EP1596974B1 - Method and device for blending small quantities of liquid in microcavities - Google Patents

Abstract

A method for treating extremely small particles of recycled polyethylene terephthalate comprises providing a quantity of RPET particles having an average mean particle size ranging from about 0.0005 inch to about 0.05 inch in diameter, heating the RPET particles to a temperature sufficient to cause at least a portion of the RPET particles to adhere to one another, and forming the adhered RPET particles into pellets, said pellets having substantially the same average surface-to-volume ratio as the bulk, un-adhered RPET particles.

Description

The invention relates to a method for mixing liquids in microcavities and to an apparatus for carrying out the method.

Microcavities, z. As in the arrangement of micro-titer plates are used in pharmaceutical research and diagnostics as reaction vessels. Based on the standard format of micro-titer plates, highly automated processes are possible in modern laboratories. So z. As pipetting robots, devices for optical readout of biological assays and the corresponding transport systems adapted to the standard format. Such standard micro-titre plates are available today with 96, 384 or 1536 cavities. Typical volumes per well are in the range of 300 μl for 96-well plates, about 75 μl for 384 microtitre plates and about 12 μl for 1536-well plates. Micro-titer plates are generally made of plastic, for. As polypropylene or polystyrene, and often coated or biologically functionalized.

The miniaturization in the form of such micro-titer plates or microcavities in general finds its justification in the often expensive reagents and in the fact that often sample material is not available in the desired amount, so that reactions at high sample concentration can only be carried out if the Volumes are reduced accordingly.

In order to accelerate the reactions as well as to ensure homogeneous reaction conditions, it is desirable to mix the reactants during the reaction. This is particularly important when a reactant ("probe") is attached, i. an inhomogeneous assay is present. Here mixing can prevent depletion of the sample on the bound probes. In general, in the absence of mixing, the diffusion of the reactants is often the time-determining step. This results in long reaction times and low sample throughput.

Micro-titer plates or generally microcavities are mixed in known methods by means of so-called shakers. Such shakers include mechanically moving parts and are difficult to integrate into highly automated lines. The mixing is also particularly in small cavities, so z. For example, 384 microtiter plates or 1536 microtitre plates are very inefficient. With such small microcavities, small amounts of liquid appear to be very viscous, and in small volumes only laminar flows are possible, i. There is no turbulence that would cause effective mixing. In order to achieve a sufficient mixing effect despite the viscosity, which appears to be high for small quantities of liquid, high power of the shaker is necessary.

Thus, WO 00/10011 describes a method by which a microcavity in the frequency range of 1 to 300 kHz is shaken. There are powers of 0.1 to 10 watts applied.

Various other methods for mixing small amounts of liquid are described in the literature.

In US 2002/0009015 A1 the utilization of cavitation is described for the mixture, ie nucleation, expansion and decay or collapse of a local vacuum space in the liquid or a bubble, ie a local gas / vapor space in the liquid, due to an acoustic pressure field. The mixing of the liquid is achieved by the momentum of the local vacuum space or the bubble, ie their expansion and decay. To reduce the acoustic power threshold to form the local vacuum spaces or bubbles, nucleation nuclei are needed. These nucleation germs increase the risk of contamination. In addition, the formation of local vacuum spaces or bubbles is often undesirable.

Other known methods (eg, "Microfluidic motion generation with acoustic waves", X. Zhu et al., Sensors and Actuators, A. Physical, Vol. 66 / 1-3, page 355 to 360 (1998) or "Novel acoustic wave micromixer ", V.Vivek et al., IEEE International Microelectronic Mechanical Systems Conference 2002, pages 668 to 673, or US 5,674,742) describe the use of membrane-like elements that vibrate in so-called" flexural plate wave modes ". The motion-mediating medium is in direct contact with the liquid. The preparation of such thin membranes is very complicated and the risk of contamination by the contact of the liquid with the motion-promoting medium is increased.

No. 6,357,907 B1 describes the use of magnetic beads which move in an external, temporally or spatially variable magnetic field. To carry out the mixing process, the beads must be introduced into the liquid, which is often undesirable because of contamination problems.

US 6,244,738 B1 describes a mixing process in an elongated closed channel. Two streams of liquid pass an ultrasonic generator and are mixed in the microchannel. To carry out the process, a complicated structure with a microchannel system is necessary and no separate individual volumes can be mixed.

US 5,736,100 describes the use of a turntable with small vessels in the micro cavities, z. B. Eppendorf caps, can be used. In these pots is z. As water, which is irradiated from the outside with ultrasound. The described device thus acts like a conventional ultrasonic bath. The water is vibrated and acts as a moving element directly on the respective potty, which is shaken in this way.

DE-A-101 17 772 describes the mixing of liquids using surface acoustic waves generated by means of interdigital transducers. The liquid is located directly on the sound-transmitting medium itself. At least with multiple use of the devices there is a risk of contamination. An insert with a micro-titer plate is not possible in the described arrangements.

US 6,168,948 B1 describes an acoustic mixing process for mixing a sample in a reaction chamber using a piezoelectric volume vibrating element at a frequency of 2 MHz.

The object of the present invention is to specify a method and a device which enable effective mixing of liquids in microcavities, in particular a microtitre plate, and which minimize the risk of contamination.

This object is achieved by a method having the features of claim 1 and a device having the features of claim 21. Subclaims are directed to advantageous embodiments.

According to the invention, with the aid of at least one piezoelectric transducer, an ultrasonic wave having a frequency greater than or equal to 10 MHz is passed through a solid layer in the direction of the at least one microcavity and the liquid therein to produce a sound-induced flow there. The extent of the solid-state layer in the sound propagation direction is greater than 1/4 of the wavelength of the ultrasonic wave.

The frequency range greater than or equal to 10 MHz ensures that a jarring of the entire device, as z. B. in shaking mechanisms of the prior Technique is used, does not occur in the inventive method. A solid-state layer greater than ¼ of the wavelength of the ultrasonic wave can effectively prevent membrane-like flexural plate wave modes or Lamb modes from forming. In the method according to the invention, the ultrasound passes through the solid-state layer directly into the microcavity and generates there a sound-induced flow. The use of the high frequency also ensures that the sound absorption in the liquid is high.

The liquid to be mixed is not in direct contact with the sound-generating medium. A contamination with multiple use is therefore excluded.

With the method of the invention, effective mixing can be achieved with performances typically less than 50 milliwatts per well. With good acoustic adjustment, the value can also be reduced to less than 5 milliwatts per cavity.

