EP2340121A2 - Reaktionsgefäss zur kristallisation einer probe aus einer lösung - Google Patents

Reaktionsgefäss zur kristallisation einer probe aus einer lösung

Info

Publication number
EP2340121A2
EP2340121A2 EP09782737A EP09782737A EP2340121A2 EP 2340121 A2 EP2340121 A2 EP 2340121A2 EP 09782737 A EP09782737 A EP 09782737A EP 09782737 A EP09782737 A EP 09782737A EP 2340121 A2 EP2340121 A2 EP 2340121A2
Authority
EP
European Patent Office
Prior art keywords
reaction vessel
range
reaction
cover
base body
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Withdrawn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
EP09782737A
Other languages
German (de)
English (en)
French (fr)
Inventor
Johann Kubicek
Bert Jungheim
Rainer Dahlke
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.)
Qiagen GmbH
Original Assignee
Qiagen 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 Qiagen GmbH filed Critical Qiagen GmbH
Publication of EP2340121A2 publication Critical patent/EP2340121A2/de
Withdrawn legal-status Critical Current

Links

Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/06Crystallising dishes
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D9/00Crystallisation
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5085Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
    • B01L3/50853Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates with covers or lids
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00Sampling; Preparing specimens for investigation
    • G01N1/28Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/40Concentrating samples
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02Adapting objects or devices to another
    • B01L2200/025Align devices or objects to ensure defined positions relative to each other
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06Fluid handling related problems
    • B01L2200/0689Sealing
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/14Process control and prevention of errors
    • B01L2200/142Preventing evaporation
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/04Closures and closing means
    • B01L2300/041Connecting closures to device or container
    • B01L2300/044Connecting closures to device or container pierceable, e.g. films, membranes
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0809Geometry, shape and general structure rectangular shaped
    • B01L2300/0829Multi-well plates; Microtitration plates

