WO2004045769A1

WO2004045769A1 - Multiple sealing system for screening studies

Info

Publication number: WO2004045769A1
Application number: PCT/EP2003/050810
Authority: WO
Inventors: Martin Szelagiewicz; Claudia Marcolli; Jörg BERGHAUSEN; Brigitte Cron-Eckhardt; Urs Christoph Hofmeier; Fritz Blatter
Original assignee: Solvias Ag
Priority date: 2002-11-18
Filing date: 2003-11-10
Publication date: 2004-06-03
Also published as: AU2003298279A1

Abstract

Devices consisting of (a) a hard or hard and elastic support (1) and (b) at least two seals (2) made of a hard or hard and elastic material, which are arranged in a row and protrude from the support on the sealing side, constitute sealing systems which are suitable for simultaneous multiple studies, especially with the use of microtitre plates and physical measurements of the results directly in the containers, inter alia for polymorphism screening, salt screening and formulation screening. These multiple studies may be used to find polymorphic and pseudo-polymorphic forms, new formulations or suitable crystallization conditions.

Description

Multiple sealing system for screening studies

The present invention relates to a sealing system consisting of (a) a support and (b) at least two seals, which are arranged in a row and protrude from the support on the sealing side. The sealing system is suitable for simultaneous multiple studies, especially with the use of microtitre plates and physical measurements of the results directly in the containers, for example of a microtitre plate.

The study of chemical reactions or physical properties of chemical substances under different conditions, or under the effect of different reactants, is costly in terms of time and material since screening studies need to be carried out. For quite some time, attempts have therefore been made to reduce the time and material outlay by using miniaturized systems, such as microtitre plates, and by developing methods for measuring the characterization of modifications directly in the reaction vessel, for example by means of microscopic, spectroscopic or diffractive methods.

In screening studies with titre plates, extended and flexible structures with raised individual seals made of silicone rubber (silicone mats) are often used, using which all the individual vessels are closed. The flexible material has several disadvantages. It is not inert with respect to many chemicals, and is therefore only of limited use. Furthermore, silicone rubber absorbs many solvents and leads to undesirable modifications of the study conditions. When it absorbs solvents, the material also softens and no longer seals sufficiently. If studies are being performed at high temperature or high pressure, extra fastening needs to be carried out owing to the softness and flexibility of the material. Extra fastening is also necessary if a determination, for example a spectroscopic determination, is intended to be carried out directly on the bottom of the individual vessels, since the deformations of the material make accurate and constant focusing of incident light or X-radiation very difficult when the microtitre plate is placed on the seal.

In Eur. Pharm. Rev. (2002), 7(2) pages 37 to 44, R. Hilfiker et al. describe polymoφhism studies on carbamazepine with the aid of microtitre plates, in which the individual containers are provided with Teflon seals. Polymorphic forms are determined by means of Raman spectroscopy. The system which is used is suitable for studies during which solvents evaporate, as well as for steady-state studies of crystal suspensions. The system and, in particular, the technical embodiment of the seal are not described in detail.

EP-A1-1 172 646 also discloses polymorphism studies with microtitre plates whose individual vessels are sealed, after having been filled, by individual O-rings made of Teflon®, for example, and then a separate glass plate. This system is time- consuming to work with, and modifications due to premature evaporation of volatile solvents cannot be ruled out.

There is a need for a sealing system for parallel multiple studies which is easy to work with and can be used flexibly, with which the number of vessels to be used can be selected, filled vessels can be closed rapidly and modifications due to losses of solvents or protective gases are substantially ruled out during studies. Furthermore, it is highly desirable for the device, consisting of the sealing system and vessels, to be fastenable without additional measures directly in frames for the study and in frames of optical measuring instruments for measurements in the vessels, or on the bottom of the vessels, by shining in light, for example, without refocusing.

The invention firstly relates to a sealing system consisting of (a) a hard or hard and elastic support (1 ) and (b) at least two seals (2) made of a hard or hard and elastic material, which are arranged in a row and protrude from the support on the sealing side.

