Dynamic acoustic field modulation and microparticle manipulation method based on digital microfluidics

Abstract

The application discloses a dynamic sound field modulation and particle control method based on digital microfluidics, realizes modulation of a sound field through a liquid drop, the liquid drop is located between an upper electrode plate and a lower electrode plate, the periphery of the liquid drop is air, and most of the energy of the sound wave can be transmitted to realize transmission because the sound impedance difference between the liquid and the glass is not large on the path of the sound wave on the lower electrode plate, the liquid drop and the upper electrode plate. Because the sound impedance difference between the air and the glass is very large, most of the sound wave energy is reflected at the air and glass interface and is difficult to transmit. By controlling the number and arrangement of the liquid drop, selective penetration of the sound wave at a specific position is realized, thereby forming a specific sound field. By controlling the real-time movement of the liquid drop, the sound field formed by the penetration is changed in real time, thereby achieving dynamic modulation of the sound field. The modulated sound field acts on a solution, the specific movement of particles is obtained through the sound field, and the particles are controlled, thereby achieving good application prospects in micro-assembly and cell control.

Description

Technical Field

[0001] This invention relates to the field of microfluidics, and more specifically to a method for dynamic sound field modulation and particle manipulation based on digital microfluidics technology. Background Technology

[0002] Acoustic manipulation offers advantages such as non-contact and remote operation, and its applications are wide-ranging, including drug delivery, cell screening, and in vitro diagnostics. The main component of an ultrasonic particle manipulation system is the ultrasonic transducer, which converts electrical energy into mechanical vibrations, generating sound waves in a fluid medium. When these sound waves interact with the fluid medium, two forces are generated: acoustic flow-induced force (ASF) and acoustic radiation force (ARF).

[0003] Acoustic flow is a steady fluid flow formed by the viscous decay of sound waves. As sound waves propagate through a fluid, the state of a fluid volume element is characterized by fluctuations in pressure and velocity. In an ideal fluid, the time-averaged displacement of the fluid element, i.e., the net flow rate, is zero everywhere. However, in real fluids, viscous decay causes the net displacement of the fluid element to be non-zero in each oscillation cycle. This localized effect leads to the formation of flow globally, thus generating acoustic flow.

[0004] The generation of acoustic radiation force is due to the transfer of wave momentum in the attenuating medium to the absorbing or scattering object. Its generation mechanism includes the dissipation of acoustic energy, reflection of incident waves, gradient changes in compressive wave velocity, and spatial inhomogeneity of energy density in standing waves.

[0005] Ultrasound can directly manipulate particles by applying acoustic radiation force, or indirectly drive particle motion by generating acoustic flow through sound pressure fields. Particles moving in fluids are also subject to viscous drag. The alpha radiation rate (ARF) is proportional to the cube of the particle radius, while the aspiral flow rate (ASF) is proportional to the particle radius. Therefore, as the particle radius decreases, the ARF decreases faster than the ASF. At the submicron scale, the ASF begins to play a dominant role in particle motion.

[0006] By leveraging acoustic radiation, suspended cells can be actively guided and precisely positioned on nodes or antinodes based on their compressibility and density characteristics. These cellular patterns can be kept fixed or dynamically reconstructed by changing the frequency or phase. For example, Armstrong et al. used sound waves to align myoblasts within a hydrogel, forming muscle tissue with bundles of myotonic tubes. These high-density tissue structures with acoustic alignment better replicate the structure of natural muscle tissue and exhibit anisotropic tensile mechanical properties. Combining acoustic manipulation with microfluidic systems can also enable the sorting of cells of different types or sizes.

[0007] Acoustic metasurfaces can be used to modulate the sound field of bulk acoustic waves. By designing and fabricating physical microstructures, the reflection, absorption, and transmission of sound waves can be effectively controlled, achieving effects such as directional sound transmission, energy focusing, and ultrasonic particle levitation. For example, by focusing ultrasound through acoustic holographic lenses, transcranial focused ultrasound can be used for non-invasive deep brain neural modulation. Kai Melde et al., by orthogonally arranging a combination of three bulk acoustic resonators and three acoustic metasurfaces, were able to generate a three-dimensional holographic sound field, enabling the three-dimensional patterning of particles and cells.

[0008] The aforementioned methods of sound field modulation using acoustic metasurfaces, or generating acoustic standing waves by arranging multiple acoustic devices, have already achieved patterned arrangements of particles and cells. However, this technology primarily produces static modulated sound fields, or merely generates regular linear or dot-like array patterns. Changing the sound field requires redesigning and manufacturing different metasurface structures. Therefore, real-time dynamic modulation of the sound field can provide acoustic operations with greater flexibility and has broader application prospects. Summary of the Invention

[0009] This invention discloses a dynamic sound field modulation method based on digital microfluidics, which can achieve dynamic modulation of the sound field. Simultaneously, this invention also discloses a dynamic particle manipulation method based on digital microfluidics, which can achieve dynamic manipulation of particles.

