrier (5) for a biological sample and with a shaking device (8) for shaking the sample holder (5) wherein the shaking device (8) has a magnetic element (9) provided outside the cooling chamber (4) which cooperates with a magnet element (10) provided inside the cooling chamber (4) on the sample carrier (5) to move the sample carrier (5) to put in a shaking motion.
    公开号:AT515423A4
    申请号:T50272/2014
    申请日:2014-04-10
    公开日:2015-09-15
    发明作者:Siegfried Dr Reipert；Helmuth Goldammer
    申请人:Universität Wien；
    IPC主号:
    专利说明:

    The invention relates to a device for freezing or cryogenic substitution, with a replaceable in a cooling chamber holder for mounting a sample carrier for a biological sample and with a shaking device for shaking the sample carrier.
    Furthermore, the invention relates to a method for freezing or cryogenic substitution, wherein a sample carrier for a biological sample is placed in a cooling chamber, wherein the sample carrier is shaken with a shaker.
    Such devices for automatic freeze substitution of biological samples have long been known in the art to improve the results of electron microscopic examinations (see, for example, DE 10 2004 046 762 B4). In this technique, a Dewar vessel filled with liquid nitrogen is usually used. The Dewar neck has a chamber that is cooled to a certain temperature. The desired temperature setting is made via a control circuit and built-in heating elements. The substitution process starts at about -90 ° C in the prior art. The frozen sample is transferred to the chamber, for which purpose various containers may be provided, with which the samples are immersed in a substitution agent, usually acetone or methanol. At this low temperature, the slow process of substitution occurs, in which the frozen water of the sample is replaced by the solvent without recrystallization.
    However, a disadvantage of the known freeze substitution systems is the long time required for the freeze substitution.
    This problem has already been the subject of scientific research. In the article "Freeze Substitution in 3 Hours or Less", K.L. McDonald et al., Journal of Microscopy,
    Vol. 243, Pt3 2011, pp. 227-233, it is proposed to provide the platform for the sample receptacle with a vibrator device to vibrate the sample during freeze substitution. It has been found that with this simple measure, the time for the frozen substitution can be significantly reduced.
    The device of McDonald et al. however, it is not suitable for use with the automatic substitution devices described above. For example, the shaking device (in the form of a laboratory shaker) for the platform could not be integrated into the Dewar vessel used in the automatic substitution devices in place of the one disclosed by McDonald et al. used dry ice container is provided. In addition, the arrangement of McDonald et al. the disadvantage that the movement of the sample container is realized in the vertical direction. This involves risks in the use of toxic additives to the substitution agents, such as osmium tetroxide (for example, by contamination of the lid of the reaction vessels or leaking closure of the sample container).
    Accordingly, the object of the present invention is to eliminate or at least alleviate the disadvantages of the prior art. The invention therefore has the particular object of providing a device and a method as described above, which can be used in conjunction with known automatic substitution devices to suspend biological samples in the freezing substitution of a shaking, with which the period for the freezing substitution can be reduced.
    To achieve this object, a device having the features of claim 1 and a method having the features of claim 19 are provided.
    According to the invention, the shaking device has a magnetic element provided outside the cooling chamber, which cooperates with a magnetic element provided inside the cooling chamber on the sample carrier in order to set the sample carrier in a shaking motion.
    Accordingly, the excitation of the biological sample during the freeze substitution via a variable magnetic interaction between a magnetic element of the shaker au outside the cooling chamber and a magnetic element to the sample carrier within the cooling chamber. Due to the variable magnetic interaction of the movably mounted sample carrier is placed in a shaking or vibrating movement, with which the Gefriersubstitution, i. the exchange of frozen sample water with a solvent such as acetone, is significantly accelerated. The shaking device according to the invention has the particular advantage that the shaking movement can be excited without contact by means of the magnetic elements in the sample carrier outside the cooling chamber. As a result, the cooling chamber can be designed in a simple manner, as in the case of conventional freeze substitution devices, and in particular allows use with a dewar vessel. It is particularly advantageous that the shaking device according to the invention can be retrofitted to existing automatic Gefriers substitution devices without changing the cooling chamber.