The support may consist of various materials, for example metals or metal alloys, for example aluminium or stainless steel, glass, quartz, ceramic and stiff (hard or hard and elastic) optionally reinforced plastics. The plastics may be thermoplastics or thermosets. Since the support does not come directly into contact with chemicals to be studied, no particular constraints are placed on the choice of material in this regard. The size of the support will be selected so that it has at least two seals. The support preferably has from 2 to 1000, more preferably from 2 to 500, particularly preferably from 4 to 100 and especially preferably from 4 to 24 seals placed in a row (one- dimensional arrangement). The support may also be designed two-dimensionally, and contain two or more than two seals placed in a row, for example from 2 to 1000, more preferably from 2 to 500 and particularly preferably from 4 to 100 rows. In this embodiment, the support constitutes a block which contains successively placed rows of seals.

In an advantageous embodiment, the support is configured so that it corresponds to the side length and the containers, arranged in a row, of a macrotitre or microtitre plate and has seals corresponding to the number of containers of such a titre plate (one-dimensional arrangement). In another embodiment, the support corresponds to the side length and the containers, arranged in a row, of a macrotitre or microtitre plate, is designed two-dimensionally and contains seals which correspond to from at least two (for example from 2 to 4) up to all the rows of containers of a titre plate. In this embodiment, the support constitutes a block which contains successively placed rows of seals corresponding to the dimensions of a titre plate.

The spacing of the seals is dimensioned so that firm and airtight closure is possible with at least two vessels. The diameter of the seals is dimensioned essentially according to the size of the vessels to be sealed and may, for example, be from 2 mm to 5 cm, more preferably from 3 mm to 3 cm. The seals may, for example, protrude by from 0.5 mm to 3 cm, and preferably by from 0.5 to 2 cm, depending on the depth of the vessels to be sealed.

The support may have a thickness of from 1 mm to 8 cm, more preferably from 2 mm to 4 cm and particularly preferably from 4 mm to 3 cm. The thickness may be dictated according to the strength of the material.

The sealing system according to the invention may, for example, be designed in the following variants.

In a first variant, the support and the protruding seal consist of the same material, for example metals, metal alloys, ceramic, glass, quartz or plastics. The seals may be integrated in the support, so that the sealing system consists of a single block from which at least two seals protrude. Such sealing systems can be produced according to known methods, for example by moulding techniques or milling from a block of material. The required hermetic closure of the vessels can be ensured by finishing, for example grinding and/or polishing, of the protruding seals. In a preferred embodiment, such sealing systems consist of plastics, the plastics being selected so that they are inert with respect to chemicals in the vessels. Expediently, in this embodiment, a circumferential sealing lip is preferably fitted on the end of the seal, in order to be able to achieve complete sealing. On grounds of their chemical and physical stability, the plastics are preferably fluorohydrocarbons, for example polydifluoroethylene or polytetrafluoroethylene, which are inert with respect to many chemicals and ensure a long service life. Polytetrafluoroethylene (Teflon®) is particularly preferred. Production of the sealing systems from plastic may, for example, be carried out by injection moulding, transfer moulding or pressing methods.

A preferred sealing system according to the invention consists of (a) a hard or hard and elastic plastic as the support (1 ) and (b) at least two seals (2) made of the same hard or hard and elastic plastic, which are arranged in a row and protrude from the support on the sealing side.

A particularly preferred sealing system consists of (a) a polytetrafluoroethylene support (1) and (b) at least two polytetrafluoroethylene seals (2), which are arranged in a row and protrude from the support on the sealing side. A circumferential sealing lip is preferably fitted in the end region of the protruding seals.

One modification of this first variant is an embodiment in which the support and the seal consist of the same material, and the seals are firmly joined to the support on the surface of the support or in optionally continuous cavities in the support. The fastening may be earned out by adhesive bonding, welding, screwing or pressing into cavities. The cavities may be continuous, so that a seal can be pressed in until it protrudes. Preferred materials for this modification are fluorohydrocarbons, for example polydifluoroethylene or polytetrafluoroethylene. In a second variant, the support and the seal consist of different materials. The support may, for example, consist of metals or metal alloys, ceramic, glass or quartz, and the seal may consist of plastic. The support preferably consists of metals or metal alloys, for example stainless steel or aluminium. In one embodiment, the seals may be joined to the support by screwing the seals together with mating threads on one surface of the support. In another preferred embodiment, the support contains at least two continuous cavities at right angles to its length direction, which essentially correspond to the size of the seals to be accommodated. The geometrical shape is arbitrary per se, cylindrical shapes open on both sides being preferred. The diameter of the cavities is preferably equal, and may for example be from 2 mm to 5 cm, more preferably from 3 mm to 3 cm.

