DEVICE FOR PRODUCING A STANDARD ULTRASONIC FIELD

Various embodiments of the present disclosure are directed to a device and a method for producing a standing ultrasonic field having the frequency f in a liquid. In one example embodiment, the device includes at least one oscillation element, a substantially dimensionally stable vessel having an outside wall and a substantially circular-cylindrical interior, the vessel receiving the liquid and the at least one oscillation element. The at least one oscillation element acoustically connected to the outside wall of the vessel and electrically excited at the frequency f. The substantially circular-cylindrical interior receives liquid with an inner radius ro at least in the region of the oscillation element. The oscillation element has a mean thickness p and a width b in the direction orthogonal to a main axis of the interior, and the width b is not greater than the inner diameter 2ro.

The invention relates to a device for producing a standing ultrasonic field having the frequency f in a liquid, in particular for concentrating, immobilizing or manipulating dispersed particles in the liquid or for retaining or separating dispersing particles from the liquid, comprising a substantially dimensionally stable vessel for receiving the liquid and at least one oscillation element acoustically connected to an outside wall of the vessel, wherein the vessel comprises, at least in the region of the oscillation element, an essentially circular-cylindrical interior for receiving the liquid with an inner radius ro, and wherein the oscillation element has a mean thickness p and a width b in the orthogonal direction to a main axis of the interior, wherein the width b is not greater than the inner diameter 2ro.

It also relates to a method for producing a standing ultrasonic field with frequency f in a liquid, in particular for concentrating dispersed particles in the liquid or for separating dispersing particles from the liquid by applying a standing ultrasonic field in a substantially dimensionally stable vessel, wherein at least one oscillation element is excited at at least one frequency f and the oscillation element oscillates the vessel and the liquid arranged in a circular-cylindrical interior, wherein the oscillation element has a mean thickness p and the interior has an inner radius ro, and wherein the oscillation element has a width b in the direction orthogonally to a main axis of the interior, wherein the width b is not greater than the inner diameter 2ro.

When a liquid is exposed to an ultrasonic field, for example by introducing oscillations from the oscillation element through the vessel into the liquid, various effects can be achieved in the liquid, such as its mixing or its heating. Using standing ultrasonic fields, acoustic technologies are used in particular for the separation or manipulation of cells, bacteria and microorganisms, fine solids, droplets, bubbles and the like, (i.e. generally particles in solid, liquid and gaseous state—hereinafter referred to as particles for simplicity) in or from the liquid (also referred to as medium). These particles can be dispersed, suspended or emulsified in the liquid and typically have a size in the range between one wavelength and one thousandth of a wavelength of the applied standing ultrasonic field. In this case, the liquid is arranged in the interior of the vessel and the acoustic system is made to oscillate by the oscillation element. The acoustic system means the part which is made to oscillate and thus comprises at least the vessel, the oscillation element and the liquid in the interior. A standing wave field is built up in the interior by reflection at the vessel wall or also by superposition of ultrasonic waves of the same frequency from opposite directions, whereby the particles collect and preferably aggregate in the oscillation bulges or nodes of the standing wave field. In this process, the liquid can also be carried through the interior continuously while the collected particles are prevented from passing through by the standing wave. Thus, even a large amount of fluid can be cleaned of these particles.

Such devices or methods are used, for example, in biotechnology or laboratory diagnostics for the separation of cells, bacteria, and other microorganisms from a nutrient medium, or also for the concentration of trace elements and pollutants (such as suspended heavy metal particles, or emulsified hydrocarbon droplets) for their improved detectability, or also for the recovery of valuable particulate materials (for example rare earths or precious metals). For the enrichment or separation of substances and particles which are too small to be detected directly by the ultrasonic field (e.g. viruses or molecules), so-called carrier particles can also be used, the surface of which is occupied by the substances sought, in order to then be separated together with the carrier particle by the ultrasonic field. The surface of such a carrier particle can also be selectively activated biotechnologically, mechanically, magnetically, electrically or chemically in order to separate only certain desired substances from the medium with the aid of the carrier particle. This technology can also be used to purify the liquid.

Acoustic separation technology is based on the mechanism of acoustic sound radiation force, known from the literature for decades, which is exerted by a standing acoustic field on particles dispersed in a liquid and concentrates them, depending on the acoustic contrast of the particles with respect to the liquid (the medium), either into the sonic bulges of the standing wave field (valid for most solid particles and dispersed droplets relevant to the application, which are heavier than the liquid), or concentrated into the sonic nodes (valid for air bubbles or droplets which are lighter than the liquid). In this case, the frequency of the wave field is typically chosen so that the wavelength of the acoustic field in the medium is one to two orders of magnitude larger than the diameter of the particles to be separated. Of practical relevance is a frequency range especially in the order of 100 kHz to 10 MHz.

Due to the acoustically induced migration of the particles into the sonic bulge or sonic node areas of the standing field, the particles are typically compressed there into particle aggregates, which in the case of liquid or gaseous particles can also lead to fusion into larger drops or bubbles. The distance between two adjacent areas where such compression occurs (i.e. between adjacent sonic bulges, or adjacent sonic nodes) is half the wavelength of the ultrasonic field in the medium.

For the stable formation of a standing wave field, the vessel must be essentially dimensionally stable in order to be able to reflect the acoustic wave in a constant direction and distance from the sound source. In particular, therefore, the dimensional stability of the vessel wall in the region of sound generation, and of the vessel wall opposite the sound generation, is of importance. Dimensionally unstable vessels such as plastic bags or the like are therefore unsuitable unless they are in turn appropriately supported by dimensionally stable devices. Vessels made of metal, glass or hard plastic have proven to be particularly stable and easy to manufacture, and especially made of materials that are also biocompatible and thus particularly suitable for biotechnological and medical applications.

Since, however, practically every acoustic standing sound field is not built up ideally homogeneously, but the acoustic energy of the standing wave field is typically distributed inhomogeneously within this vessel (for example, due to the typically inhomogeneous radiation from the surface of the sound-emitting oscillation element1, as well as due to coupling acoustic resonance fields which can also build up in the transverse direction to the sound propagation, for example, due to acoustic reflection between the lateral inner walls of the vessel), acoustic forces occur at the particle aggregates not only in the direction of the sound wave emitted by the oscillation element, but also acoustic forces acting in such transverse directions, which can counteract the entrainment of the particle aggregates with a possible movement of the liquid flowing through the acoustic area in a likewise transverse direction. In the literature, this is classically referred to as “acoustic trapping” or the macroscopic formation of particle bands or “particle columns”2. If the original particle concentration of the liquid is low, only relatively few particles are enriched in a sonic bulge or node, and the effect of acoustic trapping can be observed in a particularly pronounced manner.1Böhm H. et al: Lateral Displacement amplitude distribution of water filled ultrasonic bio-separation resonators with laser-interferometry and thermochromatic foils. IEEE Conference Proceedings (2001), page 726-728.2e.g. Withworth G et al:Particle Column Formation in a stationary ultrasonic field. J. Acoust. Soc. Am. 91 (1992), page 79-85

Due to the local concentration of particles within the sonic bulges (or nodes) and their associated compaction, if further particles are continuously introduced (e.g. when dispersion flows through the wave field), the particle aggregates trapped in this way can continue to grow over time and become too heavy to be held permanently by the acoustic forces in opposition to buoyancy or gravitational forces. If the particle aggregates become too large, this results in spontaneous precipitation of the particle aggregates by sedimentation (for particles heavier than the liquid) or flotation (for particles lighter than the liquid). However, such precipitation can also be brought about in a controlled manner (by deliberately deactivating the sound field).

The higher the initial particle concentration in the medium before entering the standing wave field, the more difficult it becomes to maintain permanent acoustic trapping, since the formed particle aggregates very quickly become too heavy (or too light) to be held by acoustic forces against buoyancy or gravity. At a particle concentration within the fluid (entering the acoustic field) of the order of >1% (v/v), typically no stable phase of random (i.e. not by stabilizing specifically generated acoustic wave geometries with strong transverse field gradients) acoustic trapping is observable; the compaction of particles into aggregates and the subsequent precipitation of the aggregates from the wave field is essentially perceived as an interflowing process.

This interflowing process of particle compaction to aggregates and precipitation of the aggregates by gravity or buoyancy is also described in the literature as “Acoustically Enhanced Sedimentation” or analogously “Acoustically Enhanced Floatation”3.3Trampler F.,Acoustic Accumulation of Acoustic Energy for industrial Processes. Ph.D. Thesis, Vienna University of Technology, (December 2000), chapter 7.

For such acoustically induced separation processes, especially for liquids with particle concentrations >1% (v/v), lateral acoustic forces are only of limited help, since due to the relatively high particle concentration, sufficient compaction can already take place within the sonic bulge or sonic node planes (forming normal to the sound propagation direction), and additional transverse forces (i.e. parallel to these sonic bulge/node planes) do not lead to further compaction of the already very large forming particle aggregates, but on the contrary to a splitting of a large one into several smaller ones, whereby an effective continuous precipitation of the aggregates from the wave field is hindered.

In practice, it has been shown that for the separation of dispersions with particle concentrations >1% (v/v) based on the principle of acoustically induced precipitation described above, the transverse acoustic forces should typically be kept an order of magnitude weaker than the longitudinal acoustic forces (which cause the primary migration of particles into the sonic bulges or node planes).

An effective method to maximize longitudinal sound forces (i.e. sound forces acting in the direction of sound propagation) over transverse sound forces is the targeted excitation of a flat standing wave field as described in patent EP 0,633,049 B1. Following this embodiment, a dominant expression of flat sonic bulge and sonic node regions parallel to the flat emitting surface of the vessel and, if applicable, of the parallel opposite flat reflector can be achieved. This strictly parallel positioning of acoustically emitting and reflecting surfaces allows the position of the sound-bulge and sound-node planes to be defined essentially by the longitudinal dimension x normal to them alone. Detailed mathematical principles for such a one-dimensional description of a standing acoustic field can be found in the literature.44e.g: Novotny H, et al: Layered piezoelectric resonators with an arbitrary number of electrodes. J. Acoust. Soc. Am. 90(3), September 1991

Commercial application of flat standing acoustic wave fields is found with the acoustic “Biosep” cell retention systems for the perfusion of bioreactors marketed by “Applikon Biotechnology By” since about 1995.5In some of the embodiments of this Biosep product family, the accidental generation of any transverse wave field (and thus the generation of acoustic forces acting transversely on the particle aggregates) is further minimized by coating the lateral walls of the acoustically active region with acoustically absorbing silicone.5Applikon Dependable Instruments BV:Biosep—the advanced cell retention device. Technical Data Sheet STS90

However, despite these measures to optimize a flat standing wave field, fundamental disadvantages remain which are associated with the associated parallel—typically rectangular—geometry of the interior of such a separator in the prior art:The rectangular cross-section of the acoustically active interior area makes cleaning more difficult and there is a risk of permanent deposits in the corner areas.Substantial manufacturing costs of the exactly parallel interior surfaces of the acoustically active rectangular area.The transitions of the typically tubular inflow and outflow to the rectangular cross-section of the intermediate acoustic area further complicate the internal geometry and sealing.

Especially for the application in disposable systems (as typical for medical and biotechnological processes), rectangular internal geometries therefore pose a considerable problem.