As a solid state layer, a separate substrate, for. B. of plastic, metal or glass. The thicknesses are depending on the ultrasonic wavelength used z. B. in the range of 0.1 mm to a few cm. Typical ultrasonic wavelengths are in the range of 10 .mu.m to 100 .mu.m. The solid state layer can also z. Example, be formed directly by the bottom of a microcavity or the bottom of a micro-titer plate, which is optionally adjusted or ground to a desired thickness, or include the ground.

The piezoelectric transducer can be excited either monochromatically by applying a high-frequency signal of the resonance energy or a harmonic (continuous or pulsed). By changing the frequency or amplitude can be selectively influenced on the resulting mixed pattern. Feeding the resonant frequency of the transducer also increases the efficiency of converting the electrical energy into acoustic energy.

Advantageously, however, it is also possible to use a needle pulse which, in addition to many other Fourier coefficients, as a rule also has those which can resonantly excite the sound transducer. This reduces the demands on the required electronics, since no special frequency must be adjustable.

Ultrasonic absorption in the liquid to be mixed is particularly effective when the wavelength of the ultrasonic wave is chosen to be less than or equal to the mean level in the microcavity in the liquid.

The sound transducer may be formed over the entire surface under the solid state layer. However, it is particularly advantageous if the lateral extent of the sound transducer is smaller than the lateral extent of the microcavity used. First, with a larger transducer, the capacitive component of its impedance is increased, thereby changing the electrical matching, and second, the mixing efficiency is smaller when the transducer is larger than the lateral extent of the microcavity. On the other hand, if the lateral extent of the sound transducer is smaller than the lateral extent of the microcavity, the ultrasonic beam has a smaller lateral extent than the lateral extent of the microcavity. Side of the upward ultrasonic beam, the liquid can flow down again, so that thereby optimal mixing of the liquid is achieved. For example, the ultrasonic wave can be coupled centrally from below into the microcavity, so that the liquid can move upwards centrally in the microcavity and can flow back downwards again at the edge of the microcavity.

The latter effect can be achieved in an alternative process by introducing between the sound transducer and the microcavity an intermediate layer comprising a sound absorbing material in an arrangement which allows the ultrasound to propagate in the direction of the microcavity only in a limited spatial area , Examples of advantageous sound-absorbing media are silicone, rubber, silicone rubber, soft PVC, wax or the like.

Between the microcavity and the solid state material, a liquid or solid compensating medium, for. As water, oil, glycerol, silicone, epoxy resin or a gel film are introduced to compensate for bumps and to ensure safe acoustic contact.

As microcavities z. As Eppendorf caps or pipette tips or other microreactors can be used. To parallelize the process, several microcavities can be used simultaneously. Particularly advantageous is the use of a micro-titer plate, which already provides a large number of cavities in a predetermined pitch.

Likewise, several micro cavities z. B. be defined by means of an adhesive film with holes on a Glasslide, preferably in the dimensions of a conventional micro-titer plate. For the purposes of the present text, the term "microtiter plate" is intended to include such an arrangement. In such an embodiment, for. B. the Glasslide be used directly as a solid layer, which is irradiated by the ultrasonic wave. In this way, a particularly compact arrangement can be realized. For the realization of only one microcavity an adhesive film with only one hole is used in an analogous manner.

The method according to the invention can also be carried out with a device analogous to a microtitre plate, in which a field of partial regions is provided on a substrate, which are preferably wetted by the liquid to be mixed and thus serve as anchorage for the liquid to be mixed. If these fields are arranged in the grid dimension of a conventional microtitre plate, then, after application of the liquid, a lateral distribution of the liquid results, as in a conventional microtitre plate, wherein individual drops are held together by their surface tension. As used herein, the term "microtitre plate" is intended to include such embodiment.

A microtiter plate can be placed on the solid layer. Is z. B. only one transducer, so the micro-titer plate on the solid state layer be moved to sonicate different cavities with ultrasound. In this way, it can be individually selected which microcavity is to be exposed to the mixing.

For mixing of liquids in the individual cavities of a micro-titer plate is in a particular embodiment of the method z. B. a field of piezoelectric transducers below the solid state layer used, which have the same arrangement as the cavities of a micro-titer plate. If these sound transducers are individually controlled, the liquids in the individual cavities can be mixed independently. Such a field of piezoelectric transducers can be easily integrated into automation solutions.

In another advantageous process control, ultrasound is coupled into the solid-state layer with the aid of an ultrasound wave generating device such that ultrasound power can be coupled into a corresponding number of microcavities at least at two outcoupling points from the solid-state layer. This can be z. B. be achieved by an ultrasonic wave generating device which radiates bidirectionally.

In the invention, the ultrasonic wave is generated by means of an interdigital transducer on a piezoelectric crystal deposited on a piezoelectric crystal.

The piezoelectric crystal carrying the interdigital transducer may be glued, pressed, bonded or bonded, pressed or bonded to the solid state layer via a coupling medium (eg electrostatically or via a gel film).

Such interdigital transducer are comb-like metallic electrodes whose double finger spacing defines the wavelength of the surface acoustic wave and by optical photolithography z. B. can be made in the range of 10 microns finger spacing. Such interdigital transducers be z. B. on piezoelectric crystals provided to excite surface acoustic waves in a conventional manner.

By means of such an interdigital transducer, volume sound waves can be generated in the solid-state layer in a different manner, which transpose this obliquely. The interdigital transducer generates a bi-directionally radiating interfacial wave (LSAW) at the interface between the piezoelectric crystal and the solid state layer on which it is deposited. This interface leakage wave radiates energy as volume sound waves (BAW) into the solid state layer. As a result, the amplitude of the LSAW decreases exponentially, with typical decay lengths of about 100 μm. The radiation angle α of the volume sound waves in the solid state layer measured against the normal of the solid state layer results from the arc sinus of the ratio of the velocity of sound V _{s of} the volume sound wave in the solid layer and the sound wave V _{SAW of} the interface sound wave generated with the interdigital transducer (α = arcsin (V _s / V An emission into the solid-state _layer is therefore possible only if the speed of sound in the solid-state layer is smaller than the speed of sound of the interface-leaky-wave In the rule, transversal waves are excited in the solid-state layer since the longitudinal speed of sound in the solid-state layer is greater For example, a typical value for the interface leakage wave velocity is 3900 m / s.

The piezoelectrically induced deformations in the piezoelectric crystal below the comb-like interdigitated interdigital transducer fingers radiate volume sound waves (BAW) also directly into the solid-state layer. In this case, an emission angle α measured against the normal of the solid-state layer results as the arc sinus of the ratio of one side of the velocity of sound in the solid-state layer V _s and on the other hand the product of the period of the interdigital transducer I _IDT and the applied high-frequency f (α = arcsin (V _s / (I _IDT · f)). For this sound-coupling mechanism, the angle of incidence relative to the normal of the solid-state layer, the levitation angle, So be predetermined by the frequency. Both effects can occur side by side.

