CN116650766A - Surface acoustic wave atomizer based on microfluidic liquid supply and preparation method thereof - Google Patents

Abstract

The invention provides a surface acoustic wave atomizer based on microfluidic liquid supply and a preparation method thereof, the surface acoustic wave atomizer based on microfluidic liquid supply comprises a surface acoustic wave device, one side of the surface acoustic wave device is provided with a micro flow channel, the micro flow channel comprises a photoresist micro flow channel positioned at a bottom layer, the upper surface of the photoresist micro flow channel is provided with a silicon dioxide film layer, a PDMS layer which is treated by oxygen plasma is arranged above the silicon dioxide film layer, and the PDMS layer is combined with the photoresist micro flow channel in a thermal bonding way to form a closed microfluidic channel. When the surface acoustic wave atomizer is adopted for atomization, proper aerosol concentration and particle size distribution can be generated, and a large amount of atomized aerosol with the size of 1-5 mu m can be generated; and the spray of large liquid drops can not be generated, the energy loss is small, the high atomization rate is ensured, and the problem of liquid leakage can not occur.

Description

Surface acoustic wave atomizer based on microfluidic liquid supply and preparation method thereof

Technical Field

The invention relates to the technical field of atomization, in particular to a surface acoustic wave atomizer based on microfluidic liquid supply and a preparation method thereof.

Background

There are two main routes of drug delivery to the lungs, one is the local action of the drug along the respiratory tract on the lung surface; the other is that the drug is delivered to the whole body through the blood. The recent 50 years of recording shows a significant increase in the rate of use of the former, and it is appreciated that the local therapeutic efficacy of the patient is relatively low compared to oral or systemic administration, but the required drug dosage level is also significantly reduced, with relatively fewer side effects and toxicity problems. Currently, inhalation therapy has been widely used to treat respiratory diseases including asthma, chronic Obstructive Pulmonary Disease (COPD), pulmonary cystic fibrosis, and pulmonary arterial hypertension. Delivery directly to the lungs by inhalation of the drug aids in the local targeted treatment of disease or specific damaged areas and drug inhalation is painless, minimizing potential systemic side effects. Asthma is a chronic inflammatory disease associated with excessive lymphocytes and eosinophils in the airway wall. This airway inflammation narrows the airways, resulting in airflow obstruction as the person breathes. In order for inhalation therapy to be most effective, the drug-loaded aerosol must be deposited primarily at the inflammatory sites of the lungs.

Recent studies have shown that high eosinophils are found throughout the lung area, from bronchi to alveoli, in certain types of asthmatic patients. Thus, the direct deposition of drugs throughout the lower respiratory tract is considered to be the most effective treatment. One of the most critical factors affecting the pulmonary deposition of particles or aerosols is the aerodynamic properties of the particles, including size, density, shape, hygroscopicity, etc. of the particles or aerosols. Many clinical studies have shown that aerosol size of nebulization is critical to the efficacy of inhalation therapy. In general, the larger the aerosol particle size, the more likely it is to deposit in the upper respiratory tract and even the extrathoracic region. And aerosol with smaller diameter can be rapidly exhaled when the aerosol is exhaled, and the particle size is as small as 0.5 mu m. Currently, many studies have shown that a nebulized aerosol particle size of 1 to 5 μm is the optimal range for pulmonary administration during normal tidal breathing.

Clinically, three types of atomizers are used: jet atomizer, ultrasonic atomizer, vibrating mesh atomizer. Although the prospects of atomizers are attractive, their use has not been very vigorous over decades since the mid twentieth century, and for this reason, there are a number of difficulties that have limited their further development, for example, jet atomizers that have poor performance in producing monodisperse or narrow disperse aerosols, are cumbersome and not portable and have loud noise due to the reliance on external compressed air supply or a large battery driven compressor. Ultrasonic nebulizers have not been widely used in clinical medicine compared to MDI or jet nebulizers due to the susceptibility of the drug to denaturation and dissociation under cavitation and hydrodynamic shear forces during ultrasonic nebulization. The new generation of nebulizers, while still in clinical trials, have shown potential capabilities as a treatment for asthma and COPD, e.g. Vibrating Mesh (VM) nebulizers, VM being essentially an ultrasonic nebulizer, however unlike conventional ultrasonic nebulizers, the generated ultrasonic waves are transmitted through the Vibrating mesh into the liquid forcing the liquid to extrude the mesh in the form of a particulate aerosol, but the requirement of biocompatibility and durability of VM nebulizers makes the manufacturing cost much more expensive than conventional nebulizers, and the mesh is prone to blockage causing problems of bacterial contamination, etc., there are a number of inconveniences.