An alternative embodiment of an acoustic separator is proposed in U.S. Pat. No. 5,164,094 in circular-cylindrical geometry. Here, the sound-emitting oscillation element is designed as a hollow cylindrical piezoceramic, whereby the acoustic standing wave field is formed as a coaxial circular-cylindrical pattern in a suspension tubularly enclosed by the piezoceramic (and/or in a suspension tubularly enclosing the piezoceramic). Such a circular-cylindrical generated field geometry can be trivially described in cylindrical coordinates, since sonic bulges and nodes are essentially formed as coaxial circular-cylindrical shell surfaces arranged around the circular-cylindrical axis, whose position is determined only by the radial dimension r (i.e. the normal distance to the cylinder axis). A striking advantage over flat standing field geometries is that there are no reflecting side walls in the transverse direction (in cylinder coordinates this is the tangential direction) through which a transverse standing wave field could build up, since the circular-cylindrical bulge/node regions are closed in on themselves (in the tangential direction).

However, the required piezoelectric elements in the form of circular-cylindrical tubes are technically complex and expensive to manufacture. Also, for medical or biotechnological applications, for example, direct contact of the suspension with the piezoceramic must be avoided, i.e. the circular-cylindrical ceramic must de facto be pushed onto a biocompatible carrier tube in an acoustically coupling manner, and/or inserted into such a carrier tube. Also with regard to the requirements for mechanical robustness in industrial applications, in many cases it is necessary to push the piezoceramic cylinder over or into a carrier tube. The production of such a carrier tube, for example from glass or steel, or even biocompatible plastics (the latter, however, is only possible in a thin-walled version due to the increased acoustic absorption of many plastics), as well as the acoustically precisely coupled bonding, is very complex and error-prone due to the necessary coaxial precision to the inner or outer diameter of the piezo tube.

A further known embodiment comprises a cylindrical vessel, on the shell of which on the outside wall one or more curved piezo elements are arranged as oscillation elements and rest against this curved wall and are firmly connected to it. Preferably, two piezo elements are always arranged opposite each other. By appropriate anti-synchronous excitation, for example of two mutually orthogonal piezo pairs, the increase in acoustic pressure amplitude in the region of the central axis caused by the focusing effect of the cylindrical geometry can be somewhat reduced. However, very high pressure amplitudes still occur in the area of the central axis, which can lead to a change or destruction of the particles. Especially in the case of living cells, this can lead to a deterioration of the viability or to the death of the cells.

Thus, it is the object of the invention to provide a device and a method of the types mentioned having a reduced risk of high pressure amplitudes.

According to the invention, this object is solved in that the oscillation element has at least one substantially flat lateral surface, and in that the oscillation element is acoustically connected via this one flat lateral surface to a substantially flat connection surface of the outside wall of the vessel in the region of the circular-cylindrical interior, wherein the connection surface is arranged parallel both to the main axis of the circular-cylindrical interior and to the oscillation element.

It is also solved in that the oscillation element transmits the oscillations to the vessel via a substantially flat side wall of the oscillation element via a substantially flat connection surface of the outside wall of the vessel in the region of the circular-cylindrical interior, and in that the connection surface is arranged parallel both to the main axis of the circular-cylindrical interior and to the oscillation element.

The present invention presents a device which combines the acoustic and fluidic advantages of a circular-cylindrical interior and the coaxial standing wave pattern caused thereby with the manufacturing advantages by using flat sound-emitting components as oscillation elements, such as flat piezoceramic plates.

Surprisingly, if the oscillation element is connected to the vessel via a flat surface, the occurrence of high pressure amplitudes in the interior, in particular in the center of the interior, can be reduced or even avoided. This reduces the risk of damage or destruction of the particles to be aggregated, which is a particular advantage in the case of cells or microorganisms. In this regard, the oscillation element is designed to be equally flat at least in the region where it is connected to the vessel. On the side facing away from the connection surface, the oscillation element can be of curved design or can be equally flat, wherein in flat embodiments of the side facing away, the two sides of the oscillation element are preferably aligned parallel to one another. The flat feed slightly disturbs or distorts the perfectly round shape of the generated wave field, which effectively prevents the occurrence of excessive pressure amplitudes in the fluid in the region of the center of the vessel. Moreover, such an embodiment greatly facilitates and cheapens the manufacturing process, since curved oscillation elements are very difficult to manufacture, especially if they are to be connected to an equally curved outside wall. On the other hand, flat, straight oscillation elements are easier and cheaper to manufacture. Preferably, the flat connection surface can be arranged on the vessel by removing a part of the vessel wall, for example by milling or planing. Alternatively, the connection surface may already be provided during the manufacture of the vessel, for example during the injection or casting of the vessel. Furthermore, the outer surface of the vessel, which is cylindrical in itself, can also be partially extended by additional elements in order to create a flat connection surface.

Preferably, it is provided that the oscillation element has at least one piezoelectric plate polarized in the thickness direction and aligned parallel to the main axis of the circular-cylindrical interior, and the piezoelectric plate has electrode surfaces normal to the thickness direction. Accordingly, it is also advantageous if at least one piezoelectric plate of the oscillation element polarized in the thickness direction and aligned parallel to the main axis of the circular-cylindrical interior oscillates the oscillation element in the thickness direction p thereof, wherein the piezoelectric plate has electrode surfaces disposed normal to the thickness direction. The piezoelectric plate can be used for the purpose of electrically exciting acoustic oscillations in the direction of the thickness p, i.e. in the thickness direction. Thus, a simple, inexpensive and electrically easily excitable embodiment for the oscillation element is found, which can be made to oscillate by applying an AC voltage with frequency f. One or also a plurality of piezoelectric plates may be provided, which in the latter case may be arranged in the oscillation element side by side or one behind the other as viewed from the vessel, i.e., in the width direction along the width b or in the thickness direction along the thickness p. In this case, the oscillation element may essentially comprise only one plate or a plurality of plates. Side by side means that the edges of the piezoelectric plates face each other, in other words that the piezoelectric plates are adjacent to each other with respect to the connection surface of the vessel. Thus, each piezoelectric plate is associated with different regions of the connection surface, wherein the electrode surfaces of the piezoelectric plates are preferably arranged at the same height. Behind one another means that the electrode surfaces of the piezoelectric plates at least partially project beyond each other and are preferably arranged congruently. Thus, two piezoelectric plates arranged one behind the other are essentially associated with the same region of the connection surface of the vessel. In this context, the described areas of the connection surface may also constitute the entire connection surface.

Typically, the oscillation element is configured as at least one flat piezoelectric plate, or comprises at least one flat piezoelectric plate on one side. The flat side wall of the oscillation element, which is acoustically connected to the connection surface of the outside wall of the vessel, may thereby be such a flat side wall of one or more piezoelectric plates.

Further, it is advantageous if the oscillation element has a substantially uniform thickness corresponding to the mean thickness p of the oscillation element. Accordingly, it is also advantageous if the oscillation element is selected to have a substantially uniform thickness corresponding to the mean thickness p of the oscillation element. In this case, uniform means that the thickness remains substantially the same along the length and width of the oscillation element.

Thus, if the oscillation element is also flat on the side facing away from the vessel, and this side is parallel to the side facing the vessel, the result is a substantially uniform thickness, this being equal to the mean thickness p.

In embodiments where the thickness varies along the width b or length, for example in curved oscillation elements, the mean thickness p is the thickness arithmetically averaged along the width.

It is advantageous if the device has a transducer array which comprises at least the oscillation element and a vessel wall section in the region of the oscillation element, and also, optionally, further parts which are arranged in the thickness direction of the oscillation element and are acoustically coupled to the oscillation element and/or the vessel wall section. In this regard, a device may comprise a plurality of transducer arrays which may be connected in series and/or in parallel. The wall parts of the vessel, which are arranged in the region of the oscillation element, resonate in the direction of sound propagation and are thus part of the transducer array. The parts of the vessel which are further away from the oscillation element, on the other hand, are not part of the transducer array, since these areas are insignificant for the transmission of the oscillations from the oscillation element into the interior of the vessel.

The acoustic system comprises the transducer array/assemblies and, optionally, opposing reflecting layers, in particular the opposing vessel wall as well as all interposed acoustically coupled solid or liquid regions, including in particular the liquid loaded with the particles in the interior of the vessel, but also any additional partitions (for example belonging to a sample container immersed in the interior of the vessel) and other acoustically coupled liquid layers (for example serving thermostatic purposes).

The longitudinal direction is understood to be the direction of sound propagation; thus defined as the direction normal to that acoustically emitting surface of the transducer array which is in direct contact with the medium to be sonicated.

Transverse directions are all directions normal to the longitudinal direction of sound propagation, thus they are oriented parallel to the acoustically emitting surface of the transducer array.

Sonic bulges are the stationary regions of a standing acoustic wave field where the acoustic amplitude of deflection reaches a local maximum with respect to the longitudinal direction. In the longitudinal direction, adjacent sonic bulges are spaced apart by half a wavelength of the sound wave in the liquid, and are parallel to each other (as well as to the emitting surface of the transducer array).

Sonic nodes are the stationary regions of a standing acoustic wave field where the acoustic deflection amplitude is zero with respect to the longitudinal direction. As a consequence, the pressure amplitude of the standing wave field reaches a local maximum in a sonic node region. Sonic nodes adjacent to each other in the longitudinal direction are at a distance of half a wavelength of the sound wave in the liquid, and are parallel to each other (as well as to the emitting surface of the transducer array).

In some of the known devices according to the prior art, the dispersion is arranged between a flat acoustically emitting surface of one transducer array and a second flat acoustically emitting surface of a second transducer array that is mirror-image and parallel opposite, wherein it is provided that the two transducer arrays that are mirror-image opposite to each other are excited with the same frequency and amplitude. Thus, a flat acoustic standing wave field is generated. Alternatively, instead of the second transducer array, a flat reflective surface may be positioned parallel opposite the first transducer array. The flat standing wave field is generated in the interposed fluid by superposition of the two emitted waves (or emitted and reflected waves, as the case may be). Viewed in the Cartesian coordinate system, the propagation of an emitted (and optionally reflected) flat sound wave is essentially along one dimension, here chosen to be x. Accordingly, the emitting surfaces of the transducer(s), and optionally an opposite reflecting surface, as well as all sonic node and sonic bulge planes of the generated flat standing wave field are normal to x and thus parallel to the directions y and z. Consequently, the position of the sonic nodes and sonic bulges can be assumed to be defined by the Cartesian dimension x.

In contrast thereto, the present invention relates to a non-flat acoustic standing wave field, and more specifically to a cylindrical acoustic standing wave field. This is generated by an acoustic system having a circular-cylindrical shaped acoustic emitting surface of the transducer array, (and analogous to the flat case, optionally by a reflecting circular-cylindrical surface positioned axially symmetrically thereto). The standing cylindrical wave field is generated in the interposed fluid around the cylinder axis by superposition of the axially symmetrically emitted waves (or, optionally, of emitted and reflected waves). Viewed in the cylindrical coordinate system, the propagation of the emitted (and, optionally, reflected) circular-cylindrical sound wave occurs essentially along the radial dimension r., which in turn allows a one-dimensional description of the generated standing wave field (now in the cylindrical direction r instead of the Cartesian direction x). Accordingly, the emitting circular-cylindrical surface of the transducer array, (and, optionally, the opposite reflecting surface, as well as all the sonic node and sonic bulge surfaces are substantially normal to r and thus parallel to the direction of the main axis H (or also called the cylindrical axis or central axis) lying in the direction z and the tangential dimension φ. As a result, the position of the sonic nodes and sonic bulges is essentially defined by the radial dimension r. A modulation of sonic node and sonic bulge shell surfaces by possible couplings with standing wave fields formed in transverse directions z and φ is of less relevance and can be neglected for this one-dimensional description of the positioning of the sonic bulge and sonic node shell surfaces.