[0010] A dynamic sound field modulation method based on digital microfluidics modulates the sound field through a droplet positioned between an upper and lower electrode plate, surrounded by air. An acoustic resonator is connected to the lower electrode plate via an ultrasonic coupling agent or water. The sound waves generated by the acoustic resonator travel through the lower electrode plate, droplet, and upper electrode plate. Due to the small difference in acoustic impedance between the liquid and glass, most of the sound wave energy can be transmitted. However, along the path between the lower electrode plate, air, and upper electrode plate, the significant difference in acoustic impedance between air and glass causes most of the sound wave energy to be reflected at the air-glass interface, hindering transmission. By controlling the number and arrangement of the droplets, selective penetration of the sound waves at specific locations is achieved, thus forming a specific sound field. By controlling the real-time movement of the droplet between the upper and lower electrode plates, the sound field formed by the penetration changes in real time, thereby achieving dynamic modulation of the sound field.

[0011] Preferably, the distribution and movement of droplets are controlled by a digital microfluidic chip.

[0012] Preferably, the upper electrode plate is a glass plate.

[0013] Preferably, the lower electrode plate is a glass plate.

[0014] Preferably, the droplet is a water droplet.

[0015] The microparticle manipulation method based on digital microfluidics applies an acoustic field obtained through the above modulation method to a solution containing microparticles. The solution is connected to an upper electrode by an ultrasonic coupler. The acoustic flow generated by the bulk acoustic wave, the acoustic radiation force, and the viscous resistance of the particles moving in the solution work together to drive the movement of the microparticles in the solution. The acoustic field is modulated by controlling the movement of the droplets, and the specific movement of the microparticles is obtained through the acoustic field, thus realizing the manipulation of the microparticles.

[0016] Furthermore, the microparticles are carbon particles, polystyrene microspheres, or cells.

[0017] Furthermore, particle motion includes particle patterning, particle capture, or particle transfer.

[0018] The beneficial effects of this invention are:

[0019] (1) A single sound field can be modulated to become a controllable, dynamically changing sound field. The rapid movement of the droplet can enable the sound field to be rapidly changed and transmitted to the next level.

[0020] (2) The dynamic modulation method of sound field proposed in this invention has been experimentally verified to capture and manipulate microparticles, realize the patterning of microparticles deposited at the bottom of the solution, realize the controllable aggregation and capture of polystyrene microspheres suspended in the solution, and the movement of droplets can also control the movement of microparticles. It has very good application prospects in micro-assembly and cell manipulation. Attached Figure Description

[0021] Figure 1 This is a schematic diagram illustrating the principle of droplet-controlled acoustic field in digital microfluidics;

[0022] Figure 2 This is an experiment and schematic diagram of dual-droplet controlled acoustic field patterning;

[0023] Figure 3 The experiment involved the suspension and aggregation of polystyrene microspheres using a modulated sound field.

[0024] Figure 4 These are experimental images showing how the movement of droplets modulates the sound field, causing aggregated polystyrene microspheres to move over a wide area.

[0025] Figure 5 It is an experiment that adjusts the frequency of the bulk acoustic resonator to control the small-range movement of aggregated polystyrene microspheres. Detailed Implementation

[0026] To make the technical problems solved by the present invention, the technical solutions adopted, and the technical effects achieved clearer, the technical solutions of the present invention will be further described below in conjunction with the accompanying drawings and specific embodiments. It should be understood that the specific embodiments described herein are merely for explaining the present invention and are not intended to limit the present invention. Furthermore, it should be noted that, for ease of description, only the parts related to the present invention are shown in the accompanying drawings, not all of them.

[0027] Sound field modulation principle:

[0028] Due to the different degrees of acoustic impedance matching between solids and liquids and gases, the propagation ability of sound waves at solid-liquid interfaces and solid-gas interfaces varies greatly. The formula for calculating acoustic impedance is: .

[0029] At an acoustic interface, when a sound wave propagates from one medium to another, partial sound wave reflection and partial sound wave transmission occur. The acoustic reflection coefficient R of the interface between two materials can be calculated from their acoustic impedance.

[0030] Assuming the acoustic impedance of medium 1 is Z1 and the acoustic impedance of medium 2 is Z2, then the formula for the acoustic reflection coefficient φ is:

[0031] ;

[0032] This formula describes the reflection of sound waves at the interface between two media with different acoustic impedances. The reflection coefficient R ranges from -1 to 1: when R = 0, it means that the acoustic impedances of the two media are equal, there is no reflection, and all sound waves are transmitted into the second medium. When R = 1 or R = -1, it means complete reflection, and sound waves cannot be transmitted into the second medium. When R is between -1 and 1, some sound waves are reflected, and some are transmitted.

