High-flux SERS (Surface Enhanced Raman Scattering) substrate preparation device based on acoustic flow control

Abstract

The invention belongs to the crossing field of a surface acoustic wave device, a microfluidic technology and a surface enhanced Raman spectrum, and relates to a high-flux SERS substrate preparation device based on acoustic flow control. The device adopted by the method comprises a heating module and an enrichment module. And the heating module controls the temperature change, so that chip breakage caused by overheating is avoided. In the enrichment module, when an alternating electric signal is applied, an interdigital electrode excites the surface of the chip to generate surface acoustic waves, and then vibration of solid particles is triggered, so that target particles move along the surface of the substrate and are enriched. Meanwhile, the device adopts a bionic shark type hydrophobic film, so that the contact angle of liquid drops reaches 140 degrees, internal particles are convenient to gather, and the enrichment speed and the drying efficiency of the particles are remarkably improved. The method is easy and convenient to operate, enrichment and drying treatment is provided for subsequent target particles, and the detection sensitivity of the target particles in Raman spectrum analysis is remarkably improved; and a solution in a liquid sample can be quickly evaporated into solid residues.

Description

Technical Field

[0001] The invention belongs to the intersecting field of surface acoustic wave (SAW) devices, microfluidics technology and surface enhanced Raman spectroscopy (SERS), and relates to a high-throughput SERS substrate preparation device based on acoustofluidics. Background Art

[0002] In the current scientific research and biomedicine fields, the demand for trace substance analysis is growing exponentially. However, traditional Raman spectroscopy technology faces bottlenecks such as insufficient sensitivity and limited spatial resolution when dealing with trace sample detection, which seriously restricts the promotion and application of this technology in practice. To address this key challenge, surface acoustic wave (SAW) technology has shown significant advantages due to its unique physical properties: through the eddy currents and acoustic radiation forces generated by the acoustic streaming effect, it can efficiently convert acoustic energy into fluid kinetic energy with an energy loss of less than 1%, thereby achieving the precise aggregation of trace particles at standing wave nodes. This technology has outstanding characteristics such as low sample consumption (up to nanoliters), fast processing speed (millisecond response), high sensitivity (single particle level) and good selectivity, showing excellent integration compatibility and application universality.

[0003] This invention innovatively combines surface-enhanced Raman spectroscopy (SERS) with surface acoustic wave enrichment technology. By precisely controlling the amplitude (0.1-10μm) and frequency (1-100MHz) of the surface acoustic wave, it achieves three-dimensional spatial focusing of dispersed particles in the detection area. The specially developed acoustically driven droplet processing system can not only achieve efficient separation and enrichment of target particles (enrichment factor >1000×), but also prepare multiple solid-state sample arrays with excellent uniformity through rapid drying (<5s). This synergistic technical solution increases the Raman signal intensity by 3 orders of magnitude and reduces the detection limit to 10^-18mol / L.

[0004] This breakthrough technology revolutionizes the field of microanalysis. First, it achieves an integrated "enrichment-detection" process through acousto-optic coupling, reducing traditional detection time from hours to minutes. Second, its modular design makes it compatible with conventional Raman spectroscopy systems, significantly expanding its application in areas such as trace drug detection, early cancer marker screening, and real-time monitoring of environmental pollution. The high-precision, rapid detection platform established by this invention not only addresses key pain points of existing technologies but also provides an innovative technical path for the development of next-generation portable detection devices. Summary of the Invention

[0005] To address the challenges of existing technologies, this invention provides a high-throughput SERS substrate preparation device based on acoustofluidics. This device, designed to efficiently concentrate and dry trace particles using surface acoustic wave technology, significantly improves the sensitivity and accuracy of Raman spectroscopy. Its simple design and efficient operation make it suitable for a variety of high-precision trace sample detection applications.

[0006] The present invention solves the core problems of low sample pretreatment efficiency and insufficient signal sensitivity in trace analysis through the synergistic effect of surface acoustic wave-driven microfluidic enrichment and rapid drying. The present invention belongs to the category of intelligent sensing and precise detection technology, and is particularly suitable for: 1. Nanoparticle manipulation: directional enrichment of submicron particles through acoustic streaming effect (and acoustic radiation force); 2. Micro-nanoscale fluid control: precise regulation of the flow field in the droplet using high-frequency surface acoustic waves (frequency range 10-100MHz); 3. In-situ detection technology: combining the integrated design of SERS substrate and acoustic enrichment to achieve full process automation of "enrichment-drying-detection". The device can be expanded to cutting-edge fields such as single-cell analysis and rapid virus screening, providing key technical support for the next generation of portable detection equipment.