The oscillation element is acoustically connected to the vessel in such a way that its oscillations are at least partially transmitted to the vessel, preferably it is glued to the vessel. However, it can also be fused directly with the vessel or, for example, be attached to the vessel wall only temporarily with an acoustically coupled gel or a liquid.

If several oscillation elements are provided, which are connected to a vessel, it can be provided that two oscillation elements are opposite each other in the cross-section, wherein these are preferably excited with the same frequency and preferably without phase shift. More than two oscillation elements may also be distributed over the cross-section, preferably rotationally symmetrically.

It is preferably provided that the oscillating member stands parallel to the cylinder axis and substantially normal and symmetrical to an inner radius roof the interior. The interior is substantially circular in cross-section at least at one level, thereby providing a center point, and is rotationally cylindrical in shape, thereby providing a main axis on which the center point lies. In this case, the inner radius means half the diameter of the interior in cross-section normal to the oscillation element. The radius of the interior extends from the center of the interior to the inner wall of the vessel. The feed of the oscillations into the circular cross-section is thus aligned parallel to the main axis.

In a preferred embodiment, it is provided that the outside wall of the vessel in the region of the circular-cylindrical interior has a substantially circular-cylindrical shape apart from the at least one connection surface to the oscillation element. In this case, the oscillation element is connected to the connection surface in an oscillating manner and can thus transmit the oscillations to the vessel. Thus, the vessel has the shape of a hollow cylinder. This is easy and inexpensive to manufacture, while nevertheless allowing predetermined size dimensions to be accurately maintained. The flat connection surface is preferably milled or otherwise removed from a previously manufactured round vessel. In this case, the connection surface may project beyond the oscillation element laterally or along the main axis, or the oscillation element may project beyond the connection surface.

Preferably, the oscillation element is configured as a piezo plate polarized in its thickness direction and having electrode surfaces substantially normal to the thickness direction, whereby it begins to oscillate when an AC voltage is applied to said electrode surfaces.

In order to optimize the acoustic characteristic of the oscillation element, which is designed as a piezoelectric plate, as a sound emitter emitting substantially in the direction of its thickness, it is advantageous if it has a length in the direction parallel to the main axis of the interior which is at least twice as large, preferably at least three times as large, as the thickness p, and has a width b in the direction orthogonal to the main axis of the interior which is at least twice as large, preferably at least three times as large, as the thickness p. Accordingly, it is also advantageous if the size of the oscillation element is chosen such that it has, in the direction parallel to the main axis of the interior, a length which is at least twice as large, preferably at least three times as large, as the thickness p, and that the width b of the oscillation element is at least twice as large, preferably at least three times as large, as the thickness p.

The inner diameter 2roof the vessel is at least as large as the width b of the oscillation element. This minimum size of the inner diameter makes it possible that as large a proportion as possible of the total acoustic energy is allotted to the wave field inside the vessel.

It is particularly advantageous if the width b of the oscillation element is less than or equal to 3·(rP·vC/f)1/2, preferably between (rP·vC/f)1/2and 2.5·(rP·vC/f)1/2, and particularly preferably between 1.5·(rP·vC/f)1/2und 2·(rP·vC/f)1/2, wherein rP=ro+coapplies, rois the inner radius of the interior, cois the minimum wall thickness of the vessel wall section in the region of the oscillation element, and vCis the sound velocity in the vessel wall section. In the case of embodiments with vessels of larger radii, it can also be advantageous if the width b of the oscillation element lies in a range between (rP·vC/f)1/2und 3·(rP·vC/f)1/2and is particularly preferably about 2·(rP·vC/f)1/2.

Width b further means the width of the oscillation element which is substantially orthogonal to the main axis of the circular-cylindrical interior of the vessel.

If the sound velocity of the vessel wall differs at different points, vCmeans the sound velocity in the area of the vessel wall located between the oscillation element and the interior.

By selecting such a width of the oscillation element, the oscillation element is sufficiently wide that the device can be well excited, but at the same time the oscillation element is still sufficiently narrow to limit the different acoustic path lengths of the oscillations between the oscillation element and the main axis, which are caused by the flat surface of the oscillation element (i.e. not coaxial to the interior of the vessel), to a sufficient extent, and thus a sufficiently strongly radially pronounced vibration pattern of the standing wave field can still be generated.

These embodiments also apply when the frequency f is chosen so that the width b of the oscillation element is less than or equal to 3·(rP·vC/f)1/2, preferably lies between (rP·vC/f)1/2und 2.5·(rP·vC/f)1/2, and particularly preferably lies between 1.5·(rP·vC/f)1/2und 2·(rP·vC/f)1/2, respectively in particular for larger radii if the frequency f is selected in such a way that the width b of the oscillation element lies in the range between (rP·vC/f)1/2und 3·(rP·vC/f)1/2, and is particularly preferably about 2·(rP·vC/f)1/2, wherein rP=ro+coapplies, rois an inner radius of the interior, cois the minimum wall thickness of a vessel wall section in the region of the oscillation element, vCis the sound velocity in the vessel wall section. In this case, the width b can also be selected at the time of construction so that this is fulfilled when the oscillation element is excited at a predetermined frequency f.

As already stated at an earlier point, it is advantageous if the device has a transducer array which comprises at least the oscillation element and a vessel wall section in the region of the oscillation element, and possibly also further parts arranged in the thickness direction of the oscillation element and acoustically coupled to the oscillation element and/or the vessel wall section. In this case, the vessel wall section has a minimum wall thickness coin the region of the oscillation element in the region of the center of the connection surface, and a maximum radial wall thickness cmax=co+Δc in the edge region of the oscillation element, wherein an equivalent average wall thickness cequof the vessel wall section is defined by cequ=co+Δc/3, and the difference Δc between the maximum radial wall thickness cmaxand the minimum wall thickness cois determined by the width b of the oscillation element via the relationship Δc=(b2/4+rP2)1/2−rP, wherein r=ro+coapplies, and rois the radius of the circular-cylindrical interior.

Apart from the actual oscillation element, the transducer array thus also comprises that fixed part or those fixed parts of the device which are acoustically coupled to the oscillation element in the propagation direction of the emitted wave. The transducer array thus comprises the actual sound-emitting element, i.e. the oscillation element (i.e. preferably a piezoelectric plate excited by an alternating electrical signal), and all solid layers acoustically coupled thereto in the thickness direction (e.g. by bonding), e.g. in particular the vessel in the region of the connection surface with the oscillation element, and possibly further acoustically coupled inner or outer transformation, insulation and/or protective layers. A transducer array is thus generally limited inwardly by the dispersion layer to be sonicated, and outwardly by the ambient air, or, depending on the embodiment, by another gaseous, sound-decoupled solid or liquid environment (for example for the purpose of cooling the transducer array).

In this context, it is advantageous if the thicknesses of the layers of the transducer array are selected in such a way that natural resonance frequencies ferof the transducer array to the desired frequency f of the ultrasonic field have distances which are greater than one fifth of the distance fer,1−fer,2, wherein fer,1and fer,2are the two nearest natural resonance frequencies ferwith respect to the frequency f. In this way it can be prevented that injected acoustic energy remains to a considerable extent in the transducer array, i.e. in the vessel wall, the oscillation element or elements and possibly in components further acoustically coupled to these parts, instead of being emitted into the liquid in the interior of the vessel and contributing there to the build-up of an effective acoustic standing wave field.

In this sense, it is also advantageous if the frequency f is chosen to be outside the natural resonance frequencies ferof a transducer array, and that the distance of the chosen frequency f to the natural resonance frequencies ferhave distances which are greater than one fifth of the distance fer,1−fer,2, wherein fer,1and fer,2are the two closest natural resonance frequencies ferwith respect to the frequency f.

The natural resonance frequencies of a transducer array are the resonance frequencies of the transducer array in the absence of medium (i.e., in the absence of fluid in the interior of the vessel). In the absence of medium, no acoustic energy can be emitted from the transducer array into the medium, which means that the acoustic system remains limited to the transducer array alone, and thus natural resonance frequencies are determined solely by geometric and acoustic parameters of the transducer array.

As with all resonance frequencies of an acoustic system in general, the natural resonance frequencies of a transducer array are characterized by the fact that at this frequency the active power consumption by the transducer array is at a maximum for an impressed excitation signal applied to the oscillation element (i.e., at a certain voltage or current amplitude of the excitation signal, or at some other electrical output characteristic defined by the output impedance of the electrical signal amplifier).

In essence, natural resonance of a transducer array occurs when the half-wave number over the total thickness of a transducer array is equal to an integer, wherein the total thickness is formed from the thicknesses p of the oscillation element, and the equivalent thickness cequ=co+Δc/3 of the vessel wall section in the region of the oscillation element, and possibly the thicknesses of the further layers of the transducer array (if present).

Thicknesses of the layers of the transducer array mean the thicknesses of those layers of which the transducer array consists. In the simplest case, this means the thicknesses of the oscillation element and the wall section in the area of the oscillation element, i.e. p and cequ. If further layers are part of the transducer array, the thicknesses of these layers are also meant.

In order to avoid the excitation of natural resonances of a transducer array, which may have any number of layers belonging to the transducer array, during the operation of a device, it is particularly advantageous if the thicknesses of the layers of the transducer array acoustically coupled in the thickness direction of the oscillation element are selected such that the half-wave number κ of the transducer array satisfies the condition

wherein n is a natural number, and the tolerance value Δn is at least less than 0.3, preferably less than 0.2, and particularly preferably less than 0.1, and the half-wave number κ of the transducer array is substantially given by

wherein vcis the sound velocity in the vessel wall section in the region of the oscillation element, vpis the sound velocity in the thickness direction in the oscillation element, and d1to diare the thicknesses and vd1to vdiare the sound velocities of further layers of the transducer array acoustically coupled in the thickness direction, insofar as these are present, and the index number “i” is a natural number indicating the number of these further layers of the transducer array.

Accordingly, it is also advantageous if the frequency f is selected so that the half-wave number κ of the transducer array satisfies the condition

wherein n is a natural number and the tolerance value Δn is at least less than 0.3, preferably less than 0.2, and particularly preferably less than 0.1, and the half-wave number κ of the transducer array is substantially given by

wherein vcis the sound velocity in the vessel wall section in the region of the oscillation element, vpis the sound velocity in the thickness direction in the oscillation element, and d1to diare the thicknesses and vd1to vdiare the sound velocities of further layers of the transducer array acoustically coupled in the thickness direction, insofar as these are present, and the index number i is a natural number which indicates the number of these further layers of the transducer array, and in that the transducer array comprises at least the oscillation element and a vessel wall section in the region of the oscillation element, and also, optionally, further parts which are arranged preferably in the thickness direction of the oscillation element and are acoustically coupled to the oscillation element and/or the vessel wall section. With respect to natural number, 0 is thus included, i.e. i={0; 1; 2; 3; 4; . . . } applies.

If, for example, a transducer array consists only of the oscillation element and the vessel wall section acoustically coupled thereto in the region of the oscillation element (hereinafter referred to as “trivial transducer array”), it is advantageous if the equivalent wall thickness cequ=co+Δc/3 of the vessel in the region of the oscillation element and the thickness of the oscillation element p are selected in such a way that the resulting natural resonance frequencies of the transducer array lie outside the desired frequency f of the ultrasonic field. In this way, it can be prevented that injected energy of the oscillations remains in the transducer array, i.e. in the vessel wall, the oscillation element or the oscillation elements.