The existing surface acoustic wave atomization technology mainly utilizes polyester fiber paper to be absorbed from a water tank to the surface of a substrate for atomization through siphoning, a large amount of liquid drop spraying phenomenon occurs in the process, and the spraying and the atomization are closely related, so that the surface acoustic wave atomization technology belongs to two stages before and after the surface acoustic wave atomization, and under the condition of larger liquid film thickness and enough energy, the sound wave energy enters the liquid to perform the spraying phenomenon firstly, and the atomization phenomenon occurs only when the critical atomization characteristic height is reached along with the great reduction of the characteristic height of the liquid film. Therefore, for the current common paper strip flow supply atomization condition, under the condition of certain energy, the spray not only greatly reduces the utilization rate of atomization energy of the surface acoustic wave, but also discovers that most of the generated aerosol particle size is concentrated in mist drops with hundreds of micrometers through experiments, the particle size distribution result after water atomization under the action of different input powers is shown as a graph in fig. 1, the experimental peak value is mainly concentrated near 3 micrometers, 10 micrometers and 1000 micrometers, wherein the peak value proportion of 1000 accessories is the highest, the quantity of the aerosol mist drops with 1-5 micrometers is small, and the accumulation is less than 20%, and obviously, the requirements of deep lung inhalation are difficult to meet. While some techniques also suggest that varying the frequency can effectively reduce aerosol particle size, the concomitant substantial reduction in atomization energy, and a corresponding substantial reduction in atomization rate, is a significant impediment to the commercial impact of atomization technology. In addition, there is also a case where atomization is achieved by supplying a flow through a micro flow channel, but most of the liquid is installed in the direction of propagation of sound waves, so that not only liquid film accumulation but also atomization is stopped easily. In addition, the sound wave energy is greatly absorbed by the micro-channel material in the propagation direction, and heat is generated to cause the channel failure, even the partial heat-generating surface acoustic wave device fracture failure is generated directly due to dielectric loss. In addition, the soft polymer micro-fluid material is adopted outside the aperture, so that the pipeline supply is formed on the surface of the substrate, and the soft polymer micro-fluid material has strong capacity of absorbing the surface acoustic wave under the surface acoustic wave atomization condition, so that the liquid leakage problem is easy to occur due to heating deformation.

Disclosure of Invention

Aiming at the technical problems, the invention discloses a surface acoustic wave atomizer based on microfluidic liquid supply and a preparation method thereof, which can generate proper aerosol concentration and particle size distribution, and the aerosol droplets have small particle size, and the droplets with the particle size of 1-5um have more occupation ratio and can not form large droplet ejection.

In this regard, the invention adopts the following technical scheme:

the utility model provides a surface acoustic wave atomizer based on micro-fluidic liquid supply, its includes surface acoustic wave device (also known as SAW, surface Acoustic Wave), one side of surface acoustic wave device is equipped with the microchannel, the microchannel is including the photoresist microfluidic channel that is located the bottom, the surface of photoresist microfluidic channel is equipped with the silica film layer, the silica film layer forms irreversible permanent bonding with photoresist microfluidic channel, the top of silica film layer is equipped with PDMS (polydimethylsiloxane) layer through oxygen plasma treatment, PDMS layer combines through the mode of thermal bonding with photoresist microfluidic channel, forms confined microfluidic channel.

Among them, SAW atomization driving frequency is high (frequency is more than 10 MHz), and aerosol with particle size in 1-10 μm can be produced in large quantity. SAW is an efficient way to transfer mechanical energy to a fluid. Unlike ultrasonic waves, which propagate energy as a whole, SAW transmitted energy is fixed to the surface of the substrate of a surface acoustic wave device until it comes into contact with a fluid. When a droplet is placed on the path of SAW propagation, the SAW will attenuate into a Leaky Surface Acoustic Wave (LSAW) mode upon reaching the boundary between the substrate of the SAW device and the liquid. The attenuation of the satellite, acoustic energy leaks into the droplet at an oblique angle known as the "Rayleigh angle". This process creates acoustic radiation pressure and a circulating flow in the droplet, known as surface acoustic wave acoustic flow. The micro flow channel is arranged on one side of the surface acoustic wave device and is not in the sound wave propagation direction, so that the sound wave propagation direction is avoided.

