U.S. patent application number 13/063130 was filed with the patent office on 2012-08-30 for reaction vessel for crystallizing a sample from a solution.
This patent application is currently assigned to QIAGEN GMBH. Invention is credited to Rainer DAHLKE, Bert JUNGHEIM, Johann KUBICEK.
Application Number | 20120219472 13/063130 |
Document ID | / |
Family ID | 41479214 |
Filed Date | 2012-08-30 |
United States Patent
Application |
20120219472 |
Kind Code |
A2 |
KUBICEK; Johann ; et
al. |
August 30, 2012 |
REACTION VESSEL FOR CRYSTALLIZING A SAMPLE FROM A SOLUTION
Abstract
The present invention relates to a reaction vessel for
crystallization of a sample from a solution and a covering foil and
an arrangement for mounting the covering foil.
Inventors: |
KUBICEK; Johann; (Koeln,
DE) ; JUNGHEIM; Bert; (Solingen, DE) ; DAHLKE;
Rainer; (Kaarst, DE) |
Assignee: |
; QIAGEN GMBH
Qiagen Str. 1
Hilden
DE
40724
|
Prior
Publication: |
|
Document Identifier |
Publication Date |
|
US 20110229381 A1 |
September 22, 2011 |
|
|
Family ID: |
41479214 |
Appl. No.: |
13/063130 |
Filed: |
September 8, 2009 |
PCT Filed: |
September 8, 2009 |
PCT NO: |
PCT/EP2009/061601 |
371 Date: |
May 23, 2011 |
Current U.S.
Class: |
422/560;
422/245.1; 422/569 |
Current CPC
Class: |
B01L 2200/142 20130101;
B01L 2300/0829 20130101; B01L 3/50853 20130101; B01L 2200/0689
20130101; B01L 3/06 20130101; B01L 2300/044 20130101; B01L 2200/025
20130101 |
Class at
Publication: |
422/560; 422/569;
422/245.1 |
International
Class: |
B01L 99/00 20100101
B01L099/00; B01D 9/00 20060101 B01D009/00 |
Foreign Application Data
Date |
Code |
Application Number |
Sep 10, 2008 |
DE |
102008046668.9 |
Claims
1. Reaction vessel (1) for crystallization of a sample from a
solution comprising several reaction chambers (2) wherein each
reaction chamber (2) has a reservoir (4) and at least one
crystallization space (6), wherein a first side wall (8) of a first
reaction chamber (2) is connected at a spacer distance via a
connection spacer (12) to a second side wall (10) of a second
reaction chamber (2), wherein the connection spacer (12) is
arranged on a shared plane with the sideways circumferential
surface (14) of the reaction vessel (1) and the plane forms a
planar surface of the reaction vessel (1).
2. Reaction vessel (1) according to claim 1, wherein the connection
spacers (12) have a width in the range of .gtoreq.1.5 mm to
.ltoreq.5 mm, especially in the range of .gtoreq.2 mm to .ltoreq.4
mm, preferably in the range of .gtoreq.2.5 mm to .ltoreq.3 mm.
3. Reaction vessel (1) according to claim 1 or 2, wherein the
connection spacers (12) preferably have a groove (16) in the
center.
4. Reaction vessel (1) according to any one of the foregoing
claims, wherein the groove (16) has a width in the range from
.gtoreq.0.2 mm to .ltoreq.0.7 mm, especially in the range of
.gtoreq.0.3 mm to .ltoreq.0.6 mm, preferably in the range of
.gtoreq.0.4 mm to .ltoreq.0.5 mm and/or a depth in the range from
.gtoreq.0.05 mm to .ltoreq.0.5 mm, especially in the range of
.gtoreq.0.1 mm to .ltoreq.0.4 mm, preferably in the range of
.gtoreq.0.2 mm to .ltoreq.0.3 mm.
5. Reaction vessel (1) according to any one of the foregoing
claims, wherein the connection spacers (12) have a recess (18) on
at least one corner of a reaction chamber (2).
6. Reaction vessel (1) according to any one of the foregoing
claims, wherein the crystallization space (6) has essentially an
elliptic shape.
7. Covering foil (20) for covering a reaction vessel comprising
reaction chambers wherein the covering foil (20) comprises a
polymer layer (22) on which an adhesive layer (24) is applied,
wherein areas (26) preferably with a width in the range from
.gtoreq.1.5 mm to .ltoreq.7.5 mm and a length in the range from
.gtoreq.1.5 mm to .ltoreq.7.5 mm are designed to be non-adhesive
within the adhesive layer (24).
8. Arrangement for the application of a covering foil onto a
reaction vessel, comprising a fastening device (30) for a covering
foil comprising a preferably rectangular base structure (32) for
receiving the covering foil, wherein the base structure (32) has a
footprint area (34) preferably with a width in the range from
.gtoreq.80 mm to .ltoreq.90 mm and a length in the range from
.gtoreq.120 mm to .ltoreq.135 mm, wherein on at least two opposing
sides of the base structure (32) fastening components (36) are
applied with which the covering foil is attachable in a stretched
manner to the base structure and wherein the base structure (32)
preferably in the corner areas has at least two positioning
elements, preferably recesses (38).
9. Arrangement according to claim 8, wherein an elastically
deformable mounting surface (40) is attached to the base structure
(32) of the fastening device (30).
10. Arrangement according to claim 8 or 9, wherein the fastening
components (36) are set in bearings so that they can rotate on an
axle (42).
11. Arrangement according to any one of the foregoing claims,
wherein the fastening components (36) can be locked in an open
position by press pins (44) and/or the fastening components (36)
can be locked in a closed position by magnets located in the base
structure (32) and in the fastening components (36).
12. Arrangement for the application of a covering foil onto a
reaction vessel comprising a receiving device (50) for a reaction
vessel, comprising a base structure (52) with a recess (54),
wherein on the base structure (52) of the receiving device (50) at
least two positioning elements, preferably pin-type positioning
elements (56) are arranged, which preferably can be brought into
mesh with the positioning elements, preferably recesses (38), of
the fastening device according to claim 8 to 11, and wherein the
dimensions of the recess (54) are such that a reaction vessel with
a width in the range from .gtoreq.80 mm to .ltoreq.90 mm can be
positioned in the recess (54).
13. Arrangement for the application of a covering foil onto a
reaction vessel, comprising a fastening device (30) for a covering
foil according to claim 8 to 11 and a receiving device (50) for a
reaction vessel according to claim 12.
14. System comprising a reaction vessel (1) according to any one of
the claims 1 to 6 and a covering foil.
15. System comprising a reaction vessel, a covering foil and an
arrangement for mounting a covering foil onto a reaction vessel
according to any one of the claims 8 to 13.
Description
FIELD OF THE INVENTION
[0001] The present invention relates to a reaction vessel for
crystallization of a sample from a solution and a cover foil for a
reaction vessel and an arrangement for mounting the cover foil.
TECHNICAL BACKGROUND
[0002] The manufacture of crystals of biological macromolecules
such as proteins and nucleic acids represents a critical factor in
the structure elucidation of these molecules. An important method
of crystallization is based on the process of vapor diffusion. In
this process, a small sample of the macromolecule dissolved in a
crystallization solvent is enclosed in a reaction vessel together
with a separate quantity of the solvent. By vapor diffusion between
the sample dissolved in the crystallization solvent and the solvent
in a reservoir, a supersaturation of the sample solution and a
crystallization of the sample can be performed.