Definitions

  • the present invention relates to a reaction vessel for crystallization of a sample from a solution and a cover for a reaction vessel and an arrangement for applying the cover.
  • microtiter plates or microwell plates are also called crystallization plates when used for crystallization.
  • microtiter or crystallization plates are known in the art.
  • the individual reaction chambers of a microtiter plate can be used for Position of a closed gas space depending on the design of the plate, for example, be closed by a lid or a film.
  • document EP 1 397 201 A1 discloses a reaction vessel for producing a sample having a plurality of reaction chambers, each having a reservoir and a plurality of reaction areas.
  • reaction vessels A disadvantage of such reaction vessels is that the individual reaction chambers are not hermetically sealable and can not form their own closed gas space. Particularly in the case of crystallization plates with many reaction chambers and correspondingly small volumes, evaporation of the solutions from the reaction chambers is a frequently occurring disadvantage.
  • the object of the present invention was therefore to provide a means which overcomes at least one of the aforementioned disadvantages of the prior art.
  • the object is achieved by a reaction vessel according to claim 1 of the present invention.
  • a reaction vessel for crystallizing a sample from a solution comprising a plurality of reaction chambers, each reaction chamber having a reservoir and at least one crystallization region, wherein a first sidewall of a first reaction chamber communicates with a second sidewall of a second reaction chamber spaced apart from each other via a connecting web is, wherein the connecting web is arranged with the laterally peripheral edge surface of the reaction vessel in a common plane which forms a flat surface of the reaction vessel.
  • reaction vessel according to the invention can provide improved coverage of the individual reaction chambers of the reaction vessel.
  • the formation of connecting webs between the reaction chambers wherein a first side wall of a first reaction chamber with a second side wall of a second reaction chamber via a connecting web is spaced from each other, and wherein the connecting webs form a flat surface with the laterally peripheral edge surface of the reaction vessel, help to make wider webs trainable.
  • this can be provided by the fact that adjacent reaction chambers have no common vessel wall, whereby adjacent reaction chambers can be spaced apart by wider webs.
  • Wider webs may advantageously provide wider bond areas for a bondable masking sheet or for application of adhesive.
  • the tightness of the reaction chambers can be significantly improved. This is particularly advantageous over conventional thin intermediate webs between reaction chambers, which have only a very small adhesive surface for a film.
  • the connecting webs form a flat surface with the laterally peripheral edge surface of the reaction vessel, a good lockability of the individual reaction chambers is further enhanced, in particular by a cover film. Unevenness of the surface, for example due to narrow intermediate webs which protrude beyond the surface of the edge regions or lie underneath, are thus avoided according to the invention and thus also the tightness of the reaction chambers is further improved.
  • the connecting webs have a width in the range of> 1.5 mm to ⁇ 5 mm, preferably in the range of> 2 mm to ⁇ 4 mm, preferably in the range of> 2.5 mm to ⁇ 3 mm, more preferably in the range of> 2.7 mm to ⁇ 2.8 mm, on.
  • a flat surface and wide connecting webs can provide a sufficient surface around the individual reaction chambers, which is suitable for closing the individual reaction chambers securely by means of a covering film.
  • a self-adhesive cover sheet can be used, or the surface of the connecting webs and the edge region of the reaction vessel can be provided with adhesive.
  • a flat surface and wide connecting webs can provide a sufficient surface around the individual reaction chambers that is suitable for securing a self-adhesive cover sheet securely around the reaction chamber.
  • the connecting webs have a groove. This is preferably arranged centrally, ie symmetrically, on the connecting web between the two upper edges of the side walls of adjacent reaction chambers.
  • the groove it is also conceivable for the groove to be asymmetrical between the upper edges of the side walls. de two adjacent reaction chambers is arranged. In this case, the distance from the upper edge of the side wall of a reaction chamber to the groove would not be identical to the distance of the upper edge of the side wall of the adjacent reaction chamber to the groove.
  • the connecting webs preferably have a groove in the center.
  • a "groove” is understood to mean an elongated or grooved depression, preferably a groove.
  • An advantage of the groove is that it can provide a defined cutting guide.
  • the film closing a reaction chamber is usually partially or completely opened or cut open with a scalpel or another cutting tool in order to reach the crystal formed.
  • a scalpel or another cutting tool in order to reach the crystal formed.
  • the surface of the film can be safely removed above a certain reaction chamber. So far, the release of the surface of the film above a reaction chamber is usually carried out by cutting the film along the webs, which separate two adjacent reaction chambers, or along the upper inner edge of the reaction chamber.
  • Accidental slippage of the cutting tool during the cutting process often leads to damage of surrounding reaction chambers.
  • the groove described above however, the accidental slipping of the cutting tool and thus the damage to the cover is more peripheral
  • the reaction vessel has a circumferential groove along the outer sides of the reaction chambers.
  • the groove does not completely surround the reaction chamber, but is arranged only on at least one side of the reaction chamber, preferably on two sides, more preferably on three sides.
  • the width of the surface of the web to the circumferential groove corresponds to the width of the connecting webs up to the groove arranged centrally in the connecting webs.
  • the reaction chambers are surrounded by webs of corresponding width.
  • the inner regions of the webs are surrounded by grooves.
  • the areas of the webs surrounded by grooves have the advantage that a defined part of a cover film can be cut out along the grooves and this film piece can be safely lifted off to the top.
  • the webs have an area in the range of> 24.75 mm 2 to ⁇ 65 mm 2 per reaction chamber, preferably in the range of> 32 mm 2 to ⁇ 56 mm 2 per reaction chamber, preferably in the range of> 38.75 mm 2 to ⁇ 45 mm 2 per reaction chamber.
  • the term "web" denotes both the connecting webs and, in the case of external reaction vessels, the webs which are formed by the edge region of the reaction vessel on the sides of external reaction vessels.
  • the area of the lands per reaction chamber designates the area surrounding the respective reaction chamber which is bounded by the grooves extending along the sides of the reaction chamber.
  • the surface of the connecting webs on both sides of the groove provides sufficient adhesive surface, so that even after the decision distant from the film over a reaction chamber, the attachment of the film over the adjacent reaction chambers is not affected.
  • the groove may be of semicircular or convex cross section, of rectangular cross section, of triangular cross section or of preferably isosceles trapezoidal shape with an outwardly slanted wall.
  • the groove has outwardly tapered walls. This can advantageously lead to the leadership of a cutting element such as a scalpel is further facilitated.
