A method and device for manipulating nanoparticles based on the principle of acoustic streaming suppression

Abstract

The present application relates to the technical field of nanomanipulation, and more particularly to a method and device for manipulating nanoparticles based on the principle of acoustic streaming suppression, the method comprising the following steps: S1. setting a microfluidic chip with a cavity; S2. establishing a target standing wave acoustic field in the cross section of the cavity, wherein the sound pressure node plane of the target standing wave acoustic field is parallel to the adjacent side wall of the cavity; S3. introducing a fluid containing nanoparticles into the cavity, and the nanoparticles can be driven to the sound pressure node region under the action of acoustic radiation force and form a stable aggregation cluster; the device comprises a microfluidic chip, the microfluidic chip is provided with a cavity, and the surface of the microfluidic chip is provided with an acoustic wave driving structure, and the sound pressure node plane of the standing wave acoustic field generated by the acoustic wave driving structure is parallel to the adjacent side wall of the cavity. The present application can realize the directional or point manipulation of nanoparticles under the action of actively suppressing acoustic streaming interference.

Description

Technical Field

[0001] This invention relates to the field of nanotechnology, and more specifically, to a method and apparatus for manipulating nanoparticles based on the principle of acoustic flow suppression. Background Technology

[0002] With the rapid development of nanotechnology, nanoparticles are increasingly being used in biomedical detection, targeted drug delivery, and micro / nano device assembly. To achieve efficient and non-destructive manipulation of nanoparticles, existing acoustic manipulation techniques are considered highly promising methods due to their advantages such as non-contact, label-free operation, and good biocompatibility. Among these, acoustic radiation force, as the core physical mechanism, can apply controllable forces to particles by adjusting acoustic field parameters, thereby achieving precise manipulation such as directional migration and spatial arrangement.

[0003] However, existing nanomanipulation methods based on acoustic radiation force still have some problems: when sound waves act on a liquid medium, in addition to generating acoustic radiation force, they also induce acoustic flow drag force caused by acoustic flow. Especially in microfluidic systems, the vortex flow induced by acoustic flow can compete with the acoustic radiation force, leading to unintended diffusion, migration trajectory deviation, or destruction of aggregate structures of nanoparticles. Although the acoustic flow effect can be reduced or balanced by lowering the sound pressure level or introducing external physical fields, such as electric fields, these methods often sacrifice manipulation efficiency or increase system complexity, making it difficult to achieve high-throughput operation. Summary of the Invention

[0004] The purpose of this invention is to overcome the shortcomings of existing technologies in terms of particle manipulation accuracy due to the acoustic flow effect, and to provide a nanoparticle manipulation method and device based on the acoustic flow suppression principle, which can achieve directional or point-to-point manipulation of nanoparticles under the effect of actively suppressing acoustic flow interference.

[0005] To solve the above-mentioned technical problems, the technical solution adopted by the present invention is as follows:

[0006] A method for manipulating nanoparticles based on the principle of acoustic flow suppression is provided, comprising the following steps:

[0007] S1. Set up a microfluidic chip with cavities;

[0008] S2. Establish a target standing wave sound field in the cross section of the cavity, wherein the sound pressure node plane of the target standing wave sound field is parallel to the adjacent sidewall of the cavity.

[0009] S3. Fluid containing nanoparticles is introduced into the cavity. Under the action of acoustic radiation force, the nanoparticles can migrate and be driven to the acoustic pressure node region, and form stable agglomerates.

[0010] The present invention provides a nanoparticle manipulation method based on the principle of acoustic flow suppression. When the acoustic pressure node plane of the target standing wave sound field is parallel to the adjacent sidewall of the cavity, the boundary layer driven acoustic flow in the cavity will be completely suppressed or eliminated. Thus, the acoustic radiation force generated by the radial acoustic pressure gradient can drive the nanoparticles to the acoustic pressure node plane, thereby realizing the directional or fixed-point manipulation of the nanoparticles.

[0011] Furthermore, in step S1, the microfluidic chip is any one of a glass microfluidic chip, a silicon microfluidic chip, a metal microfluidic chip, or a plastic microfluidic chip.

[0012] Further, in step S2, the target standing wave sound field is established based on the following target acoustic mode:

[0013]

[0014] In the formula, u L Represents the limiting velocity, ω represents the angular frequency, u1 represents the first-order sound velocity, * represents the complex conjugate, u 1|| Let u1 represent the component along the tangent direction of the fluid-solid boundary, || represent the tangent direction of the fluid-solid boundary, and d represent the differential operator.