[0033] like Figure 1 As shown, the droplet in the middle layer is in contact with the glass electrode in the vertical direction, while the remaining area around the droplet is air. During the upward propagation of sound waves, two different paths exist. One path passes through air 23, and the other passes through the droplet 21. Due to the significant difference in acoustic impedance between air and glass, a large amount of sound wave energy is reflected between the two media, hindering the propagation of sound wave energy. The difference in acoustic impedance between the liquid and the solid is not significant, allowing more sound wave energy to propagate upwards. Thus, the large-scale sound field 25 can be transformed into a small-scale sound field 20 through the droplet and transmitted upwards, completing the modulation of the sound field.

[0034] Digital microfluidic acoustic field modulation principle. Utilizing the principle of dielectric electrowetting, digital microfluidic (DMF) systems can achieve highly flexible and precise droplet manipulation at the picoliter scale. A digital microfluidic chip consists of two glass plates, one above the other, with electrodes arranged on them. Between these two plates lies a controllable droplet. By switching the electrodes on or off, changing the voltage applied to the droplet's location, its movement can be easily manipulated.

[0035] The movement of droplets in digital microfluidic chips is very flexible and fast. The movement and distribution of droplets can be dynamically controlled to determine whether the sound wave energy at different positions can be transmitted to the next stage, thereby changing the state of the sound field transmitted to the solution tank.

[0036] The modulated small-scale sound field is transmitted to the solution tank above. The acoustic flow generated by the bulk sound wave, the acoustic radiation force, and the viscous resistance of the particles moving in the solution work together to drive the movement of the particles in the solution tank.

[0037] The particles can be carbon particles, polystyrene microspheres, or cells. According to an embodiment of the invention, the particles are in an aqueous medium.

[0038] Figure 1 This demonstrates the principle of dynamic modulation of a sound field using a digital microfluidic system. The digital microfluidic chip consists of an upper electrode 22, a droplet 21, and a lower electrode 24. The upper electrode 22 is made of ITO glass, and the lower electrode 24 has electrodes disposed thereon. Both electrodes are coated with a hydrophobic material. By switching the on / off state of the electrodes on the lower electrode 24, the applied voltage can change the hydrophilicity and hydrophobicity of the droplet 21, thereby controlling the movement of the droplet 21.

[0039] A bulk acoustic resonator at the bottom of the digital microfluidic chip generates a large-scale uniform sound field 25. Both the upper and lower plates of the digital microfluidic chip are made of glass, and the droplet is surrounded by air 23. Due to the different acoustic impedance matching, as the sound field 25 propagates upwards from the bottom, almost all the sound waves reaching the air 23 interface are reflected, and the sound field can only pass through the location of the droplet 21. Therefore, the large-scale sound field, after modulation by the droplet 21, can be transformed into a small-scale sound field 20. As the droplet 21 moves, the modulated sound field 20 also changes accordingly. Furthermore, multiple droplets 21 can modulate the sound field simultaneously.

[0040] A solution tank is positioned above the digital microfluidic chip and connected to it via water or an ultrasonic coupling agent. The solution tank contains a solution. Microparticles are located within the solution. These microparticles can be carbon particles, polystyrene, or cells. A sound field modulated using a volumetric acoustic field dynamic modulation method acts on the solution in the tank. The acoustic flow generated by the volumetric acoustic waves, the acoustic radiation force, and the viscous resistance of the particles moving in the solution work together to drive the movement of the microparticles, enabling particle capture, transfer, and patterning.

[0041] Example 1: Patterning of carbon particles

[0042] like Figure 1 As shown, droplet movement in digital microfluidics is highly flexible and rapid, dynamically controlling whether acoustic energy at different locations can be transferred to the next stage. The combined effect of acoustic flow, acoustic radiation force, and viscous resistance can drive the movement of particles in the solution layer. Based on the aforementioned dynamic acoustic field modulation method and principle, the system's ability to drive deposited particles with a density greater than water was verified by driving carbon particles deposited at the bottom of the solution tank.

[0043] Figure 2 This demonstrates an experiment on carbon particle patterning. The left image shows the experiment, and the right image is a schematic diagram of the droplet actuation at the corresponding moment. The droplet is located within a digital microfluidic chip. The black area represents the carbon particles in the upper solution tank. After activating the bulk acoustic resonator, sound waves are generated in the droplet area, repelling the carbon particles outwards. The entire process, from activating the acoustic device to the carbon particles reaching their maximum size, takes approximately one second. By using the digital microfluidic chip to drive the droplet's movement, a concave carbon particle pattern can be left in the area the droplet traverses. The large-scale uniform sound field at the bottom remains unchanged. Individual control of multiple droplets allows for simultaneous pattern drawing at different locations. By planning the droplet's movement path, arbitrary target patterns can be generated.