  • the groove preferably has outwardly beveled walls which meet in the center.
  • the groove has a width in the range of> 0.2 mm to ⁇ 0.7 mm, preferably in the range of> 0.3 mm to ⁇ 0.6 mm, preferably in the range of> 0, 4 mm to ⁇ 0.5 mm.
  • the groove has a depth in the range of> 0.05 mm to ⁇ 0.5 mm, preferably in the range of> 0.1 mm to ⁇ 0.4 mm, preferably in the range of> 0 , 2 mm to ⁇ 0.3 mm.
  • the connecting webs on at least a portion of the edge of a reaction chamber which is preferably not in contact with the edge of an adjacent reaction chamber, and preferably in at least one corner of a reaction chamber on a recess.
  • the webs on the outside of the reaction chambers have a recess on at least one area, preferably on at least one corner of a reaction chamber.
  • the connecting webs at one point, preferably at a corner of a reaction chamber on a recess. It can further be provided that the connecting webs have a recess at two, three or four points, preferably corners of a reaction chamber. Preferably, the at least one recess is arranged on the side of the reaction chamber at which the crystallization region is arranged.
  • the connecting webs preferably have a recess starting from the groove arranged in the connecting web. Furthermore, the connecting webs preferably have recesses on the basis of an intersection region of the grooves.
  • the webs on the outside of the reaction chambers starting from the circumferential groove on at least one point, preferably at a corner of a reaction chamber on a recess.
  • the recesses allow a cutting tool to engage in the recess and facilitate the lifting of a film.
  • the recesses have a depth which corresponds to the depth of the groove.
  • the recesses have a depth in the range of> 0.05 mm to ⁇ 0.5 mm, preferably in the range of> 0.1 mm to ⁇ 0.4 mm, preferably in the range of> 0.2 mm to ⁇ 0, 3 mm up.
  • the recesses have an area in the range of> 0.4 mm 2 to ⁇ 1.2 mm 2 , preferably in the range of> 0.5 mm 2 to ⁇ 1 mm 2 , preferably in the range of> 0.65 mm 2 to ⁇ 0.9 mm 2 .
  • Cutting tool at a corner of the reaction chamber can be guided under the cut out along the grooves film piece and safely lifted.
  • This measure has the further advantage that a cut-out film piece, on whose side facing the reaction chamber a desired crystal can be located, can be removed without damaging the film piece and the crystal.
  • the reaction vessel according to the invention comprises a plurality of reaction chambers, each reaction chamber having a reservoir and at least one crystallization region. After capping, each reaction chamber can form its own gas space, wherein the reservoir and the crystallization area are in gas exchange with each other.
  • the reaction vessel according to the invention preferably has a format according to the dimensions recommended by the Society of Biomolecular Screening (SBS), preferably according to ANSI / SBS standards. Standards such as the Society of Biomolecular Screening (SBS, www.sbsonline.org) are known to those skilled in the art.
  • This measure has the advantage that crystallization experiments in the reaction vessel according to the invention can be carried out with the aid of standardized pipetting aids and robotic systems.
  • the reaction vessel according to the invention preferably has a number of reaction chambers which obey the formula 3 ⁇ 2 N , where N is a natural number.
  • the reaction chambers of a 96-well reaction vessel according to the SBS standard are arranged in eight rows of 12 reaction chambers, each 9 mm apart.
  • the reservoir is preferably a substantially rectangular cavity, which in preferred embodiments has a depth in the range of> 8 mm to ⁇ 12 mm, preferably in the range of> 9.5 mm to ⁇ 10.5 mm, preferably in the range of> 9, 9 mm to ⁇ 10.1 mm, wherein the depth is determined from the flat surface of the reaction vessel to the bottom of the cavity.
  • the reservoir has a width in the range of> 1.7 mm to ⁇ 3.5 mm, preferably in the range of> 2 mm to ⁇ 3.2 mm, preferably in the range of> 2.2 mm to ⁇ 3, 0 mm and / or a length in the range of> 4 mm to ⁇ 7.5 mm, preferably in the range of> 5 mm to ⁇ 7 mm, preferably in the range of> 5.6 mm to ⁇ 6.2 mm.
  • the volume of the reservoir is less than in conventional crystallization plates.
  • the reservoir has a volume in the range of> 70 ⁇ l to ⁇ 160 ⁇ l, preferably in the range of> 80 ⁇ l to ⁇ 150 ⁇ l, preferably in the range of> 130 ⁇ l to ⁇ 140 ⁇ l.
  • volume of the reservoir means the volume of the reservoir from the bottom of the reservoir to the height of the shoulder for the crystallization area.
  • the reservoir has rounded corners. More preferably, the reaction chamber has rounded corners.
  • liquid in particular the crystallization solvent, does not rise or rises to a significantly reduced extent.
  • a combination of rounded corners of the reservoir and rounded corners of the reaction chamber has proved favorable.
  • the at least one crystallization region is arranged on a shoulder in the reaction chamber.
  • the at least one crystallization region is formed by a recess.
  • the shoulder has, in preferred embodiments, a flat surface on the underside below the crystallization area.
  • the shoulder in the reaction chamber, on which the at least one crystallization region is arranged is arranged at a height in the range of> 7 mm to ⁇ 10 mm, preferably in the range of> 8 mm to ⁇ 9 mm above the vessel bottom of the reservoir ,
  • Each reaction chamber has a reservoir and at least one crystallization region.
  • the reaction chamber may have a plurality of crystallization regions, for example two or three crystallization regions, but it is preferred that the reaction chamber has a crystallization region.
  • a further advantage of the reaction vessel according to the invention can be provided by the fact that the volume of a crystallization area can be increased in comparison with a plurality of crystallization areas.
  • An increased volume of the crystallization area may provide the advantage that a sample dissolved in a crystallization solvent is not only automatically but also better manually pipetted.
  • the bottom of the recess forming the crystallization region has a curved or spherical surface, preferably an inwardly curved, concave surface.
  • the crystallization region has an oval, preferably elliptical or substantially elliptical shape. According to a particularly preferred embodiment of the reaction vessel, the crystallization region is elliptical or substantially elliptical.
  • the term "elliptically configured" preferably means that the crystallization region has an elliptical outline in plan view, with the longer axis of the ellipsoid preferably extending parallel to the longer axis of the reservoir.
  • the crystallization region, in particular the recess forming the crystallization region has the shape of a half oval, preferably of half an ellipsoid.
  • the crystallization region having an elliptical configuration or having an essentially elliptical shape has in particular the recess forming the crystallization region a width in the range of> 1.5 mm to ⁇ 4 mm, preferably in the range of> 1.8 mm to ⁇ 3.5 mm, preferably in the range of> 2.1 mm to ⁇ 3.0 mm, and / or a length in the range of> 4.5 mm to ⁇ 8 mm, preferably in the range of> 5.1 mm to ⁇ 7 mm, preferably in the range of> 5.6 mm to ⁇ 6.2 mm.
  • the advantage of a curved, in particular elliptical, surface of the crystallization region lies in particular in the fact that this enables a reproducible positioning of the sample drop. This can result in a reproducible positioning of the crystal to be formed.
  • the crystal will preferably form in the deepest part of the curve.