[0015] Furthermore, in step S2, the number of sound pressure nodes is set to one or more, and a radial gradient sound pressure distribution is formed in the target standing wave sound field, which can be used to generate acoustic radiation force pointing towards the sound pressure nodes for the nanoparticles in the fluid in step S3.

[0016] Furthermore, in step S2, a signal generator and one or more ultrasonic transducers are set up. The signal generator generates a sinusoidal signal and transmits it to the ultrasonic transducers to generate the target standing wave sound field.

[0017] Furthermore, in step S2, the ultrasonic excitation frequency of the ultrasonic transducer is the resonant frequency of the target standing wave sound field within the cavity.

[0018] Further, in step S2, a single-frequency sound field of 1 to 10 MHz is applied to the microfluidic chip.

[0019] Further, in step S3, the radius r of the nanoparticles p The range is 50-500nm.

[0020] The present invention also provides a manipulation device for a nanoparticle manipulation method, including a microfluidic chip, the microfluidic chip having a cavity, and an acoustic wave driving structure mounted on the surface of the microfluidic chip, wherein the sound pressure node plane of the standing wave sound field generated by the acoustic wave driving structure is parallel to the adjacent sidewall of the cavity.

[0021] Preferably, the cavity has an inlet and an outlet at both ends that are connected to the outside. The outlet is covered with a cover glass, and a right-angle prism is provided at one end of the outlet. The inclined surface of the right-angle prism faces the outlet, and the inclined surface of the right-angle prism is coated with an aluminum film.

[0022] Compared with the prior art, the beneficial effects of the present invention are:

[0023] 1. When the sound pressure node plane of the target standing wave sound field is parallel to the adjacent sidewall of the cavity, the boundary layer driven acoustic flow in the cavity will be completely suppressed or eliminated. Thus, the acoustic radiation force generated by the radial sound pressure gradient can drive the nanoparticles to the sound pressure node plane, realizing the directional or point-to-point manipulation of the nanoparticles.

[0024] 2. The right-angle prism setting facilitates the imaging of microparticle patterns when observing with a microscope. Attached Figure Description

[0025] Figure 1 This is a flowchart of a nanoparticle manipulation method based on the principle of acoustic flow suppression according to the present invention;

[0026] Figure 2 This is a schematic diagram of the target standing wave sound field with different numbers of sound pressure node planes when the cross-section of the cavity of the present invention has an arbitrary shape;

[0027] Figure 3 The figure shows the simulation results of the acoustic dynamics of nanoparticles of different sizes under different target standing wave acoustic fields when the cross-section of the cavity of the present invention is circular.

[0028] Figure 4 This is a cavity model when the cross-section of the cavity in this invention is a rectangle with rounded corners;

[0029] Figure 5 This diagram illustrates the evolution of the acoustic pressure node plane within the cavity under different fillet radius ratios according to the present invention.

[0030] Figure 6 This is a comparison diagram of the boundary acoustic flow velocity when the cross-section of the cavity in this invention is a rectangle with rounded corners;

[0031] Figure 7 This is an experimental diagram showing the effect of nanoparticle aggregation under different numbers of sound pressure node planes when the cross-section of the cavity is circular in this invention;

[0032] Figure 8 This is a schematic diagram of the structure of the first embodiment of the control device of the present invention;

[0033] Figure 9 This is a schematic diagram of the structure of the second embodiment of the control device of the present invention.

[0034] In the attached diagram: 100, microfluidic chip; 110, cavity; 200, acoustic wave driven structure; 300, cover glass; 400, right-angle prism; 500, chip holder. Detailed Implementation

[0035] The present invention will be further described below with reference to specific embodiments. The accompanying drawings are for illustrative purposes only, representing schematic diagrams rather than actual physical objects, and should not be construed as limiting the scope of this patent. To better illustrate the embodiments of the present invention, some components in the drawings may be omitted, enlarged, or reduced, and do not represent the actual dimensions of the product. It is understandable to those skilled in the art that some well-known structures and their descriptions may be omitted in the drawings.

[0036] Those skilled in the art will understand that embodiments of the present invention can be provided as methods, systems, or computer program products. Therefore, the present invention can take the form of a completely hardware embodiment, a completely software embodiment, or an embodiment combining software and hardware aspects.

[0037] It should be noted that the terms "comprising" and "having" and any variations thereof in the specification, claims and accompanying drawings of this invention are intended to cover non-exclusive inclusion. For example, a process, method, system, product or device that includes a series of steps or units is not necessarily limited to those steps or units explicitly listed, but may include other steps or units not explicitly listed or inherent to such process, method, product or device.

