TECHNICAL FIELD

The present invention concerns an improved device for dielectrophoretic separation.

BACKGROUND ART

As is known, in the medical field, techniques are available for cellular and/or molecular analysis of biological material, which are based on the use of millimetric or micrometric ^■ devices. These techniques include an analysis technique based on so-called dielectrophoresis (DEP) .

Dielectrophoresis is the phenomenon by which a particle, when subject to a non-uniform electric field, undergoes the action of a force. This force is manifested even if the particle is dielectric and not electrically charged; furthermore, said force does not depend on the polarity of the electric field, and therefore is manifested both in the case of an oscillating electric field and in the case of a continuous electric field.

In general, all particles exhibit a dielectrophoretic . type behaviour in the presence of electric fields. However, the dielectrophoretic behaviour is manifested mainly in particles with diameters between Ιμηη and 1mm, since below this range the effect of the Brownian motion is predominant, whereas above this range the force of gravity typically prevails over the dielectrophoretic force. In particular, the intensity of the dielectrophoretic force depends on the dielectric properties of the particles and the medium in which the particles are placed, in addition to the form of the particles, the dimensions of the particles and the frequency of the electric field. Furthermore, if the electric permittivity of the medium (also known as suspension medium) in which the particles are found is greater than the electric permittivity of the particles, the particles are directed towards regions with lower intensity of the electric field; in this case, we talk about negative dielectrophoresis . If on the other hand the electric permittivity of the suspension medium is lower than the electric permittivity of the particles, the particles are directed towards regions with high intensity of the electric field; in this case, we talk about positive dielectrophoresis .

In further detail, given an oscillating electric field, a suspension medium with complex permittivity s _m ^* and a spherical particle with radius r and complex permittivity ε _ρ ^* , the mean of the dielectrophoretic force F _DE p on a period of oscillation is equal to: in which the factor in braces is known as the Clausius- Mossotti function and depends on the frequency of the oscillating electric field.

Consequently it is possible, for example, to optimise the frequency of the electric field according to the characteristics of the particles to be manipulated, so as to act selectively only on these particles. More generally, different particles arranged within the same suspension medium are subject to dielectrophoretic forces having different intensity and directions. This effect can be exploited, for example, to separate different particles from one another, i.e. to obtain the so-called dielectrophoretic separation.

In detail, it has been demonstrated for example, given a suspension medium (for example, a liquid) containing cells of a certain type, that these cells can be separated from the suspension medium. Similarly, it has been demonstrated that these cells can be oriented along a pre-determined direction. These possibilities have been verified also for particles having dimensions in the order of a few nanometres. In further detail, a dielectrophoretic separation system typically has a planar shape and includes a channel, having thickness below one millimetre, and a pair of electrodes, which are driven by an appropriate signal generator. Although different possibilities of use of dielectrophoresis i the medical field have been envisaged and verified at prototype level, some limits of the analysis techniques based on dielectrophoresis have so far prevented widespread diffusion in the clinical field. Essentially, these limits are due to the fact that the dielectrophoretic forces are very weak. In fact, as described for example in Y. Huang, X.B. Wang, F.F. Becker and P.R.C. Gascoyne "Introducing dielectrophoresis as a new force field for field-flow fractionation", Biophysic Journal, 1118 (1997), assuming that the electric field is generated by the use of two coplanar electrodes, interdigitated and set to a potential V _RMS (expressed in root-mean-square value) , the intensity of the dielectrophoretic force acting on a particle is given, to a first approximation, by: e ^~zld

^DEP ^{∞ ∑} M^RMS ^3 in which z is the distance of the particle from the electrodes, measured along a direction perpendicular to the plane in which the electrodes lie, d is the distance between the electrodes and ε _Μ is the dielectric constant of the particle suspension medium.

To increase the intensity of the dielectrophoretic force, the electrodes may be arranged in direct contact with the suspension medium; however, in this case the phenomenon of electrolysis may occur between the suspension medium and the electrodes, or in any case electrical discharges may occur, with consequent heating by Joule effect.

