WO1992001513A1

WO1992001513A1 - Plate with at least one well for holding chemical and/or biochemical and/or microbiological substances, and a process for manufacturing the plate

Info

Publication number: WO1992001513A1
Application number: PCT/DE1991/000082
Authority: WO
Inventors: Manfred Eigen; Wolfgang Simm
Original assignee: MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V.
Priority date: 1990-07-18
Filing date: 1991-01-29
Publication date: 1992-02-06
Also published as: DE4022792C2; DE59106171D1; EP0539369B1; ATE125732T1; JPH06500727A; DE4022792A1; EP0539369A1

Abstract

Disclosed is a plate (2) with at least one well (11) designed to hold chemical and/or biochemical and/or microbiological substances. The well has an interior space delimited by its inside surface, plus a wall. The outside surface (28), remote from the inside surface, of the wall includes a heat-exchange surface (28') at least part of which can be brought into thermal contact with a temperature-equilibrating agent. The plate (2) is characterized in that the at least one well (11) has a heat-transmission coefficient which is greater than 5 x 10?-4 W/(K mm?3). The heat-transmission coefficient is given by the formula: (A . $g(l))/(V . x), in which A is the area of the heat-exchange surface (28'), $g(l) is the thermal conductivity of the wall material, V is the internal volume of the well (1) and x is the wall thickness, taken as the distance between the heat-echange surface (28') and the inside surface of the well. W represents the heat-transmission coefficient.

Description

Plate with at least one trough for receiving chemical and / or biochemical and / or microbiological substances and method for producing the plate

The invention relates to a plate with at least one trough for receiving chemical and / or biochemical and / or microbiological substances, the trough being one of its own Has inner space limited interior and a wall, the outer side of which lies away from the inner surface comprises a heat exchange surface which can be brought at least partially into thermal contact with a temperature control substance.

The invention further relates to a method for producing a plate with at least one trough for receiving chemical and / or biochemical and / or micrological substances.

Such plates are sold by several suppliers and are known as microtest plates or microtiter plates.

The known plates have a rigid base, which is surrounded on all sides by a raised edge. Troughs are arranged in the floor, which is over one millimeter thick, arranged in rows and columns. The bottom of the known plate is flat on its underside, which is remote from the depressions. The known plates are offered with different trough volumes, which are usually between a few hundred microliters and a few milliliters.

It is known to cover the edge of the plate with a cover or an adhesive film in order to protect the troughs and the interior space delimited by the edge against soiling of all kinds.

The plates made of polystyrene or polyvinyl chloride are used to keep solutions at a constant temperature. This is done either for storage purposes or to run a reaction at a certain temperature. The plates become - after filling the Solutions in the wells - covered with the lid and either placed in a refrigerator for storage or in an incubator, which is usually set to 37 ° C.

The known plates are not suitable for solutions whose reactions have to be controlled by frequent and rapid temperature changes, since cooling in a refrigerator or heating in an incubator takes far too long.

Although it is known to thermostate the plates via their flat underside, the temperature change of the samples takes a very long time of up to several minutes.

In addition, conically tapering plastic reaction vessels with a snap lid or a screw cap are known. The known plastic reaction vessels are usually several centimeters high and have an outer diameter in the range from 12 to 18 mm. With a large number of samples or solutions to be processed, the space requirement and the time required for handling the many reaction vessels are correspondingly large.

The substances accommodated in the known reaction vessels are re-heated by thermostating the reaction vessels on their outside. This is done, for example, by immersing the reaction vessels in water baths of different temperatures. However, it is also known to provide therestated metal blocks with bores for the reaction vessels, which are then thermostatted by contact with the bore walls. The heat transfer can be improved by filling the holes with water or oil. The temperature of the samples is changed by placing the reaction vessels in other water baths or metal blocks that are set to the new desired temperature.

The temperature of the substances takes on the new value only slowly, since the plastic reaction vessels have a thick wall, through which only poor heat transport is possible. The thickness of the wall is required for manufacturing reasons and because of the required mechanical strength of the reaction vessels to be handled individually. E.g. the reaction vessels are used in centrifuges that rotate at high speed. The mechanical stresses that occur are one reason for the stable thick wall of the plastic reaction vessels.

However, many of the new chemical, biochemical or microbiological methods require the reaction solutions to be brought quickly to different temperatures in the course of the test. These reactions often have to go through a certain temperature profile, which can consist of several heating and / or cooling cycles. The yield and the efficiency of the reactions depend on the speed of the temperature change in the solutions used. In particular in the case of enzymatic processes on nucleic acids, a rapid change between high temperatures for denaturing the nucleic acids and low temperatures for starting the reaction is necessary.

The invention is therefore based on the object of developing a plate of the type mentioned in such a way that the disadvantages mentioned above are avoided. In particular, it should be possible to rapidly change the temperature of a number of samples with simple handling. This object is achieved in that the at least one trough has a heat transmission value which is greater than 5 x 10 "" W / (K mm ³ ) and for which the formulaic relationship

A _ ^ _

= W

V x

applies in which A is the size of the heat exchange surface, ^ the thermal conductivity of the material forming the wall, V the volume of the interior of the trough, x the wall thickness of the wall, measured as the distance between the heat exchange surface and the inner surface, and W the heat transfer value.

The output on which the invention is based is completely solved in this way. Because the heat transfer value of the new plate is greater than 5 x 10 " ⁴ W / (K mm ³ ), rapid heat transport through the wall into and out of the trough is possible. Depending on the material selected, the Plate and the required volume of the trough, the person skilled in the art can now choose the size of the heat exchange surface and the wall thickness of the trough, taking into account the relationship given above processing, for example, reaction solutions is possible.

For plates with the same heat exchange surface and the same volume of the troughs, for example, this means on the other hand that a plate made of a material with a thermal conductivity 10 times as good but a wall thickness 10 times thicker has the same heat transfer value as the plate with the poorer one Thermal conductivity and the thinner wall. In a preferred embodiment of the plate according to the invention, the wall thickness is approximately the same at least over the entire heat exchange surface.

This measure has the advantage that the substances accommodated in the trough are heated or cooled uniformly from all sides, which prevents the formation of disturbing temperature gradients in the substances.

It is particularly preferred in this embodiment if the heat transfer value is greater than 1 x IQ ^-3 W / (K mm ³ ).

This measure enables an even faster heat transport through the wall of the trough, which leads to even better reaction results for the substances taken up in the trough.

