Sensor-equipped device for real-time fluid analysis using elastic waves

Abstract

Sensor-equipped device (100) for detecting an analyte in a fluid, comprising: a piezoelectric substrate (105) having an outer surface (105'); at least one R-SAW emitting interdigital transducer (111) positioned on the outer surface (105') and configured to emit Rayleigh-type surface acoustic waves, also known as R-SAW, in response to an electrical input signal, wherein the R-SAW is emitted along a first emission direction x; and at least one SH-SAW emitting interdigital transducer (112) positioned on the outer surface (105') and configured to emit shear horizontal-type surface acoustic waves, also known as SH-SAW, in response to an electrical input signal, wherein the SH-SAW is emitted along a second emission direction y. In particular, the piezoelectric substrate (105) is fabricated from a material selected from 64°Y-cut lithium niobate and 163°Y-cut lithium niobate so that the piezoelectric substrate (105) supports shear horizontal type surface acoustic waves as its dominant mode, and the dominant mode is defined as a surface acoustic wave exhibiting greater electromechanical coupling on the piezoelectric substrate (105). Furthermore, the first emission direction x and the second emission direction y have a relative angle a such that 80° < α < 100°.

Description

Technical Field

[0001] The present invention relates to fluid analysis and detection of specific analytes of interest.

[0002] Specifically, the present invention relates to the detection of such analytes by surface acoustic waves generated by micro or nanostructured sensors.

Background Art

[0003] In recent years, in the fields of scientific and industrial research, the development of biosensors that can perform accurate and rapid analysis without the aid of typical complex machinery in specialized laboratories has increased significantly. The aim is to integrate and in some cases replace classical diagnostic techniques and extend detection directly "on-field".

[0004] In this scenario, "lab-on-chip" (LoC) sensors are considered a true game-changer. LoC is a micro or nanostructured device capable of integrating multiple functions typical of specialized laboratories into a single chip. These operations include analyte detection, reagent mixing, particle heating and separation.

[0005] In the biomedical field, an important feature of LoC consists of highly specific recognition of biomarkers and integration with microfluidics. These devices can actually manipulate small amounts of biological samples (on the order of microliters in size) and provide a specific and sensitive response after recognition of the analyte of interest.

[0006] LoC are economical and portable sensors that are easy to use even by untrained personnel. Therefore, they present great potential to impact the future of public health. Among the most important examples of the fields of use of LoC devices are health monitoring, infectious disease screening, early diagnosis of chronic diseases, and environmental and agro-food monitoring.

[0007] In the field of LoC sensors, surface acoustic wave (SAW) based devices are being utilized as ideal applications. Due to their high surface confinement properties, SAWs are particularly sensitive to external perturbations, especially to the detection of attached mass that induces changes in wave propagation characteristics ("mass loading" effect).

[0008] As is known, SAWs are generated using interdigital transducers. In particular, an interdigital transducer (IDT) is a device consisting of two interconnected comb-shaped arrays of metal electrodes ("finger"). These metal electrodes are deposited on the surface of a piezoelectric substrate, such as quartz or lithium niobate, to form a periodic structure. This structure allows the interdigital transducer to convert electrical signals into SAWs by generating a periodically distributed mechanical force via the piezoelectric effect. The same principle applies to the conversion of SAWs back into electrical signals. These SAW generation and reception processes can be used in different types of SAW signal processing devices, such as bandpass filters, delay lines, resonators, and sensors.

[0009] SAWs can be generated and detected in a controlled manner by utilizing electromechanical coupling between electrodes with a strictly defined geometric structure and a piezoelectric substrate. By combining these features of SAWs with appropriate surface functionalization, it is possible to create fully electrically readable sensors capable of detecting specific biomarkers, such as proteins that enable the diagnosis of disease conditions.

[0010] Among the various types of saws (SAWs), Rayleigh SAWs (R-SAWs) and shear-horizontal SAWs (SH-SAWs) are distinguished.

[0011] In particular, R-SAW can also be used for mixing and manipulating liquids in microfluidic channels. Devices have been created that can utilize the potential of R-SAW in both liquid detection (drying) and manipulation. An example of such a device is shown in M. Agostini, G. Greco, M. Snipers, "A Rayleigh surface acoustic wave (R-SAW) resonator biosensor based on positive and negative reflectors with sub-nanomolar detection limit," Sensors and Actuators B 254 (2018).