[0007] The technical solution adopted in the present invention is:

[0008] A high-throughput SERS substrate preparation device based on acoustofluidics comprises an aluminum plate, a temperature sensor, a pressure sensor, an enrichment module and a heating module.

[0009] The aluminum plate serves as the core support structure, with a rectangular groove inside for accommodating the piezoelectric substrate. This piezoelectric substrate utilizes a 128° YX-tangential lithium niobate crystal. A longitudinal light-transmitting slot is defined in the center of the groove, facilitating real-time microscopic observation of droplet aggregation, contact angle changes, and morphological evolution. A temperature sensor and pressure sensor are embedded within the aluminum plate, with their hemispherical sensing tips tangent to the lower surface of the piezoelectric substrate, ensuring precise monitoring.

[0010] The enrichment module comprises radio frequency wires, a circuit board, a piezoelectric substrate, transducer electrodes, and a hydrophobic film. The transducer electrodes are interdigitated and secured to the surface of the piezoelectric substrate via wire bonding. When an alternating voltage is applied to the circuit system, the piezoelectric effect causes the lattice of the piezoelectric substrate to periodically deform, stimulating surface acoustic waves on its surface that drive the precise manipulation and positioning of the microdroplets.

[0011] The hydrophobic film adopts a shark skin bionic micro-nano composite structure, and its surface has periodically arranged micro-rib-groove units, wherein the micro-rib width is 5-10μm, the groove depth is 2-5μm, and the spacing is 20-50μm; it is formed on a polydimethylsiloxane substrate through a nanoimprinting process. The shark skin bionic micro-nano composite structure makes the film super-hydrophobic, with a static contact angle ≥160° and a rolling angle ≤5°; under the action of an acoustic shear force of 0.1-10mN / m, the contact angle hysteresis is <2°, ensuring that there is no residue during the directional migration of droplets. The film is reusable, and the contact angle decays by <3% after 50 ethanol washes. It is combined with a rectangular liquid holding tank to achieve standardized operation. The enrichment area is located between the two transducer electrodes and is the target area for directional migration of droplets.

[0012] The circuit board is spot-welded to the transducer electrodes and removably welded to the RF cable through circular holes. As part of the underlying support structure, the circuit board is securely attached to the aluminum plate via T-screws. The aluminum plate has pre-set threaded connections, and the four corners of the circuit board have mating holes. Three identical enrichment modules are evenly distributed on the heating module, enabling high-throughput processing.

[0013] The heating module utilizes a flexible silicone heating sheet, only 1-3mm thick. Through evenly distributed resistance wires and a silicone heat-conducting layer, efficient heat transfer is achieved, preventing localized overheating while maintaining the compactness of the device. The back of the aluminum plate fits snugly against the heating sheet, ensuring even temperature distribution.

[0014] The modular architecture allows for flexible disassembly and maintenance of each functional unit. The integrated design of the flexible heating film takes into account both operational stability and temperature control requirements. The see-through structure satisfies multi-angle optical observation conditions and is suitable for the debugging requirements of the microscopic imaging system.

[0015] A method for using a high-throughput SERS substrate preparation device based on acoustofluidics comprises the following steps:

[0016] S1. Attach the hydrophobic film to the piezoelectric substrate, keep the device upright, add a droplet of the test liquid to the enrichment area, and then invert the entire device. The droplet is stably suspended under the action of gravity and the adhesion force of the hydrophobic film;

[0017] S2. Connect the radio frequency lines at both ends of the device to the output end of the signal generator, and the signal generator outputs electrical energy to the piezoelectric substrate through the transducer electrodes.

[0018] S3, electrical energy is converted into surface acoustic waves through the piezoelectric substrate, and the surface acoustic waves propagate on it, driving the droplets to gather in the enriched area in the center of the hydrophobic film;

[0019] S4. When the sample reaches the enrichment effect, the heating plate heats up and the sample dries quickly. The temperature and heat dissipation are monitored in real time to prevent damage to the device and sample.

[0020] S5. Keep the device in an inverted state and place it on the microscope stage as a whole. Perform in-situ Raman spectroscopy detection through the groove at the bottom of the aluminum plate to avoid signal loss caused by transferring the substrate.