    According to a first preferred embodiment, a drive for generating a relative movement between the magnetic element outside the cooling chamber and the magnetic element is provided on the sample carrier within the cooling chamber. Advantageously, the relative movement causes a variable magnetic force between the magnetic element outside the cooling chamber and the magnetic element on the sample carrier, wherein this relative movement is converted into a shaking movement of the sample carrier. For this purpose, it is expedient for the sample carrier to be movably mounted on a bearing device of the holder which is in particular pot-shaped or basin-shaped, so that the variable magnetic effect causes a shaking movement on the sample carrier due to the relative movement. This design is advantageously structurally simple and reliable.
    According to an alternative preferred embodiment, the magnetic element outside the cooling chamber is connected to a current source for generating a variable magnetic field. In this embodiment, therefore, the magnetic element of the shaking device, for example, a magnetic coil, be arranged stationary, wherein the magnetic field with the aid of the power source is variable. Due to the variable magnetic field, the sample carrier can be set in shaking motion.
    In order to cause a shaking movement of the sample carrier by a variable magnetic field between the magnetic elements, it is favorable if the magnetic element is provided outside the cooling chamber on a magnetic holder which is connected to the drive for generating the relative movement between the magnetic elements. Accordingly, the drive outside the cooling chamber is connected to the magnetic mount to which the magnetic element is mounted to move the magnetic mount and thereby generate a variable magnetic field. Advantageously, thus a non-contact power transmission to the sample carrier can be achieved within the cooling chamber, with which the shaking motion is generated to accelerate the Kryosubstituti-on. Thus, advantageously no current feedthroughs are required in the cooling chamber, which would otherwise be exposed to extreme temperature fluctuations and could adversely affect the temperature distribution in the cooling chamber. As drive various common in the art motors, such as DC motors can be used.
    Particularly preferred is an embodiment in which the magnetic holder of the shaker is connected to a rotary drive for rotatably supporting the magnet holder. Accordingly, the magnet holder is rotated by means of the rotary drive, whereby the magnetic element is guided on the magnet holder along a circular path. Thus, the magnetic element is guided past the magnetic holder, in particular periodically past the magnetic element of the sample carrier, wherein the sample carrier is set by the magnetic interaction between the magnetic elements in the desired Schüttei or Rüttelbewegung. Preferably, the magnetic holder is mounted on a vertical axis of rotation, so that the magnetic element is rotatable in a horizontal plane. The magnetic elements are preferably arranged one above the other in each case during a rotation of the magnet holder in an excitation position. When the magnetic element provided on the magnet holder passes through the corresponding magnet element on the sample carrier in the excitation position, the sample carrier is abruptly excited by the attractive or repulsive effect between the magnet elements. Thereafter, the movement of the sample carrier swells gradually before the next passage of the magnetic element on the magnet holder stimulates the shaking movement again. This embodiment therefore has the particular advantage that even with a periodic rotational movement of the magnetic holder, an irregular shaking movement of the sample carrier can be generated. In practice, it has been shown that the frozen substitution can be carried out much faster due to the irregular excitation of the sample carrier.
    Particularly preferred is the use of a variable speed rotary drive, which can be adapted to the needs of the substitution process and subsequent process steps, such as the heating and infiltration of the samples with resin.
    In order to periodically abut the shaking movement of the sample carrier, it is advantageous if the magnetic element is provided at a free end region of the magnetic holder, whereby preferably one magnetic element is provided on opposite end regions of the magnetic holder. Depending on the design, the magnet holder can also have more than two end regions with magnetic elements in order to increase the frequency of the excitation of the sample carrier. For example, the magnet holder may have two cross-shaped holding plates, which are each provided at the ends with a magnetic element.
    In order to set the biological sample in the sample carrier in vibration, it is advantageous if the sample carrier is mounted by means of a bearing axis pivotable on a bearing device. Preferably, a circular movement of the magnet holder outside the cooling chamber is converted into a tilting movement of the sample carrier about the bearing axis on the bearing device of the holder. The operation of the device can be made particularly simple if the bearing device has at least one groove-shaped recess for placing the bearing axis for the sample carrier. Accordingly, the sample carrier can be placed over the bearing axis on the groove-shaped recess of the bearing device. Advantageously, the individual sample carrier can thus be taken out of the holder particularly easily. Preferably, opposite end portions of the bearing axis are arranged in corresponding groove-shaped recesses of the bearing device.