A further advantage is achieved in this exemplary embodiment that the heat transfer value is greater than 3 × 10 ^-3 W / (K mm ³ ).

This measure, which accelerates the heat exchange even more, makes it possible to allow reactions to take place in the troughs, which must be controlled by temperature changes in a matter of seconds. E.g. it is possible to heat or cool an aqueous solution with a volume of 50 microliters by 60 ° C in less than 20 seconds.

It is also advantageous if the plate is formed in one piece with the trough. This measure has the advantage that the new plate is easy to manufacture because the troughs do not have to be attached to the plate.

It is particularly preferred in this embodiment if the plate is made of plastic.

As a result of this measure, the plate has only a low weight and is inexpensive to manufacture, so that it can be designed as a disposable or disposable item.

Another advantage is achieved in this embodiment if the plastic is thermally deformable.

This measure makes it possible to manufacture the plate using a fast and inexpensive manufacturing process, for example a deep-drawing process.

It is further preferred in this embodiment if the heat exchange surface is arranged on the plate below its underside.

This measure has the advantage that the heat exchange surface for the respective tempering material is easily accessible from below the plate. E.g. the plate can be inserted from above into a water bath or into a metal block that has a counter surface for the heat exchange surface.

Furthermore, it is preferred in this exemplary embodiment if the trough is designed as a cup-like protuberance, the outside of which is at least in sections the heat exchange surface. This measure makes it possible to accommodate the protuberances, for example, in corresponding recesses in a metal block thermostat, whereby on the one hand the new plate is held mechanically and on the other hand the heat exchange surface extends over the entire size of the outside of the trough, which leads to a large and easily accessible heat exchange surface.

In this exemplary embodiment, it is further preferred if the cup-like protuberance has a hollow cylindrical upper section connected to the underside of the plate and a hemispherical hollow lower section connected in one piece to this.

These measures offer the advantage that in a metal block thermostat the counter surface to the heat exchange surface can be generated in a simple manner by a cylindrical blind hole with a rounded bottom. The geometrically simple shape of the outside of the trough makes it possible to ensure reproducible good heat transfer between the counter surface in the metal block thermostat and the heat exchange surface.

It is further preferred in this embodiment if the volume of the interior is less than 200 mm ³ and is preferably between 10 and 100 mm ³ .

Since most chemical and / or biochemical and / or microbiological reactions take place in this volume range, the plate according to the invention is particularly well suited for such tests by this measure. The trays of the new plate are at least filled to the extent that the solutions can regulate the moisture content of the air volume above their liquid surface without any significant changes in volume.

In a further development of this embodiment, the new plate is characterized in that the lower section has a radius between 2 and 6 mm and that the wall thickness of the trough is thinner than 0.2 mm.

This measure, which is very easy to achieve in terms of production technology, also provides the heat transmission value according to the invention, which is greater than 5 × 10 ^-4 W / (K mm ³ ), in the case of sheets of plastic films which have a rather poor thermal conductivity.

It is also preferred in this embodiment if the wall thickness is less than 0.08 mm.

This simple reduction in the wall thickness advantageously increases the heat transfer value significantly, which leads to a better heat exchange and thus to a faster temperature change of the substances in the trough.

Another advantage is achieved in this embodiment if the plate is made of polycarbonate.

This measure gives the plate sufficient mechanical strength on the one hand, and on the other hand the troughs can be formed, for example, by a deep-drawing process which is advantageous in terms of production technology. In addition, the troughs made of polycarbonate are advantageous reaction vessels for most chemical and / or biochemical and / or microbiological reactions, since polycarbonate is inert in this respect. This embodiment is further developed in an advantageous manner in that the plate is made of a polycarbonate film, the thickness of which is less than 0.5 mm.

This measure offers advantages in terms of production technology, since such polycarbonate films are available pre-assembled. In addition, when the troughs are formed in these polycarbonate films, the wall thickness is advantageously thin, which in turn leads to a large heat transfer value.

It is further preferred in this exemplary embodiment if the plate has a number of troughs which are identical to one another.

This measure, known per se, has the advantage that a large number of reactions can be carried out in parallel in the same plate, provided that all samples have to be subjected to the same temperature profile.

It is particularly preferred in this exemplary embodiment if the troughs are arranged in rows and columns which have the same spacing of approximately 10 mm from one another.

This measure has the advantage, which is also known per se, that the troughs can be filled and emptied with multiple pipettes, which greatly simplifies the work during test preparation.

A further advantage is achieved in this embodiment that a cover is provided for closing the openings in the troughs. This measure allows the troughs to be protected from dirt and dust in a manner known per se after the substances have been filled in.

A further advantage is achieved in this exemplary embodiment if each region of the cover covering the opening of a trough can be connected to the plate by means of a connecting seam going around the respective opening.

This measure ensures that, as it were, each trough is subsequently provided with its own cover, through which the trough is sealed gas-tight. Particularly in the case of small volumes of the interior spaces of the troughs, the evaporation problem occurring at high temperatures and the condensation problem occurring at low temperatures are thus completely eliminated. The liquid volume enclosed in the troughs does not change even with extreme and frequent temperature changes between high and low values.

This embodiment is developed in a particularly advantageous manner in that the cover is also made from a plastic film, in particular from the same material as the plate.

This measure makes it particularly easy to make the connection seams between the cover and the plate. E.g. the cover film can be bonded to the plate in the area of the connecting seam under pressure and / or heat. 12

An advantageous further development of this embodiment is characterized in that the respective connecting seam seals the respective trough gas-tight.

This measure ensures that no evaporation and / or condensation problems occur even with small amounts of liquid taken up in the troughs, even if the troughs are frequently re-tempered between high and low temperatures, so that an overpressure is established inside the trough because the solution taken up has been heated or heated to higher or higher temperatures.

A particularly advantageous method for producing the plate from plastic is characterized in that a thermally deformable plastic film with a thickness of less than 0.5 mm and a thermal conductivity greater than 0.1 W / (K m) with its underside first of all from above Form block is placed, the upwardly open cup-like depressions, the interior of which have volumes less than 200 mm ³ ; that a hot gas stream is directed in succession in the region of each cup-like depression from above the placed film onto its top; and that the hot gas stream has a predetermined temperature that is close to the melting temperature of the film.