Furthermore, for a trivial transducer array, it is particularly advantageous if the thickness of the equivalent vessel wall section in the region of the oscillation element cequ=co+Δc/3 and the thickness of the oscillation element p are dimensioned such that the quarter-wave number extending over these two layers approaches an odd integer as closely as possible when the oscillation element is excited at a frequency f. This can effectively prevent natural resonance frequencies of the transducer array from being hit.

Accordingly, it is equally advantageous if the frequency f is selected in such a way that the quarter-wave number of a trivial transducer array extending over the equivalent wall thickness cequand the thickness p of the oscillation element corresponds as far as possible to an odd integer. In this case, the thickness of the oscillation element p and equivalent thickness of the vessel wall section in the region of the oscillation element cequcan already be selected during construction in such a way that this is fulfilled when the oscillation element is excited at a predetermined frequency f.

One thickness-polarized piezoelectric plate (or a plurality thereof) may be selected as the oscillation element. In order to achieve the best possible electrical excitability, the thickness p of such a plate is advantageously selected so that it corresponds to essentially half a wavelength or an integral odd multiple of half a wavelength in the polarization direction of the piezoceramic for the vicinity of an operating frequency f to be intended.

Preferably, it is provided that the thickness p of the oscillation element is selected such that it corresponds essentially to half a wavelength, i.e. to the value vP/(2f), wherein vpis the sound velocity in the direction of thickness in the oscillation element, and/or that the frequency f is selected such that the thickness p of the oscillation element corresponds essentially to the value vP/(2f) and vpis the sound velocity in the oscillation element. This is particularly advantageous if the oscillation element has a substantially constant thickness p—i.e. it is designed with mutually parallel lateral surfaces. In this way, it can be achieved that the oscillation element is operated as efficiently as possible. In this sense, it is also particularly advantageous if the frequency f is selected so that it is a resonance frequency of the oscillation element.

In this case, it is particularly advantageous if the width b of the oscillation element is in the range between (rP·p·vC/vP)1/2and 4·(rP·p·vC/vP)1/2, preferably between 1.5·(rP·p·vC/vP)1/2and 3.5·(rP·p·vC/vP)1/2and particularly preferably between 2·(rP·p·vC/vP)1/2and 3·(rP·p·vC/vP)1/2, in order to obtain an optimum excitability of a radial oscillation pattern in the interior of the vessel, wherein rP=ro+coapplies, rois the inner radius of the interior, cois the minimum wall thickness of the vessel wall section in the region of the oscillation element, and vCis the sound velocity in the vessel wall section.

Further, in this case, it is particularly advantageous for a trivial transducer array if the equivalent thickness cequ=c0+Δc/3 of the vessel wall section in the region of the oscillation element corresponds approximately to an integer odd multiple of a quarter wavelength in this vessel wall section. Accordingly, it is preferably provided that the equivalent thickness cequ=c0+Δc/3 of the vessel wall section in the region of the oscillation element is selected to correspond substantially to an integral odd multiple of (p/2) (vC/vP), and/or that the frequency f is selected such that the equivalent wall thickness cequ=c0+Δc/3 corresponds approximately to an integral odd multiple of (p/2) (vC/vP), wherein vCis the sound velocity in the vessel wall section. In this case, the equivalent wall thickness cequcan already be selected during the construction of the vessel in such a way that this condition is fulfilled when the oscillation element is excited with a predetermined frequency f.

Accordingly, it follows from the preferred correspondence p=vP/(2f) and the relation Δc=(b2/4+rP2)1/2−rP, that the minimum thickness coof the vessel wall section in the region of the oscillation element of a trivial transducer array is preferably determined according to the condition

wherein (2n+1) is any odd positive integer.

Furthermore, it can be provided that the vessel outside the region of the oscillation element and at least at the level of the oscillation element has a wall thickness c which corresponds approximately to an integral odd multiple of a quarter wavelength in this vessel wall section. Accordingly, it can also be provided that the frequency f is selected such that the wall thickness c of the vessel outside the region of the oscillation element and at least at the level of the oscillation element corresponds approximately to an integral odd multiple of a quarter wavelength in this vessel wall section. In this case, the wall thickness c can also be selected already during construction in such a way that this is fulfilled when the oscillation element is excited with a predetermined frequency f.

In other words, c≈(2n+1)·vC/4f applies. The production of the vessel, for example, as a tube with a wall thickness of approximately an odd multiple of a quarter wavelength is advantageous, since acoustic losses due to natural resonance behavior of the vessel can thereby be minimized even outside the range of the piezo plate.

Additional layers (coupling layers) can be arranged between the oscillation element and the vessel wall section, for example adhesive layers, layers made of glass, ceramics or metal, or also layers formed from ultrasound gel. In order to optimize the oscillation behavior, it is advantageous if the thicknesses d′1to d′jof coupling layers of the transducer array, which are arranged acoustically coupled in the thickness direction between the oscillation element and the vessel wall section, and the minimum wall thickness coof the vessel wall section are selected so that the condition

is fulfilled, wherein vd′1to vd′jare the sound velocities of the coupling layers, wherein the index number j is a natural number indicating the number of coupling layers of the transducer array arranged between the oscillation element and the vessel wall section, and q is a natural number, and the tolerance value Δq is at least less than 0.3, preferably less than 0.2, and particularly preferably less than 0.1.

Accordingly, it is also advantageous if at least one coupling layer is arranged between the oscillation element and a vessel wall section in the region of the oscillation element, the minimum wall thickness coof the vessel wall section and the thickness d′ of the coupling layer are such that the condition

is fulfilled, wherein vd′1to vd′jare the sound velocities of the coupling layers, wherein the index number j is a natural number which indicates the number of coupling layers of the transducer array, and q is a natural number, and the tolerance value Δq is at least less than 0.3, is preferably less than 0.2, and is particularly preferably less than 0.1.

It may also be provided that the coupling layer is of negligible thickness, i.e. d′ is substantially equal to 0, or that no coupling layer is provided and the acoustic transition between the oscillation element and the vessel wall is ensured in a direct manner (for example by pressing, vacuumization, or fusion).

Furthermore, it can be provided that the thicknesses d″1to d″kof outer layers of the transducer array acoustically coupled in the thickness direction, which are arranged on the side of the oscillation element facing away from the vessel, are selected such that the condition

is fulfilled, wherein vd″1to vd″kare the sound velocities of the outer layers, wherein the index number k is a natural number indicating the number of outer layers of the transducer array which are arranged on the side of the oscillation element facing away from the vessel, and s is a natural number, and the tolerance value Δs is at least less than 0.3, preferably less than 0.2, and particularly preferably less than 0.1.

Accordingly, it can also be provided that acoustically coupled outer layers of the transducer array are arranged on the side of the oscillation element facing away from the vessel, the thicknesses d″1to d″kof which are selected such that the condition

is fulfilled, wherein vd″1to vd″kare the sound velocities of these outer layers, wherein the index number k is a natural number indicating the number of outer layers of the transducer array, and s is a natural number, and the tolerance value Δs is at least less than 0.3, preferably less than 0.2, and particularly preferably less than 0.1.

In this way, it can be achieved that the electrical excitability of the oscillation element is optimally maintained. Outer layers can be made of a wide variety of materials, such as metal, glass or ceramics. Adhesive layers in between can also represent outer layers. Thicknesses mean their thicknesses in the direction of the thickness p of the oscillation element. If several layers are provided, acoustically hard and acoustically soft layers can be arranged alternately along their thickness extension. This is especially advantageous when acoustic isolation from the environment is to be achieved. Acoustically hard (or acoustically soft) means materials having a comparable or higher acoustic impedance (or a lower acoustic impedance) than the oscillation element, wherein the acoustic impedance is given by ρ·v, and ρ indicates the density (the specific gravity) and v the sound velocity of the material. The layers preferably extend over the entire side of the oscillation element, or the adjacent layer or layers. The natural number again also includes 0, as in further consequence, i.e. s={0; 1; 2; 3; . . . } applies.

It may further be provided that the vessel has, outside the region of the oscillation element and at least at the level of the oscillation element, a wall thickness c which satisfies the condition c=vC/2f·(½+m±Δm), wherein m is a natural number, and the tolerance value Δm is at least less than 0.3, is preferably less than 0.2, and is particularly preferably less than 0.1.

Accordingly, it may also be provided that the frequency f is selected such that the condition c=vC/2f·(½+m±Δm) is fulfilled, wherein m is a natural number, and the tolerance value Δm is at least less than 0.3, preferably less than 0.2, and particularly preferably less than 0.1, and that the wall thickness c is that of the vessel outside the region of the oscillation element.

To excite the oscillation element, it can be provided that the oscillation element is connected to at least one signal generator which excites the oscillation element with at least one frequency f. The signal generator supplies the oscillation element with a signal which sets the oscillation element into a defined oscillation. For example, this can be an AC voltage source which excites a piezo element as an oscillation element with one or more frequencies.

It is particularly advantageous if the signal generator has a control circuit for measuring at least the voltage amplitude, or current amplitude, or the phase relationship between current and voltage amplitude of the emitted signal, or a combination of these electrical quantities, and is set up to fine-tune the frequency f of the ultrasonic field to a resonance frequency foptof the device filled with the liquid, which is determined from these measured quantities.

Accordingly, it may also be advantageous if the signal generator measures at least the voltage amplitude, or current amplitude, or the phase relationship between current and voltage amplitude of the emitted signal, or a combination of these electrical quantities, via a control circuit, and fine-tunes the frequency f to a resonance frequency foptof the device filled with the liquid, which is determined from these measured quantities.

Since the electrical excitability of an acoustic system is particularly high at resonance frequencies fresof the entire acoustic system (i.e. resonance frequencies which occur only with the liquid in the interior), excitation of the oscillation element at a resonance frequency fresof the acoustic system is particularly desirable (in contrast to excitation at a natural resonance ferof the transducer array and/or the vessel). Thus, it is advantageous if the operating frequency f is tuned to such a resonance frequency foptof the acoustic system which lies outside the ranges of the natural resonances ferof the transducer array. This avoids causing the transducer array to oscillate without further transmitting the energy into the fluid within the interior of the vessel.

When a resonance frequency fresis chosen as the operating frequency, the active power consumption Peffof the acoustic system reaches a local maximum Pmax:

In the case of piezoelectric excitation, the detection of a resonance frequency can thus be performed by means of an active power measurement bridge between the electrical signal source and the piezoelectric plate; e.g. by time averaging (symbolized by < >) the analog multiplication of the AC voltage signal U(f) by the AC current signal I(f), or in the case of sinusoidal AC signals also by measuring the voltage amplitude Uo(f), the current amplitude Io(f), and the phase relationship θ(f) between the AC voltage signal and AC current signal:

When excited by an impressed AC electrical signal (i.e., with the voltage amplitude Uo) held constant, the resonance frequency of the entire acoustic system is that frequency fresat which the electrical conductance G(f) of the entire system (i.e., in the presence of medium between the transducers, or between the transducer array and the reflector) reaches a local maximum:

Analogously, when excited by an impressed alternating current signal (i.e. with constant current amplitude Io), the resonance frequency fresis the frequency at which the electrical resistance R(f) of the overall system reaches a local maximum:

In principle, it is advantageous if one or more preferred operating frequencies f or a frequency band in which the device is to be operated are determined before the device or the vessel and oscillation element are constructed. The above calculations can thus be used to calculate the dimensions for the vessel and oscillation element, so that natural resonances of the transducer array can be avoided and optimum energy transfer can be ensured. However, since the exact position of the resonance frequency foptdepends on a large number of parameters, such as the exact dimensions of the transducer array within the manufacturing tolerances, the temperature or the type of liquid, etc., it may be advantageous to determine the optimum operating frequency f (i.e. the resonance frequency foptof the acoustic system) after construction before or during operation of the device, and to excite the oscillation element primarily or exclusively at this frequency.