    The bearing axis can be mounted substantially wear-free and with low friction, for which purpose preferably a roller bearing or a blade bearing is provided. Thus, the bearing axis can roll on the groove-shaped recess of the bearing device, it is advantageous if the groove-shaped recess is wider than the diameter of the bearing axis. This design is characterized by low design complexity and low wear.
    For the freezing substitution of a plurality of biological samples, it is favorable if the storage device has a plurality of groove-shaped depressions, preferably arranged along a circular bearing surface, for the bearing axes of a plurality of sample carriers. Accordingly, a plurality of sample carriers can be arranged to save space in the cooling chamber, wherein the support on the groove-shaped depressions allows easy removal of individual sample carrier.
    In this embodiment, it is also advantageous if the bearing means arranged in a central region of the holder inner bearing element with groove-shaped recesses for one end of the bearing axes of the sample carrier and arranged on the circumference of the holder outer bearing element with groove-shaped recesses for the other ends of the bearing axes Sample carrier has. Accordingly, the sample carrier can be arranged in a star shape between the inner bearing element and the outer bearing element. As a result, advantageously, a large number of sample carriers can be placed in the cooling chamber with a small space requirement. The functional principle is guaranteed even if not all sample carrier positions along the circular bearing surface are occupied. If necessary, space for pre-cooling of exchange media and for sample manipulation within the cooling chamber can be created in this way.
    To be able to lift the holder from a cooling device, in particular from a dewar vessel, it is advantageous if the inner bearing element has a holding element for lifting the holder. As a holding element, for example, a vertically upstanding from the inner bearing element holding rod may be provided.
    In order to provide high tilting moments on the sample carrier, it is expedient for the sample carrier to have a rod element which, in the state of rest, is arranged substantially vertically, on which the magnetic element is provided. The rod element is therefore designed as a lever arm, which acts on the magnetic force between the magnetic elements. Advantageously, the power transmission to the sample carrier can thus be improved. As a result of the interaction of the magnetic elements, the rod element and thus the receptacle for the biological sample are set in a tilting movement with respect to the substantially vertical resting state.
    In order to return the sample carrier to the rest or initial position, it is advantageous if the sample carrier has a weight element with respect to the bearing axis opposite the magnetic element. Thus, the weight element acts as a counterweight to the magnetic element, so that the sample carrier returns to the resting state with a decaying tilting motion as the magnetic interaction between the magnetic elements ceases.
    For stable arrangement of the shaking device on the holder, it is advantageous if the shaking device has a particular transparent viewing window exhibiting mounting member for releasable connection with a particular transparent transparent window having the cooling chamber, wherein on the mounting member preferably a circumferential retaining groove for placing on the Cover the cooling chamber is provided. Accordingly, the mounting element, for example a plate, in particular made of transparent material, can be placed on the cover of the cooling chamber, which is already present in known freeze substitution systems. Preferably, the magnetic holder is arranged with the magnetic element in this position between the mounting member and the cover of the cooling chamber. The transparent design of both the cover of the cooling chamber and the mounting member allows the observation of the sample carrier during the entire process.
    According to a preferred embodiment, the magnetic element on the magnet holder has a magnet, in particular a permanent magnet, and the magnet element on the sample carrier has an element made of a magnetizable material. Of course, the magnet holder may also comprise an element made of a magnetizable material and the sample carrier may have a magnet. In addition, both the magnetic holder and the sample carrier can have magnets. In an advantageous embodiment, the element of magnetizable material on an iron nut.
    As is customary in conventional systems for freeze substitution, the holder is preferably arranged in the cooling chamber of a vessel, in particular a Dewar vessel. The Dewar vessel may contain liquid nitrogen which allows the refrigeration chamber to be maintained at the temperatures required for freeze substitution. Preferably, the holder is arranged with the cooling chamber in the bottleneck of the Dewar vessel. For better cold contact, the cold chamber can be filled with the therein sample carrier with ethanol, so that the sample container partially immersed in cooled ethanol.