  • the crystal can thus form centrally or almost centrally in the crystallization region.
  • crystal growth in corners can be avoided, thereby making it difficult to remove the crystals or to analyze the crystals directly in the crystallization region.
  • An oval, preferably elliptical configuration also has the particular advantage that removal of the crystals is further facilitated by a device for removing the crystal, for example a so-called crystallization loop used in a conventional manner, a metal pin with a loop or a loop at the end , Is guided by the shape of the crystallization region in the direction of the deepest region.
  • a device for removing the crystal for example a so-called crystallization loop used in a conventional manner, a metal pin with a loop or a loop at the end , Is guided by the shape of the crystallization region in the direction of the deepest region.
  • the substantially elliptical shape of the crystallization region allows for easier isolation of the formed crystals.
  • a curved surface of the crystallization region may in particular have an oval, preferably elliptical, configuration of the crystallization region.
  • the reaction vessel is formed of a translucent polymer.
  • the crystallization experiments can be examined without opening with light-optical instruments.
  • Preferred polymers are selected from the group comprising polypropylene, polystyrene, acrylbutadiene styrene, polycarbonate, polymethylmethacrylate, polysulfone, cycloolefin copolymer (COC), cycloolefin polymer (COP), polymethylphenyls and / or the acrylic ester styrene-acrylonitrile.
  • polymers are resistant to organic solvents such as acetone, benzene or acetonitrile, which are often used for crystallizations. Furthermore, they are compatible with various commonly used salts, buffers or polymers used for crystallization.
  • Particularly preferred polymers are selected from the group comprising cycloolefin copolymers and / or cycloolefm polymers, preferably cycloolefin copolymers.
  • a reaction vessel in particular formed from a cycloolefin copolymer, can in particular provide good transparency.
  • vessels of cycloolefin copolymer are less permeable to water vapor and therefore less sensitive to evaporation than vessels of, for example, polystyrene.
  • Preferred cycloolefin copolymers have a water absorption of less than 0.01% at a room temperature of 23 ° C.
  • Cycloolefin copolymers which have a light transmittance in the wavelength range of 280 nm in the range from> 90% to ⁇ 100%, preferably 91%, are furthermore preferably used.
  • Preferred cycloolefin copolymers are obtainable, for example, under the trade name Topas®, in particular Topas® 8007X10, from Topas Advanced Polymers.
  • Preferred cyclo-olefin polymers (COP) are available, for example, under the trade name ZEONOR®.
  • the inventive reaction vessel is suitable for the crystallization of a sample from a solution comprising a plurality of reaction chambers, each reaction chamber having a reservoir and at least one crystallization region, according to the so-called “sitting drop” method.
  • the reaction vessel may further comprise a vessel cover.
  • the vessel cover is an elastic cover film.
  • the use of a rigid cover in this context is possible.
  • the reaction chambers are closed together altogether.
  • Another advantage of a cover film is that further a part of the reaction chambers of the reaction vessel can be selectively closed.
  • cover film advantageous that individual reaction chambers can be selectively opened by removing a portion of the cover, without surrounding reaction chambers are also necessarily opened.
  • covering foils have a lower risk of contamination.
  • adhesive cover films are easy to apply.
  • the webs and edge surfaces of the reaction vessel are covered with adhesive and a non-adhesive designed cover sheet can be applied.
  • a non-adhesive designed cover sheet can be applied.
  • an adhesive cover sheet is applied. This has significant advantages in the handling of the cover plate before bonding.
  • the cover sheet is formed of a translucent polymer.
  • the crystallization experiments can be examined without opening with light-optical instruments.
  • Preferred polymers are elastomers, fluorinated and non-fluorinated polymers, in particular selected from the group comprising polyethylene, in particular low-density polyethylene (LDPE) and high-density polyethylene (HDPE), polypropylene, polyester, polystyrene, polyethylene terephthalate, Fluoropolymers such as polyvinyl chloride (PVC), perfluoroalkoxy copolymer (PFA), ethylene-chlorotrifluoroethylene copolymer (E-CTFE), ethylene-tetrafluoroethylene copolymer (E-TFE), trifluorochlorethylene / ethylene copolymer (CTFE), polyvinylidine fluoride (PVDF ), Tetrafluoroethylene-hexafluoropropylene copolymer (FEP), polytetrafluoroethylene (PTFE), polyolefin, acrylic polymer, acrylic copolymer, ethylene acrylate, ethylene methacrylate,
  • Particularly preferred polymers are selected from the group comprising polyethylene, polypropylene, polyester, polystyrene, polymethyl methacrylate, polyoxymethylene, polyethylene terephthalate, polyamide, fluoropolymers such as polyvinyl chloride (PVC), polycarbonate and / or cycloolefm polymers (COP).
  • PVC polyvinyl chloride
  • COP cycloolefm polymers
  • a very particularly preferred polymer is polypropylene.
  • a polypropylene layer can provide good transparency of the cover film.
  • adhesive is applied to the polymer layer.
  • Suitable adhesives are selected from the group comprising reactive adhesives and / or pressure-sensitive adhesives. Preference is given to pressure-sensitive adhesives.
  • pressure-sensitive adhesives conventional pressure-sensitive adhesives known in the art can be used. Examples of pressure-sensitive adhesives are natural rubber, butyl rubber, styrene-butadiene copolymers (SBR rubber), acrylonitrile copolymers, polychloroprene, polyisobutylene, polybutadiene, polyisoprene, block copolymers, such as styrene-isoprene and styrene-isoprene-styrene (SIS) block copolymers or styrene-butadiene-styrene (SBS) block copolymers, polyesters, polyurethanes, silicones, polyvinyl ethers, acrylonitrile copolymers, acrylates, methacrylates, ethyl acrylates,
  • the pressure-sensitive adhesive is an acrylate adhesive.
  • the cover film is coated with an acrylate adhesive.
  • the well-adhering acrylate adhesive can advantageously provide a reliable closure of the reaction chambers.
  • an interaction of the invention wide webs between the individual reaction chambers with a well-adhering cover film can significantly reduce the evaporation from the reaction chambers.
  • An area above the individual reaction chambers may be formed without adhesive. In this case, no adhesive can be applied to the entire surface above the individual reaction chambers. This may allow hanging drop crystallization without contaminating the sample solution with adhesive.
  • a covering film for covering a reaction vessel comprising reaction chambers comprises a polymer layer to which an adhesive layer is applied, wherein preferably surfaces with a width in the range of> 1.5 mm to ⁇ 7.5 mm and a length in the range of > 1.5 mm to ⁇ 7.5 mm are not adhesive within the adhesive layer.
  • this has the advantage that the positioning of a drop of the sample on the cover film can be made substantially more secure by means of the orientation on adhesive-free surfaces. On the other hand, this can prevent the applied drops from running into one another during a concussion of the covering film and / or the reaction vessel and contaminating adjacent experiments.
  • the cover sheet has a number of non-adhesive surfaces conforming to the formula 3 x 2 N , where N is a natural number.