Seals are put into the cavities of the support and form a firm connection with the support. The seals protrude from the lower side of the support, and optionally also from the upper side. The seals are preferably flush with the surface of the support on the upper side. The extent to which the seals protrude depends essentially on the shape and size of the vessels which are to be joined to the seals. The distance from the surface of a reaction mixture in the vessel is expediently selected so that no contact occurs. The seals may, for example, protrude by from 0.5 mm to 1 cm, depending on the depth of the vessel. The seals may be provided with a screw thread and be screwed into the openings of the support. They may also be adhesively bonded or pressed in, so as to obtain more airtight closure. If the seals are pressed in, a seal diameter slightly greater than the diameter of the openings in the support is expediently selected, in order to ensure the desired strength. A slightly conical profile at the end of the protruding part facilitates introduction of the seal into vessels. The seals preferably have a flat surface on the protruding end. A circumferential sealing lip is preferably fitted above this surface, and provides for a high application pressure and the required leaktightness when joining to a vessel. The seal may also have two or more sealing lips. Alternatively, at least one circumferential groove may also be provided, into which a sealing ring is put for this purpose. Another possibility is for another circumferential seal to be additionally provided at the junction between the support and the inserted seal, which ensures tight closure when joining to vessels.

The sealing material may consist of metal, for example, in which case a screw connection to the support is advantageous. More expediently, the sealing material consists of a hard or hard and elastic material, for example thermoplastics, thermosets or elastomeric plastics. The seals can be readily produced from plastics by means of injection moulding or milling. Particularly preferred plastics are fluorohydrocarbons, for example polydifluoroethylene or polytetrafluoroethylene, which are inert with respect to many chemicals and ensure a long service life.

A preferred sealing system according to the invention consists of (a) a support (1) made of a metal or a metal alloy and (b) at least two seals (2) made of a hard or hard and elastic plastic, which are arranged in a row and protrude from the support on the sealing side, the seals being put into preferably continuous openings of the support and being firmly joined to the support. The individual seals preferably consist of polydifluoroethylene or polytetrafluoroethylene. The individual seals are preferably provided with at least one circumferential lip, which is designed as a bead.

The device according to the invention is outstandingly suitable for airtight closure with at least two vessels for carrying out various types of screening studies.

The invention therefore also relates to a system consisting of (a) a sealing system according to the invention and (b) at least 2 vssels, which are hermetically closed by the seals. The size of the vessels is preferably dimensioned so that studies can be carried out in the range of nanogram through microgram to gram quantities, for example in the range of from 1 μg to 10 g, more preferably from 10 μg to 5 g and particularly preferably from 100 μg to 1 g. The size of the vessels is particularly preferably selected to correspond to the study of microquantities, for example from 100 μg to 100 mg. It is furthermore expedient to provide a sufficient empty volume over a filled vessel, in order to avoid problems due to substances being spread.

The vessels may be in the form of individual vessels or vessels joined in a one- dimensional or two-dimensional row arrangement. These arrangements may be held together by clamps or in a frame so as to ensure the stability required for the studies, and the arrangement may be agitated in order to homogenize reaction mixtures. The vessels may consist of various materials, for example metals, metal oxides, ceramic, glasses or quartz. The selection of the materials depends on chemicals which are used in the intended studies and the measurement methods by which chemical modifications or changes of a physical state are intended to be determined.

The vessels preferably involve a plate with equidistant wells, in a one- or two- dimensional row arrangement, and preferably cylindrical or conical wells with a flat or rounded bottom. The volume of the wells is preferably from 10 μl to 5 ml, and particularly preferably from 100 μl to 3 ml. The diameter of the wells may, for example, be from 10 μm to 3 cm, and particularly preferably from 100 μm to 2 cm. Such plates are known and commercially available as standardized macrotitre or microtitre plates with a defined number of wells. Particularly common are the 8 x 12 format with 96 wells and the 4 x 6 format with 24 wells, the 6 x 8 format with 48 wells, and the 16 x 24 format with 384 wells. The geometry of titre plates may be arbitrary and, for example, selected from round or angular shapes (square, rectangle).