[0003] Since the crystal growth of macromolecules is dependent on
different parameters, it is often necessary to perform several
crystallization growth attempts in parallel to the greatest extent
possible, in order to test out suitable parameters. This is
customarily done on microtiter plates or microwell plates. These
are also called crystallization plates when they are used for
crystallization.
[0004] Microtiter or crystallization plates of this type are known
from the state of the art. The individual reaction chambers of a
microtiter plate can be closed in order to create a closed gas
chamber depending on the design of the plate, for example, by a
cover or a foil.
[0005] In the state of the art, different alternative microtiter
plates for the crystallization of macromolecules are known. For
example, the document EP 1 397 201 A1 discloses a reaction vessel
for manufacturing a sample having several reaction chambers which
each have a reservoir and several reaction areas.
[0006] It is disadvantageous in these reaction vessels that the
individual reaction chambers can not be sealed so that they are
air-tight and can not make a separate sealed-off gas chamber. In
particular, in crystallization plates with many reaction chambers
and correspondingly small volumes, evaporation of the solvents from
the reaction vessels is a frequently occurring disadvantage.
[0007] When a foil is used to cover reaction vessels of this type,
the foil above the corresponding reaction chamber is usually cut
open in order to remove the crystal that has formed from the
reaction vessel. In the process, it is disadvantageous that during
this type of cutting the covering of surrounding reaction chambers
is frequently also damaged so that these crystallization attempts
are then no longer sealed off so that they are air-tight and thus
can not be used.
[0008] The object of the present invention is thus to provide a
means that overcomes at least one of the aforementioned
disadvantages of the state of the art. In particular, it is the
purpose of the present invention to provide a means that makes
possible a better sealing capability of a reaction vessel.
[0009] The object is achieved by a reaction vessel according to
claim 1 of the present invention. According to this claim, a
reaction vessel for crystallization of a sample from a solution is
provided comprising several reaction chambers, wherein each
reaction chamber has a reservoir and at least one crystallization
space, wherein a first side wall of a first reaction chamber is
connected at a spacer distance via a connection spacer to a second
side wall of a second reaction chamber, wherein the connection
spacer is arranged on a shared plane with the sideways
circumferential surface of the reaction vessel and the plane forms
a planar surface of the reaction vessel.
[0010] Surprisingly it was discovered that the reaction vessel
according to the invention can provide an improved covering of the
individual reaction chambers of the reaction vessel.
[0011] In an advantageous way, the formation of connection spacers
between the reaction chambers, wherein a first side wall of a first
reaction chamber is connected spaced at a distance to a second side
wall of a second reaction chamber via a connection spacer, and
wherein the connection spacers form a planar surface with the
sideways circumferential surface of the reaction vessel, can lead
to the possibility of making wider spacers. In particular, this can
be made possible in that adjacent reaction vessels do not have any
shared vessel walls so that adjacent reaction chambers can be set
apart at a distance from each other by wider spacers. In an
advantageous way, wider spacers can make possible wider adhesion
areas for an adhesive covering foil or for applying adhesive. In
this way, the sealing capability of the reaction chambers can be
considerably improved.
[0012] This is especially advantageous compared to the customary
thin intermediate spacers between reaction chambers which only have
a very small adhesive surface for a foil.
[0013] It is further advantageous that by the connection spacers
forming a planar surface with the sideways circumferential surface
of the reaction vessel, a good sealing capacity of the individual
reaction chambers, in particular by a covering foil, is further
increased. Non-planar areas of the surface, for example, made by
narrow intermediate webs which extend out from the surface of the
edge areas or lie beneath it, are thus avoided according to the
invention and thus also the sealing capacity of the reaction
chambers is further improved.
[0014] It is of particular advantage also that wider adhesion areas
can completely or almost completely prevent an evaporation of the
solutions in the individual reaction chambers.
[0015] This is especially of advantage for crystallization plates
with many reaction chambers for example, so-called 96 well plates
and correspondingly small volumes of solutions.
[0016] After closing the individual reaction chambers, for example,
by a covering foil, they each form a separate gas chamber in which
the sample dissolved in a solvent is enclosed on or in a
crystallization space with additional solvent in a reservoir of the
reaction chamber. Reducing or even preventing the evaporation of
the solvent from out of the reaction chamber can lead, in
particular for a small volume of the solvent, to the concentration
of the solutions used for crystallization not being changed by an
evaporation of the solvent. Correspondingly for an evaluation of
the crystallization growth attempts, the concentration of a crystal
required for crystallization can be clearly better estimated. This
is especially advantageous for frequently used volatile solvents
like alcohols and acids.
[0017] According to a preferred embodiment of the reaction vessel,
the connection spacers have a width in the range of .gtoreq.1.5 mm
to .ltoreq.5 mm, especially in the range of .gtoreq.2 mm to
.ltoreq.4 mm, preferably in the range of .gtoreq.2.5 mm to
.ltoreq.3 mm, more preferably in the range of .gtoreq.2.7 mm to
.ltoreq.2.8 mm.
[0018] The specification of surface areas, widths, lengths or
depths in the form of areas within the present invention is, unless
otherwise noted, to be understood such that the lower limit
specifies the minimum value and the upper limit specifies the
maximum value.
[0019] It is advantageous that a planar surface and wide connection
spacers can provide a sufficient surface area around the individual
reaction chambers which is suitable for securely sealing off the
individual reaction chambers with a covering foil. In the process,
a self-sealing covering foil can be used or the surface area of the
connection spacers and the edge area of the reaction vessel can be
provided with adhesive. In particular, a planar surface and a wide
connection spacer can provide a sufficient surface area around the
individual reaction chambers which is suitable for attaching a
self-adhesive covering foil securely around the reaction
chamber.
[0020] According to a preferred embodiment of the reaction vessel
according to the invention, the connection spacers have a groove.
This groove is preferably arranged centrally, i.e. symmetrically,
on the connection spacer between the two upper edges of the side
walls of adjacent reaction chambers. However, it is also
conceivable that the groove is arranged asymmetrically between the
upper edges of the side walls of two adjacent reaction chambers. In
this case, the separation distance of the upper edge of the side
wall of a reaction chamber from the groove would not be identical
to the separation distance of the upper edge of the side wall of
the adjacent reaction chamber. Preferably, the connection spacers
have a groove in the center.
[0021] "Groove" in the context of the present invention is
understood to be a longitudinal or flute-shaped depth, preferably a
groove
[0022] An advantage of the groove is that it can provide a defined
cutting guide.
[0023] After a successful crystallization, the foil that seals a
reaction chamber is partially or completely opened or cut open in
the usual way with a scalpel or another cutting tool in order to
provide access to the crystal that has formed. It is especially
advantageous for a groove in the connection spacers that when the
foil is cut open along the grooves the surface of the foil can be
safely removed above a specific reaction chamber. Until now, the
removal of the surfaces of the foil above a reaction chamber was
usually done by cutting the foil along the spacers which separate
two adjacent reaction chambers or along the upper inside wall of
the reaction chamber. By accidental sliding of the cutting tool
during a cutting operation, damages to the surrounding reaction
chambers frequently can occur. However, by the groove described
above, the accidental sliding of the cutting tool and thus the
damage of the covering of the surrounding reaction chambers by the
cutting tool is prevented such that the surrounding crystallization
growth attempts are not impaired.
[0024] Most especially preferred, the reaction vessel has a
circumferential groove along the outsides of the reaction chambers.