The device may also comprise more than one vessel, wherein the vessels are preferably connected in parallel to each other, but may also be connected in series. In this way, the size of the vessels can be kept small and yet an increase in the amount of liquid to be treated can be achieved.

An oscillation element may also be connected to more than one vessel, thereby exciting more than one vessel.

Preferably, the vessel is made of glass, preferably borosilicate glass, at least in the region of the oscillation element. Equally preferably, the vessel is made of biocompatible plastic or plastics. It may also be provided that the vessel, at least outside the region of the oscillation element, is made of biocompatible plastic.

It is particularly advantageous if the vessel is separably connected to the oscillation element, for example that an acoustic coupling is established via ultrasonic gel. In this way, the vessel can be intended for single use, while the oscillation element can be reused. This is particularly advantageous for sensitive substances such as biologically active cells in a nutrient medium, as contamination can be prevented.

In the following, it will be explained by way of example how, given a desired operating frequency, suitable dimensions for producing the inner radius and general and minimum wall thickness of a carrier tube serving as a vessel, as well as the thickness and width of a piezo plate serving as an oscillation element, are determined in accordance with the invention:

The starting point is a preferred operating frequency of about 1.7 MHz empirically found for an application to an aqueous suspension, a radius rP=17 mm defining the approximate size, and a carrier tube wall thickness of at least 4 mm required for hydrostatic pressure resistance.

For the carrier tube serving as the vessel according to the invention at the level of the oscillation element, technical borosilicate glass is selected from a number of possible materials (glass, ceramics, stainless steel, but also thin-walled plastics such as PEEK, polycarbonates, polyethylenes and polystyrenes, or other e.g. biocompatible plastics, ceramics or metals). Two identical mirror-image PZT piezoceramics are chosen as sound-generating elements.

According to the material data sheet, the following material parameters are given:

Sound velocity of the carrier tube: vC=5640 m/s

Sound velocity of the piezo plate: vP=4100 m/s (for longitudinal oscillation mode in the direction of the thickness p of the plate).

It follows therefrom:

Thickness of the oscillation element: p≈vP/(2f)=1.2 mm (for optimum excitation of the piezoelectric oscillation element in its fundamental mode of thickness oscillation)

Width of the oscillation element: b≈2·(rP·vC/f)1/2=15 mm

FIGS. 1A and 1Billustrate a typical prior art acoustic device for producing a flat standing acoustic field in a vessel1filled with a dispersion100. The dispersion100represents a liquid (the dispersion medium) and particles such as cells contained therein. The transducer array200is formed by a flat piezoelectric oscillation element2coated with electrode surfaces, and by a flat vessel wall10a. The oscillation element2is acoustically precisely coupled to the vessel wall10afrom the outside (e.g. by bonding of precisely defined often highly thin layer thickness, or by an interposed acoustically coupling gel or liquid layer). The opposite reflecting, likewise flat vessel wall10bserves as an acoustic reflector wall and is oriented with its inner surface13bparallel to the emitting surface13aof the transducer array. Between transducer wall10aand reflector wall10b, a parallel pattern of alternating sonic bulge planes111and sonic node planes112is formed in dispersion100. Adjacent nodes and bulges are spaced apart by a quarter wavelength; the bulge-to-bulge or node-to-node spacing is half a wavelength.

Depending on the acoustic contrast and specific gravity of the particles relative to the dispersion medium, acoustic radiation forces drive the dispersed particles (which may be solid, liquid, or gaseous) into the sonic bulge planes111and sonic node planes112, respectively. Accordingly, most solid particles (as shown here) are driven into the sonic bulge planes, while gaseous particles (bubbles) would collect in the sonic node planes.

In the illustrated embodiment, the acoustic field is generated by applying an AC voltage U˜ to the electrodes of the oscillation element2. If an integer multiple of half wavelengths fits into the acoustic system (formed here by transducer array dispersion reflector wall), the standing wave field is in resonance and the system can be excited particularly effectively. If the distance L between the transducer wall10aand the reflector wall10bis significantly greater than the thickness of the transducer array or the reflector wall, the frequency spacing Δfresbetween adjacent resonance frequencies can be approximately estimated by the relationship Δfres=vM/(2L), wherein vMis the sound velocity of the medium of dispersion100.

The vessel walls (transducer wall10a, reflector wall10b, side walls10c) are typically made of glass or metal. As a possible measure for attenuating randomly excited transverse standing wave fields, the inner surfaces13cof the side walls are shown here with an acoustically attenuating coating15. Suitable materials for such a coating include silicone, rubber, and other materials compatible with the medium such as biocompatible plastics. Alternatively, the entire sidewall13c, or all of the vessel walls if sufficiently thin, may be made of application-specific suitable plastics (e.g., forms of PEEK, polycarbonates, polyethylenes, polypropylenes, polystyrenes, etc.). Likewise, depending on the material, the vessel may also be cast, injection molded, fused, or milled in one piece. These embodiments regarding the material and the cushioning coating may also apply to embodiments according to the invention.

Analogous toFIG. 1A,FIG. 2Aillustrates the fundamental structure of a device according to the prior art for producing a circular-cylindrical standing acoustic field. The vessel1is circular-cylindrical and continuously surrounded on an outside wall12by an equally circular-cylindrical oscillation element2, which is designed as a piezoelectric tube. The cylinder axis or main axis H lies in the viewing direction z of the observer. The transducer array200is formed by the piezoelectric tube2and by the vessel1enclosed therein and serving as a carrier tube. The piezoelectric tube and the carrier tube are acoustically coupled to each other (e.g., by bonding, or by an interposed acoustically coupling gel or liquid layer). Within the carrier tube, a parallel pattern of alternating sonic bulge cylindrical shell surfaces111and sonic node cylindrical shell surfaces112is formed in the dispersion medium or liquid100. Adjacent node shell surfaces and bulge shell surfaces are spaced apart by a quarter wavelength in the fluid100; the spacing of adjacent bulge-bulge shell surfaces and node-node shell surfaces, respectively, is one-half wavelength λ/2.

In the illustrated embodiment, the acoustic field is generated by applying an AC voltage U˜ to the electrodes of the piezoelectric tube2. If an integer multiple of half wavelengths fits into the acoustic system (here formed by transducer array medium), the standing wave field is in resonance and the system can be excited particularly effectively. If the inner radius roof the carrier tube1is significantly greater than the wall thickness of the transducer array200, the frequency spacing Δfresbetween adjacent resonance frequencies can be estimated approximately by the relationship Δfres=vM/(2ro), wherein vMis the sound velocity of the medium.

Due to the concentric excitation of the circular-cylindrical standing wave field, the acoustic energy density is inversely proportional to the distance r between the cylinder axes. Due to the increasing acoustic energy density, the pressure amplitude and thus the risk of cavitation in the area of the cylinder axis H also increases significantly. Especially for the separation of living cells, this poses a risk to the viability of the cells.

FIG. 2Billustrates a measure for reducing this risk of cavitation along the cylinder axis H, which is known from the prior art. In the illustrated variant of the cylindrical device, the piezo tube is divided into four cylinder shell segments, resulting in four oscillation elements2A1,2A2,2B1,2B2which are curved in cross-section. They are electrically wired in such a way that the excitation of two opposing piezo shell segments is synchronous in time, but the pair of piezo shell segments orthogonal thereto is antisynchronous. That is, while piezo shell segments2A1and2A2expand, piezo shell segments2B1and2B2contract, and vice versa. This at least partially compensates for the acoustic pressure amplitudes increasing towards the center in the region of the axis, and the risk of cavitation is reduced.

FIG. 3Ashows a possible embodiment variant according to the invention of a vessel1according to the device according to the invention, wherein the oscillation elements2are designed as flat piezoelectric plates and are acoustically coupled (e.g. by bonding) to connecting walls11, which are held flat, of an outside wall12of the vessel1designed as a carrier tube. Thereby, the interior14is circular-cylindrical as shown inFIG. 2B, i.e. has a circular cross-section with an inner radius r0. The interior14is bounded by a continuous, smooth inner wall13of the vessel1. Outwardly, the vessel1has a rectangular, preferably square, cross-section, resulting in an outside wall12of four flat partial walls that are parallel or at right angles to each other. Four oscillation elements2are arranged centered on each partial wall, whereby the partial walls serve at least partially as connection surfaces. Each partial wall has a minimum wall thickness coat which the vessel1is thinnest, namely halfway across the width b of each oscillation element2and partial wall. This results in a radial distance rpof the oscillation elements2from the main axis H with rp=ro+co.

FIG. 3Bshows a second embodiment according to the invention, wherein the vessel1has a circular shell and thus cylindrical outside wall12. Thus, the vessel1is essentially a hollow cylinder with an overall wall thickness c. On two sides the outside wall12is flattened, resulting in two flat connection surfaces11. In this embodiment, the connection surfaces11are arranged parallel to each other and thus face each other. An oscillation element2is arranged on each connection surface11, which are preferably excited with the same frequency f or the same frequency spectrum. Such an arrangement on two opposite sides is particularly advantageous for vessels which are made of plastic. Possible asymmetries of the wave field in the interior14of the vessel caused by damping in the vessel wall can thus be prevented.

For this purpose, the oscillation elements2can be electrically connected in series (as shown) or also electrically connected in parallel, wherein inFIG. 3Bthe polarity of the respective electrical contacting of the oscillation elements is selected in such a way that the oscillation elements expand or contract synchronously. For this purpose, the side of an oscillation element2facing away from the vessel1is connected to a first signal cable of a signal generator, and the side of the other oscillation element2facing towards the vessel1is connected to a second signal cable. The other sides of the oscillation elements2are connected to each other by a cable. In this case, the negatively polarized side of both oscillation elements2faces the vessel1. InFIG. 3Ait can be seen that such an electrical interconnection is of course also possible with several oscillation elements2.

Due to such a rotationally symmetrical arrangement of a plurality of oscillation elements2, a standing wave field111formed substantially radially about the main axis H occurs in the interior14within the dispersion100in the region between two oppositely arranged oscillation elements2, and thus the dispersed particles are compacted. Corresponding compaction also occurs transversely to this region as a result of a standing wave field which is likewise substantially radially formed but oscillates in an inverted manner, as a result of which a weakening of the radial standing wave field can occur in the transition regions113between the wave regions, but this is insignificant for the practical functionality of the device.

According to the invention, an effective excitation of an—in spite of the flat formed oscillation elements2—essentially still dominant cylindrical standing wave field within the interior14filled with liquid is possible by the fact that the oscillation elements2have a width b which approximately does not substantially exceed the relation b=2·(rP·vC/f)1/2.

According to the invention, it is sufficient that the width b is less than 3·(rP·vC/f)1/2, and preferably has a value within (rP·vC/f)1/2<b<2.5·(rP·vC/f)1/2, wherein vCis the sound velocity in the vessel wall section10in the region of the oscillation element2.

