Abstrict There is provided a system for the preparation of liquids from
at least one solid and at least one liquid phase. The system is
composed of a vessel in which the solid or solids are located and
a drying chamber which is connected to the vessel or can be connected
to the vessel. The drying chamber is separated from the vessel interior
by a separating means which is permeable to water vapour but is
impermeable to liquids. The system is suitable for the production
of liquids from moisture-sensitive solids. These solids can be stored
in the vessel since the air humidity in the interior is lowered
by the desiccant. The preparation of the liquid by addition of a
liquid phase can be carried out in one and the same vessel since
the desiccant is separated from the vessel interior.
Claims What is claimed:
1. An apparatus for the preparation of a liquid from at least one
solid and at least one liquid phase, comprising:
a vessel which defines a compartment which contains said at least
one solid, said compartment having a volume which is sufficient
to receive said at least one solid and said at least one liquid
phase;
a desiccant article which defines a desiccant chamber which contains
a desiccant; and
a separating element which is permeable to water vapor and which
separates said desiccant chamber from said compartment, such that
said desiccant can exchange water vapor with said compartment and
direct contact of liquid or solid contents in said compartment with
said desiccant is substantially prevented, wherein said separating
element is made of cardboard and has a surface tension for wetting
which is smaller than 70 mN/m.
2. An apparatus as claimed in claim 1 wherein said desiccant article
is selectively engageable with said vessel so as to close said compartment.
3. An apparatus as claimed in claim 1 wherein said vessel is composed
of a material which is at least partially permeable to water vapor.
4. An apparatus as claimed in claim 1 wherein said separating
element has a surface tension for wetting of from 25 to 65 mN/m.
5. An apparatus as claimed in claim 1 wherein said separating
element has a critical surface tension for wetting of from 30 to
40 mN/m.
6. The apparatus of claim 1 wherein said desiccant chamber is
closed to the outside by a wall.
7. The apparatus of claim 6 wherein said wall is composed of a
plastic, a metal or a cardboard material.
8. A process for the production of a liquid, comprising:
a) storing a solid in a compartment defined by a vessel, said vessel
being separated from a desiccant chamber by a separating element
which is permeable to water vapor, said desiccant chamber containing
a desiccant, such that said desiccant can exchange water vapor with
said compartment and direct contact of liquid or solid contents
in said compartment with said desiccant is substantially prevent;
b) opening said vessel;
c) adding liquid phase to said solid in said compartment;
d) closing said vessel; and
e) mixing said solid and said liquid phase so that a solution,
suspension or emulsion is formed.
9. A process as claimed in claim 8 comprising closing said vessel
with said desiccant chamber before as well as after said adding
of said liquid phase.
10. A process as claimed in claim 8 wherein said solid is placed
in said compartment in an atmosphere containing water vapor.
11. A process as claimed in claim 8 wherein said adding of said
liquid phase is carried out by a filling device.
12. A process as claimed in claim 8 wherein said solution, suspension
or emulsion is withdrawn from said compartment by a withdrawing
device.
13. A process as claimed in claim 8 wherein said liquid phase
is prepared by a mixing device.
14. A process as claimed in claim 8 wherein said storing of said
solid in said vessel serves to dry or maintain dryness of said solid.
15. A process as claimed in claim 14 wherein said storing of said
solid in said vessel serves to dry and maintain dryness of said
solid.
16. A process as claimed in claim 8 wherein said opening of said
vessel in step b) is achieved by piercing with a cannula.
17. A process according to claim 8 wherein said mixing of said
solid and said liquid phase produces a reagent solution.
18. The process of claim 8 wherein said desiccant chamber is closed
to the outside by a wall.
19. The process of claim 18 wherein said wall is composed of a
plastic, a metal or a cardboard material.
20. A process for the production of a liquid, comprising:
a) storing a solid in a compartment defined by a vessel, said vessel
being separated from a desiccant chamber by a separating element
which is permeable to water vapor, said desiccant chamber containing
a desiccant, such that said desiccant can exchange water vapor with
said compartment and direct contact of liquid or solid contents
in said compartment with said desiccant is substantially prevented;
b) opening said vessel;
c) adding liquid phase to said solid in said compartment; and
d) mixing said solid and said liquid phase in an opened vessel
so that a solution, suspension or emulsion is formed.
