The present invention relates to a device for controlling liquid motion, comprising:
A device of this type is described, for example, in the publication WO 2009/013705 filed by the present applicant, and is particularly intended for the construction of what are known as “Lab-on-a-Chip” (hereinafter referred to as “LOC”) systems, in other words miniaturized diagnostic and analysis systems which are expected to form the next generation of apparatus for use in medical and other fields (for example, environmental monitoring or food analysis).
These systems are based on liquid handling; they must be capable of precisely supplying, moving and locating very small volumes of liquid (including those measured in picoliters). At present, location is carried out by active methods based mainly on the real time visualization of the liquid flow or on the measurement of specific electrical properties of the device. These methods are usually costly and difficult to integrate, and are based on active elements or electronic instruments.
Two classes of microfluidic devices can be distinguished, namely one using a continuous flow in microchannels, and one using droplets of small dimensions (digital microfluidics). In the latter class, three main methods of controllable movement have been developed, based on electrowetting (EW), thermocapillarity, and surface acoustic waves (SAW). EW and thermocapillary systems require the whole fluidic area (FA) to be provided with metallic electrodes or microheaters, which must be activated to move the droplets. Unlike these, the SAW technology is based on standing or travelling surface acoustic waves excited by microdevices integrated into the chip but positioned outside the FA. Other advantages of SAW fluidics include low-temperature and low-voltage operation, and an absence of constraints on the polarity of the liquid.
In a widely used SAW method, the surface acoustic waves are generated along the surface of a support (a substrate of piezoelectric material or a substrate provided with a film of piezoelectric material) by means of interdigitated metallic transducers (IDT). Interdigitated transducers are periodic structures composed of a succession of metallic strips (electrodes) interleaved in comb formation, connected alternately to collecting tracks for the distribution of the electrical signal. The geometry of the transducer and the properties of the support determine the resonance frequency for the excitation of the SAW. In the conventional configuration for the propagation of SAWs on a lithium niobate support, the resonance frequencies of a transducer are typically of the order of tens or hundreds of MHz. Different operating frequencies, or different periodicities of the transducer, can be used, depending on the typical dimensions of the micro- or nanofluidic network to which the transducer is coupled.
The acoustic wave is generated on the free surface of the piezoelectric support with elastic properties by applying an electrical signal to the metallic electrodes of the transducer. When an electrical signal of suitable frequency is applied between the transducer electrodes, the piezoelectric properties of the support cause the electrical signal to be converted into a deformation of the lattice of the support material, resulting in a periodic deformation of the free surface of the support under the transducer which can excite surface acoustic waves which propagate at the interface between the support and the air, or between the support and the layer above it.
SAWs are also used for transporting and moving small quantities (drops) of liquids deposited on free surfaces, in the direction of propagation of the acoustic wave.
In another method based on transduction for converting an electrical signal into acoustic vibrations, SAWs are generated on a non-piezoelectric material coupled to a piezoelectric material. In this case, a piezoelectric substrate is bonded to the side of a non-piezoelectric layer, and bulk acoustic waves (BAWs) are generated on the piezoelectric substrate, these waves being coupled to surface acoustic waves in the non-piezoelectric means [1].