However, it is also conceivable that the groove does not completely
surround the reaction chamber, but only is arranged on at least one
side of the reaction chamber, preferably on two sides, further
preferred on three sides. Preferably, starting from the depth of
the reaction chamber, the width of the surface area of the spacer
up to the circumferential groove corresponds to the width of the
connection spacer up to the groove arranged in the center of the
connection spacers. In preferred embodiments, the reaction chambers
are surrounded with spacers with widths that correspond to each
other. Preferably, the inner areas of the spacers are surrounded by
grooves.
[0025] The areas of the spacers surrounded by grooves have the
advantage that a defined portion of the covering foil can be cut
along the groove and this foil piece can be safely lifted out to
the top.
[0026] Preferably, the spacers have an area in the range from
.gtoreq.24.75 mm.sup.2 to .ltoreq.65 mm.sup.2 per reaction chamber,
preferably in the range from .gtoreq.32 mm.sup.2 to .ltoreq.56
mm.sup.2 per reaction chamber, preferably in the range from
.gtoreq.38.75 mm.sup.2 to .ltoreq.45 mm.sup.2 per reaction chamber.
The term "spacer" indicates here both the connection spacers and,
in the case of the reaction vessels on the outside, the spacers
which are formed on the sides of reaction vessels on the outside by
the edge area of the reaction vessel. Preferably the surface area
of the spacers for each reaction chamber defines the surface
surrounding the respective reaction chamber which is defined by the
groove running along the sides of the reaction chamber.
[0027] Furthermore, it is advantageous that the surface area of the
connection spacers provides enough adhesive area on both sides of
the groove so that after the removal of the foil over the reaction
chamber, the attachment of the foil over the adjacent reaction
chamber is not damaged.
[0028] The groove can have a semi-circular or convex cross-section,
a right-angled cross-section, a triangular cross-section or
preferably a trapezoid shape having equal legs with a wall inclined
outward. Preferably, the groove has walls that are inclined to the
outside. This can, in an advantageous way, make it easier to guide
a cutting tool such as a scalpel. Preferably, the groove has walls
that are angled to the outside which meet in the center.
[0029] According to a preferred embodiment of the reaction vessel
according to the invention, the groove has a width in the range
from .gtoreq.0.2 mm to .ltoreq.0.7 mm, especially in the range of
.gtoreq.0.3 mm to .ltoreq.0.6 mm, preferably in the range of
.gtoreq.0.4 mm to .ltoreq.0.5 mm.
[0030] According to another preferred embodiment of the reaction
vessel, the groove has a depth in the range from .gtoreq.0.05 mm to
.ltoreq.0.5 mm, especially in the range of .gtoreq.0.1 mm to
.ltoreq.0.4 mm, preferably in the range of .gtoreq.0.2 mm to
.ltoreq.0.3 mm.
[0031] This can, in an advantageous way, make it easier to guide a
cutting tool such as a scalpel.
[0032] According to another preferred embodiment of the reaction
vessel according to the invention, the connection spacers have a
recess in at least one area of the edge of a reaction vessel, which
preferably is not in contact with the edge of an adjacent reaction
chamber, and preferably in at least one corner of a reaction
chamber. According to a further preferred embodiment of the
reaction vessel according to the invention, the spacers have a
recess on the outside of the reaction chamber on at least one area,
preferably on at least one corner of a reaction chamber.
[0033] Preferably the connection spacers have a recess at one
position, preferably at one corner of a reaction chamber. It can
further be provided that the connection spacers have a recess at
two, three, or four positions, preferably corners of a reaction
chamber. Preferably the at least one recess is arranged on the side
of the reaction chamber on which the crystallization space is
arranged.
[0034] Preferably, the connection spacers have a recess starting
from the groove arranged in the connection spacer. Furthermore, the
connection spacers have recesses preferably starting from a
intersection area of the grooves.
[0035] According to an additional preferred embodiment of the
reaction vessel according to the invention, the spacers have, on
the outside of the reaction chambers starting from the groove
arranged on the circumference and on at least one position, a
recess preferably on one corner of a reaction chamber.
[0036] In an advantageous way, the recesses make it possible for a
cutting tool to get into the recess and this makes easier the
removal of a foil.
[0037] In additional preferred embodiments, the recesses have a
depth which corresponds to the depth of the groove. Preferably the
recesses have a depth in the range from .gtoreq.0.05 mm to
.ltoreq.0.5 mm, especially in the range of .gtoreq.0.1 mm to
.ltoreq.0.4 mm, preferably in the range of .gtoreq.0.2 mm to
.ltoreq.0.3 mm.
[0038] Preferably, the recesses have an area in the range from
.gtoreq.0.4 mm.sup.2 to .ltoreq.1.2 mm.sup.2, preferably in the
range from .gtoreq.0.5 mm.sup.2 to .ltoreq.1 mm.sup.2, preferably
in the range from .gtoreq.0.65 mm.sup.2 to .ltoreq.0.9
mm.sup.2.
[0039] The recess has the advantage that when lifting off the
covering foil, a cutting tool can be guided on the corner of the
reaction chamber under the foil piece that can be cut out along the
groove. This measure has the additional advantage that a cut-out
foil piece, which could have a desired crystal on its side that
faces the reaction chamber, can be removed without damage to the
foil piece and the crystal.
[0040] The reaction vessel according to the invention comprises
several reaction chambers wherein each reaction chamber has a
reservoir and at least one crystallization space. After uncovering,
each reaction chamber can form its own gas chamber, wherein the
reservoir and the crystallization space are able to exchange gas
with each other.
[0041] Preferably the reaction vessel according to the invention
has a format according to the dimensions of the Recommendation of
the Society of Biomolecular Screening (SBS) preferably according to
ANSI/SBS-standards. Standards such as those of the Society of
Biomolecular Screening (SBS; www.sbsobline.org) are known to the
expert.
[0042] These measures have the advantage that crystallization
growth attempts in the reaction vessel according to the invention
can be performed with the aid of standardized pipetting aids and
robot systems.
[0043] Furthermore, the reaction vessel according to the invention
preferably has, according to the SBS-standard, a number of reaction
chambers according to the formula 3.times.2.sup.N, where N is a
natural number. For example, the reaction chambers of a 96-well
reaction vessel are arranged according to the SBS-standard in eight
rows of 12 each, which are each 9 mm apart from each other.
[0044] The reservoir is preferably an essentially rectangular
cavity which has in preferred embodiments a depth in the range of
.gtoreq.8 mm to .ltoreq.12 mm, especially in the range of
.gtoreq.9.5 mm to .ltoreq.10.5 mm, preferably in the range of
.gtoreq.9.9 mm to .ltoreq.10.1 mm, wherein the depth is determined
starting from the planar surface of the reaction vessel to the
floor of the cavity.
[0045] In preferred embodiments, the reservoir has a width in the
range of .gtoreq.1.7 mm to .ltoreq.3.5 mm, especially in the range
of .gtoreq.2 mm to .ltoreq.3.2 mm, preferably in the range of
.gtoreq.2.2 mm to .ltoreq.3.0 mm, and/or a length in the range from
.gtoreq.4 mm to .ltoreq.7.5 mm, especially in the range of
.gtoreq.5 mm to .ltoreq.7 mm, preferably in the range of
.gtoreq.5.6 mm to .ltoreq.6.2 mm.