21. A process according to claim 20 wherein said mixing of said
solid and said liquid phase produces a reagent solution.
22. The process of claim 20 wherein said desiccant chamber is
closed to the outside by a wall.
23. The process of claim 22 wherein said wall is composed of a
plastic, a metal or a cardboard material.
Description The invention concerns a system for the preparation of liquids
from at least one solid and at least one liquid phase, the system
consisting of a storage vessel with the solid and a drying chamber
with a desiccant. In addition the invention concerns a process for
the production of a solution, suspension or emulsion using the system
according to the invention. The process comprises the steps of storing
a solid in the system, adding a liquid phase to the solid and mixing
in order to produce a solution, suspension or emulsion. In a preferred
application the system serves to produce reagent solutions.
A problem which frequently occurs in laboratories is that of preparing
solutions from liquids and moisture-sensitive solids. The stability
of many solids is limited in the presence of water vapour since
they decompose. The occurrence of such problems ranges from everyday
examples such as e.g. the preparation of foods from dry powder,
over the preparation of solutions in the chemical laboratory, to
clinical analytical solutions. Especially in the latter case it
is necessary to prepare a solution from a solid and a liquid component
shortly before use if the final analytical solution has only a limited
stability.
The prevailing problem is often solved by either pre-drying the
moisture-sensitive solid and packaging it in a water-vapour-tight
package or it is packaged together with hygroscopic substances in
order to dry it and maintain dryness. In order to prepare the solution,
a certain amount of the substance is weighed and dissolved in a
measured amount of liquid. The process is imperfect, in particular
for analytical solutions, since the quantitative transfer of the
solid into a vessel, the addition of an exactly defined amount of
solvent and a complete dissolution is difficult. The said process
not only requires trained personnel but also elaborate laboratory
equipment.
In the case of so-called test kits the user undertakes the preparation
of the liquid by preparing the analytical solution from the portioned,
i.e. already weighed solids by addition of liquid according to the
instructions of the manufacturer of the kit. Stirrers or mixers
can relieve the user of the task of dissolving the solids. However,
in these cases it is nevertheless necessary to transfer a solid
into a vessel for dissolution. Consequently a defined amount of
solid in the form of tablets, powders or granulates has to be introduced
into a vessel in order to prepare a solution of a defined concentration.
In a known reagent stocking system (DE-40 39 580) the reagent is
transferred from a special container into a mixing vessel by the
opening of a chamber in which the reagent is located when it is
screwed onto the vessel. In order to prepare a solution of an exactly
defined concentration it is necessary to rinse the chamber. This
necessitates laboratory personnel or an elaborate rinsing device.
The object of the invention is to simplify the preparation of liquids
from moisture-sensitive solids and liquids by providing a vessel
suitable for drying and maintaining dryness. In particular it is
intended to facilitate the preparation of an analytical solution
by untrained personnel even under conditions of poor infrastructure.
The object is achieved with the system for the preparation of a
liquid from at least one solid and at least one liquid phase by
the combination
of a vessel which contains the at least one solid and has a volume
which is sufficient to receive the at least one solid and the at
least one liquid phase,
a desiccant chamber which contains a desiccant (D)
and a separating element which closes the desiccant chamber in
such a way that
the desiccant can exchange water vapour at any time with the contents
of the vessel but direct contact of liquid or solid contents of
the vessel with the desiccant is essentially impossible.
Accordingly the object is achieved by the combination of the following
elements:
A vessel in which at first the solid is situated and in which the
dissolution of the solid takes place.
A drying chamber connected to the vessel in which a desiccant is
located.
The solid of the solution to be prepared can be present in various
forms. These include powder, tablets, granulates, pellets or lyophilisates
manufactured by freeze-drying.