Both mechanisms (LSAW, BAW) allow oblique irradiation of the solid state layer. The entire electrical contacting of the interdigital transducer can take place on the side of the solid-state layer facing away from the microcavity or the liquid.

In an embodiment that is easy to implement, the interdigital transducer is located on the piezoelectric element on a side of the solid state layer facing away from the microcavity. Due to the described oblique coupling of the ultrasonic wave in the solid state layer also geometries are possible in which the interdigital transducer is arranged with the piezoelectric element on an end face of the solid state layer.

It is particularly advantageous if the material of the solid-state layer to be penetrated is selected with regard to the acoustic attenuation at the frequencies used and the reflection properties of the interfaces such that a partial reflection of an obliquely coupled-in ultrasonic wave takes place. For example, a compensating medium between micro-titer plate and solid state layer may be provided, so that adjusts an interface between the compensating medium and to durchschallender solid state layer, in which a reflection coefficient of z. B. sets 80% to 90% for an ultrasonic wave of the frequency used, so that 10% to 20% of the current in the solid state layer ultrasonic wave are coupled out and the rest is reflected. Between the solid state layer and air at the other boundary surface of the solid state layer, a nearly 100% reflection usually takes place. In another embodiment, in which the bottom of the microtitre plate itself is used as a solid state layer to be sonicated, 10% to 20% of the ultrasound output is coupled out of the bottom of the microtitre plate serving as a solid-state layer into the liquid in the respective microcavity, and the remainder reflected in the bottom of the microtitre plate.

Due to the reflection at the interfaces, the ultrasonic wave is guided through the solid-state layer as in a waveguide. Where the ultrasonic wave strikes the interface between the solid-state layer and the compensation medium or solid-state layer and liquid in one of the microcavities, part of the ultrasonic power is decoupled. By suitable selection of the geometries, eg. As the thickness of the solid state layer or the bottom of the micro-titer plate, the thus defined Auskopplungsorte the ultrasonic power can be determined locally accurate. In such a process management can thus z. B. several micro-cavities of a micro-titer plate are sonicated simultaneously with ultrasonic power without a large number of transducers would be necessary. Problems that z. B. could occur with the wiring of a variety of transducers are avoided in this way.

As advantageous z. B. due to low attenuation, the use of quartz glass as a solid state layer at a frequency of 10 MHz to 250 MHz proved. While nearly 100% of the solid-state layer / air interface is reflected in such a case, a certain percentage of the sound energy is coupled into the respective liquid at the solid-state layer / liquid interface (that is to say, for example, compensation medium or the liquid in the microcavity).

Using interdigital transducers with non-constant finger spacing ("tapped interdigital transducers"), as used for another application e.g. As described in WO 01/20781 A1, allow the selection of the Abstrahlungsortes the interdigital transducer using the applied frequency. In this way it can be precisely determined at which point the ultrasonic wave emerges from the solid-state layer. When using a taped Interdigitaltransducers, which additionally has not just trained finger electrodes, in particular z. B. arcuately interlocking finger electrodes, the azimuth angle θ can be controlled by varying the operating frequency. On the other hand, the levitation angle α with the frequency can be changed by the direct BAW generation at the interdigital transducer.

With the help of the described setting of the emission direction by selecting the frequency, if necessary by using appropriately shaped interdigital transducer can be very precise z. B. individual micro-cavities of a micro-titer plate are selected for mixing. By temporal variation of the operating frequency, a temporal course of the mixing location can be specified.

On the piezoelectric element are z. B. one or more interdigital transducers for generating the ultrasonic waves, which are either contacted separately or contacted together in series or parallel to each other. For example, with different finger electrode spacing they can be controlled separately via the choice of frequency and thus also offer the possibility of selecting specific areas.

In order to prevent reflections from taking place at undesired locations of the solid-state layer in an uncontrolled manner (ie at end faces, for example), the ultrasound wave can be diffusely scattered by suitably selecting a diffusely scattering surface of the solid-state layer. For this purpose, the corresponding area z. B. roughened. Targeted such a roughened surface can also be used to selectively expand the ultrasonic wave to be able to sonicate a larger area.

Suitable angularly arranged lateral end faces of the solid state layer can be used for targeted reflection and guide the sound beam defined.

A device according to the invention for carrying out the method according to the invention has a substrate on which a main surface at least one interdigital transducer is arranged, which can be electrically excited to generate an ultrasonic wave frequency greater than or equal to 10 MHz, wherein the thickness of the substrate in the sound propagation direction is greater than ¼ the ultrasonic wavelength is. The substrate may be formed separately or z. B. be formed by the bottom of a micro-titer plate or a microcavity.

The substrate may, for. Example, also include a glass lid, on which an adhesive film is fixed with preferably periodically arranged holes, to obtain in this way an array of microcavities. Such a glass slide with a glued-on perforated adhesive film can be used like a microtitre plate.

It is particularly advantageous if a large number of piezoelectric acoustic transducers are used in the pitch of a microtiter plate in order to ultrasonically irradiate the microcavities of a microtitre plate in parallel.

To be able to individually control individual sound transducers, a switching device is advantageously provided which applies high-frequency electrical power to individual sound transducers.

Advantages of other embodiments of the device according to the invention for carrying out the different embodiments of the method according to the invention result from the advantages and properties described for corresponding method configurations.

Figur 1:

zur Erläuterung den Ausschnitt eines Querschnittes einer Vorrichtung-während der Durchführung eines Mischverfahrens,

Figur 2:

zur Erläuterung den Ausschnitt eines Querschnittes einer andere Vorrichtung zur Durchführung eines Mischverfahrens,

Figur 3:

den Querschnitt einer weiteren Vorrichtung zur Durchführung eines Mischverfahrens,

Figur 4a:

die Draufsicht auf eine Mikro-Titerplatte zur Verwendung mit einer erfindungsgemäßen Vorrichtung zur Durchführung einer Ausgestaltung des erfindungsgemäßen Verfahrens,

Figur 4b:

die Anordnung eines Feldes piezoelektrischer Volumenschwinger einer Vorrichtung zur Durchführung eines Mischverfahrens,

Figur 5:

die Wirkungsweise einer Vorrichtung bzw. eines Mischverfahrens am Beispiel einer einzelnen Mikrokavität,

Figur 6:

eine erläuternde Skizze zur Wirkungsweise eines piezoelektrischen Dickenschwingers,

Figur 7a:

eine Schnittansicht durch eine Einrichtung zur Definition von einer periodischen Anordnung von Mikrokavitäten,