[0046] Preferably the volume of the reservoir is less than in
customary crystallization plates. In a preferred embodiment, the
reservoir has a volume in the range from .gtoreq.70 .mu.l to
.ltoreq.160 .mu.l, especially in the range from .gtoreq.80 .mu.l to
.ltoreq.150 .mu.l, preferably in the range of .gtoreq.130 .mu.l to
.ltoreq.140 .mu.l.
[0047] The specified "volume of the reservoir" in the context of
the present application is understood to be the volume of the
reservoir from the floor of the reservoir to the height of the
ledge for the crystallization space.
[0048] Preferably, the reservoir has rounded corners. More
preferably, the reaction chamber has rounded corners.
[0049] It is especially advantageous that when the corners are
rounded, liquid, in particular the crystallization solvent, does
not rise or rises in a clearly reduced amount. In particular, a
combination of rounded off corners of the reservoir and rounded off
corners of the reaction chamber have proven to be favorable.
[0050] Preferably the at least one crystallization space is
arranged on a ledge in the reaction chamber. It is preferred that
the at least one crystallization space is constructed as a recess.
The ledge has, in a preferred embodiment, a smooth surface on the
underside beneath the crystallization space.
[0051] Preferably the ledge in the reaction chamber, on which the
at least one crystallization space is arranged is arranged at a
height in the range from .gtoreq.7 mm to .ltoreq.10 mm, preferably
in the range from .gtoreq.8 mm to .ltoreq.9 mm above the vessel
bottom of the reservoir.
[0052] Each reaction chamber has a reservoir and at least one
crystallization space. The reaction chamber can have several
crystallization spaces, for example, two or three crystallization
spaces, but it is preferred that the reaction chamber has one
crystallization space.
[0053] An additional advantage of the reaction vessel according to
the invention can be provided by the volume of one crystallization
space being increased compared to a number of crystallization
spaces.
[0054] In a preferred embodiment, the volume in particular of the
recess of the crystallization space can be in the range from
.gtoreq.10 nl to .ltoreq.7 .mu.l, preferably in the range from
.gtoreq.50 nl to .ltoreq.5 .mu.l, more preferably in the range of
.gtoreq.100 nl to .ltoreq.1 .mu.l, especially in the range of
.gtoreq.300 nl to .ltoreq.500 nl.
[0055] An increased volume of the crystallization space can have
the advantage that a sample dissolved in a crystallization solvent
can be pipetted not only automatically but also better
manually.
[0056] Preferably the recess that forms the floor of the
crystallization space has a curved or spherical surface, preferably
a concave surface that is arched to the inside.
[0057] According to a preferred embodiment the crystallization
space has an oval preferably elliptical or essentially elliptical
shape. According to an especially preferred embodiment of the
reaction vessel, the crystallization space is shaped elliptically
or essentially elliptically.
[0058] The term "elliptically shaped" in the context of the present
invention has the meaning that the crystallization space has an
elliptical outline in overhead view such that the longer axis of
the ellipsoid preferably extends parallel to the longer axis of the
reservoir. Preferably the crystallization space, in particular the
recess that forms the crystallization space, has the shape of a
half oval and preferably a half-ellipsoid.
[0059] According to an additional embodiment, the crystallization
space that is shaped elliptically or essentially has an elliptical
shape, in particular the recess that forms the crystallization
space has a width in the range from .gtoreq.1.5 mm to .ltoreq.4 mm,
preferably in the range from .gtoreq.1.8 mm to .ltoreq.3.5 mm,
preferably in the range of .gtoreq.2.1 mm to .ltoreq.3.0 mm, and/or
a length in the range from .gtoreq.4.5 mm to .ltoreq.8 mm,
preferably in the range from .gtoreq.5.1 mm to .ltoreq.7 mm,
preferably in the range of .gtoreq.5.6 mm to .ltoreq.6.2 mm.
[0060] The advantage of a curved, in particular, elliptical surface
of the crystallization space lies especially in the fact that a
reproducible positioning of the sample droplet is made possible.
This can result in a reproducible positioning of the crystal to be
formed. For example, the crystal will form preferably in the
deepest area of the curvature. In an advantageous way, the crystal
can thus form in the center or almost in the center in the
crystallization space.
[0061] Advantages thus result in particular from the reproducible
positioning of the dissolved sample, whereby a reproducible
positioning of the crystals can be obtained.
[0062] In particular, by a rounded off surface, preferably an
elliptically shaped surface, of the crystallization space it can be
avoided that the crystal growth starts in corners whereby a removal
of the crystal or an analysis of the crystal directly in the
crystallization space would be made more difficult.
[0063] An oval and preferably elliptical design has, moreover, the
special advantage that a removal of the crystals is made easier in
that a device for removal of the crystal, for example a customary
so-called crystallization loop, a metal pin with a loop on the end,
is guided through the shape of the crystallization space in the
direction of the deepest area. Thus, the essentially elliptical
shape of the crystallization space makes possible an easier
isolation of the crystal that is formed.
[0064] Furthermore, a curved surface of the crystallization space,
in particular an oval or preferably elliptical shape, can have the
additional large advantage of preventing a reflection, in
particular a total reflection, of the light, which for example is
used for illumination for microscope examination of crystals that
have formed in the reaction vessel, as frequently occurs on flat
surfaces. In this way, a microscopic examination in the reaction
chamber can be considerably made easier.
[0065] Preferably the reaction vessel is designed from a
light-permeable polymer. In this way, the crystallization growth
attempts can be examined without opening using light-optical
instruments.
[0066] Preferred polymers are selected from the group comprising
polypropylene, polystyrene, acryl butadiene styrene, polycarbonate,
polymethyl methacrylate, polysulfone, cycloolefin-copolymer (COC),
cycloolefin-polymer (COP), polymethyl pentene and/or acryl
ester-styrene acrylnitrile.
[0067] It is advantageous that these polymers are resistant to
organic solvents such as acetone, benzene or acetonitrile which are
frequently used for crystallization. Furthermore, they are
compatible with different frequently used salts, buffers or
polymers which are used for crystallization.
[0068] Especially preferred polymers are selected from the group
comprising cycloolefin-copolymers and/or cycloolefin-polymers,
preferably cycloolefin-copolymers. A reaction vessel, in particular
designed from a cycloolefin-copolymer can provide an especially
good transparency. Furthermore, vessels made from
cycloolefin-copolymers are less permeable to water vapor and thus
are less sensitive for evaporation than vessels made for example
from polystyrene.
[0069] Preferred cycloolefin-copolymers have, at room temperature
of 23.degree. C., a water absorption of less than 0.01%. Further
preferred, cycloolefin-copolymers can be used which have a light
permeability in the wavelength range of 280 nm of .gtoreq.90% to
.ltoreq.100%, preferably 91%.
[0070] Preferred cycloolefin-copolymers can be obtained for example
under the trade name Topas.RTM., in particular Topas.RTM. 8007X10,
of the company Topas Advanced Polymers. Preferred cycloolefin
polymers (COP) are obtainable, for example, under the trade name
ZEONOR.RTM..
[0071] The reaction vessel according to the invention is suitable
for the crystallization according to the "sitting drop" procedure,
of a sample from a solution comprising several reaction chambers,
wherein each reaction chamber has a reservoir and at least one
crystallization space.
[0072] If a sample solution is applied to a cover of the reaction
vessel, in particular directly above a reaction chamber, a
crystallization can be performed according to the so-called
"hanging drop" procedure.