The plates may consist of various materials, optically transparent materials being preferred since modifications following a reaction or conversion of substances can be measured directly in the vessels by means of spectroscopic methods. Suitable transparent materials are, for example, organic glasses, which may be thermoplastics or thermosets, for example polymethacrylates, polycarbonates or polyesters. Inorganic glasses are particularly suitable, of which quartz is the one which is most particularly preferred. Materials which are highly transparent to X- radiation, and exhibit only a slight interaction with X-radiation, are likewise preferred. The surfaces of the vessels may be coated, for example with materials which prevent crystals from adhering to the vessel walls so that, with small quantities, sufficient study material is deposited on the bottom of the vessels. Coatings which have a low surface energy can prevent undesirable creep of liquids up the vessel walls. Silanization of the surface is often carried out for this purpose.

In a preferred embodiment, the system according to the invention involves

(a) a device consisting of a support (1) with from 2 to 24, preferably from 4 to 16 seals (2) made of a hard or hard and elastic plastic, which are arranged in a row, are put firmly into cavities and protrude from the support on the sealing side; and

(b) a titre plate made of optically transparent material, with whose wells the seals of the device are hermetically closed.

The titre plate preferably consists of quartz. In an advantageous embodiment, the device consists of from 1 to 3 rows of seals, which are arranged in a support and correspond to the geometry of the titre plate with wells. The device with from 1 to 3 rows of seals may be joined individually to from one to three rows of wells, and a plurality of rows of wells may be joined thereto successively or with one or more of them being omitted. Such arrangements offer the advantage that, at the same time, measurements can be carried out and new conversions can be prepared or carried out.

Particularly preferably, the device consists of a one-row arrangement of seals, which are firmly joined to corresponding wells of a titre plate. This system according to the invention can be used particularly flexibly, since it is possible to carry out conversions, measurements or preparations for conversions in individual rows, several rows or all the rows of wells of the titre plate. The substances do not need to be removed for optical or diffractometric measurement of modifications, for example in the near IR (NIR) range, the UV range and the visible range, or with X-radiation. The radiation source can be directed at the wells in the titre plate from the upper side or through the bottom of the titre plate, without having to remove the sealing device. The sealing device may, however, be replaced by other seals prior to the measurement. Air-sensitive substances in particular, but not exclusively, may be studied with this system.

If studies are not intended to be carried out in the reaction vessel, a modified substance or a reaction mixture may be removed from vessels or wells of a titre plate and studied, optionally after preparation. This preparation may be carried out either manually or automatically. In another embodiment, the sealing device may also merely be removed before the physical measurements to be carried out, which may be done under a protective gas or in air.

Figures 1, 1a, 2 and 3 illustrate the device according to the invention and the system according to the invention.

Figure 1 shows a sealing system with a support (1), and eight seals (2) which are arranged in a row, are put firmly into continuous cavities of the support, protrude from the support and have a circumferential sealing lip (3).

Figure 1a shows a detail of Figure 1 with a seal for better illustration of the seal shape with the sealing lip 3 which is formed.

Figure 2 shows the lower side of the arrangement in Figure 1.

Figure 3 shows a system according to the invention consisting of a microtitre plate, in which eight wells are respectively closed in an airtight fashion (hermetically) by eight seals of two successively arranged sealing systems according to Figure 1 (or of one device with two rows).

The invention also relates to a device for physical or chemical modification of substances and their determination by means of spectroscopic methods, consisting of a) a sealing system consisting of (a1) a hard or hard and elastic support (1) and (b1) at least two seals (2) made of a hard or hard and elastic material, which are arranged in a row and protrude from the support on the sealing side; b) at least 2 optically transparent vessels (or vessels transparent at least for the radiation source which is used), which are firmly joined to the seals; c) a radiation source for shining light into the vessels; and d) a detector for measuring spectral modifications of radiation, scattered radiation or X-radiation.

In particular, the vessels involve titre plates made of an optically transparent material, preferably quartz glass. The radiation source is preferably directed at the side of the vessel bottom.

The embodiments and preferences described above apply to the individual components of the invention.

Suitable radiation sources are lamps (for example mercury vapour lamps) or lasers (gas lasers, crystal lasers, semiconductor or diode lasers) or sources of X-radiation and synchrotron X-radiation. Customary optical means for focusing the light beam onto the bottom of a vessel and a detector may be arranged between the detector and the radiation source.

Suitable detectors are, for example, those for recording spectra in the UV range, visible range and NIR range as well as Raman spectra, or for recording X-ray diffractograms in the reflection or transmission mode, or other diffraction methods. All methods may be operated in the reflection or transmission mode. Optical assessments by means of microscopy are also possible.