[0012] On the other hand, SH-SAW, thanks to its polarization tangential to the propagation surface, can perform real-time analysis in liquid samples. With this in mind, biosensors utilizing SH-SAW for the detection of analytes in biological fluids have been developed. An example of such a biosensor is shown in U.S. Patent No. 10031135(B2).

[0013] From the perspective described above, there is a need for a SAW sensor that can utilize both R-SAW and SH-SAW in an integrated manner using a common substrate.

[0014] However, state-of-the-art SAW sensors currently generally target R-SAW generation, or alternatively, SH-SAW generation. One example can be found in U.S. Patent No. 10031140, which describes a device with a substrate suitable for R-SAW (128°YX LiNbO3) generation, but not suitable for SH-SAW generation. This document also explicitly states that the presence of different substrates is necessary for the integration of R-SAW and SH-SAW.

[0015] The literature includes several examples of sensors utilizing piezoelectric substrates capable of generating both R-SAW and SH-SAW, such as "Liquid sensor using SAW and SH-SAW on quartz" (Takashi Kogai, Hiromi Yatsuda, IEEE Ultrasonic Symposium, 2006) and "Orthogonal surface acoustic wave device based on langasite for simultaneousus biosensing and biofouling removal" (Singh, Reetu & Sankaranarayanan, Subramanian & Bhethanabotla, Appl. Phys. Lett. 94, 263503; 2009). In particular, the first document uses an ST-cut piezoelectric quartz substrate, while the second document uses a langasite piezoelectric substrate. However, in both cases, a low electromechanical coupling coefficient k is used. 2 This results in low efficiency in generating elastic waves, particularly in the mixing of liquids.

[0016] Another example is presented in "Rayleigh SAW assisted SH-SAW immunosensor on X-cut 148-Y LiTaO3" (Takashi Kogai, Hiromi Yatsuda, and Ja Kondoh; IEEE Transloopctions on Ultrasonics, ironelectrics, and Frequency control, vol.64, no.9), where a lithium tantalate piezoelectric substrate is used. However, in this paper, the transducers capable of generating two surface waves must be positioned at a precise 9° angle with respect to the SAW propagation direction, leading to considerable complexity and reduced efficiency in device manufacturing. [Overview of the Initiative]

[0017] Therefore, a feature of the present invention is to provide a sensor-equipped device for detecting analytes in a fluid, which is capable of generating both Rayleigh-type surface acoustic waves (R-SAW) for mixing and manipulating liquids and shear horizontal surface acoustic waves (SH-SAW) for real-time detection of analytes in a liquid environment.

[0018] Furthermore, a feature of the present invention is the high value of the electromechanical coupling coefficient k. 2 The objective is to provide such a sensor-equipped device having [a certain characteristic].

[0019] Furthermore, a key feature of the present invention is to provide a sensor-equipped device that reduces complexity and manufacturing costs compared to the prior art.

[0020] These and other objectives are achieved by a sensor-equipped device for detecting analytes in a fluid, and the sensor-equipped device is - A piezoelectric substrate having an outer surface, -At least one R-SAW emitting interdigital transducer disposed on the outer surface, the R-SAW emitting interdigital transducer is configured to emit Rayleigh-type surface acoustic waves, also known as R-SAWs, in response to an electrical input signal, and the R-SAW is emitted along a first emission direction x, - A configuration comprising at least one SH-SAW emitting interdigital transducer disposed on the outer surface, wherein the SH-SAW emitting interdigital transducer is configured to emit a shear horizontal type surface acoustic wave, also known as an SH-SAW, in response to an electrical input signal, and the SH-SAW is emitted along a second emission direction y, As a main feature, the piezoelectric substrate is made of a material selected from 64°Y-cut lithium niobate and 163°Y-cut lithium niobate so that the piezoelectric substrate supports a surface acoustic wave of the shear horizontal type as its main mode, and the main mode is defined as a surface acoustic wave that exhibits a larger electromechanical coupling on the piezoelectric substrate. And the first emission direction x and the second emission direction y have a relative angle α such that 80° < α < 100°.

[0021] In this way, the present invention enables the generation of both Rayleigh-type surface acoustic waves (R-SAW) for liquid mixing and manipulation and shear horizontal-type surface acoustic waves (SH-SAW) for real-time detection of analytes in a liquid environment.