[0073] According to a preferred embodiment of the reaction vessel,
the reaction vessel can also have a vessel cover. According to a
preferred embodiment, the vessel cover is an elastic cover foil. In
general, however, the use of a rigid cover is also possible in this
context. Preferably by attaching a cover foil or a rigid cover onto
the reaction vessel, the reaction chambers can all be closed
together.
[0074] An additional advantage of a cover foil is that also a part
of the reaction chambers of the reaction vessel can be
intentionally closed. In particular in the use of a cover foil it
is advantageous that individual reaction chambers can be opened
intentionally by removal of a partial piece of the cover foil
without the surrounding reaction chambers necessarily being also
opened. In particular, there is a small risk of contamination in
cover foils. Furthermore, adhesive cover foils are simple to
use.
[0075] It can also be provided that the spacers and edge areas of
the reaction vessel are covered with adhesive and a cover foil can
be applied that is not designed to be adhesive. However, it is
preferred that an adhesive cover foil is applied. This has
considerable advantages in the handling of the cover plate prior to
being adhered.
[0076] Preferably, the cover foil is made from a light-permeable
polymer. In this way, the crystallization growth attempts can be
examined without opening using light-optical instruments.
[0077] 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),
trifluorochloroethylene/ethylene copolymer (CTFE), polyvinylidine
fluoride (PVDF), tetrafluoroethylene-hexafluoropropylene copolymer
(FEP), polytetrafluoroethylene (PTFE), polyolefin, acryl polymer,
acryl-copolymer, ethylene acrylate, ethylene methacrylate, ethylene
methyl acrylate, ethylene methyl methacrylate copolymers,
acrylnitrilstyrene copolymers, acrylnitril methylacrylate
copolymers, ethylene vinyl acetate copolymers, butadiene styrene
copolymers, polybutadiene, butadiene acrylonitrile copolymers,
isobutylene isoprene copolymers, polycarbonates and/or cycloolefine
polymers (COP).
[0078] Especially preferred polymers are selected from the group
comprising polyethylene, polypropylene, polyester, polystyrene,
polymethylmethacrylate, polyoxymethylene, polyethylene
terephthalate, polyamide, fluoropolymers such as polyvinyl chloride
(PVC), polycarbonate and/or cycloolefine-polymers (COP). An
especially preferred polymer is polypropylene. In particular, a
polypropylene layer can provide a good transparency of the cover
foil.
[0079] Adhesive is preferably applied to the polymer layer.
[0080] Suitable adhesives are selected from the group comprising
reactive adhesives and/or contact adhesives. Contact adhesives are
preferred. As contact adhesives, contact adhesives customarily
known in the state of the art can be used. Usable as contact
adhesives are, for example, 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
ether, acrylonitrile copolymers, acrylates, methacrylates,
ethylacrylates, ethyl methacrylates, propyl acrylates, propyl
methacrylates, ethylacrylates, ethylmethacrylates, propylacrylates,
propylmethacrylates, n-butylacrylates, n-butylmethacrylates,
isobutylacrylates, 2-methylbutylacrylates, 2-ethylhexylacrylate,
n-octylacrylates, isooctylacrylates, isooctylmethacrylates,
isononylacrylates, isodecylacrylates, and copolymers of these
acrylates.
[0081] Proven to be especially suitable as an adhesive and in
particular a contact adhesive is an adhesive based on rubber,
synthetic rubber or acrylate. According to a preferred embodiment,
the contact adhesive is an acrylate adhesive. Preferred are
acrylate adhesives based on (meth)acrylates selected from the group
comprising methylacrylate, n-butylacrylate, tert.-butylacrylate,
2-ethylhexylacrylate, isooctylacrylate, isodecylacrylate,
isobornylacrylate, and isobornylmethacrylate and/or ethylene
acrylic acid copolymers.
[0082] Preferably, the covering foil is coated with an acrylate
adhesive. The well-adhering acrylate adhesive can provide a
reliable seal of the reaction chambers in an advantageous way. In
particular, an interaction of the wide spacers according to the
invention between the individual reaction chambers with a good
adhering covering foil can significantly reduce the evaporation
from the reaction chambers.
[0083] A surface above the individual reaction chambers can be
provided free of adhesive. Here, no adhesive can be applied on the
entire surface above the individual reaction chambers. This can
allow a crystallization according to the "hanging drop" process
without the sample solution being contaminated by adhesive.
[0084] Preferably, surfaces above the reaction areas are free of
adhesive. The entire area above the reaction areas can be free of
adhesive. Preferably only a part of the area above the reaction
areas is free of adhesive. Statements about the position of the
area here refer to the foil that is adhered to the reaction
vessel.
[0085] According to an especially preferred embodiment, a covering
foil for covering a reaction vessel comprising reaction chambers
comprises a polymer layer on which an adhesive layer is applied,
wherein preferably areas with a width in the range from .gtoreq.1.5
mm to .ltoreq.7.5 mm and a length in the range from .gtoreq.1.5 mm
to .ltoreq.7.5 mm are designed to be non-adhesive within the
adhesive layer.
[0086] This has, on the one hand, the advantage that the
positioning of a droplet of the sample on the covering foil can be
done with considerably greater certainty via the orientation to
adhesive-free surfaces. On the other hand, it can be prevented by
this that if the covering foil and/or the reaction vessel is
shaken, the applied droplets run into each other and contaminate
the adjacent growth attempts.
[0087] Preferably the covering foil has a number of non-adhesive
areas according to the formula 3.times.2.sup.N, where N is a
natural number. It is preferred that the arrangement of the
non-adhesive areas on the covering foil corresponds to the
arrangement of the reaction chambers of a reaction vessel according
to the SBS-standard where the non-adhesive areas are located in a
suitable way on the surface of the covering foil inside of the
cavity.
[0088] The non-adhesive areas are located preferably above the
reservoir.
[0089] The non-adhesive areas can have a round, oval, especially an
elliptical or essentially elliptical, or rectangular shape. In a
preferred embodiment the non-adhesive area has a round shape.
[0090] In a preferred embodiment, the covering foil can have round
areas with a diameter in the range from .gtoreq.1.5 mm to
.ltoreq.7.5 mm, preferably in the range from .gtoreq.13 mm to
.ltoreq.3 mm, especially in the range from .gtoreq.2 mm to
.ltoreq.2.5 mm, which are non-adhesive.
[0091] In further preferred embodiments, the covering foil can have
oval, in particular elliptical or essentially elliptical areas with
a width in the range from .gtoreq.1.5 mm to .ltoreq.4 mm,
preferably in the range from .gtoreq.1.8 mm to .ltoreq.3 mm,
especially in the range from .gtoreq.2 mm to .ltoreq.2.5 mm, and/or
a length in the range from .gtoreq.1.8 mm to .ltoreq.7.5 mm,
preferably in the range from .gtoreq.25 mm to .ltoreq.6 mm,
especially in the range from .gtoreq.2.5 mm to .ltoreq.3 mm, which
are non-adhesive.
[0092] In likewise preferred embodiments, the covering foil can
have rectangular areas with a width in the range from .gtoreq.1.5
mm to .ltoreq.7.5 mm, preferably in the range from .gtoreq.1.8 mm
to .ltoreq.3 mm, especially in the range from .gtoreq.2 mm to
.ltoreq.2.5 mm, and/or a length in the range from .gtoreq.1.5 mm to
.ltoreq.7.5 mm, preferably in the range from .gtoreq.1.8 mm to
.ltoreq.3 mm, especially in the range from .gtoreq.2 mm to
.ltoreq.2.5 mm, which are non-adhesive.