[0044] Example 2: Manipulation of polystyrene microspheres

[0045] The aggregation experiment of suspended polystyrene microspheres can verify the ability of the sound field obtained by the sound field modulation method of this invention to manipulate suspended particles. This invention can also be extended to the manipulation of suspended microparticles such as cells.

[0046] Figure 3 , Figure 4 , Figure 5 Experiments were conducted to demonstrate the suspension and aggregation of 20-micrometer polystyrene microspheres, the large-scale movement of aggregated droplets, and the small-scale movement controlled by frequency.

[0047] The specific preparation method of the polystyrene microsphere suspension is as follows: First, a 10 mg / ml bovine serum albumin solution is prepared using deionized water. Then, an appropriate amount of high-concentration polystyrene dispersion solution is added and the mixture is dispersed by vibration. While deionized water alone can achieve microsphere aggregation, using bovine serum albumin to adjust the solution viscosity results in a more stable suspension of the aggregated microspheres.

[0048] Add 3 ml of the spherical suspension solution to the solution tank. Adjust the control signal frequency of the bulk acoustic wave resonator to 960 kHz, turn on the bulk acoustic wave resonator, and you can see... Figure 3 The microspheres demonstrated achieved aggregation in approximately half a minute, and could stably aggregate in the central region of the controlled droplet. For example... Figure 4 As shown, after aggregation, the movement of the droplets is modulated by the acoustic field within the chip using a digital microfluidic system, allowing the aggregated microspheres to follow the droplets for a wide range of transfer. Adjusting the frequency of the acoustic waves within a range of approximately 10 kHz allows for... Figure 5 The captured particles are shown to move within a small range, the range of which is the size of the modulated droplet.

[0049] The particle control method proposed in this invention is not limited to the particles mentioned in the above examples. According to the method proposed in this invention, suspended particles or particles settled at the bottom of a solution that are not mentioned can be manipulated.

[0050] In the description of this invention, it should be noted that the terms "upper", "lower", "left", "right", "clockwise" and "counterclockwise" indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are only for the convenience of describing this 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, they should not be construed as limiting this invention.

[0051] The above embodiments merely illustrate the basic principles and characteristics of the present invention. The present invention is not limited to the above embodiments. Various changes and modifications can be made to the present invention without departing from its spirit and scope, and all such changes and modifications fall within the scope of the present invention as claimed. The scope of protection of the present invention is defined by the appended claims and their equivalents.

Claims

1. A dynamic sound field modulation method based on digital microfluidics, characterized in that, Sound field modulation is achieved through droplets positioned between the upper and lower electrodes, surrounded by air. Along the path of the sound wave passing through the lower electrode, droplet, and upper electrode, most of the sound wave energy can be transmitted due to the small difference in acoustic impedance between the liquid and glass. However, along the path of the sound wave passing through the lower electrode, air, and upper electrode, the significant difference in acoustic impedance between the air and glass causes most of the sound wave energy to be reflected at the air-glass interface, making transmission difficult. By controlling the number and arrangement of the droplets, selective penetration of sound waves at specific locations is achieved, thus forming a specific sound field. By controlling the real-time movement of the droplets between the upper and lower electrodes, the sound field formed by the penetration changes in real time, thereby achieving dynamic modulation of the sound field.

2. The dynamic sound field modulation method based on digital microfluidics as described in claim 1, characterized in that, The distribution and movement of droplets are controlled by digital microfluidic chips.

3. The dynamic sound field modulation method based on digital microfluidics as described in claim 1, characterized in that, The upper electrode plate is a glass plate.

4. The dynamic sound field modulation method based on digital microfluidics as described in claim 1, characterized in that, The lower electrode plate is a glass plate.

5. The dynamic sound field modulation method based on digital microfluidics as described in claim 1, characterized in that, The droplets are water droplets.

6. A particle manipulation method based on digital microfluidics, characterized in that, The modulation method of claim 1 is used to obtain a sound field that acts on a solution containing microparticles. The solution container is connected to an upper electrode plate via an ultrasonic coupling agent. The acoustic flow generated by the bulk acoustic wave, the acoustic radiation force, and the viscous resistance of the particles moving in the solution work together to drive the movement of the microparticles in the solution. The sound field is modulated by controlling the movement of the droplets, and the specific movement of the microparticles is controlled by the sound field to achieve manipulation of the microparticles.

7. The particle manipulation method based on digital microfluidics as described in claim 6, characterized in that, The microparticles are carbon particles, polystyrene microspheres, or cells.

8. The particle manipulation method based on digital microfluidics as described in claim 6, characterized in that, Particle motion includes particle patterning, particle capture, or particle transfer.

9. The particle manipulation method based on digital microfluidics as described in claim 6, characterized in that, By adjusting the frequency of the sound waves, the captured particles can be controlled to move within a small range.

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