For the normally practical case where a piezoelectric plate for excitation at its thickness mode fundamental frequency is used as the oscillation element2(i.e., the oscillation element has a thickness p=vP/(2f), and vpis the sound velocity in the thickness direction in the oscillation element2), an embodiment according to the invention of the width b is also given when it is less than 4·(rP·p·vC/vP)1/2or preferably within a range 1.5·(rP·p·vC/vP)1/2<b<3.5·(rP·p·vC/vP)1/2.

FIG. 3Cillustrates further key geometric dimensions of an embodiment according to the invention, which must be observed in the design in order to optimize the excitation of a circular-cylindrical acoustic field in sufficient approximation despite the use of flat sound emitting oscillation elements2. The plate-shaped oscillation element2has a thickness p and is acoustically connected to the flat connection surface11of the outside wall12of the vessel via a coupling layer23of thickness d (e.g. by bonding, or by an interposed acoustically coupling gel or liquid layer). The oscillation element thus forms, together with the coupling layer23and the vessel wall section10located in the region of the coupling layer, a transducer array200acoustically coupled in the thickness direction of the oscillation element2. Thereby, the vessel wall section10has a minimum wall thickness c0in its center and a maximum radial wall thickness cmax=c0+Δc at the edge of the coupling layer, where the radial wall thickness of c0has expanded by Δc. In this embodiment, the total wall thickness c of the vessel is greater than cmax, since the coupling surfaces11are made larger than the width b of the oscillation elements2, and therefore project beyond them. The difference Δc is determined by the width b of the oscillation element (2) via the relationship Δc=(b2/4+rP2)1/2−rP.

It is advantageous to define an equivalent thickness cequfor the vessel wall section10belonging to the transducer array200, given by cequ=c0+Δc/3, which is substantially equal to the mean radial wall thickness of this vessel wall section10.

According to the invention, in the embodiment variant illustrated withFIG. 3C, the thickness p of the oscillation element2, the thickness d of the coupling layer23, and the equivalent thickness cequof the vessel wall section10have an overall thickness of the transducer array200, so that the occurrence of natural resonances of the transducer array200is avoided when the transducer array200is excited at the desired operating frequency f. This is achieved in that the thickness p of the oscillation element, thickness d of the coupling layer23, and the equivalent thickness cequof the vessel wall section10have values which come as close as possible to the condition

which is equivalent to the condition that the half-wave number of the acoustic wave extending in the thickness direction over the entire transducer array is as close as possible to no natural number n (0, 1, 2, . . . ). Here, vcis the sound velocity in the vessel wall section10in the region of the oscillation element2, vpis the sound velocity in the thickness direction in the oscillation element2, and vdis the sound velocity in the coupling layer.

For the normally practical case that a piezoelectric plate for excitation at its thickness mode fundamental frequency is used as the oscillation element2(i.e., that the oscillation element has a thickness p=vP/(2f)), and while observing the width b of the oscillation element2which is preferable according to the invention and as explained forFIGS. 2A and 2B, the excitation of natural resonances of the transducer array is avoided, in particular, if the minimum thickness coof the vessel wall section10and the thickness d of the coupling layer have values which satisfy the condition

wherein n is a natural number (0, 1, 2, . . . ), and the tolerance value Δn is at least less than 0.3, preferably 0.2, and particularly preferably less than 0.1.

According to the invention, the coupling layer may have a thickness d so thin that it can be neglected and thus d is substantially equal to 0.

In a preferred embodiment of the device according to the invention, the wall thickness c of the vessel1around the interior14but outside the region of the connection surface11satisfies the condition

wherein m is a natural number (0, 1, 2, . . . ), and the tolerance value Δm is at least less than 0.3, preferably 0.2, and particularly preferably less than 0.1. This is equivalent to the condition that the vessel has a wall thickness c in this region which is not equal to an integer multiple of half a wavelength.

For the normally practical case where the oscillation element2is a piezoelectric plate for excitation at its thickness mode fundamental frequency (i.e., the oscillation element has a thickness p=vP/(2f)), the condition can also be expressed as

FIG. 3Dillustrates one of the possible embodiments of the oscillation element2according to the invention with thickness p and width b as an arrangement of two piezoelectric plates20aand20bof the same thickness p, which are adjacent to each other on the same plane and polarized in the thickness direction. Each of the two plates20a,20bhas an electrode surface21a,21bfacing the vessel (vessel not shown here) and an electrode surface22a,22bfacing away from the vessel. For the purpose of accessibility of electrical contacting, the electrode surfaces21a,21bfacing the vessel each have a region overlapping on the side facing away from the vessel.

In the embodiment shown here, the electrode surfaces21a,21b,22a,22bof the two piezo plates20aand20bare electrically connected in series with each other and connected to an electrical signal source U˜.

It is understood that in alternative embodiments an oscillation element2may have only a single piezoelectric plate, or may have a mosaic-like arrangement of any number of piezoelectric plates electrically connected to each other in series, or in parallel, or in a suitable combination thereof, to achieve a suitable overall electrical impedance of the oscillation element2for connection to the signal source U˜.

Further, a piezoelectric plate may have a plurality of separate electrode surface areas on one or both sides, which in turn are electrically connected to each other in such a way as to achieve a suitable overall electrical impedance of the oscillation element2. Where a plurality of piezoelectric plates20a,20bare provided for the oscillation element2, they may be directly acoustically connected to each other. For this purpose, it may be provided that the at least two piezoelectric plates are arranged with a base body of the oscillation element. In this respect, the base body may extend substantially only in the region between the piezoelectric plates. This may require that the mean thickness p of the oscillation element corresponds to the thickness of the piezoelectric plates. Alternatively, no main body may be provided and the piezoelectric plates may also be acoustically connected only via the vessel.

Further, the electrical connection between the signal source U˜ and one or more piezoelectric plates may also be supported by one or more signal transformers having suitable electrical transformation ratios to provide an overall electrical impedance of the oscillation element2suitable for connection to the signal source U˜.

FIG. 4presents the frequency response of a device built according to the invention as shown inFIG. 3C, which has dimensions according to the invention that obey the conditions presented forFIG. 3C:

Width of the swing element: b=15 mm

Thickness of the oscillation element: p=1.2 mm (basic thickness mode at 1.7 MHz)

Minimum vessel wall thickness: co=2.0 mm

General wall thickness: c=4.2 mm

Radii of the vessel: ro=15 mm and rP=ro+co=17 mm

The coupling layer23is formed of a thin liquid cured adhesive whose thickness d is of the order of only one hundredth of a wavelength, and is thus negligible (d≈0). The oscillation element consists essentially of only one piezoelectric plate, whereby the thickness and width of this plate represent the thickness and width of the oscillation element.

Sound velocity Medium (water): vM=1500 m/s Sound velocity of the carrier tube: vC=5640 m/s Sound velocity of the piezo plate: vP=4100 m/s (for longitudinal oscillation mode in the direction of thickness p of the piezo plate).

A first plot901(thin solid line) represents the conductance spectrum of the acoustic system300(vessel1filled with medium), a second plot902(thick dashed line) represents the conductance spectrum of the transducer array200(empty vessel1). In the case of excitation with an alternating electrical signal with primarily impressed voltage amplitude, the first plot901is to be equated with the resonance spectrum of the acoustic system300, while the second plot912corresponds to the natural resonance spectrum of the transducer array200.

In the range of the desired operating frequency of about 1.7 MHz, strongly pronounced radial resonance frequencies f1, f2and f3occur at the expected spacing of Δfres≈vM/(2ro)=50 kHz as a consequence of the production according to the invention. These radial resonance frequencies f1, f2, f3, and to a limited extent also f4stand out significantly from the remaining non-radial background resonance behavior (typically recognizable by the smaller but dense and irregular resonance peaks), which is particularly pronounced in the frequency ranges911and912around the natural resonance frequencies fer1(at 1550 kHz) and fer2(at 1900 kHz) of the transducer array.

According to the invention, with a distance of greater than 70 kHz from these two closest natural resonance frequencies fer1and fer2(corresponds to about 20% or one fifth of the frequency separation between these two natural resonance frequencies), the resonance frequencies f1, f2, f3and f4of the acoustic system300are also sufficiently far away from the natural resonance frequencies of the transducer array, with a distance of more than 105 kHz (corresponds to about 30% of the frequency separation between the two nearest natural resonance frequencies fer1and fer2), the frequencies f1, f2, f3are to be preferred over f4; and among these in turn the frequencies f1and f2with a spacing of more than 140 kHz (corresponds to about 40% of the frequency spacing between the two nearest natural resonance frequencies fer1and fer2).

Preferably, the alternating electrical signal source includes a device for:

(1) detecting resonance frequencies (such as by directly measuring the active electrical power absorbed by the vessel1, thus detecting the frequencies for which there are local maxima of absorbed active power) and/or

(2) for automated frequency tuning to such resonance frequencies of maximum active electrical power absorption by the acoustic system300.

With such a device, it is therefore possible to manually or even automatically fine-tune the operating frequency f to the preferred resonance frequency of the acoustic system300that most closely matches the assumed operating frequency (in this example, 1.7 MHz) on which the design is based.

It is remarkable that in the example presented, pronounced and largely mode-free radial resonances are formed only within a relatively narrow frequency range910of about 1650 to 1750 kHz; a clear indication that only for this narrow frequency range around 1.7 MHz a largely mode-pure cylindrical standing wave field is built up in the radial direction, in which no significant coupling with standing wave fields dependent on other dimensions occurs.

It should be emphasized that over the entire measured range from 1400 kHz to 2050 kHz, far-reaching mode-pure excitation of a radial standing acoustic cylinder field is possible only at f1, f2, and f3(i.e., at only 3 of about 15 possible radial resonance frequencies); it is therefore very unlikely that with only random selection of the values for width b and thickness p of the piezo plate, as well as minimum and other wall thicknesses of the carrier tube (coand c), a mode-pure radial resonance frequency could be found afterwards purely by frequency tuning, which would come sufficiently close to the desired operating range around 1.7 MHz, and at the same time would be sufficiently far away from natural resonances of the transducer array. This underlines that the present invention is indeed a device.

For vessels1with smaller circular-cylindrical inner diameter14(typically less than 50 wavelengths in the medium at operating frequency), it is sufficient for many only weakly attenuating dispersions (such as aqueous suspensions with a solids content of typ. <10% v/v) to excite the acoustic system300only on one side. By way of example,FIGS. 5A and 5Billustrate such a one-sided-only configuration of the vessel1, which is designed as a circular-cylindrical tube, with piezoelectric excitation on one side only. The criteria according to the invention for the design of the thickness and width of the oscillation element2, as well as the general wall thickness and minimum wall thickness of the carrier tube (i.e. for b, p, c and co) remain as described forFIG. 3C.

In this regard, it is visible inFIG. 5Bthat the oscillation element2extends over a major part of the section of the vessel1which has a round cross-section. In this case, however, the oscillation element2does not extend to the ends of these sections—nor do the connection surfaces11extend as far—but this may be provided in alternative embodiments. This also applies to other embodiments with several oscillation elements2.

FIG. 5Cillustrates one way of increasing the total flow cross-section by arranging a plurality of circular-cylindrical vessel tubes1in parallel, each fitted with an oscillation element2. Alternatively, of course, in other embodiments, the fitting of a plurality of oscillation elements2may be provided. If all vessel tubes1and oscillation elements2are of identical construction, the oscillation elements2may be electrically interconnected (e.g. serially, in parallel, or in a combination thereof) and operated by a common alternating electrical signal. For uniform separation performance of all such parallel acoustic systems300when operated from a common electrical source, it is advantageous if the inner diameters of the carrier tubes1differ from each other by at least no more than 0.3%, preferably no more than 0.1%; and if the minimum wall thicknesses coof the carrier tubes1and the thicknesses p of the oscillation elements2differ from each other by at least no more than 5%, preferably no more than 2%. The individual vessel tubes1are held at their ends in two receiving plates30.