[0093] In especially preferred embodiments, the covering foil can
preferably have round, non-adhesive surfaces with an area in the
range from .gtoreq.1.5 mm.sup.2 to .ltoreq.45 mm.sup.2, preferably
in the range from .gtoreq.2.5 mm.sup.2 to .ltoreq.8 mm.sup.2,
especially in the range from .gtoreq.3 mm.sup.2 to .ltoreq.5
mm.sup.2.
[0094] In also preferred embodiments, the covering foil can have
non-adhesive areas with a width in the range from .gtoreq.5.8 mm to
.ltoreq.6.6 mm, preferably in the range from .gtoreq.6.1 mm to
.ltoreq.6.3 mm, and/or a length in the range from .gtoreq.5.8 mm to
.ltoreq.6.6 mm, preferably in the range from .gtoreq.6.1 mm to
S.ltoreq.6.3 mm.
[0095] Preferably the covering foil is provided in form of a
cutting suitable for a reaction vessel according to the
SBS-standard. In preferred embodiments, a preferred cutting of the
covering foil can have a width in the range from .gtoreq.76 mm to
.ltoreq.84 mm, preferably in the range from .gtoreq.77 mm to
.ltoreq.82 mm, especially in the range from .gtoreq.78 mm to
.ltoreq.80 mm, and/or a length in the range from .gtoreq.130 mm to
.ltoreq.160 mm, preferably in the range from .gtoreq.135 mm to
.ltoreq.155 mm, especially in the range from .gtoreq.140 mm to
.ltoreq.150 mm.
[0096] Preferably the length of the cuttings of the covering foil
is longer than the length of a reaction vessel according to the
SBS-standard. Preferably the cuttings have a non adhesive area on
both sides in the length, preferably each with a length in the
range from .gtoreq.5 mm to .ltoreq.12 mm, preferably in the range
from .gtoreq.8 mm to .ltoreq.10 mm. This has the advantage that the
covering foil can be better grasped on the longitudinal side and
can be applied onto the reaction vessel with increased
certainty.
[0097] In a further preferred embodiment, the covering foil
including a polymer layer and an adhesive layer has a thickness in
the range from .gtoreq.25 .mu.m to .ltoreq.125 .mu.m, preferably in
the range from .gtoreq.50 .mu.m to .ltoreq.100 .mu.m, especially in
the range from .gtoreq.65 .mu.m to .ltoreq.70 .mu.m. This has the
advantage that the covering foil can be easily poked through.
[0098] According to a preferred embodiment, the covering foil has
on the side of the covering foil that is not covered with
adhesives, markings which indicate the position of the
adhesive-free surfaces and/or indicate the individual reaction
chambers. For example, the designation of the individual reaction
chambers can be given in mirror-reverse as well as also in the
reading direction, this has the advantage that the designation of
the individual reaction chambers can be read during the application
of the sample droplets as well as during and/or after the
application of the foil onto the reaction vessel. Furthermore, the
marking of the position of the adhesive-free surfaces makes it
possible to easily recognize the position of the often colorless
crystals formed.
[0099] Preferably, the markings are made in the form of an imprint.
The marking can also be applied onto the non-adhesive areas of the
side of the covering foil which is provided with adhesive. In
addition to a bare imprint, the marking can also be made by an
embossing for example a raised border or by a recess.
[0100] The adhesive layer can be protected by a removable
protective foil preferably by a removable silicone foil.
[0101] The present invention further relates to an arrangement for
the application of a covering foil onto a reaction vessel,
comprising a fastening device for a covering foil comprising a base
structure for receiving the covering foil wherein the base
structure has a footprint area preferably with a width in the range
from .gtoreq.80 mm to .ltoreq.90 mm and a length in the range from
.gtoreq.120 mm to .ltoreq.135 mm, wherein on at least two opposing
sides of the base structure fastening components are applied with
which the covering foil is attachable in a stretched manner to the
base structure so that it can be stretched tight, and wherein the
base structure preferably has in the corner areas at least two
positioning elements, preferably recesses.
[0102] In an advantageous way, the fastening components make
possible an attachment of the covering foil to the fastening
device.
[0103] Surprisingly it could be determined that the fastening
device makes it possible to affix a covering foil securely and then
detachable again so that the covering foil can be pipetted without
sliding. In particular, droplets of sample solution can be applied
precisely onto selected areas of a slide-proof and secure covering
foil.
[0104] The base structure is preferably a rectangular base
structure. Preferably the base structure has an area that can be
set onto a reaction vessel with a width in the range from
.gtoreq.83 mm to .ltoreq.87 mm and a length in the range from
.gtoreq.125 mm to .ltoreq.129 mm. Especially preferred, the base
structure has a surface area which can be set onto a reaction
vessel having SBS-standard format.
[0105] Preferably, the base structure has at least two side edge
surfaces which are set apart at a distance such that the base
structure can be mounted onto a reaction vessel with a width in the
range from .gtoreq.83 mm to .ltoreq.87 mm in particular of the
SBS-standard.
[0106] Preferably the base structure has a footprint area with a
width in the range from .gtoreq.83 mm to .ltoreq.87 mm and a length
in the range from .gtoreq.125 mm to .ltoreq.129 mm, preferably with
a width in the range from .gtoreq.84 mm to .ltoreq.86 mm and a
length in the range from .gtoreq.126 mm to .ltoreq.128 mm.
Preferably, the footprint area complies with the SBS-standard. The
footprint area makes possible in an advantageous way that the
fastening device can be positioned on common pipetting robots.
Thus, a pipetting of liquid on a covering foil on a fastening
device can also be done automatically as well as manually.
[0107] In a preferred embodiment, an elastically deformable
mounting surface is attached to the base structure.
[0108] Preferably, the elastically deformable mounting surface can
be connected to the base structure so that it can be separated.
Preferably, the elastically deformable mounting surface can be
mounted to the base structure so that it can be connected in an
affixed way. In a preferred embodiment, the elastically deformable
mounting surface can be mounted so that is can be affixed to the
base structure.
[0109] The term "elastically deformable" is understood in the
context of the present invention to mean that the mounting surface
can be deformed when it is pressed upon and after the end of the
applied pressure, it will return again to the non-deformed flat
shape.
[0110] By the mounting surface being elastically deformable the
mounting surface can easily be adapted to the spacers of a reaction
vessel. This makes it possible for the fastening device to be used
not only for a certain reaction vessel, but also for reaction
vessels with varying design of the surface. For example, using the
elastically deformable mounting surface, a foil can not only be
mounted on the reaction vessels with varying width, but also on
reaction vessels that do not necessarily have to have a flat
surface.
[0111] In an advantageous way, the elastically deformable mounting
surface makes it possible to uniformly adhere the covering foil
onto a reaction vessel in a planar arrangement after pipetting. In
particular, a uniform adhering or pressing of a foil that is
designed to be adhesive onto a reaction vessel or a non-adhesive
foil is made possible by a reaction vessel that is provided with
adhesive surface areas.
[0112] The elastically deformable mounting surface can be made from
an elastomer, in particular a thermoplastic elastomer, silicone or
rubber. Principally suitable in addition to plastic are other
materials that are elastically deformable after they have been
pressed flat. Preferably, the elastically deformable mounting
surface has a thickness in the range from .gtoreq.0.5 mm to
.ltoreq.2 mm, preferably in the range from .gtoreq.1.3 mm to
.ltoreq.1.5 mm.