[0038] In the accompanying drawings of the embodiments of the present invention, the same or similar reference numerals correspond to the same or similar components. In the description of the present invention, it should be understood that if terms such as "upper," "lower," "left," "right," etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the drawings, they are only for the convenience of describing the present invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, the terms used to describe positional relationships in the drawings are only for illustrative purposes and should not be construed as limiting the present patent. For those skilled in the art, the specific meaning of the above terms can be understood according to the specific circumstances.

[0039] Example 1

[0040] like Figures 1 to 7 The image shows a first embodiment of a nanoparticle manipulation method based on the principle of acoustic flow suppression according to the present invention, which includes the following steps:

[0041] S1. A microfluidic chip 100 with a cavity 110 is provided;

[0042] S2. Establish a target standing wave sound field in the cross section of cavity 110, wherein the sound pressure node plane of the target standing wave sound field is parallel to the adjacent sidewall of cavity 110.

[0043] S3. Fluid containing nanoparticles is introduced into cavity 110. Under the action of acoustic radiation force, the nanoparticles can migrate and be driven to the acoustic pressure node region, and form stable agglomeration clusters.

[0044] In this embodiment, the microfluidic chip 100 is any one of a glass microfluidic chip, a silicon microfluidic chip, a metal microfluidic chip, or a plastic microfluidic chip.

[0045] In step S2, the target standing wave sound field is established based on the following target acoustic mode:

[0046]

[0047] In the formula, u L Represents the limiting velocity, ω represents the angular frequency, u1 represents the first-order sound velocity, * represents the complex conjugate, u 1|| Let u1 represent the component along the tangent direction of the fluid-solid boundary, || represent the tangent direction of the fluid-solid boundary, and d represent the differential operator.

[0048] In this embodiment, the number of sound pressure nodes is set to one or more, forming a radial gradient sound pressure distribution within the target standing wave sound field. This distribution can be used in step S3 to generate acoustic radiation forces directed towards the sound pressure nodes on the nanoparticles within the fluid. Figure 2 The cross-section of cavity 110 is shown. The cross-section of cavity 110 is of arbitrary shape. The dashed line represents the sound pressure node plane, and the sound pressure node plane is parallel to the adjacent sidewall of cavity 110. At this time, the boundary layer driven acoustic flow in cavity 110 will be completely suppressed or eliminated. Thus, the acoustic radiation force generated by the radial sound pressure gradient can drive the nanoparticles to the sound pressure node plane in step S3, realizing the directional or point-to-point manipulation of nanoparticles.

[0049] Specifically, in step S2, a signal generator and one or more ultrasonic transducers are used to generate a sinusoidal signal, which is then transmitted to the ultrasonic transducers to produce a target standing wave sound field. In this embodiment, the ultrasonic excitation frequency of the ultrasonic transducer is the resonant frequency of the target standing wave sound field within the cavity 110. Preferably, a single-frequency sound field of 1 to 10 MHz is applied to the microfluidic chip 100.

[0050] Specifically, one method for verifying acoustic flow suppression involves selecting a circular cross-section for cavity 110 with a diameter D of 1.6 mm, introducing an aqueous solution as the fluid, and using polystyrene nanoparticles. The verification steps include:

[0051] Calculate the target standing wave acoustic field distribution and its resonant frequency within cavity 110;

[0052] Set the boundary vibration intensity to generate a target standing wave sound field in the cross section of cavity 110;

[0053] Calculate the acoustic flow and acoustic radiation force distribution under the target standing wave acoustic field;

[0054] Solve the acoustic dynamics of nanoparticles of different sizes in cavity 110 under the combined action of acoustic radiation force and acoustic flow drag force in the target standing wave acoustic field;

[0055] By changing the value of diameter D and repeating the above steps, the acoustic dynamics of nanoparticles in cavities 110 of different sizes can be calculated.

[0056] like Figure 3 As shown, (a), (b), and (c) represent the target standing wave sound fields containing single, double, and triple sound pressure node planes, respectively. The sound pressure node planes of the target standing wave sound fields are parallel to the adjacent sidewalls of the cavity 110. Under this sound field condition, the acoustic velocity at all points on the cross-section is 0, and the radial sound pressure gradient can generate an acoustic radiation force distribution pointing towards the sound pressure nodes. Figure 3 In Figures (d), (e), and (f), the motion and aggregation of nanoparticles are shown under target standing wave acoustic fields with single, double, and triple acoustic pressure nodes, respectively. Particle sonophoresis results indicate that polystyrene nanoparticles of different sizes can be driven to the acoustic pressure nodes by acoustic radiation force under different target standing wave acoustic fields. Furthermore, the variation in the cross-sectional diameter D of cavity 110 only affects the resonant frequency under the same acoustic field structure, but does not affect the distribution law of acoustic radiation force or its control precision.