By adopting the technical scheme, the micro flow channel is arranged on one side of the surface acoustic wave device, and the silicon dioxide film layer is arranged on the upper surface of the photoresist micro flow channel and is combined with PDMS to form the micro flow channel in a thermal bonding mode, so that the phenomenon that when the PDMS is directly bonded with the substrate of the surface acoustic wave device, the wave absorption is severe, the output energy is greatly reduced, the output atomization effect is influenced, a large amount of aerosol within the range of 1-10 mu m is output, and the phenomenon of liquid leakage is avoided. When the acoustic surface wave atomizer is used as a medical atomizer, continuous atomization of medicines can be provided, and the deposition efficiency of microfluidic medicine atomization is greatly improved.

As a further improvement of the invention, the height of the flow channel of the micro flow channel is 50-100 μm. When the flow channel height is less than 50 μm, the fluid is not easy to get out due to adhesion with the flow channel and the leakage condition is caused. When the flow channel height of the micro flow channel reaches 50 mu m, the condition of a film is just reached, namely, when the characteristic height of the liquid film is close to the wave length of sound waves in the liquid, atomization happens just.

As a further improvement of the present invention, the flow channel width of the micro flow channel is less than 2000 μm. The width of the flow channel can have a significant impact on the atomization process. When the width of the flow channel is 500 mu m, micro liquid drops are rapidly atomized under the action of the surface acoustic wave to generate stable aerosol flow, and large liquid drops are not ejected within 10 seconds. In contrast, when the flow channel width increases by 2000 μm, a large-volume droplet appears at the outlet of the flow channel, and then ejection of a large droplet appears at 340ms, and due to the increase in droplet volume, the liquid on the surface of the substrate fails to be atomized in time, so that the liquid on the surface is accumulated, and a large-area liquid film area is formed on the surface at 10s, so that the ejection of a large droplet is always mixed in the atomization process, and the improvement of the suction efficiency is affected.

As a further improvement of the present invention, the thickness of the silicon oxide thin film layer is not more than 500nm. Further, the thickness of the silicon dioxide film layer is 200-400nm. Further preferably, the thickness of the silicon dioxide film layer is 300nm.

As a further development of the invention, the edges of the substrate are provided with sheets of paper, which can better optimize the atomization of the droplets at the edges.

As a further improvement of the present invention, the surface acoustic wave device includes: the piezoelectric transducer comprises a piezoelectric substrate and an interdigital transducer, wherein the interdigital transducer is arranged on the piezoelectric substrate.

The invention also discloses a preparation method of the surface acoustic wave atomizer based on the microfluidic liquid supply, which comprises the following steps:

step S1, setting a surface acoustic wave device on a substrate;

s2, manufacturing a photoresist microfluidic channel by using a photoetching process, wherein the photoresist microfluidic channel is positioned at one side of the surface acoustic wave device and is not positioned in the propagation direction of sound waves;

s3, depositing a silicon dioxide film layer on the upper surface of the photoresist microfluidic channel to form irreversible permanent bonding;

and S4, manufacturing a PDMS layer above the photoresist microfluidic channel, performing oxygen plasma treatment, and combining the PDMS layer with the photoresist microfluidic channel in a thermal bonding mode.

Compared with the prior art, the invention has the beneficial effects that:

when the surface acoustic wave atomizer is adopted for atomization, proper aerosol concentration and particle size distribution can be generated, the atomized particle size is small, particularly a large amount of atomized aerosol with the size of 1-5 mu m can be generated, and when the surface acoustic wave atomizer is used for a medical atomizer, the medicine can be effectively administered; and the spray of large liquid drops can not be generated, the energy loss is small, the high atomization rate is ensured, and the problem of liquid leakage can not occur.

Experimental studies have shown that salbutamol solutions based on SU-8 microchannel liquid supplies, nebulized using SAW devices, can have a deposition rate in the lung area of up to 75%, significantly higher than 46% that typically achieved with medical nebulizers. It is worth noting that the surface acoustic wave atomizer based on microfluidic liquid supply in the technical scheme of the invention is a powerful competitor of the drug delivery technology in the market, and can be widely used for the atomized drug delivery for treating asthma and chronic obstructive pulmonary disease.