[0113] The width of the elastically deformable mounting surface is
preferably in the range from .gtoreq.75 mm to .ltoreq.87 mm,
preferably in the range from .gtoreq.77 mm to .ltoreq.85 mm,
especially in the range from .gtoreq.78 mm to .ltoreq.80 mm, and/or
the length is in the range from .gtoreq.100 mm to .ltoreq.150 mm,
preferably in the range from .gtoreq.115 mm to .ltoreq.140 mm,
especially in the range from 2.gtoreq.120 mm to .ltoreq.135 mm.
[0114] Onto the fastening device, fastening components are mounted
on at least two opposing sides of the base structure with which the
covering foil can be stretched tight in attachment onto the base
structure.
[0115] Preferably, the covering foil is attachable in a stretched
and detachable manner onto the base structure. After the
application of the sample solution onto the foil affixed to the
base structure, it can be detached again from the base structure.
The mounting can be made possible by suitable fastening
components.
[0116] Preferably, the fastening components are mounted onto the
front sides of the base structure. However, it can also be provided
that fastening components are mounted onto the longitudinal
sides.
[0117] Preferred fastening components are selected from the group
comprising hangers, loops, flaps, bands, spring elements and/or
sliding fastening components.
[0118] Preferably, the fastening components are set in bearings so
that they can rotate by a hinged connection. In an especially
preferred embodiment, the fastening components can be set on an
axle so that they can rotate. Preferred fastening components are
mounting plates that are set on an axle so that they can
rotate.
[0119] In another preferred embodiment, the fastening components
can be slidable fastening components which can fix the foil from
the side or from above. In yet another embodiment, the fastening
components can be hangers, loops, flaps, bands, or spring elements,
in particular hangers, loops, flaps, bands, or spring elements that
are affixed to the base structure.
[0120] It can be preferred that the fastening components are spring
elements that are affixed to the base structure. This makes it
possible that the foil can be affixed by it being able to slide
under the spring elements that are affixed to the base
structure.
[0121] In preferred embodiments, the foil is affixed by it being
placed on the mounting surface. The fastening components,
preferably mounting plates set in bearings so that they can rotate
on an axle can be opened for this purpose, for example, by folding
them open.
[0122] Preferably, the fastening components can be locked in the
opened position. This can prevent an undesired slamming shut of the
fastening components, for example, plates. According to a preferred
embodiment, the fastening components can be locked in the opened
position by press pins.
[0123] After the foil is placed, the fastening components,
preferably mounting plates set in bearings so that they can rotate
on an axle, can be closed shut. Preferably the foil can be clamped
fixed by closed plates on the base structure.
[0124] Preferably, the fastening components can be locked in closed
position. This can prevent an undesired opening of the fastening
components, e.g. the plates. According to a preferred embodiment,
the fastening components can be locked in a closed position by
magnets that are located in the base structure and in the fastening
components.
[0125] In a preferred embodiment, the fastening components can be
locked in an open position by press pins and/or the fastening
components can be locked in a closed position by magnets located in
the base structure and in the fastening components.
[0126] A "closed position" is understood in the context of the
present invention to be the position in which a covering foil is
affixed by fastening components in the fastening device.
Preferably, the fastening components, e.g. mounting plates set in
bearings on an axle, are closed in the process. An "open position"
in the context of the present invention is understood to be the
position in which a covering foil is not affixed by the fastening
components in the fastening device. Preferably in the process the
fastening components, e.g. mounting plates set in bearings on an
axle, are opened.
[0127] According to a further preferred embodiment, the fastening
components can be locked by a spring system, e.g. a dead-center
spring.
[0128] The fastening device has at least two positioning elements.
The at least two positioning elements are preferably mounted on
opposing sides of the fastening device. In a preferred way, the
fastening device has four positioning elements preferably arranged
symmetrically to each other. The positioning elements are
preferably provided on two positions of the base structure.
Preferably, the positioning elements are mounted in corner areas of
the base structure.
[0129] The positioning elements of the fastening device can be
recesses or raised areas such as pins or projections. The
positioning elements of the fastening device are preferably
recesses. This allows an unhindered positioning of the foil and in
particular, an unhindered application of a liquid onto the
positioned covering foil.
[0130] In preferred embodiments, the positioning elements,
preferably recesses have a diameter in the range from .gtoreq.4.2
mm to .ltoreq.8.2 mm, preferably in the range from .gtoreq.4.7 mm
to .ltoreq.7.2 mm, especially in the range from .gtoreq.5.2 mm to
.ltoreq.6.2 mm. In additional preferred embodiments, the recesses
are through-holes.
[0131] The fastening device with the covering foil, on which sample
solution was pipetted, can be turned around and placed on a
reaction vessel. Then, by pressing using the elastically deformable
mounting surface, the adhesive layer of the covering foil can be
adhered onto the reaction vessel. After the foil is stuck onto the
reaction vessel, the mounting plates can be detached and the
fastening device can be easily lifted out.
[0132] It is preferred that setting the covering foil on a reaction
vessel is done using a receiving device for a reaction vessel. This
has the advantage that the placement can be done in a directed
way.
[0133] The arrangement according to the invention for the
application of a covering foil onto a reaction vessel comprises at
least one fastening device for a covering foil.
[0134] The arrangement according to the invention for the
application of a covering foil onto a reaction vessel comprises
more preferred a receiving device for a reaction vessel wherein on
the base structure of the receiving device at least two positioning
elements, preferably pin-type positioning elements are arranged,
and wherein the dimensions of the recess are such that a reaction
vessel with a width in the range from .gtoreq.80 mm to .ltoreq.90
mm, preferably with a width in the range from .gtoreq.83 mm to
.ltoreq.87 mm, especially with a width in the range from .gtoreq.84
mm to .ltoreq.86 mm can be positioned in the recess.
[0135] 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. In a preferred way, the
receiving device has four positioning elements preferably arranged
symmetrically to each other. Preferably, the positioning elements
are mounted in the corner areas of the base structure of the
receiving device.
[0136] The positioning elements of the receiving device can be
raised areas such as pin-type elements, in particular pins or
projections, or recesses. The positioning elements of the receiving
device are preferably pin-type positioning elements.
[0137] The positioning elements of the fastening device, preferably
recesses, can interact, preferably with the positioning elements of
the receiving device, preferably raised areas such as pins. In
preferred embodiments of the receiving device, the at least two
positioning elements, preferably pin-type positioning elements, can
be made to mesh with the positioning elements, preferably recesses,
of the fastening device according to the invention.
[0138] In preferred embodiments, the positioning elements,
preferably pin-type positioning elements, have a length in the
range from .gtoreq.25 mm to .ltoreq.40 mm, preferably in the range
from .gtoreq.28 mm to .ltoreq.38 mm, especially in the range from
.gtoreq.30 mm to .ltoreq.35 mm. In additional preferred
embodiments, the positioning elements, preferably pin-type
positioning elements, have a diameter in the range from .gtoreq.4
mm to .ltoreq.8 mm, preferably in the range from .gtoreq.4.5 mm to
.ltoreq.7 mm, especially in the range from .gtoreq.5 mm to
.ltoreq.6 mm.
[0139] According to another embodiment, the fastening device can be
positioned with the aid of guide rails along the outer surfaces of
the fastening device on or in the recess device.