Methods have also been developed for the optical generation of surface acoustic waves on non-piezoelectric substrates. In historical terms, the first method of photogeneration of surface acoustic waves was that of focusing an ultra-short laser pulse on the surface of the substrate. The energy of the pulse is absorbed by the substrate which is thus heated in the illuminated area, the heating extending to the depth of penetration of the laser light into the substrate. This heating causes a deformation of the crystal lattice of the substrate by thermal expansion, generating a packet of surface acoustic waves and longitudinal acoustic waves [2, 3]. At particularly high power levels, these conditions, known as thermoelastic conditions, give way to ablation conditions, in which ions and electrons from the surface of the substrate are brought to a plasma state and extracted from the surface, and the resulting moment pulse generates the acoustic waves in the substrate by compression [2, 3]. The method in the thermoelastic regime has subsequently been refined, with the use of transient gratings [4] and surface phononic crystals [5]. In the case of generation by transient grating, the laser pulse strikes the substrate in the form of a pattern with periodic strips, and the periodic heating of the substrate induces a periodic deformation of the substrate, thereby leading to the propagation of surface acoustic waves with wavelengths equal to the period of the illumination pattern [4, 5]. These patterns can be generated either by using diffraction gratings formed by periodic modulation of the thickness of a transparent substrate [4] or by creating interference between two laser beams [5]. In the method currently used to generate surface acoustic waves at higher frequencies, the substrate is patterned with a lattice of metallic micro/nanostructures (surface phononic crystal) [6]; when the laser pulse strikes the surface of the specimen, the energy of the pulse is absorbed by the nanostructures, which are heated and expand, thereby generating a periodic deformation of the substrate and also generating surface acoustic waves at that frequency. In order to excite specific surface modes, it is possible to use the transient grating method on a substrate nanopatterned with a surface phononic crystal [7].
Regardless of the method used for generating the SAWs, the development of programmable automated digital lab-on-a-chip systems requires the movement and location of the microdrops without the direct control of the operator. The inventors are aware of three different methods which have been described up to the present time for moving microdrops and detecting their positions on a SAW-based microfluidics platform.
The first method uses a plurality of SAW delay lines defining the fluidic area [8]. A parallel set of delay lines is used to move the drop, while a second set, perpendicular to the first, is used to locate the drop. The position of the drop is determined by measuring the transfer matrices of the delay lines: the presence of the drop leads to a variation of the transmission parameter (S12 or S21).
The second method uses two SAW delay lines based on wide-band “slanted” interdigitated transducers (IDTs) [9]. Here again, the operation is based on the measurement of the modification of the diffusion matrices of the delay lines caused by the presence of the liquid drop.
The third location method is based on SAW echoes [10, 11]: the movement and measurement of the position of the drop is carried out with the same IDT. In these chips, after the high-power radio-frequency pulse which moves the drop, a second low-power radio-frequency location pulse is applied. The measurement of the delay of the echo signal determines the position of the drop.
One object of the invention is to provide a microfluidic device based on surface acoustic waves which enables liquids to be located precisely without the use of any dedicated active microdevice or electronic instrument, and which therefore allows more integratable chips to be constructed.
In accordance with this object, the invention proposes a device of the type defined initially, in which said control means further comprise acoustic resonator means placed on the path of said surface acoustic wave, comprising a resonance cavity placed between a pair of acoustic reflectors arranged consecutively with respect to one another in the propagation direction of the surface acoustic wave, said acoustic resonator means being adapted to normally allow transmission of the surface acoustic wave having a frequency equal to a resonance frequency of said acoustic resonator means, and to reflect said surface acoustic wave when said quantity of liquid is present within said acoustic resonator means.
The method also proposes a method for controlling liquid motion, comprising the following steps:
wherein acoustic resonator means are placed on the path of said surface acoustic wave, said acoustic resonator means comprising a resonance cavity placed between a pair of acoustic reflectors which are arranged consecutively with respect to one another in the propagation direction of the surface acoustic wave, and which are adapted to normally allow transmission of the surface acoustic wave having a frequency equal to a resonance frequency of said acoustic resonator means, and to reflect said surface acoustic wave when said quantity of liquid is present within said acoustic resonator means.
By contrast with the solution proposed in references [10] and [11], the present invention does not require the use of pulsed radio-frequency signals or the switching of the transducer (IDT) from a pumping configuration to a detection configuration, which implies the stopping of the liquid motion.
By contrast with the method described in [9], the present invention can also operate at a single frequency (thus simplifying the circuitry) and can also operate with uniform IDTs, which are more efficient than “slanted” IDTs in the excitation of SAWs.