FIGS. 6A and 6Bshow by way of example further embodiments according to the invention with acoustic excitation from more than 2 directions, here for 3 and 6 directions, respectively. Common to all such star-shaped forms of excitation from 3 or more directions is that the piezo plates are of identical size, these are arranged rotationally symmetrical to the axis of the circular-cylindrical interior14of the carrier tube, and for the dimensions of the oscillation elements2and of the vessel (i.e. for b, p, and co) the same geometrical criteria according to the invention apply as in the case described forFIG. 3C, so that an essentially cylindrical acoustic standing wave field can likewise be formed, the rotationally symmetrical wave antinode/wave node periodicity of which in all excitation directions can again be described essentially alone by the one-dimensional radial dimension r.

In the embodiments shown inFIG. 6A-C, the oscillation elements are of the same thickness p and the same width b. In alternative embodiments, however, oscillation elements of different sizes may also be provided.

FIG. 6Cillustrates a coupling of several parallel acoustic vessels1according toFIG. 6Binto a honeycomb-shaped arrangement acoustically coupled via the oscillation element2as a way of increasing the total flow cross-section and further uniform acoustic energy distribution when operating on a common alternating electrical signal. In this regard, two vessels1are adjacent to each oscillation element2, wherein each vessel1located inside the honeycomb-like structure is adjacent to a total of six oscillation elements2.

FIG. 7Aillustrates another way of increasing the total flow area by acoustically coupling multiple circular-cylindrical acoustic volumes drilled side-by-side in a common block. In other words, multiple vessels have a common shell that has a common outside wall12. This results in an array of vessels5, with six vessels1being evenly distributed in cross-section around a central vessel1, thus being at an angle of 60° to their adjacent vessels1. The outside wall12has connection surfaces11on which the oscillation elements2are arranged, with the connection surfaces being equally evenly arranged around the central vessel1, corresponding to the vessels1. All vessels1have the same inner radius r0and thus the same interior14, and all oscillation elements2have the same dimensions. Optimal acoustic coupling is achieved when the equivalent wall thickness c1+2·Δc/3 between two adjacent vessels2corresponds to an integral multiple of half a wavelength, i.e. preferably corresponds approximately to the relation c1+2·Δc/3=n·vC/(2f).

In contrast, it is preferred that the outside wall12bounding the vessel array to the outside be as acoustically opaque as possible. This can be achieved, for example, by removing unnecessary volumes (such as the regions marked “A” inFIG. 7A) from the overall vessel wall, and the remaining equivalent wall thickness (e.g., in the case shown, c2+2·Δc/3) corresponds to an odd multiple of a quarter wavelength, i.e., c2+2·Δc/3=(2n−1)·vC/(4f). All other characteristic dimensions (b, p, and co) preferably correspond to the case already discussed forFIG. 3A to 3C.

FIG. 7Billustrates one of the possible acoustic couplings of several vessel arrays5, as for example inFIG. 7A, as a possibility of further enlarging the flow cross-section and furthermore of distributing the acoustic energy as evenly as possible when operating on a common electrical alternating signal. In this case, corresponding toFIG. 6C, the oscillation elements2are acoustically connected to two vessel arrays5each, whereby a honeycomb-like structure is created.

FIGS. 8A-8Eillustrate further of the many possibilities for acoustically coupling a plurality of acoustic cylinders according to the invention to increase flow cross-section and uniform acoustic energy distribution when operating from a common alternating electrical signal. Again, the same criteria as discussed earlier preferably apply to the characteristic dimensions b, p, co, c1, c2.FIG. 8Ashows an embodiment of a composite vessel5with oscillation elements2arranged uniformly on the outside wall12, while the embodiment ofFIG. 8Chas only two oscillation elements2on each of two sides, each of which is associated with a vessel1. It should be emphasized that either vessels1may be coupled to individual shells via the oscillation elements2, see for exampleFIG. 8B. On the other hand, vessel arrays5can also be coupled to each other via oscillation elements2, seeFIG. 8DandFIG. 8E.

FIG. 9Aillustrates a general structure of a transducer array200formed by the oscillation element2and the vessel wall section10, as well as further acoustically coupled layers23a,23b,24,25,26, wherein one or more coupling layers23a,23b,24may be arranged between the side21facing the vessel of the oscillation element2essentially consisting of a piezoelectric plate20and the vessel wall section10. These coupling layers23a,23b,24may be necessary, for example, in order to fix the oscillation element2to a stationary support plate24by means of an adhesive layer23ainstead of permanently bonding it directly to the vessel wall10, in order to be able to acoustically couple the vessel1to the oscillation element2via this support plate24for only temporary use (for example, with a gel layer23bserving as a bonding layer and applied to the support plate24). This makes it possible, for example, to be able to manufacture the vessel1from plastic materials for single use, but to provide the oscillation element2for frequent use. In this regard, the bonding layers23a, and/or23bmay be so thin as to be negligible.

Similarly, one or more outer layers25,26may be arranged on the side22of the oscillation element2facing away from the vessel1in the thickness direction of the oscillation element2. This can serve, for example, to apply a counter-mass25to the oscillation element2outwardly via a connecting layer26for reasons of acoustic symmetry. However, the outer layers25,26can also serve, for example, to electrically and/or acoustically insulate the oscillation element2outwardly from a surrounding cooling liquid. The outer layers25,26can thereby represent insulating layers25on the one hand and connecting layers26, (for example made of adhesive) on the other hand. The connecting layers may be so thin as to be negligible. The outer layers25,26are acoustically coupled layers of the transducer array200.

Analogous to the trivial case illustrated inFIG. 3C, according to the invention the acoustically coupled layers2,10,23a,23b,24,25,26of a multilayer transducer array200illustrated as inFIG. 9Ahave thicknesses such that none of the natural resonances of the transducer array lies in the vicinity of the desired operating frequency f, and preferably occupy as large a frequency spacing as possible from the desired operating frequency f, thus the thicknesses of the layers come as close as possible to the condition

wherein vcis furthermore the sound velocity in the vessel wall section10in the region of the oscillation element2and vpis the sound velocity in the thickness direction in the oscillation element2, while d1to diare the thicknesses and vd1to vdiare the sound velocities of further layers23a,23b,24,25,26of the transducer array200acoustically coupled in the thickness direction, and the index number “i” is a natural number which indicates the number of these further layers23a,23b,24,25,26of the transducer array.

Furthermore, in a preferred embodiment, the thicknesses of the one or more outer layers25,26coupled to the side22of the oscillation element2facing away from the vessel satisfy, as far as possible, in themselves the condition

which is equivalent to the condition that, if possible, an integer half-wave number falls on the total thickness of these outer layers25, wherein d″1to d″kare the thicknesses and vd″1to vd″kare the sound velocities of these outer layers25,26, and the index number “k” is a natural number indicating the number of these outer layers.

For the normally practical case where a piezoelectric plate is used as the oscillation element2for excitation at your thickness mode fundamental frequency (i.e., the oscillation element has a thickness p=vP/(2f)), two latter conditions can also be expressed as

The width b of the oscillation element2preferably corresponds to the case already discussed forFIGS. 3A to 3C.

FIG. 9Bshows a possible embodiment variant according to the invention, in which several identically constructed tubular vessels1with transducer array200are arranged in parallel and surrounded by a common cooling medium400. In this case, a transducer array200has, in addition to the vessel wall section10and the oscillation element2, two further layers25aand25bwhich are acoustically connected (via coupling layers of negligible thickness) to the side of the oscillation element facing away from the vessel wall. In this regard, the material of these two outer layers25aand25bis selected such that the layer25alocated between the outermost layer25band the oscillation element2has a significantly lower acoustic impedance than the oscillation element2and the outermost layer25b. This provides an acoustic isolation effect that minimizes unwanted transmission of acoustic energy into the surrounding medium400. Preferably, the two outer layers25aand25beach have thicknesses corresponding to an odd multiple of a quarter wavelength at the desired operating frequency f.

FIG. 10Ashows a possible embodiment variant according to the invention, in which the transducer array200comprises the vessel wall section10, the oscillation element2, an intermediate support plate24, a negligible (therefore not shown) thin adhesive layer between the oscillation element2and the support plate24, and a temporarily applied coupling layer23between the support plate24and the vessel wall section10. This embodiment allows the vessel1to be acoustically coupled to the support plate24(for example with an acoustically transparent gel23) only temporarily for operation. This may be useful, for example, if the vessel is intended for one-time use only, but the oscillation element is designed for frequent operation.

In this case, the vessel wall section10, the coupling layer23, the support plate24, and the oscillation element2each have thicknesses according to the invention, which satisfy the criteria already discussed with respect toFIG. 9A. The width b of the oscillation element2and the wall thickness c of the vessel1preferably correspond to the case already discussed forFIGS. 3A to 3C.

FIG. 10Bshows a further possible embodiment variant according to the invention as a two-sided variant of the device presented inFIG. 10A, with transducer arrays200arranged in mirror symmetry around a detachable vessel1. This two-sided variant ofFIG. 10Ais particularly useful when the detachable (disposable) vessel is made of a material (e.g., plastic) that significantly dampens acoustics, and therefore a single-sided input of acoustic oscillations only cannot sufficiently ensure symmetry of incoming and reflected waves to produce an effective standing wave field within the dispersion100. All characteristic dimensions (b, p, coand c) preferably correspond to the case already discussed forFIG. 10A.

FIGS. 11A-11Dillustrate some of the numerous ways in which devices according to the invention can be implemented in practical use.

FIG. 11Aillustrates a simple way of implementing a device according to the invention for separating dispersion medium from a dispersion100, wherein the dispersed particles have a higher specific gravity than the medium of the dispersion100, such as is the case with biological cells dispersed in a nutrient medium.

In the illustrated arrangement, the vessel1forms a transducer array200with the oscillation element2. The transducer array200, the opposing acoustically reflective wall of the vessel1, and the dispersion100located in the interior14of the vessel form an acoustic system300. The influence region16of the vessel2located directly below the acoustic system300is immersed directly in the dispersion100without any further pipe or hose routing. A pump62is connected to the outflow region17of the vessel1located above the acoustic system300. When the pump62is operated in the forward direction, dispersion100is drawn from the vessel50into the acoustic system300substantially against the force of gravity800. The signal generator4is electrically connected to the oscillation element2and excites a standing ultrasonic field with frequency f in the acoustic system300. This results in immobilization and compaction of the dispersed particles in the region of the sonic bulges110, and possibly also in the formation of particle aggregates.

At the level of the transducer array200, the vessel1has no significant change in the cross-section of influence with respect to its region of influence16, so that particle compacts110caused by the acoustic field can sediment directly back into the container50under the influence of gravity800without being hindered by any constrictions in the region of influence16of the vessel1, as soon as the regions of the particle compacts110(or, optionally, of the particle aggregates110) have reached a size (or weight) which allows them to overcome the acoustic forces (and, optionally, the hydrodynamic entrainment forces of the dispersion100flowing into the vessel1).