In this process, the simple combination of the thermal conductivity of the film, the thickness of the film and the volume of the cup-like depressions ensures that the relationship given above for the heat transfer value is maintained by the wall thickness of the troughs which arise during deep-drawing. This method is particularly advantageously further developed in that the hot gas stream is discharged from an outlet opening, the diameter of which is approximately equal to the diameter of the cup-like depressions and the distance from the top of the film is smaller than this diameter.

This measure surprisingly results in a well-shaped trough, the entire surface of which rests against the inner wall of the cup-like depression.

A further advantage is achieved in this process in that the mold block can be temperature-controlled and has a temperature below the melting point temperature of the film, preferably approximately 100 ° C.

This measure has the effect that the wall thickness of the troughs formed is approximately the same in the area of the heat exchange surface.

In this exemplary embodiment, it is also preferred if the plastic film is a polycarbonate film.

The use of a polycarbonate film gives the plate sufficient mechanical strength so that a very large number of depressions can be introduced into the polycarbonate film. In addition, reaction vessels made of polycarbonate, such as the wells formed in the plate, are inert to the chemical and / or biochemical and / or microbiological reactions or substances under consideration.

Further advantages result from the description and the attached drawing. It goes without saying that the features mentioned above and those yet to be explained below can be used not only in the combination specified in each case, but also in other combinations or on their own without departing from the scope of the present invention.

An embodiment of the invention is shown in the drawing and is explained in more detail in the following description. Show it:

1 shows the plate according to the invention with the troughs open at the top, in a cutout and in a perspective view;

FIG. 2 shows the plate from FIG. 1, in a sectional illustration along the line II-I from FIG. 1;

3 shows a method for producing the plate from FIG. 1 in a schematic illustration;

Fig. 4, the cover of a plate of FIG. 1 with a

Cover film, in the cutout and in a perspective view;

5 shows the covered plate from FIG. 4, with ring-shaped connecting seams which are placed around the troughs and connect the cover film to the plate, in the view of the arrow V from FIG. 4;

FIG. 6 shows a welding stamp for producing the connecting seams from FIG. 5, in a sectional partial view; 7 shows the welding stamp from FIG. 6, in a partial view from above along the arrow VII from FIG. 6;

FIG. 8 shows the connecting seam from FIG. 5 in a sectional side view along the line VIII-VIII from FIG. 5;

Fig. 9 shows a device for welding the covered

The plate from FIG. 4, in which several of the welding punches from FIG. 6 are used, in a perspective view; and

FIG. 10 shows the use of the welded plate from FIG. 5 in connection with a thermoblock, in a perspective representation and in a detail.

In Fig. 1, a rectangular flexible plate 2 is shown with one of its longitudinal edges 3 and one of its side edges 4 in section. The plate 2, for example made of a rigid plastic film, has a flat top 5 and a bottom 6 parallel to it. The thickness measured between the top 5 and the bottom 6 is indicated at 7. As can be seen in FIG. 1, the thickness 7 is small compared to the transverse dimensions of the plate 2.

Through holes 9 are provided in the plate 2 and troughs 11 open at the top are formed. The troughs 11 are arranged in rows 12 and columns 13, the rows 12 running parallel to the longitudinal edge 3 and the columns 13 running parallel to the side edge 4. The rows 12 or columns 13 each have a row or column spacing indicated at 14 or 15. In the exemplary embodiment shown, the troughs 11 which are circular in cross section have an in 2 shows the inner diameter 16 which can be seen better. The row spacings 14 and the column spacings 15 are of the same size, the inner diameter 16 of the troughs 11, of course, being smaller than the row spacing 14 and the column spacing 15

The troughs 11 lie with their openings 18 surrounded by a rounded opening edge 17 in the plane of the top 5 of the plate 2. They have a wall 20 delimiting their interior 19, which is designed in the manner of a cup-like protuberance 21 and in each case the mutually identical troughs 11 lies below the underside 6 of the plate 2.

In the further course of the description, the direction from the interior 19 of the troughs 11 through the opening 18 is referred to as “upward” and the opposite direction is accordingly designated as “downward”.

As can be seen better in FIG. 2, the protuberance 21 has a hollow cylindrical upper section 22 and a hemispherical lower section 23 which is integral therewith and whose curved bottom wall 24 closes off the trough 11 at the bottom. The top 5 merges with the formation of the circumferential rounded edge 17 directly as the inner surface 25 into the interior 19 of the trough 11, the bottom 6 with the formation of a groove 27 encircling the protuberance 21 as the outside 28 of the protuberance 21 essentially parallel to the curved one Inner surface 25 extends. Crosspieces 29, which separate the individual openings 18 from one another, run between the individual troughs 11. As can also be seen in FIG. 2, the bottom wall 24 has a thickness, indicated at 31, which is measured between the inner surface 25 and the outer side 28. In the area of the hollow cylindrical upper section 22, a correspondingly measured thickness is indicated at 32, which approximately corresponds to the thickness 31. The troughs 11 each have a volume 33, which is essentially determined by their depth indicated at 34 and the inner diameter 16. The depth 34 is measured between the bottom wall 24 and an imaginary maximum fill level indicated at 35 by a dashed line. The fill level 35 is approximately at the level at which the curved opening edge 17 merges into the vertical inner surface 25. Because of the surface tension and the associated pre-curvature, the filling volume of the substances to be absorbed will be smaller than the maximum volume 33, especially in the case of small volumes 33.

The troughs 11 of the plate 2 described so far serve to hold chemical and / or biochemical and / or microbiological substances which are stored in the troughs 11 or are subjected to a reaction. The volume 33 and the number of wells 11 per plate 2 depend on the substances to be received by the wells 11. In addition to the inner diameter 16 and the depth 34, the row spacing 14 and the column spacing 15 are also largely defined via the volume 33. The thickness 7 of the plate 2 in the region of the webs 29 is selected so that the plate 2 has sufficient strength despite the closely lying troughs 11 and does not buckle when the troughs 11 are filled. The thicknesses 31 and 32 of the wall 20 of the troughs 11 are chosen from a mechanical point of view such that the filled ones Do not tear or even tear down troughs 11 under the weight of the substances ingested.

In addition to the purely mechanical point of view, the material from which the plate 2 is made and the thicknesses 31 and 32 of the wall 20 are also selected from a physical point of view. The thicknesses 31 and 32, which - as can be seen in FIG. 2 - are significantly lower than the thickness 7, enable good heat transport into the interior 19 of the troughs 11 and out of the interior 19. This makes it possible to cool or re-heat the substances in the troughs very quickly by bringing the entire outside 28 as a heat exchange surface 28 'into contact with a temperature control substance of the desired temperature.