    In the method according to the invention, a magnetic element provided outside the cooling chamber cooperates with a magnetic element provided inside the cooling chamber on the sample carrier in order to set the sample carrier in a shaking motion. The advantages and technical effects of this method have already been described above in connection with the device, so that reference can be made to these statements.
    It is particularly preferred if the shaking of the sample with the magnetic elements is carried out as a method step in an automated freeze substitution method, in which the sample receiving container with the sample alone or together with the sample carrier for the media change automatically removed and for the continuation of the process back into the sample carrier or is returned to the sample holder.
    In tests, it has surprisingly been found to be advantageous that the freezing substitution can be accelerated if the sample carrier is put into an aperiodic shaking motion by the interaction of the magnetic elements. The accelerated substitution advantageously counteracts the temporal recrystallization process, so that substitutions can also be carried out at relatively high temperatures, for example at temperatures from -60 ° Celsius to -70 ° Celsius. The irregular shaking motion can be achieved, for example, by periodically exciting the sample carrier within the cooling chamber with a rotating magnetic element outside the cooling chamber.
    The invention will be explained below with reference to a preferred embodiment, to which, however, it should not be limited. In the drawing shows:
    Fig. 1 shows schematically a sectional view of a device according to the invention for freezing or cryogenic substitution of a biological sample, in which a provided outside the cooling chamber magnetic element cooperates with a provided inside the cooling chamber magnetic element on a specimen carrier containing the sample in order to put the sample carrier in a shaking motion ;
    2 schematically shows a perspective view of the device according to FIG. 1 with the cover element removed, wherein the pivotable arrangement of a plurality of sample carriers in the cooling chamber can be seen;
    3 is a schematic view of the sample carrier according to FIGS. 1, 2.
    Fig. 1 shows a device 1 for freezing or cryogenic substitution. The device 1 has a dewar vessel 2, which can be filled with liquid nitrogen, which is well known in the prior art and is therefore only indicated schematically. In the neck region of the dewar vessel 2, a trough-shaped holder 3 with a bottom 3 'and a circumferential jacket is removably arranged. The holder 3, in which one or more sample carriers 5 are arranged, is located in a cooling chamber 4. The sample carrier 5 has a carrier element 6, in which a sample receiving container 7 for a biological sample is detachably arranged. In particular, a plurality of such sample carriers 5 can be arranged in the holder 3. In the freeze substitution, the frozen sample water of the sample in the sample receptacle 7 is replaced with substitution temperatures by a solvent such as acetone.
    As can also be seen from FIG. 1, the device 1 also has a shaking device 8 for shaking the sample carrier 5 during the freezing substitution. In the embodiment shown, the shaking device 8 has magnetic elements 9 arranged outside the cooling chamber 4, which cooperate with magnetic elements 10 arranged inside the cooling chamber 4 on the sample carrier 5 in order to set the sample carrier 5 in a shaking motion. For this purpose, a drive 11 is provided for generating a relative movement between the magnetic elements 9 outside the cooling chamber 4 and the magnetic elements 10 on the sample carrier 5 within the cooling chamber 4. The magnetic elements 9 are provided at the ends of a magnet holder 12, which is coupled to the drive 11 for generating the relative movement between the magnetic elements. In the embodiment shown, the magnetic element 9 outside the cooling chamber 4, a magnet 9 ', in particular a permanent magnet, and the magnetic element 10 on the sample carrier 5, an element 10' of a magnetizable material, here an iron nut on.
    1, the drive 11 in the embodiment shown has a rotary drive 11 'in order to set the magnet holder 12 with the magnetic elements 9 attached thereto into a rotational movement about a vertical axis of rotation (see arrow 13). As a result, the sample carrier 5 is put into an aperiodic or irregular shaking motion during the freezing substitution, which on the one hand shortens the duration of the frozen substitution. In addition, the temperature in the cooling chamber can be higher than in known systems, for example at -60 ° Celsius to -70 ° Celsius. Advantageously, so the cost of cooling can be reduced.