[0140] The positioning using pin-type positioning elements, in
particular, pins which can be brought into mesh with the recesses
of the fastening device, or guide rails, has the great advantage
that the foil can be mounted on the reaction vessel in a directed
manner. In particular, the pins or the guide rails allow the
positioned foil to be mounted onto a reaction vessel
correspondingly positioned in a receiving device so that the
surfaces of the foil that are free of adhesive and covered with
drops can be positioned with essentially greater precision above
the reaction chambers than is possible without an auxiliary
mechanism.
[0141] In a preferred way, the dimensions of the recess are square
shaped. Preferably, the dimensions of the recess are such that a
reaction vessel can be set into the recess with SBS-standard
format.
[0142] Into the recess of the receiving device, a reaction vessel
can be positioned preferably with SBS format. After drops of the
sample solution have been brought onto the covering foil, the
fastening device with the covering foil can be turned over and set
onto the receiving device. In this process, for example, pins of
the receiving device mesh into corresponding recesses of the
fastening device. Thus, the position of the reaction vessel and the
foil are coordinated to each other.
[0143] The foil can be pressed onto the reaction vessel located in
the receiving device, whereby the elastic mounting surface of the
foil can provide a uniform distribution of the force and thus a
uniform adhesion. Then, the fastening components for example plates
can be opened and the fastening device lifted off. The reaction
vessel closed with the foil can be taken out of the plate
receptacle.
[0144] In preferred embodiments, an arrangement for the application
of a covering foil on a reaction vessel comprises a fastening
device according to the invention for a covering foil and a
receiving device according to the invention for a reaction
vessel.
[0145] It is preferred that the arrangement according to the
invention for the application of a covering foil onto a reaction
vessel is made out of a polymer material. Preferred polymers are
selected from the group comprising polyoxymethylene (POM),
polymethylmethacrylate (PMMA) and/or polypropylene.
[0146] This makes it possible that the device is easy to clean.
However, it can also be preferred that the device is made of metal
or partially out of metal. Preferred metals are selected from the
group comprising special steel, in particular stainless steel
and/or aluminum. Aluminum is preferably anodized or provided with a
surface coating, preferably a varnish, in particular clear varnish,
especially duroplastic cured varnish.
[0147] The present invention relates furthermore to a system
comprising a reaction vessel according to the invention and a
covering foil. Preferably, the system comprises a reaction vessel
according to the invention and a covering foil mounted onto the
reaction vessel. It is advantageous that the reaction vessel
according to the invention can be used with any suitable covering
foil for covering the reaction chambers. Preferably, the covering
foil is a covering foil according to the invention.
[0148] For the reaction vessel and the covering foil according to
the invention, reference is hereby made in full extent to the
previous description.
[0149] The present invention relates furthermore to a system
comprising a reaction vessel, a covering foil and an arrangement
according to the invention for the application of a covering foil
onto a reaction vessel.
[0150] It is advantageous that the arrangement according to the
invention for the application of a covering foil onto a reaction
vessel can be used with any suitable reaction vessel with
SBS-standard format.
[0151] Reference is thus made in full extent to the previous
description for the arrangement according to the invention for
mounting a covering foil.
[0152] Additional details, characteristics, and advantages of the
object of the invention can be gathered from the subordinate claims
and the following description of the corresponding drawings and
examples, in which for example, embodiment examples of the present
invention are depicted.
[0153] FIG. 1 shows a schematic view of a reaction vessel according
to the invention according to an embodiment example of the
invention.
[0154] FIG. 2 shows a section view of a reaction vessel according
to the invention based on FIG. 1 along the axis I.
[0155] FIG. 3 shows an enlarged schematic view of a reaction vessel
according to the invention according to FIG. 1.
[0156] FIG. 4 shows a schematic view of a covering foil according
to the invention according to an embodiment example of the
invention.
[0157] FIG. 5 shows a schematic view of a fastening device
according to the invention according to an embodiment example of
the invention.
[0158] FIG. 6 shows a schematic view of a receiving device
according to the invention according to an embodiment example of
the invention.
[0159] FIG. 1 shows a schematic view of a reaction vessel according
to the invention for crystallization of a sample from a solution
according to an embodiment example. The reaction vessel 1 comprises
several reaction chambers 2. In the reaction chamber 2, a reservoir
4 and a crystallization space 6 are located. The crystallization
space 6 is in the form of an elliptically constructed recess. The
crystallization space is arranged on a step in the reaction chamber
2. The side walls of the reaction chambers 2 are connected to each
other via the connection spacers 12. In this way, the connection
spacers 12 form, with the sideways circumferential surfaces 14 of
the reaction vessel 1, a common flat surface. The connection
spacers 12 have a groove 16 in the middle.
[0160] The section view of the reaction vessel according to the
invention shown in FIG. 2 based on FIG. 1 along axis I shows
clearly that the connection spacers 12 form a flat surface with the
sideways circumferential surfaces 14 of the reaction vessel 1.
Here, the connection spacers 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 that is set off at a distance from it. The step,
on which the crystallization space 6 is arranged, has a flat
surface on the underside below the crystallization space.
[0161] The side walls of the reaction chamber 2 are connected to
each other via connection spacers 12 which form a flat surface with
the sideways circumferential surfaces 14 of the reaction vessel 1.
Correspondingly, the connection spacers 12 also connect, along an
axis perpendicular to the axis I shown, a first side wall, which is
perpendicular to the side wall 8, of a first reaction chamber 2, to
a second side wall, which is set apart at a distance from it and is
perpendicular to the side wall 10, of a second reaction chamber
2.
[0162] FIG. 3 shows an enlarged schematic view of the reaction
vessel according to the invention according to FIG. 1. The
connection spacers 12 have a recess 18 in a corner of a reaction
chamber 2.
[0163] FIG. 4 shows a schematic view of a covering foil according
to the invention according to an embodiment example of the
invention. The covering foil 20 comprises a polymer layer 22 on
which an adhesive is applied. Within the adhesive layer 24, are
areas 26 that are free of adhesive. Within these areas 26, a sample
drop can be applied. Furthermore, the covering foil 20 has, on both
sides in the length an adhesive-free area of the polymer layer 22.
This has the advantage that the covering foil 20 can be better
grasped on the area of the polymer layer 22 that is free of
adhesive.
[0164] FIG. 5 shows a schematic view of a fastening device 30
according to the invention according to an embodiment example of
the invention. The fastening device 30 has a base structure 32 for
receiving the covering foil. On the base structure, an elastically
deformable mounting surface 40 is affixed. Furthermore, the base
structure 32 has a footprint area 34 with a width in the range from
.gtoreq.84 mm to .ltoreq.86 mm and a length in the range from
.gtoreq.126 mm to .ltoreq.128 mm. On the face sides of the base
structure 32, mounting plates 36 are attached with which the
covering foil is stretched tight and attached to the base structure
so that it is detachable. The mounting plates 36 are set in
bearings on an axle 42 so that they can rotate. In the closed
position (shown) the mounting plates 36 are locked by magnets
inserted into the base structure and the fastening components 36.
In addition, the base structure 32 has recesses 38 in the corner
regions.
[0165] FIG. 6 shows a schematic view of a receiving device
according to the invention according to an embodiment example of
the invention. The receiving device 50 comprises a base structure
52 with a recess 54. Here, the dimensions of the recess 54 are made
so that a reaction vessel with SBS-standard format can be
positioned in the recess 54. Furthermore, the receiving device 50
has pins 56 in the corner areas of the receiving device 50 which
can be brought into mesh with recesses 38 of the fastening
device.
* * * * *
References