In the selected embodiment, the plate 2 is made of polycarbonate and has a thermal conductivity of / i = 0.21 W per Kelvin and meter. Thickness 7 is approx. 0.27 mm and the following applies to thickness 31: x = 0.04 mm. The distances 14 and 15 between the rows 12 and the columns 13 are about 10 mm and the volume 33 of the troughs 11 is: V = 85 μl. The size of the heat exchange surface 28 ′ corresponds to the outside 28 and is: A = 75 mm ² . According to the formula

A. A W =

V. x

These numerical values result in a heat transfer value of approx. 4.5 x 10 ~ ³ W / (K mm ³ ). It has been shown that for such a heat transfer value, the heat exchange through the wall 20 takes place so quickly that the determining time factor is the heat conduction in the substances themselves.

The new plate 2 thus makes it possible, for example, to carry out a large number of reactions in separate wells 11 in a small space, the reactions being very thermally controllable through the wall 20 of the wells.

In addition, the material of the plate 2 is selected such that optical analysis methods, such as e.g. Absorption measurements or fluorescence measurements are possible. For this purpose, the material must be transparent in the light wavelength range of interest, i.e. in this wavelength range it must have neither significant absorption nor fluorescence emission.

A method for producing the plate 2 from FIG. 1 will now be described with reference to FIG. 3. The starting material is a thin film 36, for example made of a polycarbonate, with a thickness of 7. This film 36 is placed on a tempered mold block 37 in which upwardly open pocket holes 38 are provided, which like the troughs 11 in Rows 12 and columns 13 are arranged. The pocket holes 38 have a wall surface 40 surrounding their interior 39, which is smooth and self-contained. The dimensions of the blind holes 38 are selected such that they correspond to the outer dimensions of the protuberances 21 to be formed. In the selected example, the pocket holes have a diameter of approximately 6 mm and a depth of approximately 4 mm. In the mold block 37 made of metal, for example aluminum, a heater, indicated schematically at 43, is provided, by means of which the mold block 37 is heated uniformly to 100 ° C. In the direction of the blind holes 38, an air nozzle 45 is arranged above the mold block 37 and can be moved in the direction of the arrow 46. The direction 46 runs parallel to the columns 13 or the rows 12, so that the air nozzle 45 can be positioned centrally over each individual blind hole 38. The direction 46 is also aligned parallel to the top 5 of the film 36 placed on the mold block 37, so that the distance between the air nozzle and the top 5 remains constant.

The air nozzle 45 emits a hot air jet 47 at approximately 280 ° C., which emerges at a speed of approximately 2-5 m / sec from its outlet opening 48 approximately perpendicularly to the mold block 37. The outlet opening 48 has a diameter of approximately 5 mm and is located 4 mm above the upper side 5 of the film 36. The air nozzle 45 is successively positioned centrally over the individual blind holes 38, where it remains for approximately 3 to 5 seconds. The hot air jet 47 striking the upper side 5 heats the film 36 to such an extent that it is plastically deformable.

The hot air jet 47 then blows the area of the film 36 originally above the blind hole 38 into the interior 39 of the respective blind hole, the latter gradually extending and the original thickness 7 of the film 36 decreasing in this area until finally the wall 20 of the trough 11 formed has the thicknesses 31 and 32 indicated in FIG. 2. In Fig. 3, the right trough 11/1 is already finished, and the air nozzle 45 is located above the blind hole 38/2, in which the trough 11/2 is being formed. The bottom 24 of the trough 11/2 has already partially moved into the interior 39/2 of the blind hole 38/2 and will continue to lie across the entire inner surface of the smooth inner wall of the blind hole 38/2. As can be seen in FIG. 3, the web 29 remains in the original thickness 7 of the film 36 between the troughs 11/1 and 11/2. When the troughs 11 are formed, the enclosed air escapes without the formation of bubbles.

Of course, it is possible to use several parallel air nozzles 45 instead of an air nozzle 45, the outlet openings 48 of which are arranged in the grid dimension of the columns 13 or the rows 12. In this way, depending on the number of air nozzles 45, all troughs 11 in a row 12 or also in a column 13 can be produced simultaneously.

As already described above, the film 36 consists of a polycarbonate with a thickness of 0.27 mm. Before the troughs 11 are formed, the film 36 is milky. However, it has been shown that the film 36 becomes transparent at a temperature of the hot air jet 47 of 280 ° C. and at a temperature of the mold block 37 of 100 ° C. in the region of the wall 20 of the molded troughs 11, as is the case for the above-mentioned optical analysis methods is required. The temperature of the mold block 37 to 100 ° C. which is not required for the actual shaping of the troughs 11 furthermore causes the outside 28 of the trough 11 to fit snugly against the wall surface 40 of the respective blind hole 38. This ensures that the outside 28 of each trough 11 is also a smooth and uniform surface 22

has, which is of great advantage for the temperature control of substances accommodated in the troughs 11. The protuberances 21 have almost identical contours, so that their heat exchange surface 28 'can be brought into direct contact with the counter surface formed correspondingly to the blind bores 38 without air layers which disturb the thermal transition. This is described below with reference to FIG. 10.

In particular, if the volume 33 of the troughs 11 is small, the troughs 11 should be closed off from the outside atmosphere. For this purpose, a cover plate shown in FIG. 4 is provided, which consists of a thin cover film 49. In the cover film 49 through holes 50 are provided, which are arranged in the same grid dimension as the through holes 9 in the plate 2. The cover film 49 has a flat top 51 and a bottom 52 parallel to it, with which it covers the plate 2 comes to rest on the top 5. The cover film 49 has a thickness 53 measured between the top 51 and the bottom 52, which is small compared to the transverse dimensions of the cover film 49. The cover film 49 is bespw. made of a 0.1 mm polycarbonate.

When it is placed on the plate 2, the cover film 49 is aligned in such a way that the through holes 50 are aligned with the through holes 9. In this way, the cover film 49 and the plate 2 can be connected to one another at the same time in a manner to be described in more detail and fastened on a carrying device. Of course, instead of the through holes 50 or the through holes 9, downward or upward projecting cylindrical pins can be provided which engage in the through holes 9 or the through holes 50 when the cover film 49 is placed on the plate 2 and thus the cover film 49 releasably connect to plate 2.