  • the arrangement of the non-adhesively configured surfaces on the covering film preferably corresponds to the arrangement of the reaction chambers of a reaction vessel according to the SBS standard, wherein the non-adhesive surfaces are suitably located on the surface of the covering film within the cavity of the reaction chamber.
  • the non-adhesive surfaces are preferably located above the reservoir.
  • the non-adhesive configured surfaces may have a round, oval, in particular an elliptical or substantially elliptical, or rectangular shape.
  • the non-adhesive configured surface has a round shape.
  • the cover film may have round surfaces with a diameter in the range of> 1.5 mm to ⁇ 7.5 mm, preferably in the range of> 1.8 mm to ⁇ 3 mm, preferably in the range of> 2 mm to ⁇ 2 , 5 mm, which are not adhesive.
  • the cover film can have oval, in particular elliptical or substantially elliptical surfaces with a width in the range of> 1.5 mm to ⁇ 4 mm, preferably in the range of> 1.8 mm to ⁇ 3 mm, preferably in the range of > 2 mm to ⁇ 2.5 mm and / or a length in the range of> 1.8 mm to ⁇ 7.5 mm, preferably in the range of> 2.5 mm to ⁇ 6 mm, preferably in the range of> 2, 5 mm to ⁇ 3 mm, which are not adhesive.
  • the covering film can have rectangular areas with a width in the range of> 1.5 mm to ⁇ 7.5 mm, preferably in the range of> 1.8 mm to ⁇ 3 mm, preferably in the range of> 2 mm to ⁇ 2.5 mm and / or a length in the range of> 1.5 mm to ⁇ 7.5 mm, preferably in the range of> 1.8 mm to ⁇ 3 mm, preferably in the range of> 2 mm to ⁇ 2.5 mm, which are not adhesive.
  • the cover film may preferably round non-adhesive surfaces having an area in the range of> 1.5 mm 2 to ⁇ 45 mm 2 , preferably in the range of> 2.5 mm 2 to ⁇ 8 mm 2 , preferably in the range from> 3 mm 2 to ⁇ 5 mm 2 .
  • the cover sheet may have areas with a width in the range of> 5.8 mm to ⁇ 6.6 mm, preferably in the range of> 6.1 mm to ⁇ 6.3 mm and / or a length in the range of> 5.8 mm to ⁇ 6.6 mm, preferably in the range of> 6.1 mm to ⁇ 6.3 mm, which is configured non-adhesive.
  • the cover sheet is in the form of a reaction vessel according to SBS standard suitable blanks.
  • a preferred blank of the cover sheet may have a width in the range of> 76 mm to ⁇ 84 mm, preferably in the range of> 77 mm to ⁇ 82 mm, preferably in the range of> 78 mm to ⁇ 80 mm and / or a length in the range of> 130 mm to ⁇ 160 mm, preferably in the range of> 135 mm to ⁇ 155 mm, preferably in the range of> 140 mm to ⁇ 150 mm.
  • the length of the blanks of the cover film is longer than the length of a reaction vessel according to SBS standard.
  • the blanks have on both sides in the length of an adhesive-free area, preferably each with a length in the range of> 5 mm to ⁇ 12 mm, preferably in the range of> 8 mm to ⁇ 10 mm. This has the advantage that the cover film on the longitudinal side is easier to grasp and can be applied to the reaction vessel with increased safety.
  • the cover film comprising a polymer layer and an adhesive layer has a thickness in the range of> 25 ⁇ m to ⁇ 125 ⁇ m, preferably in the range of> 50 ⁇ m to ⁇ 100 ⁇ m, preferably in the range of> 65 ⁇ m to ⁇ 70 ⁇ m , This has the advantage that the cover is easily pierceable.
  • the cover film on the side of the cover film, which is not covered with adhesive markings which represent the position of the adhesive-free surfaces and / or denote the individual reaction chambers.
  • markings which represent the position of the adhesive-free surfaces and / or denote the individual reaction chambers.
  • the name of the individual Reaction chambers both mirrored and in the direction of reading are given, this has the advantage that the name of the individual reaction chambers is readable both when applying the sample drops as well as during and / or after the application of the film to the reaction vessel.
  • the marking of the location of the adhesive-free surfaces allows the position of the formed, often colorless, crystals is more easily recognizable.
  • the markings are designed in the form of an imprint.
  • the marking may also be applied to the non-adhesive areas of the side of the cover film which is provided with adhesive.
  • the marking can also be formed by a survey, for example, an elevated border or by a recess.
  • the adhesive layer may be protected by a peelable protective film, preferably by a peelable silicone film.
  • the present invention furthermore relates to an arrangement for applying a cover film to a reaction vessel, comprising a fastening device for a cover film comprising a base body for receiving the cover film, the base body preferably having a width in the range of> 80 mm to ⁇ 90 mm and a length in the range of> 120 mm to ⁇ 135 mm, wherein on at least two opposite sides of the base body fastening elements are attached, with which the cover sheet stretched on the base body can be fastened, and wherein the main body preferably in the corner regions at least two Positioning elements, preferably recesses.
  • the fastening elements allow a fixation of the cover on the fastening device.
  • the fastening device according to the invention allows a cover film to be securely and detachably fastened so that the cover film can be pipetted without slipping.
  • drops of sample solution can be applied precisely to selected areas of a non-slip secured covering film.
  • the main body is preferably a rectangular base body.
  • the base body has a surface which can be placed on a reaction vessel having a width in the range of> 83 mm to ⁇ 87 mm and a length in the range of> 125 mm to ⁇ 129 mm.
  • the base body has a surface which can be placed on a reaction vessel with SBS standard format.
  • the base body has at least two lateral edge surfaces, which are spaced such that the base body can be placed on a reaction vessel having a width in the range of> 83 mm to ⁇ 87 mm, in particular SBS standard.
  • the base body has a base with a width in the range of> 83 mm to ⁇ 87 mm and a length in the range of> 125 mm to ⁇ 129 mm, preferably with a width in the range of> 84 mm to ⁇ 86 mm and a length in the range of> 126 mm to ⁇ 128 mm, on.
  • the footprint preferably corresponds to the SBS standard.
  • the stand surface advantageously makes it possible for the fastening device to be positioned on common pipetting robots. Thus, pipetting liquid onto a cover sheet on the fixture can be done manually as well as automated.
  • an elastically deformable bearing surface is attached to the base body.
  • the elastically deformable bearing surface is detachably attached to the base body connected.
  • the elastically deformable bearing surface is fixedly connected to the base body connected.
  • the elastically deformable bearing surface is fixedly mounted on the base body.
  • the term "elastically deformable” is understood to mean that the support surface can be deformed when it is pressed on and, after termination of pressing, returns to an undeformed planar shape.
  • the support surface is elastically deformable
  • the support surface can easily adapt to the webs of a reaction vessel. This allows the fastening device to be usable not only for a specific reaction vessel but for reaction vessels with a variable configuration of the surface.
  • a film can be applied not only to reaction vessels of variable width of the webs, but also to reaction vessels which do not necessarily have to have a flat surface.
  • the elastically deformable support surface makes it possible to stick the cover foil evenly to a reaction vessel after pipetting after a planar arrangement.
  • a uniform bonding or pressing of an adhesive configured film with a reaction vessel or a non-adhesive film with a provided with adhesive surface areas reaction vessel is possible.