    The shaking device 8 has a plate-shaped, transparent mounting member 21 with a circumferential retaining groove 22 to put on a cooling chamber 5 occlusive cover 23 with built-transparent glass window 20.
    As can be seen from FIG. 1, the device 1 also has a bearing device 14 with which the sample carrier 5 is pivotally mounted. For this purpose, the sample carrier 5 has a bearing axis 15 arranged horizontally in operation, which is inserted into groove-shaped depressions 16 of the bearing device 14.
    As can be seen from FIG. 2, the groove-shaped depressions 16 are slightly wider than the diameter of the bearing axes 15, so that the bearing axis 15 can roll in the groove-shaped depressions 16 during the freezing substitution. In the embodiment shown, the bearing device 14 has a disposed in a central region of the holder 3 inner bearing element 17 with groove-shaped depressions 16 for one end of the bearing axes 15 of the sample carrier 5 and arranged on the circumference of the holder 3 outer bearing member 18 with groove-shaped depressions 16 for other ends of the bearing axes 15 of the sample carrier 5. The inner bearing element 17 also has a holding element 19 for lifting the holder 3. In the embodiment shown, eight sample carriers 5 can be arranged in the cooling chamber 4, with only two sample carriers 5, of which one sample carrier 5 having a sample receiving container 7, being shown in FIG. For receiving the sample receiving container 7, the support member 6 has a bore for suspending the sample receiving container 7.
    As can be seen schematically from FIG. 2, the holder 3 has openings 3 'on the circulating jacket in the vicinity of the bottom 3' for the purpose of being flooded with cooled alcohol.
    As can be seen from FIG. 3, the sample carrier 5 has a rod element 24, which is in particular arranged substantially vertically in the rest state, on which the magnetic element 10 is provided. In addition, the sample carrier 5 has a weight element 25 opposite the magnetic element 10 with respect to the bearing axis 15.
    权利要求:
    Claims (20)
    [1]
    1. Device (1) for freezing or cryogenic substitution, with a in a cooling chamber (4) insertable holder (3) for placing a sample carrier (5) for a biological sample and with a shaking device (8) for shaking the sample carrier ( 5), characterized in that the shaking device (8) has a magnetic element (9) provided outside the cooling chamber (4), which cooperates with a magnetic element (10) provided inside the cooling chamber (4) on the sample support (5) to move the To put sample carrier (5) in a shaking motion.
    [2]
    2. Device (1) according to claim 1, characterized in that a drive (11) for generating a relative movement between the magnetic element (9) outside the cooling chamber (4) and the magnetic element (10) on the sample carrier (5) within the cooling chamber (4) is provided.
    [3]
    3. Device (1) according to claim 1, characterized in that the magnetic element (9) outside the cooling chamber (4) is connected to a current source for generating a variable magnetic field.
    [4]
    4. Device (1) according to claim 2, characterized in that the magnetic element (9) outside of the cooling chamber (4) on a magnet holder (12) is provided, which with the drive (11) for generating the relative movement between the magnetic elements (9 , 10).
    [5]
    5. Device (1) according to claim 4, characterized in that the magnetic holder (12) of the shaking device (11) with a rotary drive (11 ') for rotatably supporting the magnetic holder (12) is connected.
    [6]
    6. Device (1) according to claim 5, characterized in that the magnetic element (9) is provided at a free end region of the magnet holder (12), wherein preferably each a magnetic element (9) is provided at opposite end portions of the magnet holder (12).
    [7]
    7. Device (1) according to one of claims 1 to 6, characterized in that the sample carrier (5) by means of a bearing axis (15) is pivotally mounted on a bearing device (14).
    [8]
    8. Device (1) according to claim 7, characterized in that the bearing device (14) has at least one groove-shaped recess (16) for placing the bearing axis (15) for the sample carrier (5).
    [9]
    9. Device (1) according to claim 8, characterized in that the groove-shaped recess (16) is wider than the diameter of the bearing axis (15).
    [10]
    10. Device (1) according to claim 9, characterized in that the bearing device (14) has a plurality of, preferably along a circular bearing surface arranged, groove-shaped depressions (16) for the bearing axes (15) of a plurality of sample carrier (5).