Furthermore, the invention does not require the development of a precise model for the spatial profile of the acoustic amplitude, which is necessary in [9] for determining the position of the microdrop. The present invention differs from the device described in reference [8] in that it does not require the fabrication of a plurality of transducers (IDTs), and the circuitry and construction of the device is thus simplified. The precision of location is also improved, because the device of reference [8] cannot detect drops which are positioned in regions between two different delay lines.
Finally, the device according to the invention is compatible with the use of standard polydimethylsiloxane (PDMS) microchannels.
Further characteristics and advantages of the device according to the invention will be made clear by the following detailed description, which refers to the attached drawings, provided purely by way of non-limiting example, in which:
With reference to the drawings, a device for controlling liquid motion essentially comprises:
Although the present description refers exclusively to interdigitated transducers which, because of their simple construction, are highly suitable for the industrial production of fluidic chips, the invention is not limited to the specific procedures by which the surface acoustic waves are generated and detected. As an alternative to IDTs, it would be possible to use surface acoustic wave generators and detectors based on different methods, such as for example those described in the initial part of the present description.
Consequently, depending on the method used for generating and detecting surface acoustic waves, it would be possible to use a support comprising a non-piezoelectric substrate with a piezoelectric film, a support comprising a piezoelectric substrate coupled to a non-piezoelectric substrate, or a support containing no piezoelectric material, in place of the substrate (support) of piezoelectric material.
The aforementioned quantity of liquid may consist of one or more microdrops of liquid deposited on the surface of the support 10, or quantities of liquid travelling in micro- or nanochannels. In this second case, the device according to the invention further comprises a structured volume of material 20 (shown in
According to the invention, the means for controlling the liquid motion further comprise acoustic resonator means placed on the path of said surface acoustic wave, said acoustic resonator means being adapted to normally allow transmission of the surface acoustic wave having a frequency equal to a resonance frequency of said acoustic resonator means, and to reflect said surface acoustic wave when said quantity of liquid is present within said acoustic resonator means.
By way of example, the aforesaid acoustic resonator means comprise a resonance cavity 30 positioned between a pair of acoustic reflectors or mirrors 31a, 31b (shown, for example, in
The embodiments of
As an alternative to the pair of Bragg mirrors separated by an area without patterning, other structures can be used to form the acoustic resonator means. Considerable interest has been shown recently in the use of phononic crystals [12, 13, 14] which consist of periodic systems of two or more materials with different elastic properties. It has been demonstrated that these structures, when suitably engineered, have a frequency region (band gap) in which no surface automodes of the system are permissible, and which therefore form spectral regions in which the system can act as a reflector, even in regions in which no Bragg reflections occur [15]. Suitable SAW transmission windows can be produced in these structures by using defects, not only by means of gap, in the periodic structure of the cavities and waveguides [14]. Phononic cavities can also be formed by constructed waveguides with closed geometries, as in the case of ring resonators [16, 17].
Except as regards the specific structure of the resonator means, the operating principle of the present invention is essentially the same.
In resonance conditions, SAWs are completely transmitted through the cavity. If an absorbent material is present in the cavity, it acts as a virtually perfectly reflecting mirror, thus back reflecting the SAWs. It is important to note at this point that the reflection takes place with minimal energy losses in the SAWs; for example, in the case of cavities based on two semi-reflecting mirrors, if a perfect absorber is present in the resonance cavity the losses are proportional to the transmissivity of the entrance mirror, which can theoretically be made arbitrarily low.
Since liquids are highly efficient absorbers of SAWs, this arrangement enables the SAWs to be routed to different areas of a chip, and therefore to different specimens of liquid which may be present in the chip, depending on whether or not liquid is present in the resonance cavities.
In order to demonstrate the operating principle of the present invention, numerical simulations and experimental tests were conducted.