[0021] Compared with the prior art, the present invention has the following significant advantages:

[0022] (1) High throughput: The channel parallel enrichment structure adopts a coplanar waveguide feeding design to reduce RF crosstalk (crosstalk < -30dB), support simultaneous processing of 3×8μL samples, and increase the throughput by 240% compared with a single channel, reducing the coupling error caused by heating of the input device; modular assembly supports rapid replacement of substrates and is suitable for new SERS substrates such as gold nanostars and black phosphorus quantum dots.

[0023] (2) Improved collection efficiency: Based on the static droplet coupling mechanism of the circular film, the collection rate is increased compared to the traditional pull-up technology while maintaining the droplet hydrodynamic stability. The patented suspended droplet processing technology completely solves the problem of particle adhesion on the film surface, and the collection efficiency is higher, which is significantly improved compared to traditional methods.

[0024] (3) Portable and easy to integrate: The integrated design eliminates chip scratch defects caused by traditional pulling operations (surface roughness Ra < 0.1 μm), and the embedded spectrum detection module realizes in-situ real-time measurement, shortening the typical experimental cycle from 4.2 hours to 0.8 hours. The compact structure (180×120×60mm) complies with IVD standards (ISO 13485) 3 )Supports rapid deployment in laboratories and on-site.

[0025] (4) This method integrates particle separation, sample pretreatment, and high-sensitivity detection functions, and has the potential for efficient and convenient laboratory applications, especially in environmental monitoring, national security, biological analysis, disease prevention and control, and other aspects. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 An exploded diagram of the structure of a high-sensitivity Raman spectroscopy rapid detection device for surface acoustic wave enrichment of dried droplets provided by an embodiment of the present invention;

[0027] Figure 2 A structural diagram of a high-sensitivity Raman spectroscopy rapid detection device for surface acoustic wave-enriched dried droplets provided in an embodiment of the present invention;

[0028] In the figure: 1. RF line, 2. Hydrophobic film, 3. Piezoelectric substrate, 4. Droplet, 5. Transducer electrode, 6. Circuit board, 7. Spring pin, 8. Screw, 9. Aluminum plate, 10. Heating plate, 11. Temperature sensor, 12. Pressure sensor. DETAILED DESCRIPTION

[0029] The following will be combined with the drawings in the embodiments of the present application to clearly and completely describe the technical solutions in the embodiments of the present application. Obviously, the embodiments described are only part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without making creative efforts are within the scope of protection of this application.

[0030] Please refer to Figure 1 , which is a structural exploded diagram of a high-throughput SERS substrate preparation device based on acoustofluidics provided in an embodiment of the present invention, including an aluminum plate, a temperature sensor, a pressure sensor, an enrichment module and a heating module.

[0031] The enrichment module includes a radio frequency line 1 , a circuit board 6 , a piezoelectric substrate 3 , a transducer electrode 5 and a hydrophobic film 2 .

[0032] The RF wire 1 is removably soldered to the circuit board 6 through circular holes to ensure a good electrical connection. The piezoelectric substrate 3 is connected to the transducer electrode 5 via wire bonding technology to achieve efficient surface acoustic wave transmission. The hydrophobic film 2 is removably bonded to the piezoelectric substrate 3. Its design mimics the structure of shark skin, facilitating enrichment and subsequent observation.

[0033] The heating module is composed of two heating plates 10 that are symmetrically distributed on the left and right.

[0034] The heating plate 10 and the aluminum plate 9 are detachably bonded by organic silicon high temperature adhesive to provide uniform heat distribution.

[0035] Connection between circuit board and aluminum plate: Circuit board 6 and aluminum plate 9 are detachably connected by T-shaped screws 8. Four T-shaped areas are embedded in the circuit board and pass through the aluminum plate groove. Four cylindrical threaded areas are embedded in the aluminum plate groove to facilitate fixing by screws and threads.

[0036] A rectangular groove is provided in the aluminum plate 9, the length and width of the long part of the rectangular groove being the same as those of the piezoelectric substrate 3, for easy placement; there is a rectangular through groove inside the rectangular groove for microscope alignment; there are two small cylindrical grooves inside the rectangular groove, with the same diameter and height as the temperature sensor and pressure sensor, for easy embedding.

[0037] Design of the sensor module: The sensor module consists of a temperature sensor 11 and a pressure sensor 12, which are spliced ​​together by a cylindrical and hemispherical shape. The spherical surface is tangent to the bottom surface of the piezoelectric material, and the other surfaces are embedded in the aluminum plate 9. The spherical part is used to measure temperature and pressure to ensure the accuracy of the measurement.

[0038] The screws are T-shaped, and four T-shaped areas are embedded in the circuit board 6 and pass directly through the aluminum plate groove. The groove of the aluminum plate 9 is embedded with four cylindrical threaded areas. The circuit board 6 and the aluminum plate 9 can be fixed by screws and threads.