[0022] Furthermore, compared with prior art devices using quartz or langasite substrates, the present invention enables a significant increase in the electromechanical coupling coefficient k 2 In particular, when using a lithium niobate substrate, k equal to 0.14% for quartz and 0.36% for langasite 2 is compared, and a range of k (depending on the cut) of 5.5% to 17.2% is given. 2

[0023] Compared with prior art devices using a lithium tantalate substrate having transducers arranged at an exact angle of 9°, the angle α used in the present invention can significantly improve the error tolerance, which is advantageous from the perspective of manufacturing the sensor itself.

[0024] Advantageously, 85° < α < 95°.

[0025] In particular, each R-SAW emitting interdigital transducer and each SH-SAW emitting interdigital transducer include a plurality of fingers each having a width p and a height h, and the ratio p / h is set to 0.2% to 0.5%.

[0026] Particularly, an R-SAW reflector disposed on the outer surface is also provided, which is arranged to reflect the R-SAW toward the R-SAW emitting interdigital transducer.

[0027] Particularly, an SH-SAW reflector disposed on the outer surface is also provided, which is arranged to reflect the SH-SAW toward the SH-SAW emitting interdigital transducer.

[0028] Particularly, the surface acoustic waves emitted by each R-SAW emitting interdigital transducer and each SH-SAW emitting interdigital transducer have an optimal frequency range set at 800 MHz to 1.6 GHz.

[0029] Advantageously, at least one microfluidic channel is also provided, which is arranged to convey the fluid along a predetermined path on the outer surface, in order to enable the fluid to be contained within a small area where the analysis is performed.

Brief Description of the Drawings

[0030] The present invention will be illustrated using the following description of several exemplary embodiments, which are illustrative but not limiting, with reference to the accompanying drawings. [Figure 1] An embodiment of a sensor-equipped device according to the present invention is shown, which provides one R-SAW emitting interdigital transducer and one SH-SAW emitting interdigital transducer arranged at 90° to each other. [Figure 2] An embodiment of a sensor-equipped device according to the present invention is shown, which provides two R-SAW emitting interdigital transducers, one SH-SAW emitting interdigital transducer, and two SH-SAW reflectors. [Figure 3]An embodiment of a sensor-equipped device according to the present invention is provided, comprising one R-SAW emitting interdigital transducer, one SH-SAW emitting interdigital transducer, two R-SAW reflectors, and two SH-SAW reflectors. [Figure 4] An embodiment of a sensor-equipped device according to the present invention is provided, comprising four R-SAW emitting interdigital transducers, one SH-SAW emitting interdigital transducer, two R-SAW reflectors, and two SH-SAW reflectors. [Modes for carrying out the invention]

[0031] Description of Preferred Exemplary Embodiments Referring to Figure 1, the sensor-equipped device 100 for detecting analytes in a fluid according to the present invention comprises a piezoelectric substrate 105 having an outer surface 105', and an R-SAW emitting interdigital transducer 111 and an SH-SAW emitting interdigital transducer 112, both of which are disposed on the outer surface 105'.

[0032] In particular, the R-SAW emitting interdigital transducer 111 is positioned to emit Rayleigh-type surface acoustic waves, also known as R-SAW, along a first emission direction x, while the SH-SAW emitting interdigital transducer 112 is positioned at an angle with respect to the first emission direction x.

[0033]

number

[0034] Furthermore, according to the present invention, the piezoelectric substrate 105 is made of a cut lithium niobate crystal in an orientation such that the piezoelectric substrate 105 supports shear horizontal type surface acoustic waves as its dominant mode, and the dominant mode is defined as a surface acoustic wave that exhibits greater electromechanical coupling on the piezoelectric substrate 105.

[0035] In particular, the piezoelectric substrate 105 is made of the following materials: -64°Y-cut lithium niobate It can be prepared from one of the following: -163°Y cut lithium niobate.

[0036] Thanks to the specific material of the substrate 105, as well as the orthogonal arrangement of the x and y emission axes, the sensor-equipped device 100 according to the present invention has a high electromechanical coupling coefficient k 2 This makes it possible to obtain [the desired result] while reducing the complexity of manufacturing compared to conventional technologies.

[0037] The embodiment shown in Figure 1 can be used for both "detection in liquid" thanks to the generation of SH-SAW and "detection in dry" thanks to the generation of R-SAW. In particular, "detection in liquid" means that resonance acquisition occurs when the sensor is wet. Therefore, this measurement is suitable for "real-time" monitoring of the adhesion of analytes to the sensor found in liquid samples. "Dry detection" means that resonance acquisition is performed on a dry sensor. The sensor is then wet with a sample containing the analyte, then dried, and then resonance acquisition is performed.