Figur 7b:

eine Draufsicht auf die Einrichtung der Figur 7a,

Figur 8a:

eine Querschnittsansicht auf eine erfindungsgemäße Anordnung zur Durchführung eines erfindungsgemäßen Verfahrens,

Figur 8b:

eine Querschnittsansicht auf eine erfindungsgemäße Anordnung zur Durchführung eines erfindungsgemäßen Verfahrens zur Erläuterung einer besonderen Betriebsweise,

Figur 9:

eine Querschnittsansicht auf eine alternative erfindungsgemäße Anordnung zur Durchführung eines erfindungsgemäßen Verfahrens,

Figur 10a:

eine Draufsicht auf einen Querschnitt einer erfindungsgemäßen Anordnung zur Durchführung einer Ausgestaltung des erfindungsgemäßen Verfahrens,

Figur 10b:

eine Draufsicht auf einen Querschnitt einer weiteren erfindungsgemäßen Anordnung zur Durchführung einer Ausgestaltung des erfindungsgemäßen Verfahrens,

Figur 11:

eine seitliche Querschnittsansicht einer erfindungsgemäßen Vorrichtung zur Durchführung eines erfindungsgemäßen Verfahrens,

Figur 12:

zur Erläuterung eine seitliche Querschnittsansicht einer Vorrichtung zur Durchführung eines Mischverfahrens,

Figur 13:

eine Draufsicht auf einen Querschnitt einer weiteren erfindungsgemäßen Anordnung zur Durchführung eines erfindungsgemäßen Verfahrens,

Figur 14:

eine seitliche Teilschnittansicht durch ein erfindungsgemäße Anordnung zur Durchführung einer weiteren Ausgestaltung des erfindungsgemäßen Verfahrens,

Figur 15:

eine seitliche Teilschnittansicht durch eine erfindungsgemäße Anordnung zur Durchführung einer weiteren Ausgestaltung des erfindungsgemäßen Verfahrens,

Figur 16:

eine Draufsicht auf einen Querschnitt einer erfindugsgemäße Anordnung zur Durchführung einer weiteren Ausgestaltung des erfindungsgemäßen Verfahrens,

Fig. 17a-c:

schematische Teilschnittansichten verschiedener Ausgestaltungen der elektrischen Kontaktierung einer Vorrichtung zur Durchführung eines erfindungsgemäßen Verfahrens.

In the following special embodiments of the method and the device according to the invention will be explained in detail with reference to the accompanying figures. The figures are only schematic in nature and not necessarily to scale. It shows

FIG. 1:

to explain the section of a cross-section of a device-while performing a mixing process,

FIG. 2:

to explain the detail of a cross section of another device for performing a mixing process,

FIG. 3:

the cross section of another device for carrying out a mixing process,

FIG. 4a

the top view of a micro-titer plate for use with a device according to the invention for carrying out an embodiment of the method according to the invention,

FIG. 4b:

the arrangement of a field of piezoelectric volume oscillators of a device for carrying out a mixing method,

FIG. 5:

the operation of a device or a mixing method using the example of a single microcavity,

FIG. 6:

an explanatory sketch of the operation of a piezoelectric thickness vibrator,

FIG. 7a:

a sectional view through a device for defining a periodic arrangement of microcavities,

FIG. 7b:

a top view of the device of Figure 7a,

FIG. 8a:

a cross-sectional view of an inventive arrangement for carrying out a method according to the invention,

FIG. 8b:

3 shows a cross-sectional view of an arrangement according to the invention for carrying out a method according to the invention for explaining a special mode of operation,

FIG. 9:

a cross-sectional view of an alternative arrangement according to the invention for carrying out a method according to the invention,

FIG. 10a:

a top view of a cross section of an inventive arrangement for carrying out an embodiment of the method according to the invention,

FIG. 10b:

a top view of a cross section of a further inventive arrangement for carrying out an embodiment of the method according to the invention,

FIG. 11:

a side cross-sectional view of an apparatus according to the invention for carrying out a method according to the invention,

FIG. 12:

to explain a side cross-sectional view of an apparatus for performing a mixing process,

FIG. 13:

a top view of a cross section of a further inventive arrangement for carrying out a method according to the invention,

FIG. 14:

2 shows a lateral partial sectional view through an arrangement according to the invention for carrying out a further embodiment of the method according to the invention,

FIG. 15:

2 shows a side partial sectional view through an arrangement according to the invention for carrying out a further embodiment of the method according to the invention,

FIG. 16:

a plan view of a cross section of an inventive arrangement for carrying out a further embodiment of the method according to the invention,

Fig. 17a-c:

schematic partial sectional views of various embodiments of the electrical contacting of a device for carrying out a method according to the invention.

FIG. 1 schematically shows an arrangement in cross-section for explanation. 1 shows a piezoelectric thickness vibrator, the operation of which will be explained with reference to FIG. 9 shows the schematic cross section through a microtitre plate in the region of the cavities 3. Shown are three cavities, but microtitre plates generally have 96, 384 or 1536 cavities in a rectangular arrangement. The diameter D of a single cavity 3 is greater than the diameter d of the piezoelectric thickness vibrator 1. For example, the diameter D is a 96-well microtiter plate 6 mm and the thickness vibrator has a diameter of 3 mm. In the micro-cavities 3 of the micro-titer plate 9 is liquid 5. The liquid is shown with due to the surface tension upwardly curved surface. F denotes the mean level in a single microcavity. Between the thickness vibrator and the microcavities is solid material 15, z. B. formed from plastic, metal or glass to protect the Dickenschwingers or contacts. 19 designates a planar electrode below the substrate 15. This electrode forms an electrical connection for the piezoelectric thickness oscillator 1.

The other electrode of the thickness vibrator is designated 21. The electrodes 19, 21 are connected to the high-frequency generator 17 via electrical connections 23, 25. On the main surfaces of the substrate 15 is an optional coupling medium 11, 13, z. As water, oil, glycerol, silicone, epoxy resin or a gel film to compensate for unevenness of the individual layers and to ensure optimal sound coupling.

Shown is a state in which the thickness vibrator 1 radiates an ultrasonic wave in the direction of the central cavity shown, whereby a movement in the liquid 7 is generated.

Figure 2 shows another arrangement. Like elements are designated by like reference numerals. Individual thickness transducers for the individual microcavities of the micro-titer plate 9 are provided. With the aid of a switching device 26, the high-frequency signal of the high-frequency generator 17 can be applied to the different thickness oscillator 1. 31 schematically indicates an optional sound-absorbing medium that prevents crosstalk. This sound-absorbing medium may be a structuring or a suitably selected plastic.

Figure 3 shows an arrangement in which one or more sound transducers 33 are used, which are connected via waveguides 35 to the bottoms of various cavities. These waveguides are preferably made of a material with similar acoustic properties as the thickness oscillator itself in order to optimize the coupling, so z. B. metal rods.