A solution of several substances can be prepared by using a solid
consisting of several components. If the components are mutually
incompatible in solution or in the presence of humidity i.e. they
then react with each other in an undesired manner, it is, however,
in many cases possible to store the substances together in a dry
state without their reacting with each other. The storage stability
of the solid is increased by a drying chamber which maintains the
humidity in the interior of the vessel at a low level. The presence
of a desiccant in a chamber which can exchange water vapour with
the vessel interior leads to a decrease in the partial water vapour
pressure in the vessel interior. In the case of solids which have
a residual moisture content due to the manufacturing process it
is additionally possible to store them in the system according to
the invention in order to dry them or to remove the residual moisture.
The liquid phase can represent a liquid composed of a pure substance
(e.g. distilled water) or a mixture of several liquids. The liquid
phase can also for example contain buffers, stabilisers or further
dissolved substances so that the stability of the prepared liquid
is increased and its function is ensured.
In order to prepare the liquid, the liquid phase is added to the
solid in the vessel. This can either be carried out manually or
automatically by a device. In cases in which the prepared liquid
does not have to have an exact concentration since a wide range
of reagent concentrations lead to the same analytical results, the
measuring of the liquid phase can for example be achieved by marks
on the vessel wall. For example enzymes may completely convert an
analyte so that the result of the determination is independent of
the enzyme concentration in the reagent over wide ranges. In contrast
for the preparation of a suitable standard solution for titration
analyses, the addition of a defined amount of liquid phase, characterized
by its volume or its weight, to a defined amount of solid is necessary.
The preparation of the solution is achieved by manual or mechanical
mixing of the solid and the liquid phase. It is possible to standardize
the preparation of numerous analytical solutions. In these embodiments
the liquid phase already contains further components, e.g. buffer
and auxiliary substances, so that always one and the same liquid
phase can be used for many different analytical solutions.
The liquids produced from the solid and liquid phase in the system
according to the invention can be solutions, suspensions or emulsions.
For example an emulsion for the detection of the enzyme lipase can
be prepared by addition of water to a solid which comprises the
following substances: Tris(hydroxymethyl)aminomethane (Tris), sodium
deoxycholate, CaCl.sub.2 triolein, colipase, NaN.sub.3.
According to the invention the system contains a vessel and a drying
chamber which are separated by a separating layer which prevents
entry of liquid into the desiccant. Thus the separating layer fulfils
two contradictory requirements. On the one hand it is permeable
to water vapour and thus enables transfer of water from the vessel
interior into the drying chamber via the gas phase, on the other
hand it has a barrier effect for water in a condensed phase. For
the preparation process this results in the simplification that
the preparation of the solution can take place in the same vessel
in which the moisture-sensitive solid has previously been stored.
In a preferred embodiment, the solid is already dispensed into the
vessel during the manufacture of the system. In this case it is
not necessary for the user to transfer the solid into the vessel.
This additionally eliminates the problem of the user having to weigh
out and transfer substances which may be sensitive to moisture or
even hygroscopic. The manufacturer can fill the system under dry
room conditions and using highly accurate balances. Thus it is possible,
even for users without a laboratory, to prepare standardized analytical
solutions from moisture-sensitive solids.
A preferred embodiment enables a particularly simple, safe and
reliable handling in which the solid is located in a vessel which
is large enough to receive the solution which is formed. This vessel
has a closure, e.g. a stopper or a screw cap, to which a desiccant
chamber is attached in such a way that the desiccant which it contains
can take up water vapour from the interior of the vessel when the
vessel is closed. In this embodiment the drying chamber can serve
to dry and/or maintain dryness of the solid and it can also be used
as a closure when preparing liquids.
It is also possible to mount the drying chamber in the vessel and
to use a separate component to close the vessel. In addition embodiments
are possible in which no means of opening by for example a screw
cap or a cover is provided. In these embodiments the solid and the
drying chamber can already be introduced into the vessel during
the manufacture of the vessel. The liquid phase can be dispensed
into the vessel before the user uses the liquid e.g. by injection
with a cannula.
The system according to the invention for the preparation of liquids
in its various embodiments offers solutions to problems some of
which have contradictory requirements.
Conventional vessels constructed for receiving liquids can also
be used to store and re-dry moisture-sensitive solids by the use
according to the invention of the drying stopper. The vessel and
desiccant stopper thus become a new functional unit.