Precipitation of particle compacts110from the acoustic field by gravity800may additionally be assisted by periodic shutdown of the signal generator4by a timer or central process control unit40, during which time the ultrasonic field may additionally be interrupted, the pump62may also be stopped or operated in reverse, so that areas of dispersion101with accumulated higher particle concentration are more effectively flushed back into the container50in and below the acoustic system300.

In contrast toFIG. 11A, the exemplary arrangement illustrated inFIG. 11Bhas a narrowed inflow orifice16which allows, for example, the use of a pipe or hose line between vessel1and dispersion container50to operate the acoustic system300at a greater distance from the dispersion container50. In this regard, the optional periodic shutdown of the signal generator4described forFIG. 11A, synchronized with the reversal of the pump62, becomes a necessary process step to be provided, for example by a process control unit40, to flush the concentrated dispersion101back into the dispersion vessel.

FIG. 11Cillustrates a typical extension of the embodiment variant shown inFIG. 11B, in which the vessel1provides, in addition to the lower and upper inflow/outflow regions16and17, a lateral inflow port18disposed substantially below the acoustic system300and above the lower port16. A pump60transports dispersion100from the vessel50through the lateral inflow port18and into the vessel1, wherein the flow rate of the pump60is selected to be less than the delivery line of the pump62, thereby allowing continuous effective removal of particulate enriched dispersion101back into the dispersion vessel50via the lower outflow region16.

Optionally, precipitation of particle compacts110retained in the acoustic field may be further promoted by periodically shutting down the signal generator4, possibly also upon synchronized reversal of the pump62(as already optionally presented inFIG. 11A). Further optionally, it may be provided that the particle concentrate101is not returned to the original dispersion vessel50(as is, for example, useful for the application of cell retention in a bioreactor), but is collected in a separate vessel51(as is, for example, useful when the recovery of a particle concentrate101, and not, or not only, the recovery of the purified medium102is of interest). By way of example, the application of bioreactor “harvesting” is mentioned, in which, after completion of a cell culture run, as many cells (also referred to as “biomass”) as possible must be separated from the entire contents (i.e., from the entire cell suspension100) of a bioreactor serving as a dispersion vessel50, in order to feed the medium102freed from biomass to the further biotechnological downstream process. Returning the already separated cell concentrate101to the bioreactor, and thus remixing it with the cell suspension100still to be processed, would of course be impractical.

Especially if it is important to achieve a dispersion101of as high as possible, (or precisely defined) particle concentration at the lower outflow orifice16, it may be useful to use a pump61between the lower outflow orifice16and its own collection container51for the concentrate instead of the pump60in the circuit of the lateral inflow18(or alternatively instead of the pump62at the upper outflow orifice17). In this way, the flow rate (and hence the particle concentration) of the concentrate101withdrawn therefrom is not dependent on the difference between the flow rates of the pumps60and62, but is determined by the directly definable flow rate of the pump61(which is more accurate especially for smaller flow rates). If, for example, a certain quantity of biological cells is to be withdrawn from a bioreactor50in a controlled manner (e.g. in order not to allow the concentration of the cell suspension100in the dispersion container50to rise above a certain limit), it is particularly important to lose as little medium as possible, and therefore to achieve as highly concentrated a cell suspension101as possible in the collection container51by means of a precisely defined delivery rate at the orifice of the lower discharge region16, for which purpose the use of the pump61at this orifice is particularly advantageous.

FIG. 11Dillustrates an alternative arrangement with (as already presented inFIG. 11C) lateral inflow18. However, in this arrangement variant, the lateral pump60shown inFIG. 11Cis dispensed with, and instead a valve72is provided in the inflow line between dispersion container50and vessel1. Furthermore, a valve51is also provided in the discharge line between the lower discharge area16and the dispersion vessel50(or alternatively the separate collection vessel51for the concentrate). Furthermore, in addition to the pump62which conveys the filtrate102from the upper orifice region17of the vessel1into the filtrate collection container52, a further pump61is provided which, when activated, flushes liquid or gaseous, flushing medium suitable for the particular application from a flushing source70(possibly also via a separate port not shown) into the upper orifice region17. By suitable control of the pumps61and62, the valves71and72, as well as the signal generator4, the following operative states can thus be achieved via a control unit40:

In the forward mode, the dispersion100flows from the vessel1to the acoustic system300via the lateral port18. The particle regions110compacted by the ultrasonic field precipitate as a particle concentrate101into the lower port region16, wherein a particle concentrate101and possibly also at least partially a particle sediment103may be formed.

In the backwash mode, the formed particulate concentrate101is flushed into the dispersion container50, or alternatively into a dedicated collection container51, together with any sediment103that may also have formed.

The particular advantage of the device presented inFIG. 11Dis that it avoids pumping of the particle-laden dispersion100,101, since pump62conveys only the dispersion stream102cleaned of particles. This is particularly advantageous in biotechnological applications, since pumping cell culture suspensions can cause damage to the suspended living cells.

All devices according toFIGS. 11A-11D, but of course not limited only to the possible forms of implementation of the device according to the invention shown in these figures, may of course also comprise several oscillation elements2and transducer arrays200. These can both be arranged at substantially the same height of the vessel1and thus be part of a common acoustic system300excited by the same signal generator4, and also be arranged at different heights of the vessel1and thus be part of their own acoustic systems, and then possibly also excited by different signal generators at different frequencies.

Depending on the particular application, a variety of other configurations of pumps, valves and possible additional (optionally widening or tapering) inlet and outlet ports around the acoustic system are of course possible in addition to the arrangements shown inFIGS. 11A-11D. This includes, by way of example, identical or similar arrangements as described with the figures of WO 2017/063080 A1, and of course other alternative configurations known or readily derivable from those previously mentioned and from other sources.

Further, the orientation of the exemplary devices ofFIGS. 11A to 11Dwith respect to the direction of gravity800is such as to enable retention or separation of dispersed particles having a higher specific gravity than the medium of dispersion100. It is obviously possible to arrange these and similar devices rotated 180 degrees with respect to gravity to enable retention or separation of dispersed particles having a lower specific gravity than the medium of dispersion100, which is apparent to the average person skilled in the art of separation by sedimentation or flotation and is hereby anticipated.

FIG. 12is an exemplary detailed illustration as a longitudinal section of a device according to the invention, such as may be used in the arrangements described inFIGS. 11C and 11D.

A possible cross-section of the device presented inFIG. 12has already been substantially presented inFIG. 9B. Accordingly, the device consists of six similar acoustic systems300according to the invention and operated in parallel at the same height, each of them comprising at least one vessel1formed as a circular-cylindrical tube and an oscillation element2. According to the invention, each oscillation element2forms with the vessel wall section located in its region (and possibly further layers having an acoustically and electrically insulating effect with respect to a possible cooling medium400) an identical transducer array200, so that (if desired) all 6 parallel acoustic systems300can also be excited by a common signal generator with the same frequency.

According toFIG. 12, the dispersion100flows into the device through the lateral inflow port18and is distributed as uniformly as possible in all directions of the common lower orifice region16of the device, which is designed as a sedimentation funnel, by an influence distributor19designed here as a circular-cylindrical funnel. In the acoustic standing wave fields of the interiors of the respective vessel tubes1of all six acoustic systems300(inFIG. 12two of these six acoustic systems300are visible in cross-section), which are arranged above the inflow distributor19and are circular-cylindrical in design according to the invention, the regions110compacted with particles occur, which can subsequently be removed as dispersion concentrate101at the lowest point of the orifice area16of the device. At the same time, the dispersion medium102cleaned of particles can be removed from the device via a common upper outflow region17.

FIGS. 13A and 13Bshow transverse and longitudinal sections of a further device according to the invention for separating dispersed particles by sedimentation103from a dispersion100present in a sample container31(or by flotation, if the specific gravity of the dispersed particles is less than that of the dispersion medium). In this case, the sample container31is introduced into the interior of the vessel1, which is essentially circular-cylindrical in accordance with the invention, as coaxially as possible with the main axis H of the interior, wherein the sample container31preferably also has a circular-cylindrical shape. Spacers33, in the embodiment shown or in another expedient embodiment, may be provided to ensure as constant as possible an intermediate space32between the sample container31and the inner wall of the vessel1. The intermediate space32itself is filled with an acoustically transparent liquid or gel to provide acoustic coupling between the sample container31and the inner wall of the vessel1. Inlets and outlets39of this or other convenient design may be provided to ensure a level of liquid in the intermediate space32at least as high as the area of dispersion100to be sonicated in the sample container31.

The embodiment shown inFIG. 13Bprovides three acoustic systems300A,300B, and300C arranged one above the other, each of which is typically delimited by two transducer arrays200A-200A,200B-200B, and200C-200C (which are symmetrically opposite one another with respect to the main axis H of the interior of the vessel1), and further comprising the respective intermediate sections of the liquid or gel in the intermediate space32and the wall of the sample container31, as well as the respective section of the dispersion100at the level of the respective acoustic system. According to the invention, the transducer arrays200A,200B, and200C are respectively formed by the oscillation elements2A,2B,2C and by the respective sections of the wall of the vessel1in the region of the respective oscillation elements.

In the illustrated case, the three acoustic systems300A,300B, and300C are each driven by a signal generator4A,4B,4C with a respective alternating electrical signal UA˜, UB˜, UC˜. The wall thickness of the sample container31with respect to the three frequencies of these signals (and vice versa) is preferably provided to correspond to approximately an integer multiple of half a wavelength in the wall of the sample container31for each of these three frequencies, so as to provide uniform acoustic transparency through the wall of the sample container31. This is especially true for sample containers31made of glass or acoustically even harder material, such as metals. On the other hand, in the case where the sample container31is made of plastic (such as for the purpose of single use) or another acoustically absorbent material, the wall of the sample container31should preferably be made thin enough to just ensure sufficient mechanical stability. In this case, the condition according to a wall thickness of the sample container31of half a wavelength is secondary. A suitable wall thickness of a sample container31made of plastic is typically in the range of 1 mm or less.

In the case shown inFIG. 13B, all signal generators4A,4B,4C are activated and deactivated by a central control unit. In this case, the such individual activation/deactivation of ultrasonic fields in the acoustic systems300A,300B, and300C (as one of many alternatives) can be provided, for example, in a periodically recurring sequence A-B-C-A-B-C- . . . so that first a standing wave field is formed in the highest acoustic system300A and areas of particle compaction and/or particle aggregates110are formed there first, which can then be lowered in a controlled manner by subsequent activation of the lower-lying ultrasonic field in acoustic system B (when system A is switched off), and then C (when B is switched off), so that finally, after deactivation of system C, a particularly dense sediment103is formed at the bottom of the sample container31.

The sequential activation/deactivation of the acoustic regions A-B-C described by way of example can be optimized, for example, by also providing periods of simultaneous activation of two or all three regions, or generally simultaneous activation of the regions A, B, C with temporally staggered deactivation; or by any other appropriate combination of activated/deactivated states of the acoustic systems300A,300B,300C that optimizes such accelerated sedimentation of dispersed particles with such minimized resuspension of precipitating particle compacts and/or particle aggregates110.

Alternatively, instead of having three acoustic systems300A,300B,300C, a device according to the invention as shown inFIGS. 13Aand B may have only two, one, or more than three acoustic systems.

Alternatively, a control system40may be omitted and the ultrasonic field in the one or more acoustic systems may be activated for a fixed duration.

Further, the particles dispersed in the dispersion100may have a lower specific gravity than the dispersion medium of the dispersion100, in which case sedimentation103of the particles to the bottom of the sample container31does not occur, but instead the particles are precipitated to the surface by flotation against gravity800.