  • the elastically deformable bearing surface may be formed from an elastomer, in particular a thermoplastic elastomer, silicone or rubber. In principle, in addition to plastic, other materials are suitable, which are elastically deformable after pressing flat.
  • the elastically deformable bearing surface has a thickness in the range of> 0.5 mm to ⁇ 2 mm, preferably in the range of> 1.3 mm to ⁇ 1.5 mm.
  • the width of the elastically deformable support surface is preferably in the range of> 75 mm to ⁇ 87 mm, preferably in the range of> 77 mm to ⁇ 85 mm, preferably in the range of> 78 mm to ⁇ 80 mm and / or the length in Range of> 100 mm to ⁇ 150 mm, preferably in the range of> 115 mm to ⁇ 140 mm, preferably in the range of> 120 mm to ⁇ 135 mm.
  • fastening elements are attached to at least two opposite sides of the base body, with which the cover is stretched on the base body fastened
  • the cover film is preferably tensioned and releasably mountable on the base body. After applying the sample solution to the film attached to the base body, it can be detached again from the base body.
  • the attachment can be provided by suitable fasteners.
  • the fastening elements are attached to the end faces of the base body.
  • fastening elements are attached to the longitudinal sides.
  • Preferred fastening elements are selected from the group comprising straps, loops, straps, straps, spring elements and / or displaceable fastening elements.
  • the fastening elements are rotatably supported by a hinge connection.
  • the fastening elements are rotatably mounted on an axle.
  • Preferred fasteners are rotatably mounted on an axis mounting tabs.
  • the fasteners may be slidable fasteners that can fix the film from the side or from above.
  • the fastening elements can be brackets, loops, straps, bands or spring elements, in particular brackets, loops, straps, straps or spring elements that are firmly connected to the main body.
  • the fastening elements are firmly connected to the main body spring elements. This makes it possible that the film can be fixed in that it can be pushed under the firmly connected to the main body spring elements.
  • the film is fixed in that the film is placed on the support surface.
  • the fasteners preferably rotatably mounted on an axis mounting tabs can be opened, for example, opened, for this purpose.
  • the fasteners are locked in the open position. This can be an unintentional collapse of the fasteners, for example Prevent tabs.
  • the fastening elements can be locked in the open position by pressure pins.
  • the fastening elements can preferably be closed rotatably mounted on an axis fastening tabs, for example, be closed.
  • the film is firmly clamped by closed tabs on the body.
  • the fasteners are locked in the closed position bar. This can prevent unwanted opening of the fasteners, for example, the tabs.
  • the fastening elements in the closed position can be locked by magnets located in the base body and the fastening elements.
  • the fastening elements can be locked in the open position by pressure pins and / or the fastening elements can be locked in the closed position by magnets located in the base body and the fastening elements.
  • a "closed position” is the position in which a cover film is fixed in the fastening device by fastening elements.
  • the fastening elements for example, mounted on an axis mounting tabs are closed.
  • an "open position” is to be understood as meaning the position in which a cover film is not fixed by the fastening elements in the fastening device.
  • the fastening elements for example, mounted on an axis fastening straps open.
  • the fastening elements by a spring system such as dead center, can be locked.
  • the fastening device has at least two positioning elements.
  • the at least two positioning elements are preferably mounted on opposite sides of the fastening device.
  • the fastening device preferably has four, preferably symmetrically arranged, positioning elements.
  • the positioning elements are preferably provided at two positions of the base body. Preferably, the positioning elements are mounted in the corner regions of the base body.
  • the positioning of the fastener may be recesses, or surveys such as pins or projections.
  • the positioning elements of the fastening device are preferably recesses. This allows unimpeded positioning of the film and, in particular, unimpeded application of a liquid to the positioned cover film.
  • the positioning elements preferably recesses, have a diameter in the range of> 4.2 mm to ⁇ 8.2 mm, preferably in the range of> 4.7 mm to ⁇ 7.2 mm, preferably in the range of> 5.2 mm to ⁇ 6.2 mm.
  • the recesses are through holes.
  • the fastening device with the covering film to which sample solution has been pipetted can be turned over and placed on a reaction vessel. Then, by means of the elastically deformable support surface, the adhesive layer of the cover film can be glued onto the reaction vessel. After adhering the film to the reaction vessel, the fastening tabs can be loosened and the fastening device can be lifted off easily. It is preferred that the covering film is placed on a reaction vessel by means of a receptacle for a reaction vessel. This has the advantage that the placement can be directed.
  • the arrangement according to the invention for applying a cover film to a reaction vessel comprises at least one fastening device for a cover film.
  • the arrangement according to the invention for applying a covering film to a reaction vessel further preferably comprises a receiving device for a reaction vessel, wherein at least two positioning elements, preferably pin-shaped positioning elements, are arranged on the main body of the receiving device, and wherein the dimensions of the recess are such that a reaction vessel with a Width in the range of> 80 mm to ⁇ 90 mm, preferably with a width in the range of> 83 mm to ⁇ 87 mm, preferably with a width in the range of> 84 mm to ⁇ 86 mm, can be positioned in the recess.
  • the receiving device has at least two positioning elements.
  • the at least two positioning elements are preferably mounted on opposite sides of the receiving device.
  • the receiving device preferably has four, preferably symmetrically arranged, positioning elements.
  • the positioning elements are mounted in the corner regions of the base body of the receiving device.
  • the positioning of the receiving device may be elevations such as pin-shaped elements, in particular pins or projections, or recesses.
  • the positioning of the Aufhahmevoriques are preferably pin-shaped positioning.
  • the positioning elements of the fastening device can preferably interact with the positioning elements of the receiving device, preferably elevations, for example pins.
  • the at least two positioning elements, preferably pin-shaped positioning elements can be brought into engagement with the positioning elements, preferably recesses, of the fastening device according to the invention.
  • the positioning elements preferably pin-shaped positioning elements, have a length in the range of> 25 mm to ⁇ 40 mm, preferably in the range of> 28 mm to ⁇ 38 mm, preferably in the range of> 30 mm to ⁇ 35 mm.
  • the positioning elements, preferably pin-shaped positioning elements have a diameter in the range of> 4 mm to ⁇ 8 mm, preferably in the range of> 4.5 mm to ⁇ 7 mm, preferably in the range of> 5 mm to ⁇ 6 mm on.
  • the fastening device can be positioned on or in the receiving device by means of guide rails along the outer surfaces of the fastening device.
  • pin-shaped positioning elements in particular pins, which can be brought into engagement with the recesses of the fastening device, or guide rails
  • the positioning by means of pin-shaped positioning elements, in particular pins, which can be brought into engagement with the recesses of the fastening device, or guide rails has the great advantage that the film can be very selectively applied to the reaction vessel.