A prototype device was modelled by means of a two-dimensional finite element method capable of simulating SAWs propagated along the direction X of a plate of LiNbO3 with a size of 128Y-X, which is the preferred material at present for SAW-based microfluidics. On the path of the SAW, a Fabry-Perot acoustic cavity was constructed with a pair of distributed mirrors, each consisting of 15 pairs of vacant/solid strips (more precisely, there were 15 pairs of strips spaced apart by a distance equal to the wavelength λSAW of the surface acoustic wave, in other words a structure having 30 strips with a period of λSAW/2). The excitation of the SAWs was modelled by applying an alternating voltage with the correct spatial periodicity to the surface of the plate. The geometrical details of the simulation are shown in
As can be seen, with the chosen material and geometry the cavity supports three surface acoustic modes, and, at the resonance frequency (f1=91.14 MHz, f2=95.52 MHz, f3=100.26 MHz), the electromechanical energy density is mainly confined to the spatial region located between the mirrors and within a wavelength from the surface of the plate.
Additionally, for the central peak of the cavity (f2), the transmittance of the cavity, calculated as the ratio between the power leaving the second mirror (on the right in
The situation in which an absorbent material is present in the cavity was modelled by including a hemisphere with the electromechanical properties of water between the mirrors.
Different prototypes were then constructed on a LiNbO3 support of the 128Y-X size. Aluminium interdigitated transducers (with a period of 40 μm, a duty cycle of 50%, and 10 periods) were deposited on the support to form SAW delay lines. An acoustic cavity was fabricated within each delay line in the same stage of processing. The cavities consist of a pair of mirrors, each formed by a series of strips of Al (period 20 μm, duty cycle 50%, 25 periods). The geometrical details of one of the prototype devices, comprising an interdigitated transducer T1 for generating the SAWs and an interdigitated transducer T2 for detecting the power transmitted through the delay line and the cavity, are shown in
The characteristic curve of transmittance of the delay line of
The prototype device can position a drop of water within the cavity space. The operating procedure is as follows:
It was observed that:
When the experiment was repeated at frequencies outside the operating range of the mirror, the drop was pushed beyond the cavity, because the cavity was ineffective outside the resonance range.
The present invention therefore proposes a device which can be fabricated on microfluidic chips, for guiding surface acoustic waves passively and with minimal losses, depending on the position of the liquids on the chip. The device which has been described can therefore function in a similar way to a logic gate of an electronic microchip, making it possible to guide a plurality of fluids, such as drops deposited on a surface of the device or liquids present in microfluidic channels, into specific positions, without the need for external control or feedback. The same complex microfluidics task can thus be carried out in a repetitive way without the need for external supervision.
In this context, some possible examples of basic logic units and applications which can be produced by means of the present invention will now be described for illustrative purposes with reference to
The example in
The example in
The example in
The example in
The drops are positioned automatically after the user has deposited the two drops in the deposition area 40 and activated the radio-frequency source. A “process terminated” signal is generated by the transducer T3 when both drops have reached the chemical reaction region. If the drop D1 is missing, an error signal is generated by the transducer T2.
The operating sequence of the system shown in
The positioning of the drops in the aforesaid regions does not have to be accurate;
The example in
The operating sequence of the system is as follows:
In complex systems, the insertion and coupling losses can be compensated for by radio-frequency amplifiers positioned, for example, at the outputs of the directional couplers.
Although the examples described above relate to applications in which the fluidic device operates at a single frequency, it is possible to design devices according to the invention which also operate at a plurality of frequencies (with resonators having different resonance frequencies); using a plurality of operating frequencies, it is possible to increase the complexity of the fluidic task to be carried out, for example, drops can be moved from one resonator to another on the same delay line, or a drop can be halted and then put into motion again.
Number | Date | Country | Kind |
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TO2011A000900 | Oct 2011 | IT | national |
Filing Document | Filing Date | Country | Kind | 371c Date |
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PCT/IB2012/055472 | 10/10/2012 | WO | 00 | 4/8/2014 |