Again in order to increase the intensity of the dielectrophoretic force, the technique of flowing the suspension medium into a channel, which comprises micromachining, is known; this technique is also known as insulating-DEP . More specifically, inside the channel micromachined insulating obstacles are formed, which generate electric non-uniformity, with consequent local increase in the dielectrophoretic force. Unfortunately, the production of said micromachined obstacles is technically difficult and entails a considerable increase in production costs.

For example, the patent application US2004/0026250 describes a device that forms a channel adapted to permit flow of the suspension medium, and inside which one single electrode and a plurality of insulating structures are arranged, which allow electric non-uniformities to be created inside the cannel.

The patent US7744738 describes a dielectrophoretic separation device which includes a single wire-like electrode, which is arranged so as to form a coil, in order to increase the spatial non-uniformities of the electric field.

Although the dielectrophoretic separation devices described in US2004/0026250 and US7744738 are characterised by the ability to generate considerable dielectrophoretic forces, they do not lend themselves to clinical use, since they are substantially disposable devices. In fact, assuming that the suspension medium is a biological liquid to be analysed, after the passage of this biological liquid, each device has to be discarded, or in any case sterilised, with consequent increase in utilisation costs. DISCLOSURE OF INVENTION

The object of the present invention is to provide a dielectrophoretic separation device that solves at least partly the drawbacks of the known art.

According to. the invention, a device for dielectrophoretic separation and a method of dielectrophoretic separation as defined in the attached claims are provided.

BRIEF DESCRIPTION OF THE DRAWINGS

For a better understanding of the invention, embodiments thereof are now described, purely by way of non-limiting example and with reference to the attached drawings, in which: - Figures 1, 3, 4, 5 and 9 show perspective views of embodiments of the present dielectrophoretic separation device;

- Figure 2 shows a transversal section of a portion of the embodiment shown in Figure 1;

- Figures 6-8 show schematically transversal sections of portions of the embodiments shown in Figures 5, 3 and 4 respectively, and corresponding trends of the dielectrophoretic force (in the case ^' of positive dielectrophoretic force) ; and

- Figure 10 shows a section of a portion of the embodiment shown in Figure 9.

BEST MODE FOR CARRYING OUT THE INVENTION

Figure 1 shows a dielectrophoretic separation device 1, which comprises a first and a second support elements 2, 4, which are moveable with respect to each other and are formed of a dielectric material such as polymethylacrylate, for example.

The first support element 2 forms a first recess 6, which has a semi-cylindrical shape and is directed parallel to an axis H6. The first recess 6 is therefore delimited by a first wall S ₆ , which has the shape of a semi-cylinder,

The second support element 4 forms a second recess 8, which is semi-cylindrical and is directed parallel to an axis H8. The second recess 8 is therefore delimited by a second wall S ₈ , which has the shape of a semi-cylinder. The semi-cylinders of the first and second recesses 6, 8 have the same diameter D.

The dielectrophoretic separation device 1 furthermore comprises a first layer 10, made of dielectric material such as Mylar, for example, and delimited by a first lower surface S _a i and by a first upper surface S _b i , shown in Figure 2.

A first and a second lower conductive elements 20, 22 extend inside the first layer 10; these elements are coplanar, form corresponding electrodes and are mutually interdigitated . For example, the first and second lower conductive elements 20, 22 are at a distance of between 150μηι and 1500μιη. Furthermore, the first and second lower conducting elements 20, 22 face the first upper surface S _hl .

In a first operating condition, the first layer 10 is not deformed and has a parallelepipedal shape; furthermore, it is arranged over the first supporting element 2, so as to overlie, at a distance, the first wall S ₆ , i.e. so as to close the first recess 6 at the top. Furthermore, the first and second lower conductive elements 20, 22 form corresponding pluralities of lower transversal elements 21, 23, which have an elongated shape and extend, in the first operating condition, perpendicular to the axis H6. For example, assuming an orthogonal reference system having an axis coinciding with the axis H6 and axes X and Z such that the plane X-H6 is parallel to the first upper surface S _{bl r} the lower transversal elements extend along a direction parallel to the axis X.