  • the pins or guide rails allow the pins or guide rails, the positioned film on a suitably positioned in a receiving device reaction vessel, so that with Drop covered adhesive-free surfaces of the film can be positioned with much greater accuracy over the reaction chambers, as is possible without tools.
  • the dimension of the recess is rectangular.
  • the dimensions of the recess are such that a reaction vessel with SBS standard format can be placed in the recess.
  • a reaction vessel in the recess of the receiving device, can be preferably positioned with SBS format. After drops of the sample solution have been applied to the covering film, the fastening device with the covering film can be turned over and placed on the receiving device. In this case, for example, pins of the receiving device can engage in corresponding recesses of the fastening device. Thus, the position of the reaction vessel and the film can be coordinated.
  • the film can be pressed onto the reaction vessel located in the receiving device, wherein the elastic support surface of the film can provide a uniform distribution of the force and thus a uniform bond. Subsequently, the fasteners, for example, tabs open and the fastening device can be lifted. The reaction vessel sealed with the film can be removed from the plate holder.
  • an arrangement for applying a cover film to a reaction vessel comprises a fastening device according to the invention for a cover film and a receptacle for a reaction vessel according to the invention. It is preferred that the arrangement according to the invention for applying a cover film to a reaction vessel is made of a polymer material.
  • Preferred polymers are selected from the group comprising polyoxymethylene (POM), polymethylmethacrylate (PMMA) and / or polypropylene.
  • the device is made of metal or partly of metal.
  • Preferred metals are selected from the group comprising stainless steel, in particular stainless steel, and / or aluminum.
  • Aluminum is preferably anodised or provided with a surface seal, preferably with a coating, in particular with clear lacquer, in particular thermosetting lacquer.
  • the present invention further relates to a system comprising a reaction vessel according to the invention and a cover film.
  • the system preferably comprises a reaction vessel according to the invention and a cover film applied to the reaction vessel. It is advantageous that the reaction vessel according to the invention can be used with any suitable cover film for covering the reaction chambers.
  • the cover film is preferably a cover film according to the invention.
  • reaction vessel according to the invention and the covering film according to the invention.
  • the present invention furthermore relates to a system comprising a reaction vessel, a cover film and an arrangement according to the invention for applying a cover film to a reaction vessel. It is advantageous that the inventive arrangement for applying a cover film to a reaction vessel with any suitable reaction vessel with SBS standard format is used.
  • FIG. 1 shows a schematic view of a reaction vessel according to the invention according to an embodiment of the invention.
  • FIG. 2 shows a section of a reaction vessel according to the invention according to FIG. 1 along the axis I.
  • FIG. 3 shows an enlarged schematic view of a reaction vessel according to the invention according to FIG. 1.
  • Fig. 4 shows a schematic view of a cover according to the invention according to an embodiment of the invention.
  • Fig. 5 shows a schematic view of a fastening device according to the invention according to an embodiment of the invention.
  • 6 shows a schematic view of a picking device according to the invention according to an embodiment of the invention.
  • the reaction vessel 1 shows a schematic view of a reaction vessel according to the invention for the crystallization of a sample from a solution according to an embodiment.
  • the reaction vessel 1 comprises a plurality of reaction chambers 2.
  • the reaction chamber 2 there is a reservoir 4 and a crystallization region 6.
  • the crystallization region 6 is in the form of an elliptically configured recess.
  • the crystallization region is arranged on a shoulder in the reaction chamber 2.
  • the side walls of the reaction chambers 2 are connected to one another via connecting webs 12.
  • the connecting webs 12 with the laterally encircling edge surface 14 of the reaction vessel 1 form a common planar surface.
  • the connecting webs 12 have a groove 16 in the center.
  • the connecting webs 12 connect a first side wall 8 of a first reaction chamber 2 with a second side wall 10 of a second reaction chamber 2 spaced therefrom.
  • the shoulder on which the crystallization region 6 is arranged has a flat surface on the underside underneath the crystallization region.
  • connecting webs 12 along an axis perpendicular to the axis I shown also connect a first to the side wall 8 vertical side wall of a first reaction chamber 2 with a second side wall of a second reaction chamber 2 which is at a distance from the side wall 10 and is at a distance therefrom.
  • FIG. 3 shows an enlarged schematic view of the reaction vessel according to the invention according to FIG. 1.
  • the connecting webs 12 have a recess 18 at a corner of a reaction chamber 2.
  • Fig. 4 shows a schematic view of a cover according to the invention according to an embodiment of the invention.
  • the cover film 20 comprises a polymer layer 22 to which an adhesive is applied. Within the adhesive layer 24, surfaces 26 are free of adhesive. Within these areas 26, a drop of sample can be applied. Furthermore, the cover film 20 has an adhesive-free region of the polymer layer 22 on both sides in the length. This has the advantage that the cover film 20 is easier to grip on the adhesive-free region of the polymer layer 22.
  • Fig. 5 shows a schematic view of a fastening device 30 according to the invention according to an embodiment of the invention.
  • the fastening device 30 has a base body 32 for receiving the cover film. On the body an elastically deformable support surface 40 is firmly attached. Furthermore, the base body 32 has a standing surface 34 with a width in the range of> 84 mm to ⁇ 86 mm and a length in the range of> 126 mm to ⁇ 128 mm.
  • fastening tabs 36 are attached, with which the cover is stretched and releasably fastened to the base body.
  • the fastening tabs 36 are rotatably mounted on an axle 42.
  • the receiving device 50 comprises a main body 52 with a recess 54.
  • the dimensions of the recess 54 are such that a reaction vessel with SBS standard format in the recess 54 can be positioned.
  • the receiving device 50 pins 56 in the corner regions of the receiving device 50, which can be brought into engagement with recesses 38 of the fastening device.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Clinical Laboratory Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • Hematology (AREA)
  • Immunology (AREA)
  • General Physics & Mathematics (AREA)
  • Biochemistry (AREA)
  • Pathology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)
  • Crystals, And After-Treatments Of Crystals (AREA)
  • Peptides Or Proteins (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
EP09782737A 2008-09-10 2009-09-08 Reaktionsgefäss zur kristallisation einer probe aus einer lösung Withdrawn EP2340121A2 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102008046668A DE102008046668A1 (de) 2008-09-10 2008-09-10 Reaktionsgefäß zur Kristallisation einer Probe aus einer Lösung
PCT/EP2009/061601 WO2010029060A2 (de) 2008-09-10 2009-09-08 Reaktionsgefäss zur kristallisation einer probe aus einer lösung