As already mentioned, the material preferably used for the cover film 49 is a 0.1 mm thick polycarbonate. This film is transparent in the wavelength range of interest for the optical analysis methods used and has only a low intrinsic fluorescence. The optical analysis methods can thus also be applied from above through the cover film 49; in particular, it is possible to measure the optical density of the substances accommodated in the recesses 11 by the radiation method through the cover film 49 and the bottom wall 24 of the wells.

With the preferred small volumes 33 of the troughs 11, which are in the range between 30 and 100 μl, the volume of solutions accommodated in the troughs 11 can change due to condensation and / or evaporation effects. This applies in particular if the solutions need to be re-tempered frequently between high and low temperatures, as occurs in the polymerase chain reaction (PCR), a frequently used method for the high amplification of individual nucleic acid strands.

In order to increase the sealing effect of the cover film 49, the cover film 49 is connected to the plate 2 in the region of each trough 11 by a closed ring-shaped connecting seam 55 surrounding the opening edge 17 of the trough. In Fig. 5 it can be seen that each connecting seam 55 a delimited circular area 57 of the cover film 49, each covering the opening 18 of an associated trough 11. In this way, each trough 11 is covered, so to speak, with its own cover in the form of the circular region 57, which is connected by the connecting seam 55 to the webs 29 surrounding the trough 11 in such a way that each trough 11 is gas-tight with respect to the atmosphere and the other troughs 11 is completed

A welding stamp 59 profiled on its end face 58, which is shown in detail in FIG. 6, is used, for example, to attach the individual connecting seams 55. The welding stamp 59 has a fully cylindrical base body 60 which carries at its upper end 61 an annular attachment 62 which is integral with the base body 60. The annular extension 62 delimits a circular recess 63, which is concentric with the base body 60 and thus with its longitudinal axis 64, and carries the annular face 58 pointing away from the base body 60.

A profiling in the form of pyramids 65 arranged in rows is provided on the end face 58 surrounding the recess 63 in the form of a ring, which are formed in one piece with the annular extension 62 on their square base 66. The tips 67 of the pyramids 65 point away from the base body 60 in a direction parallel to the longitudinal axis 64 of the welding stamp 59.

FIG. 7 shows a top view of the end face 58 in the direction of arrow VII from FIG. 6 in a detail. As can be seen, the pyramids 65 are arranged in rows 68 and 69, which are offset from one another by half the width of the pyramid base 66. The arrangement is such that between two rows 68/1 and 68/2, which are parallel to each other run and are not offset from one another, a row 69/1 runs, which is accordingly offset from rows 68/1 and 68/2 by half the width of the pyramid base 66. The row 68/2 is immediately adjacent to the row 69/1 and is followed by a row 69/2, which runs parallel to the row 69/1 and is laterally aligned with it.

Returning to FIG. 6, it can be seen that the welding stamp 59 is provided with a heater, indicated schematically at 71, by means of which the welding stamp 59, which is preferably made of V2A steel, is heated to approximately 280.degree. To make the connecting seam 55, the heated welding die 59 is placed from above onto the top 51 of the cover film 49 placed on the plate 2 in such a way that, with its profiled, annular end face 58, it centrally centers the opening edge 17 of the cover film 49 and surrounds to be welded trough 11. The circular recess 63 has a diameter which is so large that the pyramid tips 67 come to lie outside the opening edge 17 on portions of the cover film 49 located above the webs 29.

The square base 66 of the pyramids 65 measures 0.5 × 0.5 mm and the tip 67 of the four-sided pyramid 65 lies 0.25 mm perpendicularly above the pyramid base 66, ie two pyramid sides lying opposite one another enclose an apex angle of 90 °. In the radial direction, up to three pyramids 65 are arranged one behind the other on the annular end face 58, so that the welding stamp 59 has an overall outer diameter which is at least 6 base lengths of a pyramid 65 larger than the diameter of the recess 63. The following method has proven itself for welding a cover film 49, the thickness 53 of which corresponds to approximately 0.1 mm, to a plate 2, the thickness 7 of which corresponds to approximately 0.27 mm.

The cover film 49 is placed on the plate 2 from above so that it covers the troughs 11 and that the through holes 50 are aligned with the through holes 9. The welding stamp 59, heated to 280 ° C., is placed with its end face 58 at the top from above onto the upper side 51 of the cover film 49 in such a way that it is located centrally over a trough 11 which is located under the cover film 49 and is to be welded. The pyramids 65 on the end face 58 now lie on the top 51 with their tips 67, which may penetrate somewhat into the material of the cover film 49, and heat them. In this way, the cover film 49 is preheated for about 13 seconds by the honeycomb-like profile of the end face 58. Then the welding stamp 59 is pressed downward by approximately 0.1-0.2 mm onto the covering film 49, so that each pyramid 67 penetrates into the covering film 49 and this in turn penetrates into the webs 29 of the plate 2. The welding stamp 59 remains in this position for two seconds, then it is completely lifted off the cover film 49.

The resulting connection seam 55, which is a type of weld seam, is shown in FIG. 8 in a cross section along the line VIII-VIII from FIG. 5. The cooled connecting seam 55 has a corresponding profiling as the welding stamp 59. The pyramids 65 have pressed pyramid-like depressions 73 which are upside down into the preheated upper side 51 of the cover film 49 and correspond in shape to the pyramids 65. The cover film 49 is also in the area of Indentations 73 penetrated with their underside 52 into the upper side 5 of the webs 29, which was indirectly preheated through the cover film 49, and there formed indentations 74 which correspond to the indentations 73. In this way, a contact surface 75 has formed between the underside 52 of the cover film 49 and the top side 5 of the plate 2, which has a zigzag cross-section. As a result of this zigzag-shaped course, the contact surface 75 is larger than the contact surface which existed before the welding between the underside 52 of the cover film 49 and the upper side 5 of the plate 2 in the intended area of the connecting seam 55.

The heat effect of the pyramids 65 not only increased the contact area, the cover film 49 and the webs 29 were also integrally welded to one another along the contact area 75. It has been shown that this connecting seam 55 ensures a good not only liquid-tight but also gas-tight closure of the individual troughs 11 even with frequent changes between high and low temperatures on the underside 6 and on the outside 28. This also applies if there is an overpressure in the interior of the troughs because, for example, the solutions taken up have been heated to such temperatures that the gas volume above the solution tends to expand. The connecting seam 55 also withstands the usual mechanical loads to which the closed plate 2 is exposed in everyday laboratory work, as well as the slight changes in shape and stresses associated with the temperature change.