The dielectrophoretic separation device 1 furthermore comprises a second layer 24, made of dielectric material such as Mylar, for example, and delimited by a second lower surface S _a2 and by a second upper surface S _b2 . In the first operating condition, the second layer 24 is not deformed and also has a parallelepipedal shape; furthermore, it is arranged below the second supporting element 4, so as to underlie, at a distance, the second wall S ₈ , i.e. so as to close the second recess 8 at the bottom.

Inside the second layer 24, a first and a second upper conductive elements 26, 28 extend, which are coplanar, form corresponding electrodes and are mutually interdigitated . For example, the first and second upper conductive elements 26, 28 are at a distance between 150μπι and 1500 m. Furthermore, the first and second upper conductive elements 26, 28 face the second lower surface S _a2 .

The first and second upper conductive elements 26, 28 form corresponding pluralities of upper transversal elements 27, 29, which have an elongated shape and extend, in the first operating condition, along a direction parallel to the axis X, perpendicular to the axis H8. In. further detail, the first and second layers 10, 24 have, for example, the same thickness w. Furthermore, the first upper conductive element 26 is the same as the first lower conductive element 20, while the second upper conductive element 28 is the same as the second lower conductive element 22. In addition, the first and second layers 10, 24 can be arranged so that the first upper conductive element 26 is aligned with the first lower conductive element 20, along a direction parallel to the axis Z, and the second upper conductive element 28 is aligned with the second lower conductive element 22, along this direction parallel to the axis Z. The dielectrophoretic separation device 1 is adapted to accommodate a tubular element 30, made of dielectric material such as, for example, polytetrafluorineethylene (PTFE) or silicone, or a copolymer obtained from tetrafluorineethylene and 4, 5-difluorine-2 , 2-bis (trifluorinemethyl) -1, 3-dioxol. In a per se known manner, the tubular element 30 defines a fluidic channel having cylindrical section (for example) , in which a suspension medium in the fluid state can flow.

More, specifically, the tubular element 30 may be of non- micromachined type, i.e. it may define an internal cavity, which is adapted to accommodate the suspension medium and does not present any non-uniformity. Therefore, the tubular element 30 is easy and inexpensive to produce.

In practice, the tubular element 30 may be made of a tube of known type such as, for example, a tube of the type used in dialysis or drip feed systems. Even more specifically, the tubular element 30 may be of the disposable type, i.e. intended to accommodate the passage of the biological liquid of one single patient.

In the embodiment shown in Figure 1, the transversal section of the tubular element 30 has the shape of a circular crown; furthermore, the tubular element 30 has an external diameter which is at the most equal to the difference between the diameter D of the first and second recess 6, 8 and double the thickness w. In particular, the tubular element 30 can have an internal diameter,, for example, between 0.2 mm and 4 mm, and an external diameter, for example, between 0.5 mm and 6 mm.

In use, the tubular element 30 is inserted between the first and second supporting elements 2, 4, which are initially spaced at a distance greater than the external diameter of the tubular element 30. For example, the tubular element 30 can be rested on the first layer 10, aligned with respect to the first recess 6 below.

Subsequently, the first and second supporting elements 2, 4 are moved close to each other, for example by moving the second supporting element 4 parallel to the axis Z towards the first supporting element 2. This movement is performed so that, as previously mentioned, the first and second upper conductive elements 26, 28 are respectively aligned with the first and second lower conductive elements 20, 22.

In this way, the tubular element 30 comes into contact with both the first and second layers 10, 24, causing the elastic deformation of the latter.

In particular, during a second operating condition, the tubular element 30 contacts the first upper surface S _bl and the second lower surface S _a2 . Furthermore, the first layer 10 deforms in such a way that the first lower surface S _ai adheres to the first wall S ₅ , while the second layer 24 deforms in such a way that the second upper surface S _h2 adheres to the second wall S ₈ . The tubular element 30 is therefore housed inside the cavity formed by the first and second recesses 6, 8, which has a cylindrical shape and is filled by the tubular element 30. In particular, the cavity formed by the first and second recesses 6, 8 has the shape of a cylinder with axis HT parallel to the axes H6 and H8. Furthermore, the tubular element 30 extends along a respective longitudinal axis, which is assumed to coincide, during the second operating condition, with the axis HT, without any loss of generality.