The system for preparing solutions allows the dispensing of moisture-sensitive
filling materials in containers which are not completely water-vapour-tight
for the purpose of putting them into circulation.
Solid filling materials may, due to the manufacturing process,
have a higher mobile moisture content when they are dispensed than
is desirable for storage. Such filling materials can be redried
with the system according to the invention to the minimum residual
moisture content necessary for stability.
The separating element combines a high vapour permeability with
a good barrier effect against liquids.
A process for the preparation of liquids using the system according
to the invention can be carried out in the following steps:
Storage of a solid in a closed vessel.
Opening the system e.g. by unscrewing a cap.
Filling the vessel which already contains the solid with the liquid
phase.
Closing the system e.g. by screwing on a cap.
Mixing the liquid phase and solid.
The filling of the vessel with the liquid phase can be carried
out manually or by machine, the automatic filling of the vessel
within an automated analyser representing a preferred embodiment.
The vessel can be closed with the cap belonging to the system or
with a further cap. In this step in the process it is also possible
to employ manual as well as automatic procedures. In special embodiments
of the process according to the invention it is possible to omit
the step of closing the vessel when liquid does not escape from
the vessel during mixing. This can for example be achieved by stirring
or suitable rotation of the vessel. Apart from mechanical stirring
with a rotor which is immersed in the liquid, so-called magnetic
stirrers are known among others in the state of the art in which
a usually rod-shaped magnet is located within the vessel that is
brought into motion by a magnetic field. In addition rockers for
bacterial cultures are for example known which mix the contents
of a vessel without the substances in the vessel escaping through
an opening present in the upper side of the vessel. If the mixing
process is carried out in a closed vessel then the aforementioned
methods are available. In addition it is possible to use those methods
in which the vessel can take up any position such as is usually
the case for manual mixing. After the mixing process the prepared
liquid is present in a vessel. It can be withdrawn from this for
example by piercing the vessel with a cannula or by further devices
provided in the vessel. However, the liquid is preferably withdrawn
after removing the cap containing the desiccant by opening the vessel.
An advantage of the system according to the invention is that the
storage vessel for the solid can also serve as the vessel to mix
the solid with the liquid phase and to store the prepared liquid
without it being necessary to close or remove the desiccant chamber
after addition of the liquid phase.
A further advantage of the system is that the cap containing the
desiccant can be used during storage of the solid as well as during
storage of the prepared liquid and preferably even during mixing
of the solid with the liquid phase.
The invention is elucidated further in the following by the figures:
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1: A desiccant chamber with desiccant according to the invention
in longitudinal section.
FIG. 2: Possible embodiments of the vessel (arranged in a circle)
and of the desiccant chamber (in the middle).
FIG. 3: Steps in the process of preparing a liquid using the system
according to the invention.
FIG. 4: Moisture content of a solid when stored in various systems
according to the invention.
A preferred embodiment of the desiccant chamber is that as a result
of its construction it is suitable for closing the vessel. Such
a desiccant chamber is denoted desiccant stopper in the following.
The desiccant stopper (1) in FIG. 1 is closed to the outside by
a wall (2). This can consist of numerous materials e.g. plastic,
metal and cardboard. However, in the preferred case the wall is
comprised of a plastic since this material combines some advantageous
properties. Plastics of adequate wall thickness, preferably larger
than 0.5 mm, have the property of separating the desiccant in the
interior of the stopper from the environment in such a way that
although humidity can be exchanged to a slight extent between the
environment and desiccant, a substantial consumption of the desiccant
by external moisture is, however, avoided. In addition plastics
can easily be made into shapes which include a thread (3) as well
as a space for the desiccant (4).
The desiccant (4) is located in the interior of the stopper. The
known substances from the specialist literature are available when
selecting a suitable desiccant such as molecular sieves, silica
gel, sodium sulfate, potassium sulfate etc. A zeolite type of molecular
sieve which is suitable for the stated use is obtainable from the
Grace GmbH Company under the name "Molekularsieb Typ 511".