During the welding described above, the circular section 57 of the cover film 49 covering the opening 18 bulges up like a dome, so that a closed and welded plate 2 as described above has a lenticular curvature 76 of the cover film 49 above each trough 11. However, since the curvature 76 is only formed in the case of troughs 11 welded in a gastight manner, it is at the same time a visual indication that the formed connecting seam 55 has ensured a gas-tight closure of the trough 11 in question, which also withstands excess pressure inside the trough. If the cover film 49 does not have any bulges 76 after the welding, the welding process, for example, was faulty with regard to the dwell times, the temperature of the welding stamp 59 or the depth of penetration of the pyramids 65 into the upper side 51.

The temperature of the welding stamp 59, the dimensions of the pyramids 65 and the depth of penetration of the pyramids 65 into the upper side 51 of the cover film 49 are only examples of a cover film made of polycarbonate with a thickness of 0.1 mm and a plate 2 made of polycar ¬ bonat with a thickness of 0.27 mm. In the case of thicker polycarbonate films, the depth of penetration of the pyramids, which roughly corresponds to the thickness of the cover film, must be adapted to the new thicknesses.

In addition to the correct observance of the dwell time of the welding stamp 49, first on the upper side 51 and then in the state that has penetrated into the upper side, the depth by which the pyramids 65 penetrate into the material of the cover film 59 is essential for the success of the welding process. Although the welding process described above can be carried out by hand, the yield of correctly placed connecting seams 55 is significantly increased by using a welding device 78 shown in FIG. 9. The welding device 78 has a flat, rectangular base plate 79 and a flat top plate 80 arranged above the base plate 79, which shows approximately the same transverse dimensions as the base plate 79. The top plate 80 is attached to the base plate by means of four guide rods 81 Base plate 79 attached. Of the four guide rods 81, which are screwed into the base plate 79 from above in the area of one of the four corners, the front right guide rod 81/4 in FIG. 9 has been broken out for reasons of a clear representation.

Between the base plate 79 and the head plate 80, a height-adjustable support plate 82 is provided, in the outer corners of which ball bushings 83 are embedded, through which the guide rods 81 pass. As a drive for the height adjustment of the carrier plate 82, an electrically operated drive motor 84 is fastened away from the carrier plate 82 with its flange 85 from above on the head plate 80. Motor 84 has a motor shaft indicated at 86, which is connected to a ball screw drive indicated at 87. The ball screw drive 87, on the other hand, is connected to the support plate 82 and serves to convert the rotary movement of the motor shaft 86 into the adjustment movement of the support plate 82 along the guide rods 81.

Remote from the ball screw drive 87, a heating block 89 is provided in the center below the support plate 82, which is fastened to the support plate 82 from below by means of four spacer bolts 90. The heating block 89 made of copper fulfills the function of the heating for the welding punches 59 indicated at 71 in FIG. 6, three of which are indicated in FIG. 9 30th

are. The welding punches 59/1, 59/2 and 59/3 are remote from the spacer bolts 90 in the heating block 89 from below and point with their end faces 58 pointing downward from the heating block 89.

In the heating block 89 there is a blind hole 91 which penetrates it almost completely from right to left in FIG. 9 and into which an electrically heatable heating cartridge is inserted, which is not shown for reasons of clarity. The temperature of the heating block 89 is measured in a suitable manner by a temperature sensor, not shown further, and is passed to a control circuit, also not shown, which in turn controls the heating cartridge. In a manner known per se, a closed control loop is thus formed, by means of which the temperature of the heating block 89 is kept at a constant value, for example 280 ° C. The heating block 89 heats the carrier plate 82 via the spacer bolts 90, which can lead to the ball bushings 83 jamming on the guide rods 81. For this reason, coolant bores 92 are provided in the carrier plate 82, via which the carrier plate 82 is connected to a thermostatic cooling circuit. In this way, the temperature of the support plate 82 can be regulated independently of the temperature of the heating block 89 via an external thermostat, so that an easy adjustment of the support plate 82 along the guide rods 81 is ensured.

Approximately in the middle under the heating block 89, which is height-adjustable via the support plate 82, an upward-facing receiving block 93 is provided on the base plate 79. The receiving block 93 has a coolant bore 94 passing through it, which in the same way as the coolant bore 92 of the carrier plate 82 is connected to an external thermostat circuit which keeps the receiving block 93 at a constant and adjustable temperature.

The receiving block 93 has upwardly open cups 95 which are designed to receive the protrusions 21 projecting downward beyond the plate 2. The cups 95 therefore have the same dimensions as the blind holes 38 shown in FIG. 3 in the mold block 37 and are arranged in rows 12 and columns 13 like the troughs 11.

From above, a plate 2 is placed on the receiving block 93, which in turn is covered by a cover film 49. A perforated mask 96, which overlaps the receiving block 93 from all sides from above, is placed over the covering film 49, which presses the covering film 49 onto the plate 2 and this in turn, with its depressions 11, into the receiving block 93. Through holes 97 aligned with the welding punches 59 are provided in the shadow mask 96, which are also arranged in rows 12 and columns 13 such that a hole 97 is aligned centrally over each trough 11. For reasons of clarity, the shadow mask 96, the cover film 49 and the plate 2 are shown broken off offset with respect to the receiving block 93.

Of course, a hole 97 and a welding stamp 59 are provided for each trough 11 of the plate 2.

On both sides of the receiving block 93 two identical upward-facing bases 98 are arranged on the base plate 79 for fastening the shadow mask 96, of which the right-hand base 98/2 is shown broken off. The base 98/1 has one mounting hole 99 pointing upwards, to which a mounting clip, which can be designed, for example, as a spring clip or as a bolt, is attached in order to press the perforated mask 96 down onto the receiving block 93.

For the sake of clarity, the fastening clip has been omitted in FIG. 9.

The welding device 78 described so far operates as follows:

The carrier plate 82 is in the raised starting position shown in FIG. 9. After the shadow mask 96 has been removed from the receiving block 93, a plate 2 to be welded is placed on the receiving block 93 from above such that the troughs 11 with their protuberances 21 come to rest in the cups 95. The troughs II with their opening 18 facing upwards are already filled with the desired substances and covered by a cover film 49, or are now filled accordingly and then covered with a cover film 49, which is oriented in such a way that their through holes 50 are connected to the through holes. aligned holes 9 in the plate 2, the perforated mask 96 is put over the plate 2 covered in this way, their through holes 97 coming to lie centrally over the troughs 11. With the aid of the fastening clips provided on the bases 98, the shadow mask 96 is pressed firmly down onto the receiving block 93.