FIG. 4 shows the arrangement in a grid. FIG. 4a shows the top view of a 96-well microtitre plate. Figure 4b shows the top view of the arrangement of individual piezoelectric thickness vibrator 27 on a substrate 29. The pitch of the micro-titer plate R is also observed for the distance of the piezoelectric thickness vibrator 27. Alternatively, the thickness vibrator may be fully applied to the substrate 29 and only the electrode assembly may correspond to the pattern of the microtitre plate.

Figure 5 shows in detail the cross section through a single microcavity for explanation. 2 shows the ultrasonic wave which is emitted by the thickness oscillator. 6 designates the meniscus without irradiated ultrasonic wave and 4 the meniscus during irradiation. The thickness of the substrate 15 including the possible coupling media 11, 13 is greater than ¼ of the wavelength of the ultrasonic wave in the substrate, which is typically in the range of a few hundred microns. As materials for the substrate z. As metal, such as aluminum, glass or plastic in question. By "thickness" is meant the thickness of the substrate 15 in the sound propagation direction. In a substrate made of aluminum, the wavelength of a 20 MHz sound wave z. B. 315 microns, in glass 275 microns and in plastic 125 microns,

Figure 6 illustrates the principle of the piezoelectric thickness vibrator 1. When applying a high frequency field by means of the high frequency generator 17 to the electrodes 19, 21 of the thickness vibrator, an ultrasonic wave is generated perpendicular to the surface area of the thickness vibrator. The oscillation direction is designated 37. At a thickness of the thickness of z. B. 200 microns results in a wavelength of 400 microns, when the fundamental is excited. As materials come piezoelectric single crystals, z. As quartz, lithium niobate or lithium tantalate in question. Other vibrators have piezoelectric layers, e.g. As cadmium sulfide or zinc sulfide or piezoelectric ceramics, for. As lead zirconate titanate, barium titanate or each with admixtures to optimize the speed of sound on the solid on. Likewise, piezoelectric polymers (eg, polyvinylidene difluoride) or composite materials are possible. It is particularly advantageous if the material of the solid 15 or of the microtiter plate 9 is acoustically adapted to the sound transducer, that is to say has a similar speed of sound and density.

Figure 7 shows a device which can be used like a one-piece microtitre plate. A perforated adhesive film 110 is applied to a glass lid (eg a slide) 109. FIG. 7b shows a plan view in which the cutting direction AA 'of the section shown in FIG. 7a is indicated. The grid R of holes corresponds to z. B. the pitch of a conventional micro-titer plate. The periodically arranged holes 3 define microcavities which are also present in a microtitre plate. A device of Figure 7 may be employed as a microtitre plate, and for purposes of the present text, the term "microtitre plate" shall also include a corresponding arrangement.

A mixing method can be performed with the above-described apparatuses as follows.

On the substrate 15, the micro-titer plate 9 is placed. For optimum compensation of unevenness, a compensation medium 11, for. As water, are arranged in between. The micro-titre plate 9 is placed in such a way that it is arranged with a cavity 3 above the piezoelectric thickness oscillator 1 (FIG. 1). The liquid 5 is introduced into the microcavities 3, taking care that the filling level F is sufficiently high to be greater than the wavelength of the ultrasound which can be generated by the thickness oscillator. Applying high frequency to the electrodes 19, 21 of the thickness oscillator 1 by means of the high-frequency generator 17 generates an ultrasonic wave perpendicular to the thickness vibrator 1, which propagates in the direction of the middle shown cavity 3 and causes a mixing of the liquid 7 therein.

The ultrasonic beam, whose lateral extent is the size of the thickness vibrator 1, strikes the microcavity 3 from below and generates an impulse and a flow upwards in the liquid, which can lead to a deformation of the meniscus 4 (see FIG. 5). Laterally to the upward ultrasonic beam, the liquid can flow down again, so that thereby a mixing of the liquid is achieved.

After mixing the liquid in a microcavity, the microtiter titer may be added to expose another microcavity to the ultrasound.

In an arrangement of Figure 2, the micro-titer plate 9 is also placed on the substrate 15. The microcavity, whose fluid is to be mixed, can be selected with the aid of the switching device 26. FIG. 4b shows the plan view of an arrangement of the piezoelectric thickness oscillators 27 used for this purpose.

In an arrangement of Figure 3, the ultrasound is generated by means of the ultrasound generator 33 and passed through waveguide 25 under the microcavities, which are then sonicated simultaneously with ultrasound.

The high-frequency excitation can be done in all embodiments in the form of an intense needle pulse. This contains many Fourier coefficients, so that the resonance frequency of the thickness vibrator 1 is taken. Alternatively, the high frequency signal is equal to the resonance frequency of the thickness vibrator or a harmonic fed. Typical frequencies are in the range of greater than or equal to 10 MHz. By the operation of the piezoelectric thickness oscillator resulting heat dissipation in the form of heat, if it is undesirable, can be very easily dissipated in that the thickness vibrator is mounted on a heat sink.

FIG. 8 a shows an embodiment according to the invention in which an interdigital transducer 101, which is indicated only schematically, is used to generate the sound wave. 115 denotes the substrate, e.g. B. of quartz glass. 102 is a piezoelectric crystal element, e.g. B. from lithium niobate. On the piezoelectric crystal element 102 and thus between the piezoelectric crystal element 102 and the substrate 115 is an interdigital transducer 101, the z. B. was applied in advance on the piezoelectric crystal 102. An interdigital transducer is typically formed of comb-like interdigitated metallic electrodes whose double finger spacing defines the wavelength of a surface acoustic wave generated by applying a high frequency alternating field (in the range of, for example, several MHz to several hundred MHz) to the interdigital transducer in the piezoelectric crystal be stimulated. For the purposes of the present text, the term "surface acoustic wave" is also intended to encompass interfacial waves at the interface between piezoelectric element 102 and substrate 115. A low acoustic attenuation material at the frequencies used is used as the substrate 115. For example, quartz glass is suitable for Frequencies in the range of 10 MHz to 250 MHz Interdigital transducers are described in DE-A-101 17 772 and known from surface wave filter technology Electrodes of the interdigital transducer 101 serve metallic leads, which are not shown in FIG. 8a and will be explained in more detail with reference to FIG.

With the aid of the bidirectionally radiating interdigital transducer 101, ultrasonic waves 104 can be generated in the indicated direction, which as described above, pass through the glass body 115 at an angle α to the normal of the substrate 115 volume sound waves. 111 denotes an optional coupling medium between glass body 115 and micro-titer plate 109, as described above for another embodiment. 108 designate the regions of the interface between glass body 115 and coupling medium 111, which are essentially hit by the volume sound waves 104. 106 denotes the reflection points at the interface substrate 115 / air. 109 describes a microtitre plate in whose cavities 103 the liquid 105 is located.