Publications (1)

Publication Number Publication Date
EP2340121A2 true EP2340121A2 (de) 2011-07-06

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EP09782737A Withdrawn EP2340121A2 (de) 2008-09-10 2009-09-08 Reaktionsgefäss zur kristallisation einer probe aus einer lösung

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US (1) US8668878B2 (zh)
EP (1) EP2340121A2 (zh)
JP (1) JP5501363B2 (zh)
KR (1) KR101624761B1 (zh)
CN (1) CN102149470A (zh)
AU (1) AU2009290982B2 (zh)
CA (1) CA2734816C (zh)
DE (1) DE102008046668A1 (zh)
WO (1) WO2010029060A2 (zh)

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US20120220045A1 (en) * 2011-02-25 2012-08-30 Colin Bozarth Double Trench Well for Assay Procedures
FR2972432B1 (fr) 2011-03-10 2014-06-13 Bio Rad Pasteur Receptacle de type carte gel muni d'un opercule comportant une predecoupe
CN116809131A (zh) * 2014-06-02 2023-09-29 安捷伦科技有限公司 用于分析生物样本的单列微板系统和载体
CN109164130B (zh) * 2018-08-31 2021-05-04 马鞍山尚元冶金科技有限公司 一种凝固过程冷态实验方法
CN114668094A (zh) * 2022-03-10 2022-06-28 林磊 一种富硒果蔬固体饮料及其生产工艺
CN117462989B (zh) * 2023-12-28 2024-03-01 山西铱倍力科技有限公司 一种氯铱酸生产用结晶设备

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Publication number Priority date Publication date Assignee Title
US6039804A (en) 1998-09-09 2000-03-21 Emerald Biostructures, Inc. Crystallization tray
US6913732B2 (en) * 2001-03-19 2005-07-05 Corning Incorporated Microplate for performing crystallography studies and methods for making and using such microplates
WO2002102503A1 (de) 2001-06-18 2002-12-27 Greiner Bio - One Gmbh Reaktionsgefäss zur herstellung von proben
US6656267B2 (en) * 2001-07-10 2003-12-02 Structural Genomix, Inc. Tray for macromolecule crystallization and method of using the same
EP1699538B1 (en) 2003-01-17 2008-01-30 Nextal Biotechnologie Inc. Pre-filled crystallization plates and methods for making and using same

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Publication number Publication date
KR20110057215A (ko) 2011-05-31
CA2734816A1 (en) 2010-03-18
AU2009290982B2 (en) 2014-12-18
WO2010029060A2 (de) 2010-03-18
DE102008046668A1 (de) 2010-03-11
CA2734816C (en) 2016-03-29
WO2010029060A3 (de) 2010-07-01
US20110229381A1 (en) 2011-09-22
CN102149470A (zh) 2011-08-10
AU2009290982A1 (en) 2010-03-18
JP2012501950A (ja) 2012-01-26
US8668878B2 (en) 2014-03-11
US20120219472A2 (en) 2012-08-30
JP5501363B2 (ja) 2014-05-21
KR101624761B1 (ko) 2016-05-26

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