The heating block 89 is heated to 280 ° C. via the heating cartridge inserted in the blind hole 91. This temperature also has that which is thermally conductively connected to the heating block 89 Welding stamp 59 on. Via the ball screw drive 87, the rotational movement of the motor shaft 86 of the drive motor 84 is converted into a downward movement of the carrier plate 82 which is guided via the ball bushings 83 and the guide rods 81. When the carrier plate 82 and thus the heating block 89 go down, the welding punches 59/1 and 59/2 slide from above into the associated holes 97/1 and 97/2 of the shadow mask 96. The translation of the ball screw drive 87 and the number of revolutions the motor shaft 86 are dimensioned such that at the end of the downward movement of the carrier plate 82 the welding punches 59 with their end face 58 or the tips 67 of the pyramids 65 come to lie precisely on the upper side 51 of the cover film 49, as has already been described above.

In this position, in which the welding punches 59 preheat the cover film 49 and the plate 2 in the region of the connecting seams 55 to be applied, the welding device 78 remains for approximately 13 seconds. After this preheating time, the carrier plate 82 is gradually moved downward by 0.1 mm further from the motor 84 via the ball screw drive 87 to the receiving block 93, so that the pyramids 65 on the end face 58 of the welding stamp 59 into the cover film 49 and this into the Penetrate webs 29 of the carrier plate 2. After a further two seconds, the motor 84 is actuated so that its motor shaft 86 rotates in the opposite direction to the previous direction of rotation and thus via the ball screw drive 87 the carrier plate 82 and thus the heating block 89 and the welding stamp 59 again in the starting position shown in FIG. 9 starts up.

After loosening the fastening clips, the shadow mask 96 can be removed and the welded plate 2 as shown in FIG. 5 is removed from the receiving block 93. Now the next plate 2 is placed on the receiving block 93 and the welding process starts again.

For many experiments it is necessary to keep the substances contained in the troughs 11 at low temperatures and to prevent them from being heated up during the welding process just described. For this purpose, the receiving block 93 and thus its cups 95 are thermostated via the coolant bore 94 to a temperature as required by the respective substances, for example to 10 ° C. The troughs 11 lie with their heat exchange surface 28 'closely against the inner wall of the respective cup 95, so that, due to the low thickness 31 of the wall 20 of the troughs 11, the substances in the troughs 11 are kept at the same temperature as the receiving block 93 itself. The heat possibly supplied to the substances during welding is instantaneously dissipated through the wall 20 into the receiving block 93 because of the good heat transfer.

In this way, substances which react very sensitively to temperature fluctuations can also be welded into the troughs 11 of the new plate 2 with the aid of the new welding device 78. This makes it possible to a large extent to package temperature-sensitive substances or solutions or highly infectious substances in a gas-tight manner in a small space. The substances can, for example, be prepared reaction solutions for biochemical and / or microbiological test methods, which are supplied to the user in portioned and welded form in the new plates 2. The substances to be examined by the user can, for example, be contained in the troughs 11 Test solutions are introduced by piercing the arches 76 covering the openings 18 of the troughs 11 from above with a thin cannula. The substances to be examined are then injected into the test solutions located in the wells 11.

After withdrawing the cannula, which is, for example, a syringe that is commonly used in everyday laboratory work, a capillary-like channel remains in the curvature 76. No moisture exchange with the surrounding atmosphere is possible via this channel, so that the volume of the substances or solutions accommodated in the gas-tight welded troughs 11 does not change due to condensation or evaporation effects.

Usually, however, the troughs 11 of the new plate 2 are filled on site, for example in the chemical laboratory, and sealed gas-tight with a cover film 49 using the new welding device. The fixed grid dimension of the columns 13 and rows 12 makes it possible to fill several troughs 11 simultaneously with a known multiple pipette.

FIG. 10 shows a plate 2 with gas-tightly closed troughs 11, in which there are, for example, solutions whose course of the reaction can be influenced via their temperature. The solutions were either filled into the troughs 11 on site or were already in the welded plate 2 and were subsequently inoculated by the user with the substances to be examined - for example DNA molecules to be examined.

The plate 2 prepared in this way is inserted from above into a thermoblock 101 which has pocket holes 102 open at the top, which serve to receive the cup-like protuberances 21. The blind holes 102 have the same shape as the blind holes 38 in the mold block 37 used to produce the plate 2. After the protuberances 21 have been inserted into the blind holes 102, their inner wall 103 lies directly against the heat transfer surface 28 ′ of the protuberances 21. There are therefore no air layers interfering with the heat transfer between the thermoblock 101 and the interior 19 of the troughs 11 between the outside 28 and the inner wall 103 acting as counter surface 103 '.

In the thermoblock, upwardly open threaded bores 104 are also provided, which, when the plate 2 is inserted in the thermoblock 101, are aligned with the through holes 50 and 9 in the cover film 49 and in the plate 2, respectively. Through the through holes 50 and 9, screws 105 are screwed into the threaded bores 104 from above and thus the plate 2 closed with the cover film 49 is firmly connected to the thermoblock 101. The upper side of the thermoblock 101 comes to lie close to the underside 6 of the plate 2, and the protuberances 21 are pressed firmly onto the inner wall 103 of the pocket holes 102 with their heat exchange surface 28 '.

Because of the smooth surface of the outside 28, which is in direct thermal contact with the inner wall 103, and because of the large heat transfer value described, the solutions in the troughs 11 take on the temperature of the thermoblock 101 within a few seconds. If, for example, the solutions are to be stored for a long time at a low temperature, the thermoblock 101, which is made of a good heat-conducting metal, is tempered, for example, to + 4 ° C. by means of a thermostat connected to it. If the reaction in the solutions is to be started, the thermoblock 101 is heated in a suitable manner to the reaction temperature of the solutions, which follow the temperature change of the thermoblock 101 almost immediately because of the good heat transfer. The temperature change of the thermoblock 101 itself can be effected in a manner known per se by immersing the thermoblock 101 in water baths of different temperatures, bringing it into heat-conducting contact with preheated other metal blocks or moving it along a metal rail on which a temperature gradient is established is.