The arrangement according to the invention is suitable, in particular, for carrying out various types of multiple studies (high throughput screening, HTS). These multiple studies are suitable, in particular but not exclusively, for carrying out screenings: a) to find polymorphic and pseudo-polymorphic forms (hydrates, solvates) of pharmaceuticals, active agrochemical agents, pigments, dyes and other organic or inorganic compounds, as well as their amorphous forms in the presence of solvents (including water) and solvent mixtures;

b) to find new formulations with improved properties in the presence of solvents and solvent mixtures, auxiliaries or mixtures of solvents and auxiliaries; c) to find suitable crystallization conditions for pharmaceuticals, active agrochemical agents, pigments, dyes, peptides and proteins, and other organic or inorganic compounds in the presence of solvents and solvent mixtures; d) to obtain nucleation seeds for the production of desired crystalline forms of pharmaceuticals, active agrochemical agents, pigments, dyes, peptides and proteins, and other organic or inorganic compounds in the presence of solvents and solvent mixtures; e) to form salts and study their crystalline forms; f) to study the formation of mixed crystals.

Examples of relevant conversions include: physical modifications of pharmaceuticals, active agrochemical agents, pigments, dyes and other organic or inorganic compounds in the presence of solvents (including water), solvent mixtures, auxiliaries or mixtures of solvents and auxiliaries for the production of polymorphic forms, hydrates, solvates, and their amorphous forms; chemical conversions, for example salt formation, and study of dyes or dye mixtures. The effect of air and/or a particular humidity, as well as defined solvent vapours on substances or substance mixtures, can also be studied when the unclosed vessels are exposed to corresponding conditions and then closed with the sealing system according to the invention for desired measurements. In aqueous systems, the said modifications may also be caused by pH variation.

The invention also relates to a method for the simultaneous physical or chemical modification of substances or substance mixtures in at least two vessels under different physical or chemical conditions, which is characterized in that at least two vessels of the system according to the invention are filled with a substance, a substance mixture or a reaction mixture, which differ from one another, and then predetermined physical conditions are set up, a physical process or a chemical reaction is earned out, and the content is subsequently measured directly in the vessels by means of spectral modifications.

After the measurements, the seals may be removed and further studies may be carried out in the vessels, or after having removed the substances.

The embodiments and preferences described above apply to the method. In particular, the reaction vessels involve an optically transparent material, preferably in the form of a titre plate, in order to be able to carry out the measurement of the products by spectroscopic methods in the vessel. The method is very particularly suitable for polymoφhism studies in a substance or in formulations, or studies of salt formation and crystalline forms of these salts, by using UV, NIR or visible radiation sources and determining the results by means of NIR or Raman spectra, or X-ray diffractograms.

In the scope of the invention, "modification" may for example mean the formation of other physical forms (polymoφhism), formation of mixed crystals, formation of crystals with a different habitus, formation of solvates and hydrates, as well as chemical reactions. Such modifications may be caused by differences of a substance, a substance mixture or a reaction mixture, for example by the polymoφhic or pseudo-polymorphic form which is used, quantities, quantity ratios, different solvents or solvent mixtures, different auxiliaries (such as pharmaceutical formulation additives), different reactants and different reaction promoters or quantities thereof (catalysts, cocatalysts). Such changes in the physical conditions may be, for example: pressure, temperature, radiation or the effect of gases or vapours in open vessels, as well as the duration of the treatment with the said physical conditions, as well as combinations of such parameters. "Modification" may also mean that comparative studies are carried out between static and moved systems (agitation, stirring).

The method according to the invention can be carried out in a manner which is known per se. The filling, as well as the spectroscopic measurement of products, may be performed manually or automatically by program-assisted control systems. For crystallization studies, besides evaporation of solvents it is also possible to add solvent vapours. Chemical reactions are also found to be particularly straightforward, since used solvents are fully evaporated after the end of the reaction and measurements can then be carried out on the reaction residue.

Using the method according to the invention, a multiplicity of data in the micro scale up to small quantities can be generated in short time periods with screening studies, which ensures good economic viability. Studies can also be controlled, and necessary studies can be accelerated significantly.

For example, the method according to the invention is particularly suitable for producing and studying crystalline forms and salts, optionally by means of precipitation reactions.