[0039] The transducer electrodes are ladder-shaped metal patterns, and the electrodes are connected to the circuit board 6 via spring pins 7 .

[0040] Please refer to Figure 2 This is a structural diagram of a high-throughput SERS substrate preparation device based on acoustofluidics. Figure 1 The four parts of aluminum plate, temperature sensor, enrichment device, and heating device were assembled.

[0041] Method and steps for using the above device:

[0042] Use a metal mold cutting blade to cut out a handle-shaped PDMS mold and spread it flat on the central area of ​​the acoustic tweezers device to avoid bubbles. Adjust the signal generator to the operating frequency and voltage range of the acoustic tweezers device to ensure that the operating power of the acoustic tweezers device is 20-23dBm. After turning on the signal, drip a suitable volume of droplets containing metal nanoparticles (3-10 microliters is best) into the central area of ​​PDMS. The particle size of the metal nanoparticles can be above 50nm. During the operation of the acoustic tweezers device, turn on the bottom heating platform to accelerate the volatilization of the droplets. The bottom temperature is best controlled at 60-80℃. After the droplets evaporate, peel off the PDMS film and place it on a glass slide to complete the preparation of the highly sensitive Raman substrate material.

[0043] When in use, simply drop the solution containing the target onto the enriched area in the center of the PDMS film. After the sample dries naturally, send it to a confocal Raman microscope for detection.

[0044] A specific method for using a high-throughput SERS substrate preparation device based on acoustofluidics includes the following steps:

[0045] S1. Precisely attach a hydrophobic polymer film 2 to the surface of a piezoelectric substrate 3, and then add a small amount of a test droplet 4 to a predetermined enrichment area.

[0046] S2. Connect the radio frequency wires 1 at both ends of the detection device to the output end of the signal generator through the radio frequency wires, and output an excitation voltage with specific parameters (frequency f, amplitude V) through the signal generator. The electrical signal is introduced into the piezoelectric substrate 3 through the interdigital transducer electrodes 5;

[0047] S3. Lithium niobate crystal with a 128° YX orientation is selected as the material of the piezoelectric substrate 3. Under the action of an alternating electric field, the inverse piezoelectric effect is stimulated, and surface acoustic waves (SAW) are induced to propagate along the surface of the substrate. The generated acoustic streaming effect promotes the directional migration of droplets toward the central enriched area of ​​the hydrophobic film 2.

[0048] S4. Observe the sample in the droplet 4 under a microscope to achieve the desired enrichment effect. The heater 10 can be used to increase the temperature, rapidly drying the water in the droplet 4 to obtain the enriched product. The temperature sensor 11 can detect the maximum temperature of the device in real time, preventing excessive temperatures from irreversibly damaging the piezoelectric substrate 3 and preventing the prepared Raman substrate from losing its function. Once the droplet 4 is observed to be dry, the heater 10 can be used to reduce the temperature.

[0049] S5. The entire device is placed upside down and suspended in the air under a microscope, and the Raman substrate for Raman detection is obtained by observing the rectangular groove.

[0050] The present invention provides a high-throughput SERS substrate preparation device based on acoustic fluidics, which has a sophisticated design, convenient operation, efficient particle enrichment ability and excellent detection sensitivity. Compared with traditional detection methods, this device can significantly improve the enrichment efficiency of trace particles and greatly improve the signal intensity and uniformity of Raman spectra. Driven by surface acoustic waves, the device has little impact on the sample during operation, and is particularly suitable for trace samples that require precise detection, and has significant advantages in particle distribution uniformity, detection sensitivity and operational stability. The present invention is suitable for trace particle detection, environmental monitoring, biomedical testing and other fields, especially in high-sensitivity detection scenarios such as trace pathogen enrichment and low-concentration analysis, showing a wide range of application prospects. Although the above is a specific embodiment of the present invention, the scope of protection of the present invention is not limited thereto. For those familiar with the technology in this field, any changes or substitutions made within the technical scope disclosed by the present invention should be deemed to fall within the scope of protection of the present invention.

[0051] Finally, it should be noted that the scope of protection of this application is not limited to the applications and technical solutions disclosed in the embodiments. Anyone skilled in the art, within the technical scope disclosed in this application, may make appropriate changes and substitutions based on specific application requirements and environmental conditions. These possible changes and substitutions, including but not limited to material selection, structural adjustments, functional expansion, and integration with other technologies, should be considered part of the scope of protection of this application.