Drawings

FIG. 1 shows the particle size distribution of the water atomized under the action of different input powers in the prior art.

Fig. 2 is a schematic flow chart of a surface acoustic wave atomizer based on microfluidic liquid supply according to an embodiment of the present invention.

Fig. 3 is a sequence diagram of atomized aqueous solutions of the micro-channel integrated surface acoustic wave device with different widths according to the embodiment of the present invention.

The reference numerals include: 1-SAW devices, 2-SU-8 microfluidic channels, 3-silicon dioxide thin film layers.

Detailed Description

Preferred embodiments of the present invention are described in further detail below.

The utility model provides a surface acoustic wave atomizer based on micro-fluidic liquid supply, its includes the piezoelectricity base member, be equipped with interdigital transducer on the piezoelectricity base member, constitute surface acoustic wave device (also known as SAW, surface Acoustic Wave), one side of surface acoustic wave device is equipped with the microchannel, the microchannel is including the photoresist microfluidic channel that is located the bottom, the surface of photoresist microfluidic channel is equipped with the silica film layer, the silica film layer forms irreversible permanent bonding with photoresist microfluidic channel, the top of silica film layer is equipped with the PDMS layer through oxygen plasma treatment, PDMS layer combines through the mode of thermal bonding with photoresist microfluidic channel, forms confined microfluidic channel. Wherein, the surface acoustic wave device adopts the device structure of the prior art.

In order to increase the deposition rate of inhaled lung, it is very critical to reduce the ejection of large droplets entrained during atomization, and droplet ejection will occur when the volume of fluid in the surface acoustic wave propagation path exceeds the film conditions, i.e. the characteristic height of the fluid is greater than the wavelength of sound waves in the liquid. Therefore, in the case of determining the input power and the supply flow rate, it is important to reduce the characteristic height of the liquid film in the atomization zone. Therefore, the photoetching of the micro-flow channel on the surface of the aperture side of the substrate is a good choice.

As shown in fig. 2, the preparation method of the surface acoustic wave atomizer based on microfluidic liquid supply comprises the following steps:

step S1, manufacturing a SAW device 1 on a substrate;

step S2, photoetching a micro-channel on the surface of the aperture side of a substrate, specifically, manufacturing an SU-8 micro-channel 2 by utilizing a photoetching process, so that the SU-8 micro-channel 2 is positioned on one side of the SAW device 1 and is not in the acoustic wave propagation direction;

step S3, plating a silicon dioxide film layer 3 on the surface of the SU-8 micro-flow channel 2 to form irreversible permanent bonding; considering that the bonding between the PDMS thin layer and SU-8 surface is achieved by intermolecular interaction forces, i.e., van der waals forces, liquid exudation is easily caused during the experiment. Thus, a silicon dioxide film layer 3 is plated on the surface of the SU-8 micro-flow channel 2, thereby forming irreversible permanent bonding. In this embodiment, the thickness of the silicon dioxide thin film layer 3 is 300nm.

And S4, manufacturing a PDMS layer 4 above the silicon dioxide film layer 3, performing oxygen plasma treatment, and combining the PDMS layer 4 with the SU-8 micro-flow channel 2 in a thermal bonding mode.

In this embodiment, the height of the micro flow channel is 50-100 μm. The flow channel width of the micro flow channel is smaller than 2000 mu m.

The results of the following comparison are shown in fig. 3, where fig. 3 (a) is a chart of the atomization of different surface acoustic wave action times with a flow channel width of 500 μm, fig. 3 (b) is the atomization of different surface acoustic wave action times with a flow channel width of 2000 μm, and fig. 3 (c) is the atomization of different surface acoustic wave action times with a flow channel width of 500 μm, and a paper sheet is placed on the edge of the substrate. It can be seen that when the flow channel width is 500 μm, the micro droplets are rapidly atomized under the surface acoustic wave to generate stable aerosol flow, and no large droplet ejection occurs within 10 seconds, as shown in fig. 3 (a). As the flow channel width increases by 2000 μm, a large volume droplet appears at the outlet of the flow channel, and then ejection of a large droplet appears at 340ms, as shown in fig. 3 (b), due to the increase of the droplet volume, the liquid on the surface of the substrate fails to be atomized in time, which will cause accumulation of the liquid on the surface, and a large area liquid film area is formed on the surface at 10s, which causes ejection of a large droplet to be always entrained in the atomization process, which has a great influence on the improvement of the suction efficiency. For a 500 μm wide microchannel in which droplets are atomized while being driven by SAW, in order to prevent a small portion of the droplets from being pumped out of the substrate surface, placing a sheet of paper on the edge of the substrate can better optimize the atomization of the droplets at the edge, as shown in fig. 3 (c), it can be seen that most of the droplets are atomized before being pumped to the sheet of paper.