With the aid of the interdigital transducer 101, to which the high frequency is applied in a known manner via the leads, not shown in FIG. 8a, volume sound waves 104 entering the substrate are generated obliquely. These impinge at the points 108 on the interface between substrate 115 and coupling medium 111. Appropriate selection of substrate material 115 causes part of the ultrasonic wave 104 to be reflected at points 108 and another part to be coupled out. In this case, the materials are selected such that at the interface between substrate 115 and coupling medium 111, a partial reflection takes place, at the interface between substrate 115 and air, ie at points 106, an almost complete reflection begins. For example, when using SiO ₂ glass results in a reflection factor at the interface between coupling medium and glass of about 80% to 90%, so a coupling into the coupling medium of about 10% to 20%. Assuming a reflection factor of 80%, the intensity of the beam 104 reflected multiple times in the glass substrate decreases by about 10 dB after ten reflections. At a substrate thickness of 3 mm, the beam has already covered a lateral distance of 250 mm. By suitable selection of the geometry, for. As the thickness of the substrate, can on this Way the points 108, at which a part of the ultrasonic wave from the substrate 115 is coupled into the coupling medium, are locally determined precisely and adapted to the pitch of the micro-titer plate 109 used.

In an alternative, not shown, the bottom of the micro-titer plate 109 itself serves as a substrate, on the underside of which the piezoelectric crystal 102 is attached or pressed. The ultrasonic wave 104 is then coupled directly into the bottom of the microtiter plate and decoupled into the liquid at the interface formed by the bottom of the individual microcavities, as described for the embodiment shown for coupling into the coupling medium.

FIG. 8b serves to explain how with an embodiment according to the invention of FIG. 8a different coupling-in angles can be set by selecting different frequencies. With direct excitation of volume modes (BAW), the emission angle α can be adjusted into the substrate 115 by varying the excitation frequency. In the interdigital transducer 101 it can involve a simple Normalinterdigitaltransducer, wherein the levitation α according to the relation sin .alpha = V _s / (I _IDT · f) is established, where V _s is the sound velocity of the ultrasonic wave, f is the frequency and I _IDT the Periodicity of the interdigital transducer electrodes. By varying the frequency so can the radiation angle z. From α to α '. In this way, the decoupling points 108 z. B. to the pitch of a micro-titer plate 109 are optimally adapted.

Figure 9 shows a variation of Figure 8. Shown is a lateral. Sectional View From the bidirectionally radiating interdigital transducer 101, a beam 104L in the figure 9 goes to the left and a beam 104R to the right obliquely into the substrate 115. At the edge 112 of the substrate 115, the sound beam 104L is reflected and in the direction of the interface between substrate 115 and Coupling medium 111 deflected. By suitable selection of the geometry, for. As the thickness of the substrate 115, so also the impact points 108 can be adapted to the pitch of a micro-titer plate.

In one embodiment, not shown, the interdigital transducer 101 is located on the piezoelectric element 102 not on a major surface of the substrate 115, but on an end face, for. B. at the edge 112, as is visible in Figure 9. In this way, it is also possible with the bidirectionally emitting interdigital transducer 101 to produce two volume sound waves 104, which pass obliquely through the substrate 115 and can be used analogously to the method procedure shown in FIG. 9.

In both the embodiment of FIG. 8 and the embodiment of FIG. 9, a plurality of interdigital transducers may be juxtaposed on one or more piezoelectric elements 102 to sonicate not only a row of microcavities 103 but a field of juxtaposed rows, as shown corresponds to a conventional micro-titer plate.

FIG. 10 a shows a plan view of a cross-section of an arrangement according to the invention, approximately at the level of the surface of the substrate 115, which enables a special steering of the sound beam in the substrate 115. From the interdigital transducer 101, in a manner as described with reference to FIG. 8, sound beams 104 strike at the points 108 on the upper boundary surface of the substrate 115. Not visible in the illustration of the figure, therefore, the beam is guided through the substrate 115 in the form of a zigzag line analogous to the sectional illustration in FIG. 8a. The thus-directed sound beam 104 is deflected at interfaces 110 of the substrate 115. By suitable geometry of the surfaces 110, a desired movement pattern of the sound beam can be generated.

FIG. 10b shows an arrangement according to the invention with which it can be achieved that a planar substrate 115 can be covered almost completely by means of only one bidirectionally emitting interdigital transducer 101 in this way, this being done with the aid of multiple reflections on the side surfaces 110 of the substrate 115 is reached. In FIG. 10b, the reflection points on the main surface of the substrate 115 are not shown for the sake of clarity, but only the propagation direction the ultrasonic waves 104, by reflection on the major surfaces of the substrate 115, such as. B. described with reference to Figure 8a, is effected.

FIG. 11 shows a lateral section through another arrangement according to the invention for carrying out a method according to the invention. The beam cross-section is effectively broadened here by using a plurality of interdigital transducers 101 for generating parallel beams 104. In this way, in almost homogeneous manner, the upper boundary surface of the substrate 115 are sonicated to z. Example, several micro-cavities 105 of a micro-titer plate 109 to sonicate simultaneously.

Fig. 12 shows an arrangement with volume oscillator for illustrative purposes only. A piezoelectric volume oscillator 130, for example, a piezoelectric thickness oscillator, is used, which is arranged such that an oblique coupling of the sound wave takes place for this purpose, a so-called wedge transducer is used. The angle of incidence α to the surface normal of the surface on which the wedge transducer was applied, is determined by the angle β, under which it is applied, and the ratio of the sound velocities of the wedge transducer v _w and the substrate 115 v _s according to α = arcsin (v _s / v _w ) - sinβ].

FIG. 13 shows an embodiment according to the invention in which an edge 108 of the substrate 115 is roughened in order to achieve a diffuse reflection of the impinging sound wave 104. This can be useful to disable an unwanted sound beam reflected at an edge. The sound beam 104 in such an embodiment, similar to that explained with reference to FIG. 8, is guided by the substrate 115 in the manner of a waveguide by reflections on the upper and lower main surfaces of the substrate 115. At the roughened surface 118 diffuse reflection into the individual beams 120 takes place. In this way, the directional sound beam 104 can be made ineffective or widened such that a homogeneous irradiation of a plurality of microcavities which are located on the substrate 115 is possible. FIG. 13 again shows a plan view to a cross section approximately corresponding to the upper boundary surface of the substrate 115.