[0038] Furthermore, in the embodiment shown in Figure 1, the generation of R-SAW enables the mixing of liquid samples, which has a beneficial effect with respect to the specific adhesion of the analyte.

[0039] As is known, referring again to Figure 1, the interdigital emission transducers 111 and 112 comprise a plurality of "fingers" 111' and 112', respectively, having width p and height h. Advantageously, the p / h ratio is 0.2% to 0.5%. Thus, when h has a typical value of 100 nm, the p value is 0.4 to 1.0 μm. This range of values ​​corresponds to surface acoustic waves with an optimal frequency range of 800 MHz to 1.6 GHz.

[0040] Referring to Figures 2, 3, and 4, the sensor-equipped device 100 may include multiple R-SAW emitting interdigital transducers and multiple SH-SAW emitting interdigital transducers, depending on the reason for use.

[0041] Furthermore, at least one R-SAW reflector 113 and at least one SH-SAW reflector 114 are provided to constitute a resonator configuration. This configuration ensures greater spatial confinement of the surface waves converted to standing waves, resulting in greater energy confinement in the sensing area. Moreover, this configuration leads to an increase in the Q value of the resonance peak in the S11 reflection analysis. In this way, the efficiency of identifying the analyte in the fluid is increased.

[0042] The exemplary embodiments described herein will fully illustrate the invention in conceptual terms, and as a result, others may modify and / or adapt such embodiments for various uses without further study and without departing from the invention by applying the current knowledge, and it should be understood that such adaptations and modifications should therefore be considered equivalent to the particular embodiments. For this reason, the means and materials for achieving the different functions described herein may have different properties without departing from the art of the invention. It should be understood that the expressions or terms used herein are for illustrative purposes only and not limiting.

Claims

1. A sensor-equipped device (100) for detecting analytes in a fluid, wherein the sensor-equipped device (100) is - Piezoelectric substrate (105) having an outer surface (105'), - At least one R-SAW emitting interdigital transducer (111) disposed on the outer surface (105'), wherein the R-SAW emitting interdigital transducer (111) is configured to emit Rayleigh-type surface acoustic waves, also known as R-SAWs, in response to an electrical input signal, and the R-SAWs are emitted along a first emission direction x, - At least one SH-SAW emitting interdigital transducer (112) disposed on the outer surface (105'), wherein the SH-SAW emitting interdigital transducer (112) is configured to emit a shear horizontal type surface acoustic wave, also known as an SH-SAW, in response to an electrical input signal, and the SH-SAW is emitted along a second emission direction y, comprising at least one SH-SAW emitting interdigital transducer (112), The sensor-equipped device (100) is such that the piezoelectric substrate (105) supports the shear horizontal type surface acoustic wave as its dominant mode, the piezoelectric substrate (105) is made of a material selected from 64°Y-cut lithium niobate and 163°Y-cut lithium niobate, and the dominant mode is defined as the surface acoustic wave exhibiting greater electromechanical coupling on the piezoelectric substrate (105). A sensor-equipped device (100) characterized in that the first emission direction x and the second emission direction y have a relative angle α such that 80° < α < 100°.

2. The sensor-equipped device (100) according to claim 1, wherein 85° < α < 95°.

3. The sensor-equipped device (100) according to claim 1, wherein each R-SAW emitting interdigital transducer (111) and each SH-SAW emitting interdigital transducer (112) comprises a plurality of fingers (111', 112') having a width p and a height h, and the ratio p / h is set to 0.2% to 0.5%.

4. A sensor device (100) according to claim 1 is also provided, wherein an R-SAW reflector (113) is disposed on the outer surface (105') and is arranged to reflect the R-SAW toward the R-SAW emitting interdigital transducer (111).

5. A sensor device (100) according to claim 1 is also provided, wherein an SH-SAW reflector (114) is disposed on the outer surface (105'), the SH-SAW reflector (114) is disposed to reflect the SH-SAW toward the SH-SAW emitting interdigital transducer (112).

6. The sensor-equipped device (100) according to claim 1, wherein the surface acoustic waves emitted by each R-SAW emitting interdigital transducer (111) and each SH-SAW emitting interdigital transducer (112) have an optimal frequency range set to 800 MHz to 1.6 GHz.

7. The sensor device (100) according to claim 1 is also provided, which is arranged to transport the fluid along a predetermined path on the outer surface (105') in order to allow the fluid to be contained within a small area in which the analysis is performed.

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