Claims

1. A high-throughput SERS substrate preparation device based on acoustofluidics, characterized in that: It includes an aluminum plate (9), a temperature sensor (11), a pressure sensor (12), an enrichment module and a heating module; The aluminum plate (9) serves as a core supporting structure, and a rectangular groove is provided inside the aluminum plate (9) for accommodating the piezoelectric substrate (3); a light-transmitting groove is longitudinally provided in the center of the groove to facilitate real-time observation of the droplet aggregation state, contact angle change, and morphology evolution by a microscope; a temperature sensor (11) and a pressure sensor (12) are embedded in the aluminum plate (9), and their hemispherical detection ends are tangent to the lower bottom surface of the piezoelectric substrate (3); The enrichment module comprises a radio frequency line (1), a circuit board (6), a piezoelectric substrate (3), a transducer electrode (5) and a hydrophobic film (2); the transducer electrode (5) is an interdigitated transducer electrode, and the transducer electrode (5) is fixed to the surface of the piezoelectric substrate (3) by wire bonding technology; when an alternating voltage is applied to the circuit system, the piezoelectric effect is utilized to cause the lattice of the piezoelectric substrate (3) to undergo periodic deformation, exciting surface acoustic waves (SAW) on its surface, which are used to drive the precise manipulation and positioning of the micro-droplets; The hydrophobic film (2) adopts a shark skin biomimetic micro-nano composite structure, and its surface has periodically arranged micro-rib-groove units, wherein the micro-rib width is 5-10 μm, the groove depth is 2-5 μm, and the spacing is 20-50 μm; it is formed on a polydimethylsiloxane (PDMS) substrate by a nanoimprinting process; the enriched area is located between the two transducer electrodes (5) and is the target area for the directional migration of droplets; The circuit board (6) is connected to the transducer electrode (5) and is detachably welded to the radio frequency line (1) through a circular hole; the circuit board (6) is a part of the lower support structure and is firmly connected to the aluminum plate (9) through T-shaped screws; three identical enrichment modules are evenly distributed on the heating module to achieve high-throughput processing; The heating module adopts a flexible silicone heating sheet with a thickness of 1-3 mm, and realizes efficient heat transfer through evenly distributed resistance wires and a silicone heat-conducting layer. The back of the aluminum plate (9) is tightly fitted with the heating sheet to ensure even temperature distribution.

2. The high-throughput SERS substrate preparation device based on acoustofluidics according to claim 1, characterized in that: The piezoelectric substrate (3) adopts a 128° YX tangential lithium niobate crystal.

3. The high-throughput SERS substrate preparation device based on acoustofluidics according to claim 1, characterized in that: The shark skin biomimetic micro-nano composite structure makes the film super-hydrophobic, with a static contact angle of ≥160° and a rolling angle of ≤5°; the contact angle hysteresis is less than 2° under the action of an acoustic shear force of 0.1-10mN / m, ensuring that there is no residue during the directional migration of droplets; the film is reusable, with a contact angle attenuation of less than 3% after 50 ethanol washes, and standardized operation is achieved in conjunction with a rectangular liquid receiving tank.

4. The high-throughput SERS substrate preparation device based on acoustofluidics according to claim 1, characterized in that: The aluminum plate (9) is preset with a corresponding threaded interface, and the four corners of the circuit board (6) are provided with engaging holes.

5. The method for using the acoustofluidic-based high-throughput SERS substrate preparation device according to claims 1 to 4, characterized in that: Here are the steps: S1. Attach the hydrophobic film (2) to the piezoelectric substrate (3), keep the device upright, drip a droplet of the test liquid onto the enrichment area, and then invert the entire device. The droplet is stably suspended under the action of gravity and the adhesion force of the hydrophobic film (2); S2, connecting the radio frequency wires (1) at both ends of the device to the output end of the signal generator, and the signal generator outputs electrical energy to the piezoelectric substrate (3) through the transducer electrode (5); S3, the electrical energy is converted into surface acoustic waves through the piezoelectric substrate (3), and the surface acoustic waves propagate on it, driving the droplets to gather in the enriched area in the center of the hydrophobic film (2); S4. When the sample reaches the enrichment effect, the heating plate heats up and the sample is quickly dried. The temperature and heat dissipation are monitored in real time to prevent damage to the device and sample. S5. Keep the device in an inverted state and place it as a whole on a microscope stage. Perform in-situ Raman spectrum detection through the groove at the bottom of the aluminum plate (9) to avoid signal loss caused by transferring the substrate.

Images