Furthermore, the method according to the invention is suitable for screening in respect of suitable crystallization conditions for a multiplicity of possible substances, especially pharmaceuticals, active agrochemical agents, pigments, dyes, proteins and other organic or inorganic compounds in the presence of solvents, solvent mixtures, auxiliaries or mixtures of solvents and auxiliaries. In this type of screening, it is also possible to operate by adding suitable nucleation seeds.

In another application, the method according to the invention can also be used to find and produce suitable nucleation materials.

Studies involving recrystallization from supersaturated solution can be carried out according to the invention by applying solvent and substance to the vessels, then dissolving the substance by heating, and then allowing crystallization to take place by cooling. An arrangement according to the invention can also be used to produce and study crystalline substances or formulations in suspensions with different solvents. The crystallization may also be initiated by solvent evaporation.

In the arrangement according to the invention, crystallizations may be initiated by either homogeneous or heterogeneous nucleation.

The arrangement according to the invention may, for example, be used in the synthesis of lead structures, the development of synthesis methods, in process development and optimization, in combinatorial chemistry, in active agent analysis, active agent research and active agent development, food research, environmental analysis and the study of catalytic reactions.

The filling of the reaction spaces, the measurement of physical measured quantities (analysis) on products, and the evaluation of the measurement results may be earned out manually, semiautomatically with computer assistance, or fully automatically.

The high leaktightness of the sealing system and the high chemical stability of the sealing system are particularly advantageous for studies with the device according to the invention, so that studies can be carried out under constant conditions even with volatile solvents and over a prolonged period of time. The device is therefore also suitable, in particular, for the study of air-sensitive substances. When titre plates are used, the measurement of spectral modifications is found to be very straightforward since the plate bottom defines the measurement plane and, in the ideal case, the incident light only needs to be focused once, which is of great importance for automatic measurements.

The following examples explain the invention in more detail. Sealing systems such as those which are represented in Figure 1 are used. Example 1 :

The solubility of carbamazepine is determined in 43 solvents and solvent mixtures.

Inter alia, alcohols, ethers, ketones, hydrocarbons, DMSO, n-methylpyrrolidone and water are used as the solvents, and ethanol/water, methanol/water and THF/water in various mixing ratios are used as the solvent mixtures.

According to the solubility, three times the quantity of substance which is soluble in the corresponding solvent or solvent mixture is introduced into an 8 12 titre plate, and 100 μl of the said solvents or solvent mixtures are introduced into each of the corresponding wells of the titre plate, so that the first six rows of 8 of the plate are filled and can be closed with six sealing systems consisting of a row of 8 seals. The titre plate is then agitated in an automatic agitator for 20 h at 23°C.

The solids are studied directly by means of Raman spectroscopy in the wells. The measurements are carried out through the bottom of the titre plate so that no solvent can evaporate, and operation is carried out with humidity being excluded. The spectra are divided into various classes according to their spectral similarity; one class may correspond to one polymorphic or pseudo-polymoφhic form.

In a second study, the suspensions of the substance are agitated, isothermally or with a cyclic temperature programme, for 2 days and then analysed.

Example 2:

Operation is carried out as in Example 1, but the sealing system is removed after the agitation and the titre plate is left to stand open at room temperature for 48 h. The sealing systems are put back on, in order to prevent unevaporated solvent from flowing out during the measurement through the bottom. The measurement and evaluation are carried out as described in Example 1 Example 3:

Operation is carried out as in Example 1 , but about 1.7 times the quantity of substance which is soluble in the corresponding solvent at room temperature is introduced.

The active substance is dissolved by heating the titre plate while agitating, and cooled for recrystallization in a refrigerator (about 5°C).

The measurement and evaluation are earned out as described in Example 1.

Claims

Patent Claims:

1. Device consisting of (a) a hard or hard and elastic support (1 ) and (b) at least two seals (2) made of a hard or hard and elastic material, which are arranged in a row and protrude from the support on the sealing side.

2. Device according to Claim 1 , characterized in that the support consists of metals, metal alloys, glass, quartz, ceramic or optionally reinforced and stiff plastics.

3. Device according to Claim 1 , characterized in that the support is designed one-dimensionally and contains from 4 to 24 seals placed in a row.

4. Device according to Claim 3, characterized in that it corresponds to the side length and the containers, arranged in a row, of a macrotitre or microtitre plate and has seals corresponding to the number of a row of containers in such a titre plate.

5. Device according to Claim 1 , characterized in that the support and the seals consist of a block and the same material.