In particular, the metal rail with the temperature gradient enables the temperature of the thermoblock 101 and thus the temperature of the solutions in the wells 11 to be changed cyclically. In order to carry out the polymerase chain reaction in the wells 11, the thermoblock 101 is initially 37, for example, for 60 seconds ° C, then for 120 seconds to 72 ° C, then for 60 seconds to 94 ° C and then again for 60 seconds to 37 ° C etc. Because of the gas-tight closure of the individual troughs, even at high temperatures, none escapes then water vapor-saturated air from inside the troughs. The water vapor content of the air volume above the absorbed liquid is regulated by the liquid, but since no air can escape, there are no evaporation processes, so that the initially set concentrations in the solutions do not change over the course of the many temperature cycles. This ensures a good yield in the experiments. The time that is required to bring the solutions to the individual temperatures is also decisive for the course of the polymerase chain reaction. While a typical reaction sequence in the known plastic reaction vessels lasts more than 10 hours and is usually carried out overnight, the reaction is completed in less than 4 hours when the new plate is used. Such an experiment can now be prepared, carried out and analyzed within one day.

After the end of the test, the solutions are at least partially reused, for example to analyze them using a separating gel. For this purpose, the curvature 76 is pierced with the syringe indicated at 107 in FIG. 10 and part of the solution is removed. After the syringe 107 has been withdrawn, the solution remaining in the trough 11 can be stored, for example, in the manner described above. Although the hole formed during the removal from the curvature 76 does not result in any significant moisture exchange, it can be described. close it again with an adhesive film.

Finally, for the sake of completeness, it should be mentioned that the transverse dimensions of the new plate 2 and the row and column spacings 14 and 15 essentially depend on the filling volume 33 of the troughs 11 desired in each case. The thermoblocks 101, receiving blocks 93 and mold blocks 37 used in each case are adapted to these distances. In any case, however, the thickness 7 of the film 36 is selected so that the troughs 11 in the finished plate 2 have a bottom wall 24, the thickness 31 of which is in the range of 0.04 mm, so that the heat transmission value is the required high value having.

Claims

Patent claims

Plate (2) with at least one trough (11) for receiving chemical and/or biochemical and/or microbiological substances, the trough (11) having an interior space (19) delimited by its inner surface (25) and a wall (20 ) whose outer side (28) remote from the inner surface (25) comprises a heat exchange surface (28') which can be brought into thermal contact at least partially with a tempering agent (101), characterized in that the at least one trough (11) has a heat transfer value, the greater than

^{5 χ} -_° ^~4 W is and K mm ³ for which is the formulaic relationship

V. X applies, in which means:

A - size of the heat exchange surface (28'),

^" ) - Thermal conductivity of the wall (20) forming

Material, V - volume (33) of the interior (19) of the trough

(11), x - wall thickness (31) of the wall (20), measured as

Distance between the heat exchange surface

(28') and the inner surface (25), and W - heat transfer value.

Plate (2) according to claim 1, characterized in that the wall thickness (31, 32) is approximately the same size at least over the entire heat exchange surface (28').

3. Plate (2) according to one of the preceding claims, characterized in that the heat transfer value is greater than 1 x 10 ^~3 W.

K mm ³

4. Plate (2) according to one of the preceding claims, characterized in that the heat transfer value is greater than 2 x 10 ^~3 W.

K mm ³

5. Plate (2) according to one of the preceding claims, characterized in that it is formed in one piece with the trough (11).

6. Plate (2) according to claim 5, characterized in that it is made of plastic.

7. Plate (2) according to claim 6, characterized in that the plastic is thermally deformable.

8. Plate (2) according to one of the preceding claims, characterized in that the heat exchange surface (28 ') is arranged below its underside (6).

9. Plate (2) according to one of the preceding claims, characterized in that the trough (11) is designed as a cup-like protuberance (21), the outside (28) of which is at least partially the heat exchange surface (28*).

10. Plate (2) according to claims 8 and 9, characterized gekenn¬ characterized in that the cup-like protuberance (21) is connected to the underside (6) of the plate (2). has a hollow cylindrical upper section (22) and a hemispherical hollow lower section (23) integrally connected thereto.

11. Plate (2) according to one of the preceding claims, characterized in that the volume (33) of the interior space (19) is smaller than 200 mm ³ and is preferably between 10 and 100 mm ³ .

12. Plate (2) according to claims 10 and 11, characterized in that the lower section (23) has a radius between 2 and 6 mm and that the wall thickness (31, 32) of the trough (11) is thinner than 0 .2 mm.

13. Plate (2) according to claim 12, characterized in that the wall thickness (31) is thinner than 0.08 mm.

14. Plate (2) according to claims 6 and 13, characterized in that it is made of polycarbonate.

15. Plate (2) according to claim 14, characterized in that it is made from a polycarbonate film whose thickness is less than 0.5 mm.

16. Plate (2) according to one of the preceding claims, characterized in that it has a number of troughs (11) which are identical to one another.

17. Plate (2) according to claim 16, characterized in that the troughs (11) are arranged in rows (12) and columns (13) which have equal distances (14, 15) from one another of approximately 10 mm.

18. Plate (2) according to claim 16 or 17, characterized in that a cover (49) is provided for the troughs (11) to close their openings (18).

19. Plate (2) according to claim 18, characterized in that each area (57) of the lid (49) covering the opening (18) is a trough (11) by means of a connecting seam (55) going around the respective opening (18). can be connected to the plate (2).

20. Plate (2) according to one of claims 18 or 19, characterized in that the lid (49) is made of a plastic film, in particular of the same material as the plate (2).

21. Plate (2) according to claim 20, characterized in that the respective connecting seam (55) seals the respective trough (11) in a gas-tight manner.

22. A method for producing a plate according to claims 1 to 21, which is made of plastic, characterized in that a thermally deformable plastic film with a thickness of less than 0.5 mm and a thermal conductivity greater than 0.1 watt / ( K m) is placed with its underside first from above on a mold block, which is cup-like and open at the top Includes depressions whose interiors have a volume of less than 200 mm ³ ; that a hot gas stream is directed successively from above the placed film onto the top side of each cup-like depression for a certain period of time; and that the hot gas stream has a fixed temperature which is close to the melting temperature of the film.

23. The method according to claim 22, in which the hot gas stream flows out of an outlet opening whose diameter corresponds approximately to the diameter of the cup-like depression and whose distance from the top of the film is smaller than this diameter.

24. The method according to claim 23, in which the mold block can be tempered and is kept at a temperature below the melting point temperature of the film, preferably at approximately 100 ° C.

25. The method according to claim 24, in which the plastic film is a polycarbonate film.