    [11]
    11. Device (1) according to claim 10, characterized in that the bearing device (14) arranged in a central region of the holder (3) inner bearing element (17) with groove-shaped recesses (16) for one ends of the bearing axes (15) Sample carrier (5) and on the circumference of the holder (3) arranged outer bearing element (18) with groove-shaped recesses (16) for the other ends of the bearing axes (15) of the sample carrier (5).
    [12]
    12. Device (1) according to claim 11, characterized in that the inner bearing element (17) has a holding element (19) for lifting the holder (3).
    [13]
    13. Device (1) according to one of claims 1 to 12, characterized in that the sample carrier (5) in the idle state, in particular substantially vertically arranged rod member (24), on which the magnetic element (10) is provided.
    [14]
    14. Device (1) according to one of claims 1 to 13, characterized in that the sample carrier (5) with respect to the bearing axis (15) opposite the magnetic element (10) has a weight element (25).
    [15]
    15. Device (1) according to one of claims 1 to 14, characterized in that the holder (3) on a circumferential jacket, preferably adjacent to a bottom (3 '), openings for the passage of cooled alcohol.
    [16]
    16. Device (1) according to claim 15, characterized in that the shaking device (8) has in particular a transparent viewing window exhibiting mounting element (21) for releasable connection with a particular another transparent viewing window (20) having cover (23) of the cooling chamber ( 5), wherein on the mounting member (21) preferably a circumferential retaining groove (22) for placing on the cover (23) of the cooling chamber (5) is provided.
    [17]
    17. Device (1) according to one of claims 1 to 16, characterized in that the magnetic element (9) on the magnetic holder (12) has a magnet (9 '), in particular a permanent magnet, and the magnetic element (10) on the sample carrier ( 5) comprises an element (10 ') made of a magnetizable material.
    [18]
    18. Device (1) according to one of claims 1 to 17, characterized in that the holder (3) in the cooling chamber of a vessel, in particular a dewar vessel (2), is arranged.
    [19]
    19. A method for freezing or cryogenic substitution, wherein a sample carrier (5) for a biological sample in a cooling chamber (4) is arranged, wherein the sample carrier (5) with a shaking device (8) is shaken, characterized in that one outside the Cooling chamber (4) provided magnetic element (9) with a within the cooling chamber (4) provided magnetic element (10) on the sample carrier (5) cooperates to put the sample carrier (5) in a shaking motion.
    [20]
    20. The method according to claim 19, characterized in that the sample carrier (5) is offset by the interaction of the magnetic elements (9, 10) in aperiodische shaking.
    类似技术:
    公开号 | 公开日 | 专利标题
    DE102011012887B4|2012-09-20|cryostorage
    DE2944464C2|1987-12-03|
    DE102014110722B4|2016-06-09|Charging station for reloading frozen samples at low temperatures
    DE102009061068B4|2015-05-07|Method for producing microscopic thin sections of tissue samples
    WO2008131840A2|2008-11-06|Sample holder for a microscope
    DE3042578A1|1982-06-24|INCUBATIONAL DEVICE FOR THE FIXATION, DRAINAGE AND EMBEDDING OF BIOLOGICAL OBJECTS FOR MICROSCOPIC, IN PARTICULAR ELECTRON MICROSCOPIC EXAMINATIONS
    DE102008059284A1|2009-07-30|Micromanipulator for a cryomicrotome
    DE2211423B2|1979-03-15|METHOD AND APPARATUS FOR OBSERVING BIOLOGICAL SAMPLES WITH A SCANNING ELECTRON MICROSCOPE
    AT515423B1|2015-09-15|Apparatus and method for freezing or cryogenic substitution
    EP3002056A1|2016-04-06|Mixing equipment for mixing a sample during a solid phase microextraction | process