In practice, during the second operating condition,, the first and the layers 10, 24 deform so as to envelop, respectively, a lower portion and an upper portion of the tubular element 30. In this way, in the second operating condition, each of the first and second lower conductive elements 20, 22 and the first and second upper conductive elements 26, 28 partially envelops the tubular element 30, with which it is in direct contact .

The dielectrophoretic separation device 1 furthermore comprises a voltage generator 40 of alternating type, which is adapted to generate voltages between 50 and 3000 V _RMS (where V _RMS indicates the root-mean-square voltage) , preferably between 1000 V _RMS and 2000 V _RMS , and with frequencies between 5 kHz and 10 MHz.

In detail, a first terminal of the voltage generator 40 is connected to the first lower conductive element 20 and to the first upper conductive element 26; furthermore this first terminal of the voltage generator 40 is connected to ground.

A second terminal of the voltage generator 40 is connected to the second lower electrode 22 and to the second upper electrode 28.

In use, i.e. when the dielectrophoretic separation device 1 operates in the above-mentioned second operating condition and the voltage generator 40 delivers a voltage between its tw.o terminals, a time-periodic electric field is established between the first and second supporting elements 2, 4. Assuming that a fluid containing particles flows in the tubular element 30, this electric field causes the onset of dielectrophoretic forces, which allow separation of the particles .

In particular, due to the arrangement taken on, in the second operating condition, by the first and second upper conductive elements 20, 26 and by the first and second lower conductive elements 22, 28, the electric field present inside the tubular element 30 is such that, in each section of the tubular element 30 orthogonal to the axis HT, the dielectrophoretic force has a radial trend, with respect to the axis of the tubular element 30, which is assumed to coincide, during the second operating condition, with the axis HT, without any loss of generality.

Therefore, particles subject to a positive dielectrophoretic force are attracted towards the walls of the tubular element 30, where the flow of the suspension medium is slowed, down with respect to the central region of the tubular element 30. On the contrary, particles subject to a negative dielectrophoretic force are directed towards the central region of the tubular element 30, i.e. towards the portion of the cavity defined by the same tubular element which is farthest from the inner walls of the tubular element; in this central region, the suspension medium flows at maximum speed. Therefore, separation of the particles is particularly facilitated and can be performed more selectively, unlike what happens in the devices of known type in which, unless particularly complex and costly solutions are employed, the particles are directed to regions at low speed of the suspension medium, independently of the sign of the dielectrophoretic force.

According to a different embodiment, shown in Figure 3, the dielectrophoretic separation device 1 includes, in addition to the first and second supporting elements 2, 4, the first lower conductive element (here designated by 50), which is wire-like and is arranged parallel to the axis H6. More specifically, the first lower conductive element 50 is arranged in contact with the first wall S ₆ , on the bottom of the first recess 6.

The first layer 10 is absent, while the second layer (here designated by 54) is made of conducting material. Furthermore, the first terminal of the voltage generator 40 is connected to the second layer 54 and is connected to ground, while the second terminal is connected to the first lower conductive element 50. For example, the second layer 54 may be made of an aluminium sheet. In use, the embodiment shown in Figure 3 behaves, in mechanical terms, analogously to the embodiment shown in Figure 1. In particular, the second layer 54 deforms and partially envelops the tubular element 30, with which it is in direct contact.

The embodiment shown .in Figure 3 is characterised by great construction simplicity. Furthermore, in use, the dielectrophoretic separation device 1 generates a non-uniform electric field which is directed, in a first approximation, along a direction perpendicular to the axis of the tubular element 30. Therefore, the dielectrophoretic force is directed perpendicular to the axis of the tubular element 30 and, in a first approximation, parallel to the direction that connects the axis of the tubular element 30 to the first lower conductive element 50.