[0057] Specifically, for the second verification method of acoustic flow suppression, the cross-section of cavity 110 is selected as a rectangle with rounded corners, the cross-sectional width L is 1.6mm, and the rounded corner radius R is variable, such as... Figure 4 As shown, the fluid introduced is an aqueous solution, and the nanoparticles are polystyrene nanoparticles; the verification operation steps include:

[0058] Calculate the target standing wave acoustic field distribution and its resonant frequency in cavity 110 under different R values;

[0059] Set the boundary vibration intensity to generate a sound field with the same sound pressure amplitude in cavity 110 under different R values, and set the sound pressure amplitude to be the same as the sound pressure amplitude of one of the verification methods;

[0060] Calculate and compare the magnitude of acoustic velocity within cavity 110 under different R values;

[0061] The acoustic dynamics of nanoparticles of different sizes in a cavity under the combined action of acoustic radiation force and acoustic flow drag force under different R values ​​are determined; the lower limit of particle size that can be controlled by acoustic radiation force in a cavity under different R values ​​is compared.

[0062] Among them, such as Figure 5 As shown, with the increase of the fillet radius ratio (0.05≤R / L<0.5), the shape of the sound pressure node plane gradually transitions to a rounded square, eventually approaching a circle, and the parallelism between the sound pressure node plane and the sidewall of cavity 110 is significantly enhanced. The sound radiation force can overcome the sound flow interference and gradually approaches complete overcoming it; as shown... Figure 6 As shown, by adjusting the fillet radius ratio and analyzing it, we can obtain the limiting velocity u of cavity 110 under the same sound pressure amplitude. L The pressure decreases rapidly as R increases. Therefore, it can also be concluded that when the sound pressure node plane is parallel to the adjacent sidewall of cavity 110, the boundary layer driven acoustic flow within cavity 110 will be completely suppressed or eliminated.

[0063] Specifically, one experimental method for manipulating nanoparticles involves selecting a glass microfluidic chip, a cavity 110 with a circular cross-section and a diameter D of 1.6 mm, and an ultrasonic transducer operating at the resonant frequency f of the cavity 110. r The operating steps include:

[0064] An aqueous solution containing polystyrene nanoparticles is injected into cavity 110, wherein the radius r of the nanoparticles is... p 50-500nm;

[0065] Apply 20Vpp at a frequency of f r The ultrasonic drive, wherein the signal generator generates a continuous sinusoidal signal to drive the ultrasonic transducer to vibrate at ultrasonic frequency;

[0066] The aggregation of polystyrene nanoparticles under a target standing wave acoustic field was observed using a microscope.

[0067] like Figure 7 As shown, radius r p Polystyrene nanoparticles in the 50-500nm range can be precisely driven to the sound pressure node plane region under the action of acoustic radiation force and form a stable cluster. By changing the excitation frequency of the ultrasonic transducer, different order resonant sound fields can be excited in the cavity 110, and different numbers of sound pressure node planes can be generated in the cross section of the cavity 110, realizing efficient directional manipulation of nanoparticles to single or multiple nodes.

[0068] Example 2

[0069] like Figure 8The illustration shows a first embodiment of a manipulation device according to the present invention, applied to the nanoparticle manipulation method based on the principle of acoustic flow suppression described in Embodiment 1. The manipulation device includes a microfluidic chip 100, which has a cavity 110. An acoustic wave driving structure 200 is mounted on the outer surface of the microfluidic chip 100. The sound pressure node plane of the standing wave sound field generated by the acoustic wave driving structure 200 is parallel to the adjacent sidewall of the cavity 110. In this embodiment, the acoustic wave driving structure 200 includes one or more ultrasonic transducers, and also includes a signal generator electrically connected to the ultrasonic transducers. The ultrasonic transducers are attached to the outer surface of the microfluidic chip 100.

[0070] Example 3

[0071] This embodiment is a second embodiment of a control device. This embodiment is similar to Embodiment 2, except that, as shown in the example... Figure 9 As shown, the cavity 110 has an inlet and an outlet at both ends, respectively, that communicate with the outside. A coverslip 300 is abutted at the outlet, and a right-angle prism 400 is provided at one end of the outlet. The inclined surface of the right-angle prism 400 faces the outlet, and the inclined surface of the right-angle prism 400 is coated with an aluminum film. This embodiment also includes a chip holder 500, on which the microfluidic chip 100 and the right-angle prism 400 are placed, facilitating the placement of the control device under a microscope for observation. Preferably, the right-angle prism 400 is an isosceles right-angle prism.