    DE2704300A1|1977-08-11|Microscopy or electron microscopy preparations - are made from native histological objects and physical chemical products by cryofixation on deep frozen metal surfaces
    DE3416789A1|1985-11-21|DEVICE FOR ALTERNATIVE CRYOFIXATION BY IMMERSION OR ON THE METAL MIRROR
    DE3332586C2|1986-03-20|Device for avoiding splashing of liquid cooling media when quickly introducing biological-medical objects into a cooling bath as part of an immersion cryofixation
    EP3106225A1|2016-12-21|Device and method for the thermal storage of samples
    EP0611445A1|1994-08-24|Process and device for making microscope, especially electron-microscope, preparations for preparing sections
    EP0935773B1|2001-02-21|Appartus for placing a cover on a histological and biological specimen
    EP3175279A1|2017-06-07|Light microscope having a sample stage for cryomicroscopy
    DE1623054A1|1971-03-25|Method and device for determining the pour point of a liquid
    EP0611446A1|1994-08-24|Device for dehydrating and/or embedding samples
    DE619785C|1935-10-07|Machine for testing lubricants
    DE2851591A1|1979-10-31|DEVICE FOR DETERMINING SORPTION ISOTHERMS
    DE60313170T2|2007-08-23|TREATMENT OF TISSUE SAMPLES
    DE3332739C2|1985-10-31|Device for immersion cryofixation of biological or medical objects
    EP3792612A1|2021-03-17|Device for processing and infiltrating histological and biological samples
    DE2739497A1|1979-01-04|MIXER FOR FILLS CONTAINING LIQUID
    同族专利:
    公开号 | 公开日
    AT515423B1|2015-09-15|
    WO2015154118A1|2015-10-15|
    DE212015000100U1|2017-01-04|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    AT343941B|1976-02-06|1978-06-26|Reichert Optische Werke Ag|METHOD AND DEVICE FOR PRODUCING PREPARATIONS FOR MICROSCOPY, IN PARTICULAR ELECTRON MICROSCOPY FROM NATIVE HISTOLOGICAL OBJECTS AND PHYSICOCHEMICAL SIMILAR PRODUCTS BY CRYOFIXATION|
    DE3332739A1|1983-09-10|1985-04-04|C. Reichert Optische Werke Ag, Wien|IMMERSION CRYOFIXATION WITH FOLLOWING ROTATION OF THE OBJECT|
    DE3712531C1|1987-04-13|1988-05-19|Kernforschungsanlage Juelich|Apparatus for keeping the temperature of biological samples constant for their cryosubstitution|
    FR2997175A1|2012-10-18|2014-04-25|Air Liquide|Apparatus, used to cool e.g. samples of cells/living tissue, comprises tank accommodating fluid and stirring unit to stir fluid medium during all or part of immersion of products in fluid, where stirring unit comprises movable support unit|
    DE2944464C2|1979-11-03|1987-12-03|C. Reichert Optische Werke Ag, Wien, At|
    AT354441T|2003-12-17|2007-03-15|Mikrowellen Systeme Mws Gmbh|DEVICE FOR HEATING A FABRIC IN A CONTAINER|
    DE102004041965B4|2004-08-31|2009-08-13|Leica Mikrosysteme Gmbh|Device and method for freeze substitution and embedding of biological samples|
    DE102004046762B4|2004-09-24|2009-01-15|Leica Mikrosysteme Gmbh|Device for the polymerization of biological samples in the freezing substitution and use of diodes with UV components|
    EP2619541A1|2010-09-21|2013-07-31|FEI Company|Method of preparing a biological sample for inspection with electron microscopy and fluorescent light microscopy|CN112044102B|2020-08-31|2022-02-08|江苏康祥实业集团有限公司|A multistage evaporation plant for evaporation of sodium hypophosphite aqueous solution|
    法律状态:
    2021-12-15| MM01| Lapse because of not paying annual fees|Effective date: 20210410 |
    优先权:
    申请号 | 申请日 | 专利标题
    ATA50272/2014A|AT515423B1|2014-04-10|2014-04-10|Apparatus and method for freezing or cryogenic substitution|ATA50272/2014A| AT515423B1|2014-04-10|2014-04-10|Apparatus and method for freezing or cryogenic substitution|
    PCT/AT2015/050093| WO2015154118A1|2014-04-10|2015-04-10|A device and method for freeze or cryogenic temperature substitution|
    DE212015000100.8U| DE212015000100U1|2014-04-10|2015-04-10|Device for freezing or cryogenic substitution|
    [返回顶部]