Embodiments of the type shown in Figure 4 are also possible. In particular, Figure 4 shows an embodiment comprising, in addition to the first and second supporting elements 2, 4, the first lower conductive element 50 and the second lower conductive element (here designated by 52), which are both wire-like and are arranged substantially coplanar. In particular, the first and second lower conductive elements 50, 52 are arranged parallel to the axis H6 and in positions such that the respective axes lie on a plane parallel, for example, to the first upper surface S _b i .

Furthermore, this embodiment comprises the first upper conductive element (designated by 56) which is wire-like, arranged parallel to the axis H8 and in contact with the upper end of the second recess 8. Therefore, during the second operating condition, the first upper conductive element 56 and the first and second lower conductive elements 50, 52 are arranged along the lateral edges of a prism having as its base an isosceles triangle, and axis parallel to the axis HT. Preferably, the axis of this prism coincides with the axis HT, and therefore with the longitudinal axis ^' of the tubular element 30.

The first terminal of the voltage generator 40 is connected to the first upper conductive element 56, . and is furthermore connected to ground. The second terminal of the voltage generator 40 is connected to the first and second lower conductive elements 50, 52. In this way, in a first approximation the dielectrophoretic force is directed perpendicular to the axis of the tubular element 30.

It is furthermore possible, although not shown, to interpose a 180° phase shifter between the second terminal of the voltage generator 40 and the first and second lower conductive elements 50, 52 in order to optimise the electrochemical behaviour of the suspension medium.

Figure 5 shows an embodiment in which, compared to the embodiment shown in Figure 4, there is a third lower conductive element 60, which is wire-like and extends in contact with the bottom of the first recess 6, parallel to the axis H6. Furthermore, the third lower conductive element 60 is connected to the first terminal of the voltage generator 40, therefore it is connected to ground.

As shown in greater detail in Figure 6, during the second operating condition, the first, second and third lower conducting elements 50, 52, 60 and the first upper conducting element 56 are arranged along the lateral edges of a parallelepiped with square base, having axis parallel to the axis HT; preferably, this axis coincides with the axis HT, and therefore with the longitudinal axis of the tubular element 30, as shown in Figure 6. Furthermore, the first and second lower conductive elements 50, 52 are diametrically opposite with respect to the axis HT; similarly, also the third lower conductive element 60 and the first upper conductive element 56 are diametrically opposite with respect to the axis HT, and therefore with respect to the longitudinal axis of the tubular element 30. As shown in Figure 6, thanks to the shape and arrangement of the electrodes, the dielectrophoretic force has a radial profile, i.e. it is directed along radial directions. Therefore, also the embodiment .. shown in Figure 6 allows, attraction of the particles subject to a positive dielectrophoretic force towards the walls of the tubular element 30, and attraction of the particles subject to negative dielectrophoretic force towards the central region of the tubular element 30. Furthermore, this embodiment is characterised by considerable construction simplicity, since the electrodes are wire-like.

By way of example, Figures 7 and 8 show the transversal trends of the dielectrophoretic force generated in the embodiments shown in Figures 3 and 4 respectively, as described previously.

Figure 9 shows an embodiment which comprises, in addition to the first and second lower conductive elements 20, 22, the third lower conductive element (indicated by 90) and a fourth lower conductive element, designated by 97.

The first, second, third and fourth lower conductive elements 20, 22, 90, 97 are mutually interdigitated . In particular, each of the first, second, third and fourth lower conductive elements 20, 22, 90, 97 forms a corresponding plurality of lower transversal elements, the lower transversal elements of each of these corresponding pluralities being designated by 21, 23, 91 and 98 respectively. Each lower transversal element has an elongated shape and defines a sort of prong of the corresponding lower conductive element; furthermore, the lower transversal elements extend parallel to the first upper surface S _b i , along the same direction perpendicular to the axis H6. In detail, as shown in Figure 10, the first and second lower conductive elements 20, 22 are arranged coplanar and extend both between a first depth pi (null, in the example of Figure 10) and a second depth p2 of the first layer 10. The third and fourth lower conductive elements 90, 97 are arranged coplanar and extend both between a third depth p3 and a fourth depth p4 of the first layer 10. Assuming that the depths refer to the first upper surface S i , the relation p4>p3>p2>pl holds. In further detail, the first, second, third and fourth lower conductive elements 20, 22, 90, 97 are interdigitated so that a hypothetical electromagnetic wave that moves parallel to the axis H6 meets a first lower electromagnetic unit Ul formed, in order, of a lower transversal element 21 of the first lower conductive element 20, a lower transversal element 23 of the second lower conductive element 22, a lower transversal element 91 of the third lower conductive element 90, and a lower transversal element 98 of the fourth lower conductive element 97. Subsequently, the electromagnetic wave meets a second lower electromagnetic unit U2, equal to the first lower electromagnetic unit, and so on. The lower electromagnetic units therefore form a portion of a periodic structure.