FIG. 14 shows an embodiment according to the invention, in which the back surface 114 of the substrate 115 is roughened. The interdigital transducer 101 is located on this rear surface. In the described coupling of the ultrasonic wave into the substrate 115, the beam 104 is widened by diffraction due to the roughened surface. This effect is further enhanced in the further reflections on the surface 114. With increasing distance of the Einkoppelpunkte 108 from the substrate into the coupling medium, not shown, on which the micro-titer plate is located, the Einkoppelpunkt is widened accordingly. FIG. 14 shows a partial cross-sectional view in which the microtitre plate was not shown.

A similar effect can be achieved with an inventive embodiment of FIG. Here, the expansion of the sound beam 104 after coupling from the interdigital transducer 101 into the substrate 115 is achieved by reflection at a curved reflection edge 116. Just as an expansion is described here, focusing can be achieved with the aid of a correspondingly designed reflection edge. Also, Fig. 15 shows only a partial cross-sectional view in which the substrate 115 is shown. On the substrate 115 are in described and not shown here, for. B. the coupling medium 111 and the micro-titer plate 109th

Figure 16 shows a further embodiment of the invention in a schematic representation. Here, too, the view of the interface between substrate 115 and coupling medium 111 is shown. As in the other illustrations, only a few interdigitated fingers of the interdigital transducer 201 are shown here for clarity, although a realized interdigital transducer has a larger number of finger electrodes. The spacing of the individual finger electrodes of the interdigital transducer 201 is not constant. The interdigital transducer 201 therefore radiates at a high frequency fed only in a place where the finger spacing correlates with the frequency, as it is for another application z. B. in WO 01/20781 A1 is described.

In the embodiment of Figure 16, the finger electrodes are also not straight, but arcuate. Since the interdigital transducer radiates substantially perpendicular to the orientation of the fingers, the direction of the radiated surface acoustic wave can be determined in this way by selecting the supplied high frequency. FIG. 16 shows, by way of example, the emission directions 204 for two frequencies f1 and f2, wherein at the frequency f1 the emission direction is indicated by the angle θ1 and for the frequency f2 by the angle θ2. 16 schematically shows the plan view of the interface between the piezoelectric substrate 102 on which the interdigital transducer 201 is applied and the substrate 115 which is in contact with the piezoelectric substrate 102.

FIGS. 17a to 17c show different possibilities for electrical contacting of the interdigital transducer electrodes in the embodiments of FIGS. 8, 9, 10, 11, 13, 14, 15 or 16. In the embodiment as illustrated in FIG. 17a, metallic traces are formed on the Substrate 115 applied on the back. The piezoelectric crystal 102 with the interdigital transducer 101 is placed on the substrate 115 so as to overlap the metallic electrode on the substrate 115 with an electrode of the interdigital transducer 101 on the piezoelectric substrate 102. When bonding the piezoelectric transducer to the substrate is glued in the overlap region with electrically conductive adhesive, whereas the remaining surface is glued with conventional non-electrically conductive adhesive. If necessary, purely mechanical contact is sufficient. The electrical contact 122 of the metallic interconnects on the substrate 115 in the direction of the high-frequency generator electronics, not shown, is done by a solder joint, an adhesive connection or a spring contact pin.

In the electrical contacting embodiment of FIG. 17b, the piezoelectric crystal 102 on which the interdigital transducer electrodes with leads 124 are applied is applied to the substrate 115 such that a protrusion from the first to the second results. In this case, the contacting continues 122 directly on the applied on the piezoelectric crystal 102 electrical leads 124. The contact can be soldered, glued or bonded or done by means of a spring contact pin.

In the embodiment of the electrical contact, as shown in Figure 17c, the substrate 115 is provided with a hole 123 per electrical contact and the piezoelectric crystal 102 is placed directly on the substrate 115, that applied to the piezoelectric transducer electrical leads through the holes 123 can be contacted through. The electrical contact can be made in this case by a spring contact pin directly on the electrical leads on the piezoelectric crystal 102. Another possibility is to fill the hole with a conductive adhesive 123 or glue it to a metallic bolt. The further contacting 122 in the direction of high-frequency generator electronics then takes place by means of a solder connection, a further adhesive connection or a spring contact pin.

Another possibility of supplying the electrical power to the piezoelectric transducer is the inductive coupling. In this case, the electrical leads to the interdigital transducer electrodes are formed such that they serve as an antenna for contactless control of the high-frequency signal. In the simplest case, this is an annular electrode on the piezoelectric substrate, which serves as a secondary circuit of a high-frequency transformer whose primary circuit is connected to the high-frequency generator electronics. This is kept external and is mounted directly adjacent to the piezoelectric transducer.

Individual embodiments of the methods and the features of the described embodiments can also be combined in a suitable form in order to simultaneously achieve the effects and effects achieved thereby.

With the method according to the invention an efficient mixing of very small amounts of liquid is possible. It is not necessary that the liquid with the movement-mediating medium itself comes into contact. It must z. B. no mixing element are introduced into the liquid. The method and the device can be used simply and inexpensively with today's laboratory machines used in biology, diagnostics, pharmaceutical research or chemistry. The use of high frequencies effectively avoids the formation of cavitation. Finally, a flat design can be realized and the device can be easily used in laboratories.

Claims (37)