The amount of desiccant used and thus the drying capacity must be
such that, if desired, a possible mobile moisture content of the
solid is taken up and that humidity which penetrates from outside
can be absorbed up to the time of preparing the solution. On the
other hand the amount of desiccant should be small enough that when
the prepared liquid is stored in the preparation system there is
no significant change in concentration caused by uptake of water
from the solution by the desiccant. In the case of the desiccant
amounts which are preferably used in the range of a few grams and
liquid amounts in the range of decilitres, the error caused by the
desiccant is in an acceptable range for analytical solutions. In
many cases the liquid will be used in an analytical apparatus soon
after its preparation. In a preferred embodiment the vessel without
desiccant stopper is placed at a location provided therefor within
the apparatus. In this case the liquid is only in direct or indirect
contact with the desiccant stopper during the period of its preparation.
Thus a drying effect of the solution is likely to occur only to
a very slight extent. The drying effect can in all cases be prevented
by replacing the desiccant stopper after mixing solid and liquid
phase with a cap without desiccant.
The separating element (6) which separates the desiccant and the
interior of the vessel from one another represents an important
aspect of the invention. The separating element preferably has a
critical surface tension for wetting of from 25 to 65 mN.backslash.m,
more preferably from 30 to 40 mN.backslash.m. The material of the
separating element is of such a kind that although it is permeable
to water vapour it is a complete barrier to the final reagent solutions.
In recent years special plastics have been developed which combine
both these properties (e.g. EP-A 0 500 173). However, it is also
possible to use other materials such as e.g. impregnated fabrics
and cardboard. In a preferred embodiment of the invention cardboard
with a surface tension is used which prevents liquids from entering
into the desiccant chamber and permeation of the desiccant with
liquid. Suitable cardboards are for example sold by the Buchmann
GmbH Company under the name GC1 and GC2 and by the Laakmann GmbH
Company under the name UD2. The water repellent action is primarily
ensured by a coating, the so-called coat, which is composed of pigments
and synthetic binding agents. If the cardboard has a surface tension
which is less than 70 mN/m then the cardboard can no longer be wetted
by water and penetration of water is basically impossible; it is,
however, still permeable to water vapour. In the case of liquids
which have a smaller surface tension, a separating element with
a smaller surface tension is also necessary in order to prevent
penetration of liquids. The surface tension of the cardboard can
be determined in a simple manner with commercial test inks from
e.g. the "Arcotec Oberflachentechnik GmbH Company".
A possible arrangement for the separating element is shown in FIG.
1. The separating element (6) is fitted into a hollow plug (5) in
such a way that the liquid is prevented from passing from the vessel
interior to the desiccant. In a preferred embodiment this is achieved
by the fact that the separating element (6) lies on the opening
of the hollow plug (5) that faces the vessel interior. A flanging
(7) is connected mechanically to the hollow plug which is used to
mount the separating element (6) on the hollow plug. The flanging
(7) closes the space formed by the desiccant chamber (4) and separating
element (6) to liquids. Possible slight leakiness is sealed by the
fact that the separating element swells up on contact with water
and fills the gaps. Example 1 demonstrates the separating effect
of the cardboard used towards an aqueous reagent liquid even on
direct contact.
FIG. 2 shows a circular arrangement of vessels with desiccant stoppers
according to the invention and in their middle it shows two desiccant
stoppers with two and four ml capacity for desiccants. Not only
the shapes but also the wall thicknesses of the vessels can be varied
within wide limits. The materials of the vessels must be impermeable
to water, but can be partly permeable to water vapour. Plastics
are for example suitable for the vessel such as those which are
used in the manufacture of bottles for storing liquids. However,
wall thicknesses which are larger than 0.5 mm are preferred for
reasons of mechanical stability and water vapour permeability. The
manufacturing methods for the vessels, e.g. injection moulding or
injection blowing, are not subject to any restrictions provided
an adequate wall thickness can be ensured.
FIG. 3 shows the preparation of a liquid from a solid and a liquid.
In representation A the solid is located in the vessel closed by
the desiccant stopper. After opening the vessel (removal of the
desiccant stopper) representation B shows the addition of liquid
to the solid. After closing the vessel with the aforementioned cap
or with a new cap, the solid is mixed in representation C with the
liquid phase by shaking. |