According to this embodiment, the dielectrophoretic separation device 1 furthermore comprises a first, a second and a third phase shifters 100, 102, 104, each of which has a respective first terminal connected to the second terminal of the voltage generator 40, the first terminal of which is connected to ground. The first, second and third phase shifters 100, 102, 104 are configured to supply, on the respective second terminals, voltages phase-shifted by 90°, 180°, 270° respectively, with respect to the voltages present on the corresponding first terminals. Furthermore, the second terminals of the first, second and third phase shifters 100, 102, 104 are connected to the second, third and fourth lower conductive elements 22, 90, 97 respectively. The first lower conductive element 20 is connected to the second terminal of the voltage generator 40, without the interposition of any phase shifter. According to the embodiment shown in Figure 10, the dielectrophoretic separation device 1 furthermore comprises, in addition to the first and second upper electrodes 26, 28, also a third and a fourth upper electrodes 110, 112. In particular, each of the first, second, third and fourth upper conductive elements 26, 28, 110, 112 forms a corresponding plurality of upper transversal elements, the upper transversal elements of each of these corresponding pluralities being designated by 27, 29, 111 and 113 respectively. Each upper transversal element has an elongated shape and defines a sort of prong of the corresponding upper conductive element; furthermore, the upper transversal elements extend parallel to the second lower surface S _a2 , along the same direction perpendicular to the axis H8.

In further detail, the first, second, third and fourth upper conductive elements 26, 28, 110, 112 are interdigitated so that a hypothetical electromagnetic wave which moves parallel to the axis H8 meets a first upper electromagnetic unit Tl formed, in order, of an upper transversal element 27 of the first upper conductive element 26, an upper transversal element 29 of the second upper conductive element 28, an upper transversal element 111 of the third upper conductive element 110, and an upper transversal element 113 of the fourth upper conductive element 112. Subsequently, the electromagnetic wave meets a second upper electromagnetic unit T2, equal to the first upper electromagnetic unit, and so on.

In use, each upper electromagnetic unit is aligned, parallel to the axis Z, with a corresponding lower electromagnetic unit. Therefore, the first, second, third and fourth upper conductive elements 26, 28, 110, 112 are aligned with the first, second, third and fourth lower conductive ^" elements 20, 22, 90, 97 respectively. Furthermore, the first, second, third and fourth upper conductive elements. 26, 28, 110, 112 are supplied so that the respective voltages have the same phases, respectively, as the voltages present on the first, second, third and fourth lower conductive elements 20, 22, 90, 97.

The embodiment shown in Figure 10 allows the generation of a longitudinal component of the dielectrophoretic force, directed parallel to the longitudinal axis of the tubular element 30. This longitudinal component can be used as a further degree of freedom, in order to better separate the particles. Furthermore, this longitudinal component can be used to flow the suspension medium inside the tubular element 30, this task being generally performed by an external pump (not shown) ; in this case, it is therefore possible not to use any external pump. The advantages of the present dielectrophoretic separation device emerge clearly from the preceding description.

In particular, the present dielectrophoretic separation device lends itself to a clinical use, since it is compatible with tubular elements commonly found in this ambit. The present dielectrophoretic separation device can therefore be used with several tubular elements of known type, which may be of the disposable type. Furthermore, in some embodiments, the electric separation between suspension medium and electrodes is provided exclusively by the same dielectric walls of the tubular element, with consequent increase in the electric field present within the tubular element.