6. Device according to Claim 5, characterized in that it constitutes a sealing system consisting of (a) a hard or hard and elastic support (1 ) and (b) at least two seals (2) made of the same hard or hard and elastic material, which are arranged in a row and protrude from the support on the sealing side.

7. Device according to Claim 5, characterized in that the sealing system consists of (a) a polytetrafluoroethylene support (1) and (b) at least two polytetrafluoroethylene seals (2), which are arranged in a row and protrude from the support on the sealing side.

8. Device according to Claim 5 or 6, characterized in that a circumferential sealing lip (3) is fitted in the end region of the protruding seals.

9. Device according to Claim 1 , characterized in that the support and the seal consist of different materials.

10. Device according to Claim 9, characterized in that the support consists of a metal or metal alloy and the seal consists of a plastic.

11. Device according to Claim 9, characterized in that at least two continuous cylindrical cavities, into which plastic seals are put, are arranged in the support at right angles to its length direction.

12. Device according to Claim 11 , characterized in that the diameter of the cavities is from 2 mm to 5 cm.

13. Device according to Claim 11 , characterized in that the seals have a flat surface on the protruding end.

14. Device according to Claim 13, characterized in that a circumferential sealing lip is fitted above the surface.

15. Device according to Claim 10, characterized in that the plastic is polytetrafluoroethylene.

16. Device according to Claim 9, characterized in that it consists of (a) a support (1 ) made of a metal or a metal alloy and (b) at least two seals (2) made of a hard or hard and elastic plastic, which are arranged in a row and protrude from the support on the sealing side, the seals being put into continuous openings of the support and being firmly joined to the support, the individual seals consisting of polydifluoroethylene or polytetrafluoroethylene and the individual seals being provided with at least one circumferential sealing lip, which is designed as a bead.

17. System consisting of (a) a device according to Claim 1 and (b) at least 2 vessels, which are firmly closed by the seals.

18. System according to Claim 17, characterized in that the vessels are in the form of individual vessels or vessels joined in a one-dimensional or two-dimensional row arrangement.

19. System according to Claim 17, characterized in that the vessels involve a plate with equidistant wells, in a one- or two-dimensional row arrangement, and cylindrical wells with a flat or rounded bottom.

20. System according to Claim 19, characterized in that the volume of the wells is from 10 μl to 5 ml and the diameter of the wells is from 10 μm to 3 cm.

21. System according to Claim 19, characterized in that it involves standardized macrotitre or microtitre plates with a defined number of wells.

22. System according to Claim 17, characterized in that it involves

(a) a device consisting of a support (1) made of a hard or hard and elastic material with from 2 to 24, preferably from 4 to 16 seals (2) made of a hard or hard and elastic material, which are arranged in a row, are put firmly into cavities and protrude from the support on the sealing side; and

(b) a titre plate made of optically transparent material, to whose wells the seals of the device are firmly joined.

23. System according to Claim 22, characterized in that the titre plate consists of quartz, and the surfaces are optionally treated.

24. System according to Claim 22, characterized in that the device consists of a single-row arrangement of seals, which are firmly joined to a row of wells of the titre plate.

25. System according to Claim 22, characterized in that the device consists of a single-row arrangement of seals, and from at least two up to all the rows of wells of the titre plate are firmly joined to a one-row arrangement of seals.

26. Device consisting of a) a sealing system consisting of (a1) a hard or hard and elastic support (1) and (b1) at least two seals (2) made of a hard or hard and elastic material, which are arranged in a row and protrude from the support on the sealing side; b) at least 2 optically transparent vessels, which are firmly joined to the seals; c) a radiation source for shining light into the vessels; and d) a detector for measuring spectral modifications of radiation, scattered radiation or X-radiation.

27. Method for the simultaneous physical or chemical modification of substances or substance mixtures in at least two vessels under different physical or chemical conditions, characterized in that at least two vessels of the system according to Claim 17 are filled with a substance, a substance mixture or a reaction mixture, which differ from one another, and then predetermined physical conditions are set up or a chemical reaction is carried out.

28. Method according to Claim 27, characterized in that the system involves an arrangement according to Claim 22.

29. Method according to Claim 27, characterized in that the system involves an arrangement according to Claim 22 and modifications of substances or substance mixtures are measured by means of spectral modifications or X-ray diffractometry.

30. Method according to Claim 29, characterized in that polymorphic forms are studied by means of NIR or Raman spectra.