1. A method for mixing liquids (105) in at least one microcavity (3, 103) using a sound-induced flow, wherein, for generating a sound-induced flow into the at least one microcavity (3, 103), at least one ultrasonic wave (104, 204) of a frequency greater than or equal to 10 MHz is sent with the aid of at least one interdigital transducer (101, 201) provided on a piezoelectric crystal through a solid state layer (115) of a dimension in the direction of sound propagation which is greater than ¼ of the wavelength of the ultrasonic wave.
2. A method in accordance with claim 1, wherein the wavelength of the ultrasonic wave in the liquid is selected such that it is less than the average filling level (F) in the at least one microcavity (3; 103).
3. A method in accordance with claim 1 or claim 2, wherein the lateral extent of the at least one interdigital transducer (101) is less than the lateral dimension of the microcavity (3, 103).
4. A method in accordance with any one of the claims 1 to 3, wherein an intermediate layer is introduced between the at least one interdigital transducer and the microcavity (3), the intermediate layer including an ultrasound-absorbing material in an arrangement such that the ultrasound can propagate in the direction of the microcavity (3) only in a limited spatial area, preferably an area smaller than the lateral dimension of the microcavity (3).
5. A method in accordance with any one of the claims 1 to 4, wherein an equilibrium medium (111) is introduced between the microcavity-(3, 103) and the solid state layer (115).
6. A method in accordance with any one of the claims 1 to 5, wherein a plurality of microcavities (3, 103) are used.
7. A method in accordance with claim 6, wherein the microcavities (3, 103) of a microtitre plate (9, 109) are used.
8. A method in accordance with claim 6 or claim 7, wherein a plurality of interdigital transducers are used which are preferably controlled individually.
9. A method in accordance with claim 7, wherein an interdigital transducer is used, whose lateral dimension is less than the diameter of a cavity of the microtitre plate (9), and the microtitre plate is applied for individual mixing of liquid in a selected cavity with this selected cavity above the interdigital transducer (1) on the solid state layer.
10. A method in accordance with claim 7 or claim 8, wherein a microtitre plate (9) having a plurality of interdigital transducers is used which in the pitch (R) of a plate (9) are arranged on the solid state material (15).
11. A method in accordance with claim 6 or claim 7, wherein by means of the interdigital transducer (101, 201) ultrasound (104,204) is sent through the solid state layer (115) such that ultrasonic output is coupled in at at least two coupling out points (108) from the solid state layer into a corresponding number of microcavities (103).
12. A method in accordance with claim 11, wherein the at least one ultrasonic wave (104, 204) is sent obliquely through the solid state layer (115).
13. A method in accordance with any one of the claims 1 to 12, wherein an interdigital transducer (101, 201) is used on a piezoelectric crystal (102) and is adhered, pressed or bonded to the solid state layer or is adhered, pressed or bonded to the solid state layer via a coupling medium.
14. A method in accordance with any one of the claims 11 to 13, wherein an ultrasonic wave (104) is coupled into the solid state layer (115) such that it is reflected at least once inside the solid state layer, with a material being selected for the solid state layer, in which the reflection (106) on the surface remote from the at least one microcavity (103) is total, where possible, and on the surface (108) facing the microcavity or the liquid is lossy, but not equal to 0, and the acoustic damping inside the solid state layer (115) is as low as possible.
15. A method in accordance with any one of the claims 11 to 14, wherein the at least two uncoupling points are generated by temporal variation in the direction of radiation of the at least one interdigital transducer (201).
16. A method in accordance with any one of the claims 1 to 15, wherein the at least one ultrasonic wave is generated with the aid of an interdigital transducer (201) on a piezoelectric element, whose finger electrodes engaging into one another have a spacing from one another which is not spatially constant, and the radiation site is set by changing the frequency applied at the interdigital transducer (201).
17. A method in accordance with claim 16, wherein an interdigital transducer (201) is used, whose finger electrodes engaging into one another are not straight, but are in particular curved, and the direction of radiation (204) is chosen by selection of the frequency of the applied radio frequency field.
18. A method in accordance with any one of the claims 1 to 17, wherein the at least one ultrasonic wave (104, 204) is generated with the aid of an interdigital transducer (101, 201) on a piezoelectric element (102) on. a. side of the solid state layer (115) remote from the at least one microcavity (103).
19. A method in accordance with any one of the claims 1 to 18, wherein a solid state layer (115) is used, which has at least one diffusively scattering surface (114, 118), in order to propagate the at least one ultrasonic wave (104) in the solid state layer.
20. A method in accordance with any one of the claims 1 to 19, wherein the direction of propagation of the at least one ultrasonic wave (104) is deflected in the solid state layer (115) by reflection surfaces (110).
21. A device for mixing liquids in at least one microcavity (3, 103), in particular in the microcavities of a microtitre plate (9, 109), for the carrying out of a method in accordance with claim 1, comprising

    - a substrate (15, 115), and

    - at least one interdigital transducer (101, 201) which is provided on a piezoelectric element (102) and which is arranged on a main surface of the substrate (15, 115) and which can be excited for electrically generating an ultrasonic wave (104, 204) of a frequency greater than or equal to 10 MHz, with the dimension of the substrate (115) being greater than ¼ of the ultrasonic wavelength in the direction of sound propagation.
22. A device in accordance with claim 21 with a plurality of interdigital transducers (1) in the pitch (R) of a microtitre plate (9).
23. A device in accordance with claim 22 with a switching mechanism (26) for controlling individual interdigital transducers.
24. E1 device in accordance with any one of the claims 21 to 23, wherein the at least one interdigital transducer (101, 201) is selected such that the ultrasonic wave generated by it has a wavelength which is less than the height extent of the at least one cavity (3).
25. A device in accordance with any one of the claims 21 to 24, wherein the lateral extent of the at least one interdigital transducer is less than the lateral extent of a cavity (3) of a microtitre plate (9).
26. A device in accordance with any one of the claims 21 to 23 with an intermediate layer on a main surface of the substrate which has an ultrasound-absorbing medium in an arrangement which spatially bounds the ultrasonic radiation in the direction of the microcavity (3), preferably in the arrangement of the microcavities of a microtitre plate (9).
27. A device in accordance with any one of the claims 21 to 26, wherein the interdigital transducer (101, 201) is configured such that at least one ultrasonic wave is coupled obliquely into the substrate (115).
28. A device in accordance with claim 27, wherein the at least one interdigital transducer (101, 201) radiates bidirectionally.
29. A device in accordance with claim 27 or claim 28, wherein the material of the substrate (115) is selected such that the reflections (106) on the surface remote from the microcavity (103) are total, where possible, and the reflections (108) on the side facing the microcavity or the liquid are lossy, but not equal to 0, and the acoustic damping inside the solid state layer (115) is as low as possible.
30. A device in accordance with any one of the claims 21 to 29, wherein the at least one interdigital transducer (101, 201) is arranged on a piezoelectric element (102) which is adhered, pressed or bonded to the solid state layer (115) or is adhered, pressed or bonded to the solid state layer via a coupling medium.
31. A device in accordance with claim 30, wherein the electrical connection of the at least one interdigital transducer (101) is formed by a first supply line on the piezoelectric element and by a second supply line (116) on the substrate (115), said supply lines being arranged such that they overlap one another.
32. A device in accordance with claim 30, wherein the piezoelectric element (102) has a projection (124) over the substrate (115), on which a contact point for the electric supply line (122) to the at least one interdigital transducer (101) is located.
33. A device in accordance with any one of the claims 21 to 30, wherein the at least one interdigital transducer (101) is contacted via a hole (123) through the substrate, is preferably filled with a conductive adhesive.
34. A device in accordance with any one of the claims 21 to 30, wherein the interdigital transducer has antenna devices which can be used for contact-free coupling in of a high frequency signal.
35. A device in accordance with any one of the claims 21 to 34, wherein the finger electrodes of the interdigital transducer (201) do not have a spatially constant spacing from one another.
36. A device in accordance with claim 35, wherein the finger electrodes of the interdigital transducer (201) are not straight, but are in particular curved.
37. A device in accordance with any one of the claims 21 to 36, wherein the substrate has at least one diffusively scattering surface (114, 118).

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