The present dielectrophoretic separation device is therefore compatible with the current instruments for haemodialysis or plasma/platelet separation. Furthermore, the present dielectrophoretic separation device lends itself, for example, to the separation/trapping/manipulation . of tumour cells present in biological liquids, for diagnostic or therapeutic purposes.

The present dielectrophoretic separation device furthermore allows the use of high electric potentials, with consequent increase in the dielectrophoretic force, and elimination of concentration effects in the vicinity of the electrodes. In fact, the particles are generally concentrated in regions with a high electric field. However, in the present device, the particles do not contact the electrodes, and therefore do not access regions with high electric field; in turn this characteristic is due to the fact that the present device guarantees high uniformity of the dielectrophoretic force, which allows the use of sufficiently uniform electric fields, and therefore with lower maximum amplitude values.

In addition, some embodiments allow the generation of a dielectrophoretic force having a high uniformity in a transversal section of the tubular element, with consequent increase in separation effectiveness.

Lastly, it is evident that modifications and variations can be made to the present dielectrophoretic separation device, without departing from the scope of the present invention, as defined by the attached claims.

For example, the conductive elements described as connected to the first or to the second supporting element 2, 4 may be connected to the other supporting element. Moreover, also the number of conductive elements may be higher than the one shown and described.

Furthermore, with reference to the embodiment shown in Figure 1, the first and second lower conductive elements 20, 22, while still extending into the first layer 10, may not directly face onto the first upper surface S _b i . In other words, the first and second lower conductive elements 20, 22 may be overlain by corresponding portions of the first layer 10, which perform a protective function and may have a thickness of 200μπι, for example. Similarly, the first and second upper conductive elements 26, 28, while still extending into the second layer 24, may not directly face onto the second lower surface S _a2 . The first and the second upper conductive element 26, 28 may therefore overlie corresponding portions of the second layer 24, which perform a protective function and may have a thickness of 200ym, for example.

With reference again to the embodiment shown in Figure 1, a third layer, which is arranged above and in direct contact with the first upper surface S _b i , and a fourth layer, which is arranged above and in direct contact with the second lower surface S _a2 , may furthermore be present. Hybrid embodiments are also possible, which comprise portions of different embodiments previously described.

Embodiments are also possible in which the first and second recesses, and therefore also the cavity formed by them and the tubular element, have curved forms. In this case, in place of the axes H6, H8 and HT, it is possible to refer to a first and a second recess symmetry line (and therefore, to a cavity symmetry line) and to a symmetry line of the tubular element, the latter being formed for example of a cylindrical tube bent so as to form one or more curves. In practice, taking the tubular element as an example, the corresponding symmetry line is such that, when it is sectioned at a point with a plane perpendicular to this symmetry line, the section of tubular element thus formed does not vary when the point at which the section is made varies; analogous considerations apply to the symmetry lines of the recesses and cavity. Furthermore, taking the tubular element as an example again, it has an elongated shape along the respective symmetry line, in the sense that the dimension along this symmetry line is greater than the dimensions of the tubular element in a plane perpendicular to the symmetry line.

According to these embodiments, the arrangement of the electrodes is consequently modified with respect to the corresponding embodiments shown previously. For example, referring, purely by way of example, to the embodiment shown in Figure 3, in the case in which the tubular element is curved, and therefore the symmetry line of the first recess is curved, the first lower conductive element is parallel to the symmetry line of the first recess; in other words, since they are three-dimensional curves, the first lower conductive element and the symmetry line of the first recess are two equidistant curves. Analogous considerations can be made in relation to all the electrodes cited previously, the arrangements of which have been described with respect to axes .

With reference to the embodiments shown in Figures 1 and 9, similar embodiments are possible, but in which the first and second lower conductive elements 20, 22 extend into the first supporting element 2, instead of into the first layer 10, and in which the first and second upper conductive elements 26, 28 extend into the second supporting element 4, instead of into the second layer 24. In these embodiments, the first and second layers 10, 24 are therefore absent. Lastly, it is possible to use a phase shifter also in the embodiments shown in Figures 3 and 5.