Through a large number of experimental statistics, when the surface acoustic wave atomizer based on microfluidic liquid supply of the embodiment is used for atomizing, the frequency of a surface acoustic wave device is 60MHz, the size of a micro-channel is 50um thick and 500um wide, the deposition efficiency of a lung model can reach 75 percent, the deposition efficiency of the lung model is 50 percent (30 MHz and 50um thick and 500um wide), the ejection of a large number of liquid drops occurs (30 MHz and 50um thick and 2000um wide), the deposition efficiency of the lung model is 21 percent, the deposition efficiency of the lung model is 60MHz and 50um thick and 2000um wide, and the deposition efficiency of the lung model is 32 percent. The deposition efficiency of the lung model (60 MHz, 100um thickness and 500um width) can reach 69%, and the deposition efficiency of the lung model (30 MHz, 100um thickness and 500um width) can reach 43%. The deposition efficiency of the existing ohm dragon medical atomizer is 30 percent when the existing ohm dragon medical atomizer atomizes, and P is less than 0.01, so that obvious statistical significance exists on the difference between the existing ohm dragon medical atomizer and the existing ohm dragon medical atomizer. Therefore, from the dosage point of view only, the result shows that the surface acoustic wave atomizer based on the microfluidic liquid supply has better effect compared with the prior art.

The foregoing is a further detailed description of the invention in connection with the preferred embodiments, and it is not intended that the invention be limited to the specific embodiments described. It will be apparent to those skilled in the art that several simple deductions or substitutions may be made without departing from the spirit of the invention, and these should be considered to be within the scope of the invention.

Claims (7)

1. A surface acoustic wave atomizer based on microfluidic liquid supply is characterized in that: the surface acoustic wave device comprises a substrate, wherein an interdigital transducer is arranged on the substrate, one side of the surface acoustic wave device is provided with a micro flow channel, the micro flow channel comprises a photoresist micro flow channel positioned at the bottom layer, the surface of the micro flow channel is provided with a silicon dioxide film layer, a PDMS layer which is subjected to oxygen plasma treatment is arranged above the silicon dioxide film layer, and the PDMS layer is combined with the photoresist micro flow channel in a thermal bonding mode to form a closed micro flow channel.

2. The microfluidic liquid supply based surface acoustic wave atomizer according to claim 1, wherein: the height of the micro flow channel is 50-100 mu m.

3. The microfluidic liquid supply based surface acoustic wave atomizer according to claim 2, wherein: the flow channel width of the micro flow channel is smaller than 2000 mu m.

4. The microfluidic liquid supply based surface acoustic wave atomizer according to claim 1, wherein: the thickness of the silicon dioxide film layer is 200-400nm.

5. The microfluidic liquid supply based surface acoustic wave atomizer according to claim 4, wherein: the thickness of the silicon dioxide film layer is 300nm.

6. The microfluidic liquid supply based surface acoustic wave atomizer according to claim 4, wherein: the surface acoustic wave device comprises a piezoelectric substrate and an interdigital transducer, wherein the interdigital transducer is arranged on the piezoelectric substrate.

7. The method for preparing the surface acoustic wave atomizer based on microfluidic liquid supply according to any one of claims 1 to 6, comprising the steps of:

step S1, arranging an interdigital transducer on a piezoelectric substrate to obtain a surface acoustic wave device;

s2, manufacturing a photoresist microfluidic channel by using a photoetching process, wherein the photoresist microfluidic channel is positioned at one side of the piezoelectric substrate and is not in the propagation direction of sound waves;

s3, depositing a silicon dioxide film layer on the upper surface of the photoresist microfluidic channel to form irreversible permanent bonding;

and S4, manufacturing a PDMS layer above the photoresist microfluidic channel, performing oxygen plasma treatment, and combining the PDMS layer with the photoresist microfluidic channel in a thermal bonding mode.