[0072] In use, the ultrasonic transducer excites an ultrasonic standing wave field within the cavity 110 of the microfluidic chip 100. The ultrasonic transducer is driven by a sinusoidal signal generated by a signal generator, amplified by a power amplifier, and the signal is monitored by an oscilloscope. The outlet of the cavity 110 is sealed with a cover glass 300 to block fluid flow and provide an optical observation window. An isosceles right-angled prism is placed next to the cover glass 300, with the inclined surface of the isosceles right-angled prism facing the cover glass 300, imaging the particle pattern of the cross-section of the cavity 110 at a magnification of 40x.

[0073] In the specific implementation of the above embodiments, the technical features can be combined in any non-contradictory way. For the sake of brevity, not all possible combinations of the above technical features are described. However, as long as the combination of these technical features is not contradictory, it should be considered to be within the scope of this specification.

[0074] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the implementation of the present invention. Those skilled in the art will recognize that other variations or modifications can be made based on the above description. It is neither necessary nor possible to exhaustively describe all possible implementations here. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the scope of protection of the claims of the present invention.

Claims

1. A method for manipulating nanoparticles based on the principle of acoustic flow suppression, characterized in that, Includes the following steps: S1. A microfluidic chip (100) with a cavity (110) is provided; S2. Establish a target standing wave sound field in the cross section of the cavity (110), wherein the sound pressure node plane of the target standing wave sound field is parallel to the adjacent sidewall of the cavity (110). S3. Fluid containing nanoparticles is introduced into the cavity (110). The nanoparticles can migrate and be driven to the sound pressure node region under the action of acoustic radiation force, and form a stable agglomeration cluster.

2. The nanoparticle manipulation method based on the principle of acoustic flow suppression according to claim 1, characterized in that, In step S1, the microfluidic chip (100) is any one of glass microfluidic chip, silicon microfluidic chip, metal microfluidic chip, and plastic microfluidic chip.

3. The nanoparticle manipulation method based on the principle of acoustic flow suppression according to claim 1, characterized in that, In step S2, the target standing wave sound field is established based on the following target acoustic mode: In the formula, u L Represents the limiting velocity, ω represents the angular frequency, u1 represents the first-order sound velocity, * represents the complex conjugate, u 1|| Let u1 represent the component along the tangent direction of the fluid-solid boundary, || represent the tangent direction of the fluid-solid boundary, and d represent the differential operator.

4. The nanoparticle manipulation method based on the principle of acoustic flow suppression according to claim 1, characterized in that, In step S2, the number of sound pressure nodes is set to one or more, and a radial gradient sound pressure distribution is formed in the target standing wave sound field, which can be used to generate sound radiation force pointing to the sound pressure nodes for nanoparticles in the fluid in step S3.

5. The nanoparticle manipulation method based on the principle of acoustic flow suppression according to claim 1, characterized in that, In step S2, a signal generator and one or more ultrasonic transducers are set up. The signal generator generates a sinusoidal signal and transmits it to the ultrasonic transducers to generate the target standing wave sound field.

6. The nanoparticle manipulation method based on the principle of acoustic flow suppression according to claim 5, characterized in that, In step S2, the ultrasonic excitation frequency of the ultrasonic transducer is the resonance frequency of the target standing wave sound field in the cavity (110).

7. The nanoparticle manipulation method based on the principle of acoustic flow suppression according to claim 1, characterized in that, In step S2, a single-frequency sound field of 1 to 10 MHz is applied to the microfluidic chip (100).

8. The nanoparticle manipulation method based on the principle of acoustic flow suppression according to claim 1, characterized in that, In step S3, the radius r of the nanoparticles p The range is 50-500nm.

9. A manipulation device applied to the nanoparticle manipulation method according to any one of claims 1 to 8, characterized in that, The device includes a microfluidic chip (100), which has a cavity (110). The surface of the microfluidic chip (100) is equipped with an acoustic wave driving structure (200), and the sound pressure node plane of the standing wave sound field generated by the acoustic wave driving structure (200) is parallel to the adjacent sidewall of the cavity (110).

10. The control device according to claim 9, characterized in that, The cavity (110) has an inlet and an outlet at both ends that are connected to the outside. A cover glass (300) is provided at the outlet. A right-angle prism (400) is provided at one end of the outlet. The inclined surface of the right-angle prism (400) faces the outlet, and the inclined surface of the right-angle prism (400) is coated with an aluminum film.

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